Prostate cancer is
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
of the
prostate
The prostate is both an Male accessory gland, accessory gland of the male reproductive system and a muscle-driven mechanical switch between urination and ejaculation. It is found only in some mammals. It differs between species anatomically, ...
. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a
gland
In animals, a gland is a group of cells in an animal's body that synthesizes substances (such as hormones) for release into the bloodstream (endocrine gland) or into cavities inside the body or its outer surface (exocrine gland).
Structure
De ...
in the
male reproductive system
The male reproductive system consists of a number of sex organs that play a role in the process of human reproduction. These organs are located on the outside of the body and within the pelvis.
The main male sex organs are the penis and the tes ...
that surrounds the
urethra
The urethra (from Greek οὐρήθρα – ''ourḗthrā'') is a tube that connects the urinary bladder to the urinary meatus for the removal of urine from the body of both females and males. In human females and other primates, the urethra con ...
just below the
bladder
The urinary bladder, or simply bladder, is a hollow organ in humans and other vertebrates that stores urine from the kidneys before disposal by urination. In humans the bladder is a distensible organ that sits on the pelvic floor. Urine enters ...
. It is located in the hypogastric region of the abdomen. To give an idea of where it is located, the bladder is superior to the prostate gland as shown in the image The rectum is posterior in perspective to the prostate gland and the ischial tuberosity of the pelvic bone is inferior. Only those who have male reproductive organs are able to get prostate cancer. Most prostate cancers are slow growing. Cancerous cells may
spread
Spread may refer to:
Places
* Spread, West Virginia
Arts, entertainment, and media
* ''Spread'' (film), a 2009 film.
* ''$pread'', a quarterly magazine by and for sex workers
* "Spread", a song by OutKast from their 2003 album ''Speakerboxxx/T ...
to other areas of the body, particularly the
bones
A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, an ...
and
lymph nodes
A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that includ ...
. It may initially cause no symptoms. In later stages, symptoms include pain or difficulty
urinating
Urination, also known as micturition, is the release of urine from the urinary bladder through the urethra to the outside of the body. It is the urinary system's form of excretion. It is also known medically as micturition, voiding, uresis, ...
,
blood in the urine
Hematuria or haematuria is defined as the presence of blood or red blood cells in the urine. “Gross hematuria” occurs when urine appears red, brown, or tea-colored due to the presence of blood. Hematuria may also be subtle and only detectable w ...
, or
pain in the pelvis or back.
Benign prostatic hyperplasia
Benign prostatic hyperplasia (BPH), also called prostate enlargement, is a noncancerous increase in size of the prostate gland. Symptoms may include frequent urination, trouble starting to urinate, weak stream, inability to urinate, or loss o ...
may produce similar symptoms. Other late symptoms include fatigue, due to
low levels of red blood cells.
Factors that increase the risk of prostate cancer include older age, family history and
race
Race, RACE or "The Race" may refer to:
* Race (biology), an informal taxonomic classification within a species, generally within a sub-species
* Race (human categorization), classification of humans into groups based on physical traits, and/or s ...
.
About 99% of cases occur after age 50.
[ A ]first-degree relative
A first-degree relative (FDR) is a person's parent (father or mother), full sibling (brother or sister) or child. It constitutes a category of family members that largely overlaps with the term nuclear family, but without spouses.
If the persons ...
with the disease increases the risk two- to three-fold.[ Other factors include a ]diet
Diet may refer to:
Food
* Diet (nutrition), the sum of the food consumed by an organism or group
* Dieting, the deliberate selection of food to control body weight or nutrient intake
** Diet food, foods that aid in creating a diet for weight loss ...
high in processed meat
Processed meat is considered to be any meat which has been modified in order to either improve its taste or to extend its shelf life. Methods of meat processing include salting, curing, fermentation, smoking, and/or the addition of chemical pre ...
and red meat
In gastronomy, red meat is commonly red when raw and a dark color after it is cooked, in contrast to white meat, which is pale in color before and after cooking. In culinary terms, only flesh from mammals or fowl (not fish) is classified as ...
,[ while the risk from a high intake of ]milk products
Dairy products or milk products, also known as lacticinia, are food products made from (or containing) milk. The most common dairy animals are cow, water buffalo, nanny goat, and ewe. Dairy products include common grocery store food items in th ...
is inconclusive. An association with gonorrhea
Gonorrhea, colloquially known as the clap, is a sexually transmitted infection (STI) caused by the bacterium '' Neisseria gonorrhoeae''. Infection may involve the genitals, mouth, or rectum. Infected men may experience pain or burning with ...
has been found, although no reason for this relationship has been identified. An increased risk is associated with the ''BRCA ''mutations. Diagnosis is by biopsy
A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a diseas ...
. Medical imaging
Medical imaging is the technique and process of imaging the interior of a body for clinical analysis and medical intervention, as well as visual representation of the function of some organs or tissues (physiology). Medical imaging seeks to rev ...
may be done to assess whether metastasis
Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...
is present.[
]Prostate cancer screening
Prostate cancer screening is the screening process used to detect undiagnosed prostate cancer in men without signs or symptoms. When abnormal prostate tissue or cancer is found early, it may be easier to treat and cure, but it is unclear if early ...
, including prostate-specific antigen
Prostate-specific antigen (PSA), also known as gamma-seminoprotein or kallikrein-3 (KLK3), P-30 antigen, is a glycoprotein enzyme encoded in humans by the ''KLK3'' gene. PSA is a member of the kallikrein-related peptidase family and is secreted b ...
(PSA) testing, increases cancer detection but whether it improves outcomes is controversial. Informed decision making is recommended for those 55 to 69 years old. Testing, if carried out, is more appropriate for those with a longer life expectancy. Although 5α-reductase inhibitors
5α-Reductases, also known as 3-oxo-5α-steroid 4-dehydrogenases, are enzymes involved in steroid metabolism. They participate in three metabolic pathways: bile acid biosynthesis, androgen and estrogen metabolism. There are three isozymes of ...
appear to decrease low-grade cancer risk, they do not affect high-grade cancer risk, and are not recommended for prevention.[ ]Vitamin
A vitamin is an organic molecule (or a set of molecules closely related chemically, i.e. vitamers) that is an Nutrient#Essential nutrients, essential micronutrient that an organism needs in small quantities for the proper functioning of its ...
or mineral
In geology and mineralogy, a mineral or mineral species is, broadly speaking, a solid chemical compound with a fairly well-defined chemical composition and a specific crystal structure that occurs naturally in pure form.John P. Rafferty, ed. ( ...
supplementation does not appear to affect risk.
Many cases are managed with active surveillance or watchful waiting
Watchful waiting (also watch and wait or WAW) is an approach to a medical problem in which time is allowed to pass before medical intervention or therapy is used. During this time, repeated testing may be performed.
Related terms include ''expec ...
.[ Other treatments may include a combination of ]surgery
Surgery ''cheirourgikē'' (composed of χείρ, "hand", and ἔργον, "work"), via la, chirurgiae, meaning "hand work". is a medical specialty that uses operative manual and instrumental techniques on a person to investigate or treat a pat ...
, radiation therapy
Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radia ...
, hormone therapy
Hormone therapy or hormonal therapy is the use of hormones in medical treatment. Treatment with hormone antagonists may also be referred to as hormonal therapy or antihormone therapy. The most general classes of hormone therapy are oncologic horm ...
, or chemotherapy
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
.[ Tumors limited to the prostate may be curable.] Pain medication
An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It i ...
s, bisphosphonate
Bisphosphonates are a class of drugs that prevent the loss of bone density, used to treat osteoporosis and similar diseases. They are the most commonly prescribed drugs used to treat osteoporosis. They are called bisphosphonates because they ...
s, and targeted therapy
Targeted therapy or molecularly targeted therapy is one of the major modalities of medical treatment (pharmacotherapy) for cancer, others being hormonal therapy and cytotoxic chemotherapy. As a form of molecular medicine, targeted therapy blocks ...
, among others, may be useful.[ Outcomes depend on age, health status and how aggressive and extensive the cancer is.][ Most men with prostate cancer do not die from it.][ The ]United States
The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...
five-year survival rate
The five-year survival rate is a type of survival rate for estimating the prognosis of a particular disease, normally calculated from the point of diagnosis. Lead time bias from earlier diagnosis can affect interpretation of the five-year surviva ...
is 98%.
Globally, it is the second-most common cancer. It is the fifth-leading cause of cancer-related death in men. In 2018, it was diagnosed in 1.2 million and caused 359,000 deaths. It was the most common cancer in males in 84 countries,[ occurring more commonly in the ]developed world
A developed country (or industrialized country, high-income country, more economically developed country (MEDC), advanced country) is a sovereign state that has a high quality of life, developed economy and advanced technological infrastruct ...
.[ Rates have been increasing in the ]developing world
A developing country is a sovereign state with a lesser developed industrial base and a lower Human Development Index (HDI) relative to other countries. However, this definition is not universally agreed upon. There is also no clear agreem ...
. Detection increased significantly in the 1980s and 1990s in many areas due to increased PSA testing.[ One study reported prostate cancer in 30% to 70% of Russian and Japanese men over age 60 who had died of unrelated causes.][
]
Signs and symptoms
Early prostate cancer usually has no clear symptoms. When they do appear, they are often similar to those of benign prostatic hyperplasia
Benign prostatic hyperplasia (BPH), also called prostate enlargement, is a noncancerous increase in size of the prostate gland. Symptoms may include frequent urination, trouble starting to urinate, weak stream, inability to urinate, or loss o ...
. These include frequent urination, nocturia
Nocturia is defined by the International Continence Society (ICS) as “the complaint that the individual has to wake at night one or more times for voiding (''i.e. to urinate'').” The term is derived from Latin ''nox, night'', and Greek '' αο ...
(increased urination at night), difficulty starting and maintaining a steady stream of urine, hematuria
Hematuria or haematuria is defined as the presence of blood or red blood cells in the urine. “Gross hematuria” occurs when urine appears red, brown, or tea-colored due to the presence of blood. Hematuria may also be subtle and only detectable w ...
(blood in the urine), dysuria
Dysuria refers to painful or uncomfortable urination.
It is one of a constellation of ''irritative'' bladder symptoms (also sometimes referred to as lower urinary tract symptoms), which includes nocturia and urinary frequency.
Diagnosis
The clin ...
(painful urination) as well as fatigue due to anemia, and bone pain. One study found that about a third of diagnosed patients had one or more such symptoms.
Prostate cancer is associated with urinary dysfunction as the prostate gland surrounds the prostatic urethra
The prostatic urethra, the widest and most dilatable part of the urethra canal, is about 3 cm long.
It runs almost vertically through the prostate from its base to its apex, lying nearer its anterior than its posterior surface; the form of ...
. Changes within the gland directly affect urinary function. Because the vas deferens
The vas deferens or ductus deferens is part of the male reproductive system of many vertebrates. The ducts transport sperm from the epididymis to the ejaculatory ducts in anticipation of ejaculation. The vas deferens is a partially coiled tube ...
deposits seminal fluid into the prostatic urethra, and secretions from the prostate are included in semen content, prostate cancer may also cause problems with sexual function and performance, such as difficulty achieving erection
An erection (clinically: penile erection or penile tumescence) is a physiological phenomenon in which the penis becomes firm, engorged, and enlarged. Penile erection is the result of a complex interaction of psychological, neural, vascular, ...
or painful ejaculation
Ejaculation is the discharge of semen (the ''ejaculate''; normally containing sperm) from the male reproductory tract as a result of an orgasm. It is the final stage and natural objective of male sexual stimulation, and an essential componen ...
.
Metastatic
Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...
prostate cancer can cause additional symptoms. The most common symptom is bone pain
Bone pain (also known medically by several other names) is pain coming from a bone, and is caused by damaging stimuli. It occurs as a result of a wide range of diseases or physical conditions or both, and may severely impair the quality of life. ...
, often in the vertebrae
The spinal column, a defining synapomorphy shared by nearly all vertebrates,Hagfish are believed to have secondarily lost their spinal column is a moderately flexible series of vertebrae (singular vertebra), each constituting a characteristic i ...
(bones of the spine), pelvis
The pelvis (plural pelves or pelvises) is the lower part of the trunk, between the abdomen and the thighs (sometimes also called pelvic region), together with its embedded skeleton (sometimes also called bony pelvis, or pelvic skeleton).
The ...
, or rib
In vertebrate anatomy, ribs ( la, costae) are the long curved bones which form the rib cage, part of the axial skeleton. In most tetrapods, ribs surround the chest, enabling the lungs to expand and thus facilitate breathing by expanding the ches ...
s. Spread of cancer into other bones such as the femur
The femur (; ), or thigh bone, is the proximal bone of the hindlimb in tetrapod vertebrates. The head of the femur articulates with the acetabulum in the pelvic bone forming the hip joint, while the distal part of the femur articulates with ...
is usually to the part of the bone nearer to the prostate. Prostate cancer in the spine
Spine or spinal may refer to:
Science Biology
* Vertebral column, also known as the backbone
* Dendritic spine, a small membranous protrusion from a neuron's dendrite
* Thorns, spines, and prickles, needle-like structures in plants
* Spine (zoolog ...
can compress the spinal cord
The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone). The backbone encloses the central canal of the spi ...
, causing tingling, leg weakness, and urinary
The urinary system, also known as the urinary tract or renal system, consists of the kidneys, ureters, bladder, and the urethra. The purpose of the urinary system is to eliminate waste from the body, regulate blood volume and blood pressure, con ...
and fecal incontinence
Fecal incontinence (FI), or in some forms encopresis, is a lack of control over defecation, leading to involuntary loss of bowel contents, both liquid stool elements and mucus, or solid feces. When this loss includes flatus (gas), it is referred ...
.
Risk factors
The primary risk factors
In epidemiology, a risk factor or determinant is a variable associated with an increased risk of disease or infection.
Due to a lack of harmonization across disciplines, determinant, in its more widely accepted scientific meaning, is often use ...
are obesity
Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's we ...
, age, and family history. Obese men have been found to have a 34% greater death rate from prostate cancer than those with normal weight. Prostate cancer is uncommon in men younger than 45, but becomes more common with advancing age. The average age at the time of diagnosis is 70. Autopsy studies of Chinese, German, Israeli, Jamaican, Swedish, and Ugandan men who died of other causes found prostate cancer in 30% of men in their 50s, and in 80% of men in their 70s.
Men with high blood pressure are more likely to develop prostate cancer. A small increase in risk is associated with lack of exercise. Elevated blood testosterone
Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testes and prostate, as well as promoting secondar ...
levels may increase risk.
Genetics
Genetics may affect risk, as suggested by associations with race, family, and specific gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
variants. Men who have a first-degree relative (father or brother) with prostate cancer have twice the risk of developing prostate cancer, and those with two first-degree relatives affected have a five-fold greater risk compared with men with no family history. This risk appears to be greater for men with an affected brother than for those with an affected father. In the United States, prostate cancer more commonly affects black men than white or Hispanic men, and is also more deadly in black men. In contrast, the incidence and mortality rates for Hispanic men are one-third lower than for non-Hispanic whites. Twin studies
Twin studies are studies conducted on identical or fraternal twins. They aim to reveal the importance of environmental and genetic influences for traits, phenotypes, and disorders. Twin research is considered a key tool in behavioral genetics a ...
in Scandinavia
Scandinavia; Sámi languages: /. ( ) is a subregion#Europe, subregion in Northern Europe, with strong historical, cultural, and linguistic ties between its constituent peoples. In English usage, ''Scandinavia'' most commonly refers to Denmark, ...
suggest that 58% of prostate cancer risk can be explained by inherited factors.
Many genes are involved in inherited risk for prostate cancer. The first gene linked to inherited prostate cancer in families was hereditary prostate cancer gene 1 (''HPC1''). Mutations within the HOXB13
Homeobox protein Hox-B13 is a protein that in humans is encoded by the ''HOXB13'' gene.
Function
This gene encodes a transcription factor that belongs to the homeobox gene family. Genes of this family are highly conserved among vertebrates and ...
gene can also carry strong risk for prostate cancer. Inherited genetic variation of the chromosome 8q24 locus, one that is prominently observed through genome-wide association study
In genomics, a genome-wide association study (GWA study, or GWAS), also known as whole genome association study (WGA study, or WGAS), is an observational study of a genome-wide set of Single-nucleotide polymorphism, genetic variants in different i ...
(GWAS) of both familial and sporadic prostate cancer, can carry near-Mendelian (up to 20-fold) risk for prostate cancer. This region encompasses regulatory elements, non-coding genes, and the stem cell related POU5F1B gene. Roughly 4% of families in which multiple men are affected by prostate cancer carry mutations in HOXB13, and another 4% carry mutations at 8q24. Mutations in ''BRCA1
Breast cancer type 1 susceptibility protein is a protein that in humans is encoded by the ''BRCA1'' () gene. Orthologs are common in other vertebrate species, whereas invertebrate genomes may encode a more distantly related gene. ''BRCA1'' is a h ...
'' and ''BRCA2
''BRCA2'' and BRCA2 () are a human gene and its protein product, respectively. The official symbol (BRCA2, italic for the gene, nonitalic for the protein) and the official name (originally breast cancer 2; currently BRCA2, DNA repair associated) ...
'' (important risk factors for ovarian cancer
Ovarian cancer is a cancerous tumor of an ovary. It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the inner lining of the abdomen. The ovary is made up of three different c ...
and breast cancer
Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a re ...
in women) have also been implicated.
Two large GWAS discovered common low-risk single-nucleotide polymorphism
In genetics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a sufficiently lar ...
s (SNPs) that are associated with prostate cancer in 2008. These studies identified several relevant SNPs. For example, individuals with TT allele pair at SNP rs10993994 were reported to be at 1.6 times higher risk than those with the CC allele pair. This SNP explains part of the increased risk faced by African-Americans. The C allele is much more prevalent in the latter; this SNP is located in the promoter region of the ''MSMB'' gene, thus affects the amount of MSMB
Beta-microseminoprotein is a protein that in humans is encoded by the ''MSMB'' gene. For historical reasons, the scientific literature may also refer to this protein as Prostate secretory protein 94 (PSP94), microseminoprotein (MSP), microseminopr ...
protein synthesized and secreted by epithelial cells of the prostate.
While fewer studies have been conducted assessing the risk of being diagnosed with aggressive prostate cancer, a GWAS of 12,518 prostate cancer cases identified two loci associated with high Gleason sum score, SNP rs78943174 nearest to the gene '' NAALADL2'' and SNP rs35148638 nearest to ''RASA1
RAS p21 protein activator 1 or RasGAP (Ras GTPase activating protein), also known as RASA1, is a 120-kDa cytosolic human protein that provides two principal activities:
* Inactivation of Ras (protein), Ras from its active Guanosine triphosphate, G ...
''.
A number of somatic mutations (acquired rather than inherited) have also been defined in prostate tumors that drive their growth. TMPRSS2
Transmembrane protease, serine 2 is an enzyme that in humans is encoded by the ''TMPRSS2'' gene. It belongs to the TMPRSS family of proteins, whose members are transmembrane proteins which have a serine protease activity. The TMPRSS2 protein is f ...
- ETS gene family fusion
Fusion, or synthesis, is the process of combining two or more distinct entities into a new whole.
Fusion may also refer to:
Science and technology Physics
*Nuclear fusion, multiple atomic nuclei combining to form one or more different atomic nucl ...
, specifically TMPRSS2-ERG
The erg is a unit of energy equal to 10−7joules (100 nJ). It originated in the Centimetre–gram–second system of units (CGS). It has the symbol ''erg''. The erg is not an SI unit. Its name is derived from (), a Greek word meaning 'work' o ...
or TMPRSS2-ETV1
ETS translocation variant 1 is a protein that in humans is encoded by the ''ETV1'' gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' ...
/4 promotes cancer cell growth. These fusions can arise via complex rearrangement chains called chromoplexy Chromoplexy refers to a class of complex DNA rearrangement observed in the genomes of cancer cells. This phenomenon was first identified in prostate cancer by whole genome sequencing of prostate tumors. Chromoplexy causes genetic material from one o ...
.
Dietary
Plant-based diet
A plant-based diet is a diet consisting mostly or entirely of plant-based foods. Plant-based diets encompass a wide range of dietary patterns that contain low amounts of animal products and high amounts of plant products such as vegetables, fru ...
s are associated with a lower risk for prostate cancer. Switching to a plant-based diet shows favorable results for cancer outcomes in men with prostate cancer. Especially vegan
Veganism is the practice of abstaining from the use of animal product—particularly in diet—and an associated philosophy that rejects the commodity status of animals. An individual who follows the diet or philosophy is known as a vegan. Di ...
diets consistently show favorable associations with prostate cancer risk and outcomes.
Consuming fruits and vegetables has been found to be of little preventive benefit. Some studies report that higher meat consumption was associated with higher risk.
The consumption of milk may be related to prostate cancer. A 2020 systematic review found the results on milk consumption and prostate cancer inconclusive but stated that individuals with higher risk may reduce or eliminate milk. A 2019 overview stated that the evidence that linked milk to higher rates of prostate cancer was inconsistent and inconclusive. A 2021 study from Japan looking at 26,464 men found that milk consumption increased the risk of prostate cancer by 37%.
Lower blood levels
Reference ranges (reference intervals) for blood tests are sets of values used by a health professional to interpret a set of medical test results from blood samples. Reference ranges for blood tests are studied within the field of clinical chem ...
of vitamin D
Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group are vitamin D3 (c ...
may increase risks. One study found no effect of folic acid
Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and ...
supplements on risk.
Medication exposure
Some links have been established between prostate cancer and medications, medical procedures, and medical conditions. Statin
Statins, also known as HMG-CoA reductase inhibitors, are a class of lipid-lowering medications that reduce illness and mortality in those who are at high risk of cardiovascular disease. They are the most common cholesterol-lowering drugs.
Low- ...
s may also decrease risk.
Infection
Prostatitis
Prostatitis is an umbrella term for a variety of medical conditions that incorporate bacterial and non-bacterial origin illnesses in the pelvic region. In contrast with the plain meaning of the word (which means "inflammation of the prostate"), the ...
(infection
An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...
or inflammation
Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
) may increase risk. In particular, infection with the sexually transmitted infection
Sexually transmitted infections (STIs), also referred to as sexually transmitted diseases (STDs) and the older term venereal diseases, are infections that are Transmission (medicine), spread by Human sexual activity, sexual activity, especi ...
s ''Chlamydia'', gonorrhea
Gonorrhea, colloquially known as the clap, is a sexually transmitted infection (STI) caused by the bacterium '' Neisseria gonorrhoeae''. Infection may involve the genitals, mouth, or rectum. Infected men may experience pain or burning with ...
, or syphilis
Syphilis () is a sexually transmitted infection caused by the bacterium ''Treponema pallidum'' subspecies ''pallidum''. The signs and symptoms of syphilis vary depending in which of the four stages it presents (primary, secondary, latent, an ...
seems to increase risk.
Papilloma virus
''Papillomaviridae'' is a family of non- enveloped DNA viruses whose members are known as papillomaviruses. Several hundred species of papillomaviruses, traditionally referred to as "types", have been identified infecting all carefully inspected ...
has been proposed to have a potential role, but as of 2015, the evidence was inconclusive; as of 2018, the increased risk was debated.
Environment
US war veterans who had been exposed to Agent Orange
Agent Orange is a chemical herbicide and defoliant, one of the "tactical use" Rainbow Herbicides. It was used by the U.S. military as part of its herbicidal warfare program, Operation Ranch Hand, during the Vietnam War from 1961 to 1971. It ...
had a 48% increased risk of prostate cancer recurrence following surgery.
Sex
Although some evidence from prospective cohort studies
A prospective cohort study is a Longitudinal study, longitudinal cohort study that follows over time a group of similar individuals (cohort (statistics), cohorts) who differ with respect to certain factors under study, to determine how these fact ...
indicates that frequent ejaculation
Ejaculation is the discharge of semen (the ''ejaculate''; normally containing sperm) from the male reproductory tract as a result of an orgasm. It is the final stage and natural objective of male sexual stimulation, and an essential componen ...
may reduce prostate cancer risk, no randomized controlled trial
A randomized controlled trial (or randomized control trial; RCT) is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical te ...
s reported this benefit. An association between vasectomy
Vasectomy, or vasoligation, is an elective surgical procedure for male sterilization or permanent contraception. During the procedure, the male vasa deferentia are cut and tied or sealed so as to prevent sperm from entering into the urethra and ...
and prostate cancer was found, but causality has not been established.
Pathophysiology
The prostate
The prostate is both an Male accessory gland, accessory gland of the male reproductive system and a muscle-driven mechanical switch between urination and ejaculation. It is found only in some mammals. It differs between species anatomically, ...
is part of the male reproductive system
The reproductive system of an organism, also known as the genital system, is the biological system made up of all the anatomical organs involved in sexual reproduction. Many non-living substances such as fluids, hormones, and pheromones are als ...
that helps make and store seminal fluid
Semen, also known as seminal fluid, is an organic bodily fluid created to contain spermatozoa. It is secreted by the gonads (sexual glands) and other sexual organs of male or hermaphroditic animals and can fertilize the female ovum. Semen i ...
. In adult men, a typical prostate is about 3 cm long and weighs about 20 g. It is located in the pelvis
The pelvis (plural pelves or pelvises) is the lower part of the trunk, between the abdomen and the thighs (sometimes also called pelvic region), together with its embedded skeleton (sometimes also called bony pelvis, or pelvic skeleton).
The ...
, under the urinary bladder
The urinary bladder, or simply bladder, is a hollow organ in humans and other vertebrates that stores urine from the kidneys before disposal by urination. In humans the bladder is a distensible organ that sits on the pelvic floor. Urine enters ...
and in front of the rectum
The rectum is the final straight portion of the large intestine in humans and some other mammals, and the Gastrointestinal tract, gut in others. The adult human rectum is about long, and begins at the rectosigmoid junction (the end of the s ...
. The prostate surrounds part of the urethra
The urethra (from Greek οὐρήθρα – ''ourḗthrā'') is a tube that connects the urinary bladder to the urinary meatus for the removal of urine from the body of both females and males. In human females and other primates, the urethra con ...
, the tube that carries urine
Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excretion, excreted from the body through the urethra.
Cel ...
from the bladder during urination
Urination, also known as micturition, is the release of urine from the urinary bladder through the urethra to the outside of the body. It is the urinary system's form of excretion. It is also known medically as micturition, voiding, uresis, ...
and semen during ejaculation
Ejaculation is the discharge of semen (the ''ejaculate''; normally containing sperm) from the male reproductory tract as a result of an orgasm. It is the final stage and natural objective of male sexual stimulation, and an essential componen ...
. The prostate contains many small gland
In animals, a gland is a group of cells in an animal's body that synthesizes substances (such as hormones) for release into the bloodstream (endocrine gland) or into cavities inside the body or its outer surface (exocrine gland).
Structure
De ...
s, which make about 20% of the fluid constituting semen
Semen, also known as seminal fluid, is an organic bodily fluid created to contain spermatozoa. It is secreted by the gonads (sexual glands) and other sexual organs of male or hermaphroditic animals and can fertilize the female ovum. Semen i ...
.
Superiorly, the prostate base is contiguous with the bladder outlet. Inferiorly, the prostate's apex heads in the direction of the urogenital diaphragm, which is pointed anterio-inferiorly. The prostate can be divided into four anatomic spaces: peripheral, central, transitional, and anterior fibromuscular stroma. The peripheral space contains the posterior and lateral portions of the prostate, as well as the inferior portions of the prostate. The central space contains the superior portion of the prostate including the most proximal aspects of the urethra and bladder neck. The transitional space is located just anterior to the central space and includes urethra distal to the central gland urethra. The neurovascular bundles course along the posterolateral prostate surface and penetrate the prostatic capsule there as well.
Most of the glandular tissue is found in the peripheral and central zones (peripheral zone: 70-80% of glandular tissue; central zone: 20% of glandular tissue). Some is found in the transitional space (5% of glandular tissue). Thus, most cancers that develop from glandular tissue are found in the peripheral and central spaces, while about 5% is found in the transitional space. None is found in the anterior fibromuscular stroma since no glands are in that anatomic space.
The prostate glands require male hormone
A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...
s, known as androgen
An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This inc ...
s, to work properly. Androgens include testosterone
Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testes and prostate, as well as promoting secondar ...
, which is made in the testes
A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testoster ...
;dehydroepiandrosterone
Dehydroepiandrosterone (DHEA), also known as androstenolone, is an endogenous steroid hormone precursor. It is one of the most abundant circulating steroids in humans. DHEA is produced in the adrenal glands, the gonads, and the brain. It functio ...
, made in the adrenal gland
The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex which ...
s; and dihydrotestosterone
Dihydrotestosterone (DHT, 5α-dihydrotestosterone, 5α-DHT, androstanolone or stanolone) is an endogenous androgen sex steroid and hormone. The enzyme 5α-reductase catalyzes the formation of DHT from testosterone in certain tissues includi ...
, which is converted from testosterone within the prostate itself. Androgens are also responsible for secondary sex characteristic
Secondary sex characteristics are features that appear during puberty in humans, and at sexual maturity in other animals. These characteristics are particularly evident in the sexually dimorphic phenotypic traits that distinguish the sexes of a sp ...
s such as facial hair and increased muscle mass.
Because of the prostate's location, prostate diseases often affect urination, ejaculation, and rarely defecation
Defecation (or defaecation) follows digestion, and is a necessary process by which organisms eliminate a solid, semisolid, or liquid waste material known as feces from the digestive tract via the anus. The act has a variety of names ranging f ...
. In prostate cancer, the cells of these glands mutate
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitos ...
into cancer cells.
Most prostate cancers are classified as adenocarcinoma
Adenocarcinoma (; plural adenocarcinomas or adenocarcinomata ) (AC) is a type of cancerous tumor that can occur in several parts of the body. It is defined as neoplasia of epithelial tissue that has glandular origin, glandular characteristics, or ...
s, or glandular cancers, that begin when semen-secreting gland cells mutate into cancer cells. The region of the prostate gland where the adenocarcinoma is most common is the peripheral zone. Initially, small clumps of cancer cells remain within otherwise normal prostate glands, a condition known as carcinoma ''in situ'' or prostatic intraepithelial neoplasia
High-grade prostatic intraepithelial neoplasia (HGPIN) is an abnormality of prostatic glands and believed to precede the development of prostate adenocarcinoma (the most common form of prostate cancer).
It may be referred to simply as prostatic i ...
(PIN). Although no proof establishes that PIN is a cancer precursor, it is closely associated with cancer. Over time, these cells multiply and spread to the surrounding prostate tissue (the stroma) forming a tumor
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
.
Eventually, the tumor may grow large enough to invade nearby organs such as the seminal vesicles
The seminal vesicles (also called vesicular glands, or seminal glands) are a pair of two convoluted tubular glands that lie behind the urinary bladder of some male mammals. They secrete fluid that partly composes the semen.
The vesicles are 5 ...
or the rectum, or tumor cells may develop the ability to travel in the bloodstream
The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...
and lymphatic system
The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system, and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphatic or lymphoid o ...
.
Prostate cancer is considered a malignant
Malignancy () is the tendency of a medical condition to become progressively worse.
Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...
tumor because it can invade other areas of the body. This invasion is called metastasis
Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...
. Prostate cancer most commonly metastasizes to the bone
A bone is a Stiffness, rigid Organ (biology), organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red blood cell, red and white blood cells, store minerals, provid ...
s and lymph node
A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that inclu ...
s, and may invade the rectum, bladder
The urinary bladder, or simply bladder, is a hollow organ in humans and other vertebrates that stores urine from the kidneys before disposal by urination. In humans the bladder is a distensible organ that sits on the pelvic floor. Urine enters ...
, and lower ureters after local progression. The route of metastasis to bone is thought to be venous
Veins are blood vessels in humans and most other animals that carry blood towards the heart. Most veins carry deoxygenated blood from the tissues back to the heart; exceptions are the pulmonary and umbilical veins, both of which carry oxygenated b ...
, as the prostatic venous plexus
The prostatic veins form a well-marked prostatic plexus which lies partly in the fascial sheath of the prostate and partly between the sheath and the prostatic capsule. It communicates with the pudendal and vesical plexuses.
The prostatic veno ...
draining the prostate connects with the vertebral veins.
The prostate is a zinc
Zinc is a chemical element with the symbol Zn and atomic number 30. Zinc is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodi ...
-accumulating, citrate
Citric acid is an organic compound with the chemical formula HOC(CO2H)(CH2CO2H)2. It is a colorless weak organic acid. It occurs naturally in citrus fruits. In biochemistry, it is an intermediate in the citric acid cycle, which occurs in t ...
-producing organ. Transport protein
A transport protein (variously referred to as a transmembrane pump, transporter, escort protein, acid transport protein, cation transport protein, or anion transport protein) is a protein that serves the function of moving other materials within ...
ZIP1
Zinc transporter ZIP1 is a protein that in humans is encoded by the ''SLC39A1'' gene.
The protein ZIP1 is responsible for the active transport of zinc into prostate cells. In many prostate cancer
Prostate cancer is cancer of the prostate. Pros ...
is responsible for the transport of zinc into prostate cells. One of zinc's important roles is to change the cell's metabolism to produce citrate, an important semen component. The process of zinc accumulation, alteration of metabolism, and citrate production is energy inefficient, and prostate cells require enormous amounts of energy ( ATP) to accomplish this task. Prostate cancer cells are generally devoid of zinc. Prostate cancer cells save energy by not making citrate, and use the conserved energy to grow, reproduce and spread.
The absence of zinc is thought to occur via silencing the gene that produces ZIP1. It is called a tumor suppressor gene product for the gene '' SLC39A1''. The cause of the epigenetic
In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...
silencing is unknown. Strategies that transport zinc into transformed prostate cells effectively eliminate these cells in animals. Zinc inhibits NF-κB
Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a protein complex that controls transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellular ...
pathways, is antiproliferative, and induces apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
in abnormal cells. Unfortunately, oral ingestion of zinc is ineffective since high concentrations of zinc into prostate cells is not possible without ZIP1.
Loss of cancer suppressor genes, early in prostatic carcinogenesis, have been localized to chromosomes'' 8p'', ''10q'', ''13q'', and ''16q''. P53
p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...
mutations in the primary prostate cancer are relatively low and are more frequently seen in metastatic settings, hence, p53 mutations are a late event in the pathology. Other tumor suppressor genes that are thought to play a role include ''PTEN'' and ''KAI1
CD82 (Cluster of Differentiation 82), or ''KAI1'', is a human protein encoded by the gene.
This metastasis suppressor gene product is a membrane glycoprotein that is a member of the tetraspanin/transmembrane 4 superfamily. Expression of this g ...
''. "Up to 70 percent of men with prostate cancer have lost one copy of the ''PTEN'' gene at the time of diagnosis". Relative frequency of loss of E-cadherin
Cadherin-1 or Epithelial cadherin (E-cadherin), (not to be confused with the APC/C activator protein CDH1) is a protein that in humans is encoded by the ''CDH1'' gene. Mutations are correlated with gastric, breast, colorectal, thyroid, and ovarian ...
and CD44
The CD44 antigen is a cell-surface glycoprotein involved in cell–cell interactions, cell adhesion and migration. In humans, the CD44 antigen is encoded by the ''CD44'' gene on chromosome 11. CD44 has been referred to as HCAM (homing cell adhes ...
has also been observed. Loss of the retinoblastoma (RB) protein induces androgen receptor deregulation in castration-resistant prostate cancer by deregulating 'E2F1
Transcription factor E2F1 is a protein that in humans is encoded by the ''E2F1'' gene.
Function
The protein encoded by this gene is a member of the E2F family of transcription factors. The E2F family plays a crucial role in the control of cell ...
expression''.''
The factors that drive disease progression and clinical prognosis remain only partly understood but a variety of molecular determinants has been identified that appear to be involved. The most important of these might be the tyrosine phosphatase ACP1
Low molecular weight phosphotyrosine protein phosphatase is an enzyme that in humans is encoded by the ''ACP1'' gene.
The product of this gene belongs to the phosphotyrosine protein phosphatase family of proteins. It functions as an acid phospha ...
of which the expression might outperform the Gleason grading system
The Gleason grading system is used to help evaluate the prognosis of men with prostate cancer using samples from a prostate biopsy. Together with other parameters, it is incorporated into a strategy of prostate cancer staging which predicts prog ...
for predicting disease course. Other molecules identified include the transcription factor RUNX2
Runt-related transcription factor 2 (RUNX2) also known as core-binding factor subunit alpha-1 (CBF-alpha-1) is a protein that in humans is encoded by the ''RUNX2'' gene. RUNX2 is a key transcription factor associated with osteoblast differentia ...
which may prevent cancer cells from undergoing apoptosis, the PI3k/Akt signaling cascade in conjunction with the transforming growth factor beta
Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three different mammalian isoforms (TGF-β 1 to 3, HGNC symbols TGFB1, TGFB2, TGFB3) and many other sign ...
/ SMAD signaling cascade that also protect against apoptosis. Pim-1 is upregulated in prostate cancer. X-linked inhibitor of apoptosis (XIAP
X-linked inhibitor of apoptosis protein (XIAP), also known as inhibitor of apoptosis protein 3 (IAP3) and baculoviral IAP repeat-containing protein 4 (BIRC4), is a protein that stops apoptotic cell death. In humans, this protein (XIAP) is produ ...
) is hypothesized to promote cancer cell survival and growth, the Macrophage inhibitory cytokine-1 (MIC-1) that stimulates the focal adhesion kinase
PTK2 protein tyrosine kinase 2 (PTK2), also known as focal adhesion kinase (FAK), is a protein that, in humans, is encoded by the ''PTK2'' gene. PTK2 is a focal adhesion-associated protein kinase involved in cellular adhesion (how cells stick to ...
(FAK) signaling pathway. Nevertheless, it is fair to say that the molecular factors that determine why some patients have quiescent disease while otherdisplay prognosis remain largely obscure.
The androgen receptor
The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone in th ...
helps cancer cells to survive. Prostate-specific membrane antigen
Glutamate carboxypeptidase II (GCPII), also known as N-acetyl-L-aspartyl-L-glutamate peptidase I (NAALADase I), NAAG peptidase, or prostate-specific membrane antigen (PSMA) is an enzyme that in humans is encoded by the ''FOLH1'' (folate hydrola ...
(PSMA) stimulates cancer development by increasing folate levels, helping the cancer cells to survive and grow; it increases available folates for use by hydrolyzing glutamated folates.
Diagnosis
The American Cancer Society
The American Cancer Society (ACS) is a nationwide voluntary health organization dedicated to eliminating cancer. Established in 1913, the society is organized into six geographical regions of both medical and lay volunteers operating in more than ...
's position regarding early detection by PSA testing is:
Several other tests can be used to gather information about the prostate and the urinary tract. Digital rectal examination
Digital rectal examination (DRE; la, palpatio per anum, PPA) is an internal examination of the rectum, performed by a healthcare provider. Prior to a 2018 report from the U.S. Preventive Services Task Force, the DRE was a common and "dreaded" co ...
may allow a doctor to detect prostate abnormalities. Cystoscopy
Cystoscopy is endoscopy of the urinary bladder via the urethra. It is carried out with a cystoscope.
The urethra is the tube that carries urine from the bladder to the outside of the body.
The cystoscope has lenses like a telescope or microscope ...
shows the urinary tract from inside the bladder, using a thin, flexible camera tube inserted in the urethra
The urethra (from Greek οὐρήθρα – ''ourḗthrā'') is a tube that connects the urinary bladder to the urinary meatus for the removal of urine from the body of both females and males. In human females and other primates, the urethra con ...
. Transrectal ultrasonography
Transrectal ultrasonography, or TRUS in short, is a method of creating an image of organs in the pelvis, most commonly used to perform an ultrasound-guided needle biopsy evaluation of the prostate gland in men with elevated prostate-specific ant ...
creates a picture of the prostate using sound waves from a probe in the rectum, but the only test that can fully confirm the diagnosis of prostate cancer is a biopsy
A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a diseas ...
, the removal of small pieces of the prostate for microscopic examination.
Imaging
Ultrasound
Ultrasound is sound waves with frequency, frequencies higher than the upper audible limit of human hearing range, hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hea ...
and magnetic resonance imaging
Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio wave ...
(MRI) are the two main imaging methods used for prostate cancer detection.
MRI
Appearance of prostate on MRI
On MRI, the central and transitional zones both have lower T2 signal than the peripheral zone. Since the central and transitional zones cannot be distinguished from each other, they can be best described as the central gland on MRI. Thus, the peripheral gland has a higher signal on T2WI than the central gland. In the peripheral gland, prostate cancer appears as a low-intensity lesion
A lesion is any damage or abnormal change in the tissue of an organism, usually caused by disease or trauma. ''Lesion'' is derived from the Latin "injury". Lesions may occur in plants as well as animals.
Types
There is no designated classifi ...
. However, in the central gland, low-intensity lesions cannot be distinguished from the low-intensity central gland. Diffusion restriction is instrumental in identifying and characterizing central gland lesions. Combined diffusion-weighted (DW) imaging and dynamic contrast-enhanced MRI for distinguish malignant from benign prostate lesions can be used. The merged images, of DW and MRI with dynamic contrast enhancement, can visualise areas with low signal intensity and fast wash-out effect - characteristic of carcinomas. Lymphadenopathy
Lymphadenopathy or adenopathy is a disease of the lymph nodes, in which they are abnormal in size or consistency. Lymphadenopathy of an inflammatory type (the most common type) is lymphadenitis, producing swollen or enlarged lymph nodes. In cli ...
can be seen best on postcontrast, fat-suppressed T1WI. Other regions can be described on MRI. The anterior fibromuscular stroma and the prostate capsule along the posterior and lateral prostate have a low T2WI signal, in contrast with the bright signal of the peripheral zone. Extraprostatic extension can be seen with disruption of capsule integrity.
MRI for the detection of prostate cancer
As of 2011, MRI was used to identify targets for prostate biopsy using fusion MRI with ultrasound (US) or MRI-guidance alone. An MRI alone will correctly identify 91% of men with clinically significant prostate cancer but will misclassify 63% of men at risk for prostate cancer as having clinically significant prostate cancer. An MRI-targeted biopsy will correctly identify 80% of men with prostate cancer. However, it will classify 6% of men at risk for prostate cancer as having clinically significant prostate cancer. Detection of clinically insignificant cancer has been shown to be decreased when MRI-targeted biopsy is combined with standard biopsy for men with positive results on MRI, as compared with a standard biopsy method.
Following an MRI, regions of interest within the scan which may be cancer are often graded on a likelihood scale between 1 and 5. One such scale is the prostate imaging-reporting and data system (PI-RADS) scale which defines standards of clinical service for multiparametric MRI (mpMRI), including image creation and reporting. PI-RADS version 2 scoring has shown a specificity and sensitivity of 73% and 95%, respectively, for detection of prostate cancer.
When an MRI is used to decide whether to do a biopsy in men who have had a prior biopsy, it is 5% more likely to make a correct diagnosis than a standard biopsy and is 12% more likely to be correct for men who may or may not have had a prior biopsy. In men who have had a negative biopsy, this combination is 44% more likely to lead to a correct diagnosis.
Other uses for MRI
Prostate MRI is also used for surgical planning for robotic prostatectomy
Prostatectomy (from the Ancient Greek language, Greek , "prostate" and , "excision") as a medical term refers to the surgical removal of all or part of the prostate gland. This operation is done for benignity, benign conditions that cause urina ...
. It helps surgeons decide whether to resect or spare the neurovascular bundle, determine return to urinary continence, and help assess surgical difficulty. MRI is used in other types of treatment planning, for both focal therapy and radiotherapy. MRI can also be used to target areas for research sampling in biobanking.
Biological basis for prostate cancer visibility on MRI
The biological properties which determine whether or not a tumour is visible on MRI is poorly understood. One theory is that tumour cells undergo several genetic changes during transformation
Transformation may refer to:
Science and mathematics
In biology and medicine
* Metamorphosis, the biological process of changing physical form after birth or hatching
* Malignant transformation, the process of cells becoming cancerous
* Trans ...
which alter the cellular rate of growth and formation of new blood vessels, leading to tumours with more aggressive histological
Histology,
also known as microscopic anatomy or microanatomy, is the branch of biology which studies the microscopic anatomy of biological tissues. Histology is the microscopic counterpart to gross anatomy, which looks at larger structures vis ...
patterns, hypoxic
Hypoxia means a lower than normal level of oxygen, and may refer to:
Reduced or insufficient oxygen
* Hypoxia (environmental), abnormally low oxygen content of the specific environment
* Hypoxia (medical), abnormally low level of oxygen in the t ...
regions and increased cell density among other features. Having larger, more dense tumours with changes in blood vessel distributions may feasibly alter signal on MRI through restriction of water and/or fluid movement.
Some studies have linked the presence of rare histological
Histology,
also known as microscopic anatomy or microanatomy, is the branch of biology which studies the microscopic anatomy of biological tissues. Histology is the microscopic counterpart to gross anatomy, which looks at larger structures vis ...
patterns within the tumour such as cribriform pattern. Although recent research suggests there is a number of histopathological features which may influence tumour detection by MRI. At a genetic level, prostate cancer visibility on MRI seems to be linked with genetic features of aggressive disease including processes such as cell proliferation
Cell proliferation is the process by which ''a cell grows and divides to produce two daughter cells''. Cell proliferation leads to an exponential increase in cell number and is therefore a rapid mechanism of tissue growth. Cell proliferation re ...
, tumour hypoxia
Hypoxia means a lower than normal level of oxygen, and may refer to:
Reduced or insufficient oxygen
* Hypoxia (environmental), abnormally low oxygen content of the specific environment
* Hypoxia (medical), abnormally low level of oxygen in the tis ...
and DNA damage
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA da ...
. The gene changes consistently observed in MRI-visible tumours include loss of tumour suppressor PTEN, increased expression of proliferation associated genes CENPF
Centromere protein F is a protein that in humans is encoded by the ''CENPF'' gene. It is involved in chromosome segregation during cell division. It also has a role in the orientation of microtubules to form cellular cilia.
Function
CENPF is pa ...
, AGR2
Anterior gradient protein 2 homolog (AGR-2), also known as secreted cement gland protein XAG-2 homolog, is a protein that in humans is encoded by the ''AGR2'' gene. Anterior gradient homolog 2 was originally discovered in ''Xenopus laevis''. In ''X ...
and growth factor GDF15
Growth/differentiation factor 15 (GDF15) was first identified as Macrophage inhibitory cytokine-1 or MIC-1.
It is a protein belonging to the transforming growth factor beta superfamily. Under normal conditions, GDF-15 is expressed in low concent ...
as well as a number of other genes. Changes in these pathways and genes may facilitate increased tumour growth, changes in vasculature
The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...
and density which ultimately change the signal on MRI.
Ultrasound
Ultrasound imaging can be obtained transrectally and is used during prostate biopsies. Prostate cancer can be seen as a hypoechoic lesion in 60% of cases. The other 40% of cancerous lesions are either hyperechoic or isoechoic. On Color Doppler, the lesions appear hypervascular.
Biopsy
If cancer is suspected, a biopsy is offered expediently. During a biopsy, a urologist
Urology (from Greek οὖρον ''ouron'' "urine" and ''-logia'' "study of"), also known as genitourinary surgery, is the branch of medicine that focuses on surgical and medical diseases of the urinary-tract system and the reproductive organ ...
or radiologist
Radiology ( ) is the medical discipline that uses medical imaging to diagnose diseases and guide their treatment, within the bodies of humans and other animals. It began with radiography (which is why its name has a root referring to radiatio ...
obtains tissue samples from the prostate via either the rectum or the perineum. A biopsy gun inserts and removes special hollow-core needles (usually three to six on each side of the prostate) in less than a second. Prostate biopsies are routinely done on an outpatient basis and rarely require hospitalization. Systematic biopsies correctly identify 63% of men as having clinically significant prostate cancer but will miss the rest. For men at risk for prostate cancer, biopsy will not misclassify any of the men as having clinically significant prostate cancer.
Antibiotic
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...
s should be used to prevent complications such as fever
Fever, also referred to as pyrexia, is defined as having a body temperature, temperature above the human body temperature, normal range due to an increase in the body's temperature Human body temperature#Fever, set point. There is not a single ...
, urinary tract infection
A urinary tract infection (UTI) is an infection that affects part of the urinary tract. When it affects the lower urinary tract it is known as a bladder infection (cystitis) and when it affects the upper urinary tract it is known as a kidney ...
s, and sepsis
Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
even if the most appropriate course or dose is undefined. About 55% of men report discomfort during prostate biopsy.
Histopathologic diagnosis
A histopathologic
Histopathology (compound of three Greek words: ''histos'' "tissue", πάθος ''pathos'' "suffering", and -λογία ''-logia'' "study of") refers to the microscopic examination of tissue in order to study the manifestations of disease. Spec ...
diagnosis mainly includes assessment of whether a cancer exists, as well as any subdiagnosis, if possible. Histopathologic subdiagnosis has implications for the possibility and methodology of Gleason scoring. The most common histopathological subdiagnosis is acinar adenocarcinoma, constituting 93% of diagnoses. The most common form of acinar adenocarcinoma, in turn, is "adenocarcinoma, not otherwise specified", also termed conventional, or usual acinar adenocarcinoma.
Biochemical diagnosis
Alkaline phosphatase
The enzyme alkaline phosphatase (EC 3.1.3.1, alkaline phosphomonoesterase; phosphomonoesterase; glycerophosphatase; alkaline phosphohydrolase; alkaline phenyl phosphatase; orthophosphoric-monoester phosphohydrolase (alkaline optimum), systematic ...
is more elevated in metastatic
Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...
than non-metastatic cells. High levels of alkaline phosphatase is associated with a significant decrease in survival.
Gleason score
The Gleason grading system
The Gleason grading system is used to help evaluate the prognosis of men with prostate cancer using samples from a prostate biopsy. Together with other parameters, it is incorporated into a strategy of prostate cancer staging which predicts prog ...
is used to help evaluate the prognosis
Prognosis (Greek: πρόγνωσις "fore-knowing, foreseeing") is a medical term for predicting the likely or expected development of a disease, including whether the signs and symptoms will improve or worsen (and how quickly) or remain stabl ...
and helps guide therapy. A Gleason score is based upon the tumor's appearance. Cancers with a higher Gleason score are more aggressive and have a worse prognosis. Pathological scores range from 2 through 10, with a higher number indicating greater risks and higher mortality.
ISUP score
In 2014, the International Society of Urological Pathology (ISUP) provided a new prostate cancer grading system called the ISUP scores.
Tumor markers
Tissue samples can be stained for the presence of PSA
PSA, PsA, Psa, or psa may refer to:
Biology and medicine
* Posterior spinal artery
* Primary systemic amyloidosis, a disease caused by the accumulation of abnormal proteins
* Prostate-specific antigen, an enzyme used as a blood tracer for pros ...
and other tumor marker
A tumor marker is a biomarker found in blood, urine, or body tissues that can be elevated by the presence of one or more types of cancer. There are many different tumor markers, each indicative of a particular disease process, and they are used in ...
s to determine the origin of malignant cells that have metastasized.
Small cell carcinoma
Small-cell carcinoma is a type of highly malignant cancer that most commonly arises within the lung, although it can occasionally arise in other body sites, such as the cervix, prostate, and gastrointestinal tract. Compared to non-small cell car ...
is a rare (1%) type that cannot be diagnosed using PSA. researchers were investigating ways to screen for this type, because it is quick to metastasize.
The oncoprotein
An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels. BCL-2
Bcl-2 (B-cell lymphoma 2), encoded in humans by the ''BCL2'' gene, is the founding member of the Bcl-2 family of regulator proteins that regulate cell death (apoptosis), by either inhibiting (anti-apoptotic) or inducing (pro-apoptotic) apoptosis. ...
is associated with the development of androgen-independent prostate cancer, due to its high levels of expression in androgen-independent tumours in advanced stages. The upregulation of BCL-2 after androgen ablation in prostate carcinoma cell lines and in a castrated-male rat model further established a connection between BCL-2 expression and prostate cancer progression.
Staging
An important part of evaluating prostate cancer is determining the stage
Stage or stages may refer to:
Acting
* Stage (theatre), a space for the performance of theatrical productions
* Theatre, a branch of the performing arts, often referred to as "the stage"
* ''The Stage'', a weekly British theatre newspaper
* Sta ...
, or degree of spread. Knowing the stage helps define prognosis
Prognosis (Greek: πρόγνωσις "fore-knowing, foreseeing") is a medical term for predicting the likely or expected development of a disease, including whether the signs and symptoms will improve or worsen (and how quickly) or remain stabl ...
and is useful when selecting therapies. The most common system is the four-stage TNM system (abbreviated from tumor/nodes/metastases). Its components include the size of the tumor, the number of involved lymph node
A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that inclu ...
s, and the presence of any other metastases
Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...
. In the United Kingdom the Cambridge Prognostic Group (CPG) is used for categorising prostate cancer into 5 risk groups (CPG1 to CPG5).
The most important distinction made by any staging system is whether the cancer is confined to the prostate. In the TNM system, clinical T1 and T2 cancers are found only in the prostate, while T3 and T4 cancers have metastasized. Several tests can be used to look for evidence of spread. Medical specialty
A medical specialty is a branch of medical practice that is focused on a defined group of patients, diseases, skills, or philosophy. Examples include those branches of medicine that deal exclusively with children (paediatrics), cancer (oncology), ...
professional organizations
A professional association (also called a professional body, professional organization, or professional society) usually seeks to further a particular profession, the interests of individuals and organisations engaged in that profession, and the ...
recommend against the use of PET scans
Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, r ...
, CT scans, or bone scans when a physician stages early prostate cancer with low risk for metastasis.[
*
*
* ] Those tests would be appropriate in cases such as when a CT scan evaluates spread within the pelvis, a bone scan looks for spread to the bones, and endorectal coil magnetic resonance imaging evaluates the prostatic capsule and the seminal vesicles
The seminal vesicles (also called vesicular glands, or seminal glands) are a pair of two convoluted tubular glands that lie behind the urinary bladder of some male mammals. They secrete fluid that partly composes the semen.
The vesicles are 5 ...
. Bone scans should reveal osteoblast
Osteoblasts (from the Greek language, Greek combining forms for "bone", ὀστέο-, ''osteo-'' and βλαστάνω, ''blastanō'' "germinate") are cell (biology), cells with a single Cell nucleus, nucleus that synthesize bone. However, in the p ...
ic appearance due to ''increased'' bone density in the areas of bone metastasis
Bone metastasis, or osseous metastatic disease, is a category of cancer metastases that results from primary tumor invasion to bone. Bone-originating primary tumors such as osteosarcoma, chondrosarcoma, and Ewing's sarcoma are rare; the most common ...
—the reverse of what is found in many other metastatic cancers. Approved radiopharmaceutical
Radiopharmaceuticals, or medicinal radiocompounds, are a group of pharmaceutical drugs containing radioactive isotopes. Radiopharmaceuticals can be used as diagnostic and therapeutic agents. Radiopharmaceuticals emit radiation themselves, which is ...
diagnostic agents used in PET: fluciclovine (2016), Ga 68 PSMA-11 (2020), piflufolastat (2021).
After a biopsy, a pathologist
Pathology is the study of the causal, causes and effects of disease or injury. The word ''pathology'' also refers to the study of disease in general, incorporating a wide range of biology research fields and medical practices. However, when us ...
examines the samples under a microscope. If cancer is present, the pathologist reports the grade
Grade most commonly refers to:
* Grade (education), a measurement of a student's performance
* Grade, the number of the year a student has reached in a given educational stage
* Grade (slope), the steepness of a slope
Grade or grading may also ref ...
of the tumor. The grade tells how much the tumor tissue differs from normal prostate tissue and suggests how fast the tumor is likely to grow. The pathologist assigns a Gleason number from 1 to 5 for the most common pattern observed under the microscope, then does the same for the second-most common pattern. The sum of these two numbers is the Gleason score. The Whitmore-Jewett stage is another method.
In men with high-risk localised prostate cancer, staging with PSMA PET/CT may be appropriate to detect nodal or distant metastatic spread. In 2020, a randomised phase 3 trial compared Gallium-68 PSMA PET/CT to standard imaging (CT and bone scan). It reported superior accuracy of Gallium-68 PSMA-11 PET/CT (92% vs 65%), higher significant change in management (28% vs 15%), less equivocal/uncertain imaging findings (7% vs 23%) and lower radiation exposure (10 msV vs 19 mSv). The study concluded that PSMA PET/CT is a suitable replacement for conventional imaging.
File:ScleroticmetastaticdiseasespineLCT.png, Sclerosis of the bones of the thoracic spine due to prostate cancer metastases (CT image)
File:Scleroticmetastaticdiseasespine.png, Sclerosis of the bones of the thoracic spine due to prostate cancer metastases (CT image)
File:ScleroticmetastaticdiseasePelvis.png, Sclerosis of the bones of the pelvis due to prostate cancer metastases
Prevention
Diet and lifestyle
The data on the relationship between diet and prostate cancer are poor.[ However, the rate of prostate cancer is linked to the consumption of the Western diet.] Little if any evidence associates trans fat
Trans fat, also called trans-unsaturated fatty acids, or trans fatty acids, is a type of unsaturated fat that naturally occurs in small amounts in meat and milk fat. It became widely produced as an unintentional byproduct in the industrial pro ...
, saturated fat
A saturated fat is a type of fat in which the fatty acid chains have all single bonds. A fat known as a glyceride is made of two kinds of smaller molecules: a short glycerol backbone and fatty acids that each contain a long linear or branched c ...
, and carbohydrate
In organic chemistry, a carbohydrate () is a biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 (as in water) and thus with the empirical formula (where ''m'' may or ma ...
intake and prostate cancer.[ Evidence does not support a role for ]omega-3 fatty acid
Omega−3 fatty acids, also called Omega-3 oils, ω−3 fatty acids or ''n''−3 fatty acids, are polyunsaturated fatty acids (PUFAs) characterized by the presence of a double bond, three atoms away from the terminal methyl group in their chem ...
s in preventing prostate cancer.[ ]Vitamin supplements
A vitamin is an organic molecule (or a set of molecules closely related chemically, i.e. vitamers) that is an essential micronutrient that an organism needs in small quantities for the proper functioning of its metabolism. Essential nutrie ...
appear to have no effect and some may increase the risk.[ High supplemental calcium intake has been linked to advanced prostate cancer.
Fish may lower prostate-cancer deaths, but does not appear to affect occurrence. Some evidence supports lower rates of prostate cancer with a ]vegetarian
Vegetarianism is the practice of abstaining from the consumption of meat (red meat, poultry, seafood, insects, and the flesh of any other animal). It may also include abstaining from eating all by-products of animal slaughter.
Vegetarianism m ...
diet, lycopene
Lycopene is an organic compound classified as a tetraterpene and a carotene. Lycopene (from the neo-Latin ''Lycopersicum'', the tomato species) is a bright red carotenoid hydrocarbon found in tomatoes and other red fruits and vegetables.
Occu ...
, selenium
Selenium is a chemical element with the symbol Se and atomic number 34. It is a nonmetal (more rarely considered a metalloid) with properties that are intermediate between the elements above and below in the periodic table, sulfur and tellurium, ...
cruciferous vegetables, soy, beans and/or other legume
A legume () is a plant in the family Fabaceae (or Leguminosae), or the fruit or seed of such a plant. When used as a dry grain, the seed is also called a pulse. Legumes are grown agriculturally, primarily for human consumption, for livestock f ...
s.[
Regular exercise may slightly lower risk, especially vigorous activity.]
Medications
In those who are regularly screened, 5-alpha-reductase inhibitors (finasteride
Finasteride, sold under the brand names Proscar and Propecia among others, is a medication used to treat hair loss and benign prostatic hyperplasia (BPH) in men. It can also be used to treat excessive hair growth in women and as a part of horm ...
and dutasteride
Dutasteride, sold under the brand name Avodart among others, is a medication primarily used to treat the symptoms of a benign prostatic hyperplasia (BPH), an enlarged prostate not associated with cancer. A few months may be required before benefi ...
) reduce the overall risk of prostate cancer. Data are insufficient to determine if they affect fatality risk and they may increase the chance of more serious cases.
Screening
Prostate cancer screening
Screening may refer to:
* Screening cultures, a type a medical test that is done to find an infection
* Screening (economics), a strategy of combating adverse selection (includes sorting resumes to select employees)
* Screening (environmental), a ...
searches for cancers in those without symptoms. Options include the digital rectal exam
Digital rectal examination (DRE; la, palpatio per anum, PPA) is an internal examination of the rectum, performed by a healthcare provider. Prior to a 2018 report from the U.S. Preventive Services Task Force, the DRE was a common and "dreaded" ...
and the PSA blood test. Such screening is controversial,[ and for many, may lead to unnecessary disruption and possibly harmful consequences.] Harms of population-based screening, primarily due to overdiagnosis (the detection of latent
Latency or latent may refer to:
Science and technology
* Latent heat, energy released or absorbed, by a body or a thermodynamic system, during a constant-temperature process
* Latent variable, a variable that is not directly observed but inferred ...
cancers that would have otherwise not been discovered) may outweigh the benefits.[ Others recommend shared decision-making, an approach where screening may occur after a physician consultation.
The ]United States Preventive Services Task Force
The United States Preventive Services Task Force (USPSTF) is "an independent panel of experts in primary care and prevention that systematically reviews the evidence of effectiveness and develops recommendations for clinical preventive services". ...
(USPSTF) suggests the decision whether to have PSA screening be based on consultation with a physician for men 55 to 69 years of age. USPSTF recommends against PSA screening after age 70.[ The ]Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...
endorsed USPSTF's conclusion.[Prostate Cancer Screening](_blank)
CDC, updated April 6, 2010 The American Society of Clinical Oncology
The American Society of Clinical Oncology (ASCO) is a professional organization representing physicians of all oncology sub-specialties who care for people with cancer. Founded in 1964 by Fred Ansfield, Harry Bisel, Herman Freckman, Arnoldus G ...
and the American College of Physicians
The American College of Physicians (ACP) is a national organization of internists, who specialize in the diagnosis, treatment, and care of adults.Sokanu "What is an Internist?" Retrieved October 20, 2014 With 161,000 members, ACP is the largest ...
discourage screening for those who are expected to live less than 10–15 years, while those with a greater life expectancy a decision should individually balance the potential risks and benefits. In general, they concluded, "it is uncertain whether the benefits associated with PSA testing for prostate cancer screening are worth the harms associated with screening and subsequent unnecessary treatment."
American Urological Association
The American Urological Association (AUA) is a professional association in the United States for urology professionals. It has its headquarters at the William P. Didusch Center for Urologic History in Maryland.
AUA works with many international o ...
(AUA 2013) guidelines call for weighing the uncertain benefits of screening against the known harms associated with diagnostic tests and treatment. The AUA recommends that shared decision-making should control screening for those 55 to 69, and that screening should occur no more often than every two years. In the United Kingdom
The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom (UK) or Britain, is a country in Europe, off the north-western coast of the continental mainland. It comprises England, Scotland, Wales and North ...
as of 2018, no program existed to screen for prostate cancer.[
]
Management
The first decision is whether treatment is needed. Low-grade forms found in elderly men often grow so slowly that treatment is not required. Treatment may be inappropriate if a person has other serious health problems or is not expected to live long enough for symptoms to appear. Approaches in which treatment is postponed are termed "expectant management".[ Expectant management is divided into two approaches: ]Watchful waiting
Watchful waiting (also watch and wait or WAW) is an approach to a medical problem in which time is allowed to pass before medical intervention or therapy is used. During this time, repeated testing may be performed.
Related terms include ''expec ...
, which has palliative intent (aims to treat symptoms only), and active surveillance, which has curative intent (aims to prevent the cancer from advancing).[
Which option is best depends on disease stage, the Gleason score, and the PSA level. Other important factors are age, general health and a person's views about potential treatments and their possible side effects. Because most treatments can have significant ]side effect
In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...
s, such as erectile dysfunction
Erectile dysfunction (ED), also called impotence, is the type of sexual dysfunction in which the penis fails to become or stay erect during sexual activity. It is the most common sexual problem in men.Cunningham GR, Rosen RC. Overview of male ...
and urinary incontinence
Urinary incontinence (UI), also known as involuntary urination, is any uncontrolled leakage of urine. It is a common and distressing problem, which may have a large impact on quality of life. It has been identified as an important issue in geria ...
, treatment discussions often focus on balancing the goals of therapy with the risks of lifestyle alterations. A 2017 review found that more research focused on person-centered outcomes is needed to guide patients. A combination of treatment options is often recommended.
Guidelines for specific clinical situations require estimation of life expectancy. As average life expectancy increases due to advances in the treatment of other diseases, more patients will live long enough for their prostate cancer to express symptoms. An 18-item questionnaire was proposed to learn whether patients have adequate knowledge and understanding of their treatment options. In one 2015 study, most of those who were newly diagnosed correctly answered fewer than half of the questions.
The widespread use of PSA screening in the US has resulted in diagnosis at earlier age and cancer stage, but almost all cases are still diagnosed after age 65, while about 25% are diagnosed after age 75. Though US National Comprehensive Cancer Network guidelines recommend using life expectancy to help make treatment decisions, in practice, many elderly patients are not offered curative treatment options such as radical prostatectomy
Prostatectomy (from the Greek , "prostate" and , "excision") as a medical term refers to the surgical removal of all or part of the prostate gland. This operation is done for benign conditions that cause urinary retention, as well as for prosta ...
or radiation therapy
Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radia ...
and are instead treated with hormonal therapy
Hormone therapy or hormonal therapy is the use of hormones in medical treatment. Treatment with hormone antagonists may also be referred to as hormonal therapy or antihormone therapy. The most general classes of hormone therapy are hormonal therap ...
or watchful waiting.
Surveillance
Many men diagnosed with low-risk prostate cancer are eligible for active surveillance. The tumor is carefully observed over time, with the intention of initiating treatment if signs of progression appear. Active surveillance is ''not'' synonymous with watchful waiting
Watchful waiting (also watch and wait or WAW) is an approach to a medical problem in which time is allowed to pass before medical intervention or therapy is used. During this time, repeated testing may be performed.
Related terms include ''expec ...
, a term which implies no treatment or specific program of monitoring, with the assumption that only palliative treatment would be used if advanced, symptomatic disease develops.[
Active surveillance involves monitoring the tumor for growth or symptoms, which trigger treatment. The monitoring process may involve PSA tests, digital rectal examination, or repeated biopsies every few months. The goal of active surveillance is to postpone treatment, and avoid ]overtreatment
Unnecessary health care (overutilization, overuse, or overtreatment) is health care provided with a higher volume or cost than is appropriate.
In the United States, where health care costs are the highest as a percentage of GDP, overuse was the ...
and its side effects, given a slow-growing or self-limited tumor that in most people is unlikely to cause problems. This approach is not used for aggressive cancers, and may cause anxiety
Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...
for people who wrongly believe that all cancers are deadly or that their condition is life-threatening. Between 50 and 75% of patients die from other causes without experiencing prostate symptoms. In localized disease, based on long-term follow-up, radical prostatectomy
Prostatectomy (from the Greek , "prostate" and , "excision") as a medical term refers to the surgical removal of all or part of the prostate gland. This operation is done for benign conditions that cause urinary retention, as well as for prosta ...
results in significantly improved oncological outcomes when compared with watchful waiting. Prostatectomy is associated with increased rates of urinary incontinence and erectile dysfunction, but these findings are based primarily on men diagnosed before widespread PSA screening and cannot be highly generalized.[ When compared to active monitoring/surveillance, on follow-up at ten years, radical prostatectomy probably has similar outcomes for disease-specific survival and probably reduces risk of disease progression and spreading.][ Urinary and sexual function are probably decreased in patients treated with radical prostatectomy.][
]
Active treatment
Both surgical and nonsurgical treatments are available, but treatment can be difficult, and combinations can be used. Treatment by external beam radiation therapy
External may refer to:
* External (mathematics), a concept in abstract algebra
* Externality
In economics, an externality or external cost is an indirect cost or benefit to an uninvolved third party that arises as an effect of another party' ...
, brachytherapy
Brachytherapy is a form of radiation therapy where a sealed radiation source is placed inside or next to the area requiring treatment. ''Brachy'' is Greek for short. Brachytherapy is commonly used as an effective treatment for cervical, prosta ...
, cryosurgery
Cryosurgery is the use of extreme cold in surgery to destroy abnormal or diseased tissue; thus, it is the surgical application of cryoablation. The term comes from the Greek words cryo (κρύο) ("icy cold") and surgery (''cheirourgiki'' – χ ...
, high-intensity focused ultrasound
High-intensity focused ultrasound (HIFU) is a non-invasive therapeutic technique that uses non-ionizing ultrasonic waves to heat or ablate tissue. HIFU can be used to increase the flow of blood or lymph or to destroy tissue, such as tumors, via ...
, and prostatectomy are, in general, offered to men whose cancer remains within the prostate. Hormonal therapy and chemotherapy are often reserved for metastatic disease. Exceptions include local or metastasis-directed therapy with radiation may be used for advanced tumors with limited metastasis. Hormonal therapy is used for some early-stage tumors. Cryotherapy
Cryotherapy, sometimes known as cold therapy, is the local or general use of low temperatures in medical therapy. Cryotherapy may be used to treat a variety of tissue lesions. The most prominent use of the term refers to the surgical treatment, s ...
(the process of freezing the tumor), hormonal therapy, and chemotherapy may be offered if initial treatment fails and the cancer progresses. Sipuleucel-T
Sipuleucel-T, sold under the brand name Provenge, developed by Dendreon Pharmaceuticals, LLC, is a cell-based cancer immunotherapy for prostate cancer (CaP). It is an autologous cellular immunotherapy.
Medical uses
Sipuleucel-T is indicated ...
, a cancer vaccine
A cancer vaccine is a vaccine that either treats existing cancer or prevents development of cancer. Vaccines that treat existing cancer are known as ''therapeutic'' cancer vaccines or tumor antigen vaccines. Some of the vaccines are "autologous", ...
, was reported to offer a four-month increase in survival in metastatic prostate cancer, but the marketing authorisation for it was withdrawn on 19 May 2015.
If radiation therapy fails, radical prostatectomy may be an option, though it is a technically challenging surgery. However, radiation therapy ''after'' surgical failure may have many complications. It is associated with a small increase in bladder and colon cancer. Radiotherapy and surgery appear to result in similar outcomes with respect to bowel, erectile and urinary function after five years.
Nonsurgical treatment
Non-surgical treatment may involve radiation therapy, chemotherapy, hormonal therapy, external beam radiation therapy, and particle therapy, high-intensity focused ultrasound, or some combination.
Prostate cancer that persists when testosterone levels are lowered by hormonal therapy is called castrate-resistant prostate cancer (CRPC). Many early-stage cancers need normal levels of testosterone to grow, but CRPC does not. Previously considered "hormone-refractory prostate cancer" or "androgen-independent prostate cancer", the term CRPC emerged because these cancers show reliance upon hormones, particularly testosterone, for androgen receptor
The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone in th ...
activation.
The cancer chemotherapeutic docetaxel
Docetaxel (DTX or DXL), sold under the brand name Taxotere among others, is a chemotherapy medication used to treat a number of types of cancer. This includes breast cancer, head and neck cancer, stomach cancer, prostate cancer and non-small-ce ...
has been used as treatment for CRPC with a median survival benefit of 2 to 3 months. A second-line chemotherapy treatment is cabazitaxel
Cabazitaxel, sold under the brand name Jevtana, is a semi-synthetic derivative of a natural taxoid. It is a microtubule inhibitor, and the fourth taxane to be approved as a cancer therapy.
Cabazitaxel was developed by Sanofi-Aventis and was ap ...
. A combination of bevacizumab
Bevacizumab, sold under the brand name Avastin among others, is a medication used to treat a number of types of cancers and a specific eye disease. For cancer, it is given by slow injection into a vein (intravenous) and used for colon cancer, l ...
, docetaxel
Docetaxel (DTX or DXL), sold under the brand name Taxotere among others, is a chemotherapy medication used to treat a number of types of cancer. This includes breast cancer, head and neck cancer, stomach cancer, prostate cancer and non-small-ce ...
, thalidomide
Thalidomide, sold under the brand names Contergan and Thalomid among others, is a medication used to treat a number of cancers (including multiple myeloma), graft-versus-host disease, and a number of skin conditions including complications of ...
and prednisone
Prednisone is a glucocorticoid medication mostly used to immunosuppressive drug, suppress the immune system and decrease inflammation in conditions such as asthma, COPD, and rheumatologic diseases. It is also used to treat high blood calcium ...
appears effective in the treatment of CRPC.
Immunotherapy
Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...
treatment with sipuleucel-T
Sipuleucel-T, sold under the brand name Provenge, developed by Dendreon Pharmaceuticals, LLC, is a cell-based cancer immunotherapy for prostate cancer (CaP). It is an autologous cellular immunotherapy.
Medical uses
Sipuleucel-T is indicated ...
in CRPC appeared to increase survival by four months. However, marketing authorisation for sipuleucel-T was withdrawn on 19 May 2015. The second line hormonal therapy abiraterone
Abiraterone acetate, sold under the brand name Zytiga among others, is a medication used to treat prostate cancer. Specifically it is used together with a corticosteroid for metastatic castration-resistant prostate cancer (mCRPC) and metastat ...
increases survival by about 4.6 months. Enzalutamide
Enzalutamide, sold under the brand name Xtandi, is a nonsteroidal antiandrogen (NSAA) medication which is used in the treatment of prostate cancer. It is indicated for use in conjunction with castration in the treatment of metastatic castrat ...
is another second line hormonal agent with a five-month survival advantage. Both abiraterone and enzalutamide are currently in clinical trials in those with CRPC who have not previously received chemotherapy.
Not all patients respond to androgen signaling-blocking drugs. Certain cells with characteristics resembling stem cells
In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type o ...
remain unaffected. Therefore, the desire to improve CRPC outcomes resulted in increasing doses or combination therapy with synergistic androgen-signaling blocking agents. But even these combination will not affect stem-like cells that do not exhibit androgen signaling.
For patients with metastatic prostate cancer that has spread to their bones, doctors use a variety of bone-modifying agents to prevent skeletal complications and support the formation of new bone mass. Zoledronic acid (a bisphosphonate
Bisphosphonates are a class of drugs that prevent the loss of bone density, used to treat osteoporosis and similar diseases. They are the most commonly prescribed drugs used to treat osteoporosis. They are called bisphosphonates because they ...
) and denosumab (a RANK-ligand-inhibitor) appear to be effective agents, but are associated with more frequent and serious adverse events.[
]
Surgery
Radical prostatectomy
Prostatectomy (from the Greek , "prostate" and , "excision") as a medical term refers to the surgical removal of all or part of the prostate gland. This operation is done for benign conditions that cause urinary retention, as well as for prosta ...
is considered the mainstay of surgical treatment of prostate cancer, where the surgeon removes the prostate, seminal vesicle
The seminal vesicles (also called vesicular glands, or seminal glands) are a pair of two convoluted tubular glands that lie behind the urinary bladder of some male mammals. They secrete fluid that partly composes the semen.
The vesicles are 5 ...
s, and surrounding lymph node
A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that inclu ...
s. It can be done by an open technique (a skin incision at the lower abdomen), or laparoscopically
Laparoscopy () is an operation performed in the abdomen or human pelvis, pelvis using small Surgical incision, incisions (usually 0.5–1.5 cm) with the aid of a camera. The laparoscope aids diagnosis or therapeutic interventions with a few ...
. Radical retropubic prostatectomy
Radical retropubic prostatectomy is a surgical procedure in which the prostate gland is removed through an incision in the abdomen (in comparison with perineal prostatectomy, done through the perineum). It is most often used to treat individual ...
is the most commonly used open surgical technique. Robotic-assisted prostatectomy has become common. Men with localized prostate cancer, having laparoscopic radical prostatectomy or robotic-assisted radical prostatectomy, might have shorter stays in the hospital and get fewer blood transfusions than men undergoing open radical prostatectomy. How these treatments compare with regard to overall survival or recurrence-free survival is unknown.[
]Transurethral resection of the prostate
Transurethral resection of the prostate (commonly known as a TURP, plural TURPs, and rarely as a transurethral prostatic resection, TUPR) is a urological operation. It is used to treat benign prostatic hyperplasia (BPH). As the name indicates, ...
is the standard surgical treatment for benign enlargement of the prostate
Benign prostatic hyperplasia (BPH), also called prostate enlargement, is a noncancerous increase in size of the prostate gland. Symptoms may include frequent urination, trouble starting to urinate, weak stream, inability to urinate, or loss o ...
.[ In prostate cancer, this procedure can be used to relieve symptoms of ]urinary retention
Urinary retention is an inability to completely empty the bladder. Onset can be sudden or gradual. When of sudden onset, symptoms include an inability to urinate and lower abdominal pain. When of gradual onset, symptoms may include loss of bladd ...
caused by a large prostate tumor, but it is not used to treat the cancer itself. The procedure is done under spinal anesthesia, a resectoscope is inserted inside the penis and the extra prostatic tissue is cut to clear the way for the urine to pass.
Complications
The two main complications encountered after prostatectomy and prostate radiotherapy are erectile dysfunction
Erectile dysfunction (ED), also called impotence, is the type of sexual dysfunction in which the penis fails to become or stay erect during sexual activity. It is the most common sexual problem in men.Cunningham GR, Rosen RC. Overview of male ...
and urinary incontinence
Urinary incontinence (UI), also known as involuntary urination, is any uncontrolled leakage of urine. It is a common and distressing problem, which may have a large impact on quality of life. It has been identified as an important issue in geria ...
, mainly stress-type. Most men regain continence within 6 to 12 months after the operation, so doctors usually wait at least one year before resorting to invasive treatments.
Stress urinary incontinence
Stress incontinence, also known as stress urinary incontinence (SUI) or effort incontinence is a form of urinary incontinence. It is due to inadequate closure of the Urinary bladder, bladder outlet by the Urethral sphincters, urethral sphincter.
...
usually happens after prostate surgery or radiation therapy due to factors that include damage to the urethral sphincter or surrounding tissue and nerves. The prostate surrounds the urethra, a muscular tube that closes the urinary bladder. Any of the mentioned reasons can lead to incompetent closure of the urethra and hence incontinence. Initial therapy includes bladder training
Bladder training, also known as scheduled voiding and bladder re-education is urinating at specific times of the day. It is used as a first line treatment of overactive bladder on mixed urinary incontinence
Urinary incontinence (UI), also known ...
, lifestyle changes, kegel exercise
Kegel exercise, also known as pelvic-floor exercise, involves repeatedly contracting and relaxing the muscles that form part of the pelvic floor, now sometimes colloquially referred to as the "Kegel muscles". The exercise can be performed many ti ...
s, and the use of incontinence pad
An incontinence pad is a small, impermeable multi-layered sheet with high absorbency that is used in the incontinence and health-care industries as a precaution against fecal or urinary incontinence. It is generally made of cotton if washable, or p ...
s. More invasive surgical treatment can include the insertion of a urethral sling A urethral sling is a device that is surgically implanted to stabilize the pelvic tissues and organs of women. The surgery that implants this device can help treat urinary incontinence and uterine prolapse. An alternative treatment to the placement ...
or an artificial urinary sphincter
An artificial urinary sphincter (AUS) is an implanted device to treat moderate to severe stress urinary incontinence, most commonly in men. The AUS is designed to supplement the function of the natural urinary sphincter that restricts urine flo ...
, which is a mechanical device that mimics the function of the urethral sphincter, and is activated manually by the patient through a switch implanted in the scrotum
The scrotum or scrotal sac is an anatomical male reproductive structure located at the base of the penis that consists of a suspended dual-chambered sac of skin and smooth muscle. It is present in most terrestrial male mammals. The scrotum cont ...
. The latter is considered the gold standard in patients with moderate or severe stress urinary incontinence.
Erectile dysfunction happens in different degrees in nearly all men who undergo prostate cancer treatment, including radiotherapy or surgery; however, within one year, most of them will notice improvement. If nerves were damaged, this progress may not take place. Pharmacological treatment includes PDE-5 inhibitors such as viagra
Sildenafil, sold under the brand name Viagra, among others, is a medication used to treat erectile dysfunction and pulmonary arterial hypertension. It is unclear if it is effective for treating sexual dysfunction in women. It is taken by ...
or cialis
Tadalafil, sold under the brand name Cialis among others, is a medication used to treat erectile dysfunction (ED), benign prostatic hyperplasia (BPH), and pulmonary arterial hypertension. It is taken by mouth. Onset is typically within half ...
, or injectable intracavernous drugs injected directly into the penis (prostaglandin E1
Prostaglandin E1 (PGE1), also known as alprostadil, is a naturally occurring prostaglandin which is used as a medication. In infants with congenital heart defects, it is delivered by slow injection into a vein to open the ductus arteriosus unti ...
and vasoactive drug mixtures). Other nonpharmacological therapy includes vacuum constriction devices and penile implant
A penile implant is an implanted device intended for the treatment of erectile dysfunction, Peyronie's disease, ischemic priapism, deformity and any traumatic injury of the penis, and for phalloplasty or metoidioplasty, including in gender-affi ...
s.
Psychological
Psychological interventions such as psychoeducation
Psychoeducation (a portmanteau of psychological education) is an evidence-based therapeutic intervention for patients and their loved ones that provides information and support to better understand and cope with illness. Psychoeducation is most oft ...
, cognitive behavioural therapy
Cognitive behavioral therapy (CBT) is a psycho-social intervention that aims to reduce symptoms of various mental health conditions, primarily depression and anxiety disorders. CBT focuses on challenging and changing cognitive distortions (su ...
(CBT) and mindfulness
Mindfulness is the practice of purposely bringing one's attention to the present-moment experience without evaluation, a skill one develops through meditation or other training. Mindfulness derives from ''sati'', a significant element of Hind ...
are recommended for the management of mental and emotional complications of disease symptoms and those associated with active treatment. Due to limited research and inadequate methodological rigor of published literature, solid recommendations cannot be made on the effectiveness of mindfulness in men with prostate cancer.
Prognosis
Many prostate cancers are not destined to be lethal, and most men will ultimately not die as a result of the disease. Mortality varies widely across geography and other elements. In the United States, five-year survival rates range from 29% (distant metastases) to 100% (local or regional tumors). In Japan, the fatality rate rose to 8.6/100,000 in 2000. In India
India, officially the Republic of India (Hindi: ), is a country in South Asia. It is the seventh-largest country by area, the second-most populous country, and the most populous democracy in the world. Bounded by the Indian Ocean on the so ...
in the 1990s, half of those diagnosed with local cancer died within 19 years. One study reported that African-Americans have 50–60 times more deaths than found in Shanghai, China. In Nigeria
Nigeria ( ), , ig, Naìjíríyà, yo, Nàìjíríà, pcm, Naijá , ff, Naajeeriya, kcg, Naijeriya officially the Federal Republic of Nigeria, is a country in West Africa. It is situated between the Sahel to the north and the Gulf o ...
, 2% of men develop prostate cancer, and 64% of them are dead after 2 years. Most Nigerian men present with metastatic disease with a typical survival of 40 months.
In patients who undergo treatment, the most important clinical prognostic indicators of disease outcome are the stage, pretherapy PSA level, and Gleason score. The higher the grade and the stage, the poorer the prognosis. Nomogram
A nomogram (from Greek , "law" and , "line"), also called a nomograph, alignment chart, or abac, is a graphical calculating device, a two-dimensional diagram designed to allow the approximate graphical computation of a mathematical function. ...
s can be used to calculate the estimated risk of the individual patient. The predictions are based on the experience of large groups of patients. A complicating factor is that the majority of patients have multiple independent tumor foci upon diagnosis, and these foci have independent genetic changes and molecular features. Because of this extensive inter-focal heterogeneity, it is a risk that the prognostication is set based on the wrong tumor focus.
An important aspect of decision making on the value of treatment is how to balance prognosis from prostate cancer with other causes of mortality and the morbidity of treatment. The PREDICT Prostate algorithm (https://prostate.predict.nhs.uk) is a multivariable prognostic model that provides individualised cancer-specific and overall long-term survival estimates in early stage non-metastatic PCa patients. In addition to the use of routinely available preoperative clinical-pathological variables such as PSA, biopsy Gleason score (ISUP grade group), and clinical T-stage, the PREDICT Prostate tool also includes the impact of patient characteristics (age and comorbidity status) and radical treatment (radical prostatectomy or radiotherapy) on survival. The tool provides patients with estimated survival rates after treatment in the context of absolute mortality rate, which allows patients to make an informed decision as to the value of treatment and its potential side effects. Thurtle et al. performed an external validation of their previously published PREDICT Prostate model. The tool outperformed other widely used models and was proven to have high c-indices for all-cause and PCa-specific mortality, and the model calibration was good and remained accurate within the treatment subgroups. Recent work has also shown that it significantly alters clinician treatment recommendations and improves patients confidence in decision making and in their understanding of mortality risks from a new prostate cancer diagnosis Predict Prostate is endorsed for use as a decision aid for prostate cancer by the UK National Institute for Health and Care Excellence
Androgen ablation therapy causes remission in 80–90% of patients undergoing therapy, resulting in a median progression-free survival of 12 to 33 months. After remission, an androgen-independent phenotype typically emerges, wherein the median overall survival is 23–37 months from the time of initiation of androgen ablation therapy. How androgen-independence is established and how it re-establishes progression is unclear.
Classification systems
Several tools are available to help predict outcomes, such as pathologic stage and recurrence after surgery or radiation therapy. Most combine stage, grade, and PSA level, and some include the number or percentage of biopsy cores positive, age, and/or other information.
*The D'Amico classification stratifies men by low, intermediate, or high risk based on stage, grade and PSA. It is used widely in clinical practice and research settings. The major downside to the three-level system is that it does not account for multiple adverse parameters (e.g., high Gleason score ''and'' high PSA) in stratifying patients.
*The Partin tables predict pathologic outcomes (margin status, extraprostatic extension, and seminal vesicle invasion) based on the same three variables and are published as lookup tables.
*The Kattan nomograms predict recurrence after surgery and/or radiation therapy, based on data available at the time of diagnosis or after surgery. The Kattan score represents the likelihood of remaining free of disease at a given time interval following treatment.
*The UCSF Cancer of the Prostate Risk Assessment (CAPRA) score predicts both pathologic status and recurrence after surgery. It offers accuracy comparable to the Kattan preoperative nomogram and can be calculated without tables or a calculator. Points are assigned based on PSA, grade, stage, age, and percentage of cores positive; the sum yields a 0–10 score, with every two points representing roughly a doubling of risk of recurrence. The CAPRA score was derived from community-based data in the CaPSURE database. It has been validated among over 10,000 prostatectomy patients, including patients from CaPSURE; the SEARCH registry, representing data from several Veterans Health Administration
The Veterans Health Administration (VHA) is the component of the United States Department of Veterans Affairs (VA) led by the Under Secretary of Veterans Affairs for Health that implements the healthcare program of the VA through a national ...
and military medical centers; a multi-institutional cohort in Germany; and the prostatectomy cohort at Johns Hopkins University. More recently, it has been shown to predict metastasis and mortality following prostatectomy, radiation therapy, watchful waiting, or androgen deprivation therapy.
* The UK National Institute for Health and Care Excellence guidelines recommends use of the Cambridge Prognostic Groups (CPG) 5-tier model when determining treatment options. The rationale for the change related to recent evidence, which suggests that 5-tier risk stratification model was better at predicting prostate cancer specific mortality than older 3-tier models The CPG model has been tested and validated in studies including >80,000 men The NICE CPG model and treatment recommendations can be viewed at the NICE guideline website.
Life expectancy
Life expectancy projections are averages for an entire male population, and many medical and lifestyle factors modify these numbers. For example, studies have shown that a 40-year-old man will lose 3.1 years of life if he is overweight (BMI 25–29) and 5.8 years of life if he is obese (BMI 30 or more), compared to men of normal weight. If he is both overweight and a smoker, he will lose 6.7 years, and if obese and a smoker, he will lose 13.7 years.
No evidence shows that either surgery or beam radiation has an advantage over the other in this regard. The lower death rates reported with surgery appear to occur because surgery is more likely to be offered to younger men with less severe cancers. Insufficient information is available to determine whether seed radiation extends life more readily than the other treatments, but data so far do not suggest that it does.
Men with low-grade disease (Gleason 2–4) were unlikely to die of prostate cancer within 15 years of diagnosis. Older men (age 70–75) with low-grade disease had a roughly 20% overall survival at 15 years due to deaths from competing causes. Men with high-grade disease (Gleason 8–10) experienced high mortality within 15 years of diagnosis, regardless of their age.
Epidemiology
As of 2012, prostate cancer is the second-most frequently diagnosed cancer (at 15% of all male cancers) and the sixth leading cause of cancer death in males worldwide. In 2010, prostate cancer resulted in 256,000 deaths, up from 156,000 deaths in 1990. Rates of prostate cancer vary widely. Rates vary widely between countries. It is least common in South and East Asia, and more common in Europe, North America, Australia, and New Zealand. Prostate cancer is least common among Asian men and most common among black men, with white men in between.[Overview: Prostate Cancer – What Causes Prostate Cancer?](_blank)
American Cancer Society (2 May 2006). Retrieved on 5 April 2007[Prostate Cancer FAQs.](_blank)
State University of New York School of Medicine Department of Urology (31 August 2006). Retrieved on 5 April 2007
The average annual incidence rate of prostate cancer between 1988 and 1992 among Chinese men in the United States was 15 times higher than that of their counterparts living in Shanghai and Tianjin, but these high rates may be affected by higher rates of detection. Many suggest that prostate cancer may be under-reported, yet benign prostatic hyperplasia incidence in China and Japan is similar to rates in Western countries.
More than 80% of men develop prostate cancer by age 80.
United States
Prostate cancer is the third-leading cause of cancer death in men, exceeded by lung cancer and colorectal cancer. It accounts for 19% of all male cancers and 9% of male cancer-related deaths.
Cases ranged from an estimated 230,000 in 2005 to an estimated 164,690 In 2018.
Deaths held steady around 30,000 in 2005 and 29,430 in 2018.
Age-adjusted incidence rates increased steadily from 1975 through 1992, with particularly dramatic increases associated with the spread of PSA screening in the late 1980s, later followed by a fall in incidence. A decline in early-stage incidence rates from 2011 to 2012 (19%) in men aged 50 years and older persisted through 2013 (6%).
Declines in mortality rates in certain jurisdictions may reflect the interaction of PSA screening and improved treatment. The estimated lifetime risk is about 14.0%, and the lifetime mortality risk is 2.6%.
Between 2005 and 2011, the proportion of disease diagnosed at a locoregional stage was 93% for whites and 92% for African Americans; the proportion of disease diagnosed at a late stage was 4% for European Americans and 5% for African Americans.
Prostate cancer is more common in the African American
African Americans (also referred to as Black Americans and Afro-Americans) are an ethnic group consisting of Americans with partial or total ancestry from sub-Saharan Africa. The term "African American" generally denotes descendants of ens ...
population than the European American
European Americans (also referred to as Euro-Americans) are Americans of European ancestry. This term includes people who are descended from the first European settlers in the United States as well as people who are descended from more recent Eu ...
population. An autopsy study of White and Asian men also found an increase in occult prostate cancer with age, reaching nearly 60% in men older than 80 years. More than 50% of cancers in Asian men and 25% of cancers in White men had a Gleason score of 7 or greater, suggesting that Gleason score may be an imprecise indicator of clinically insignificant cases.
Canada
Prostate cancer is the third-leading type of cancer in Canadian men. In 2016, around 4,000 died and 21,600 men were diagnosed with prostate cancer.
Europe
In Europe in 2012, it was the third-most diagnosed cancer after breast and colorectal cancers at 417,000 cases.
In the United Kingdom, it is the second-most common cause of cancer death after lung cancer, where around 35,000 cases are diagnosed every year, of which around 10,000 are fatal.
History
The prostate was first described by Venetian anatomist Niccolò Massa
Niccolò Massa (; 1485–1569) was an Italian anatomist who wrote an early anatomy text ''Anatomiae Libri Introductorius'' in 1536. In 1536 he described the cerebrospinal fluid.
Massa graduated from the Venetian College of Physicians with a degre ...
in 1536, and illustrated by Flemish
Flemish (''Vlaams'') is a Low Franconian dialect cluster of the Dutch language. It is sometimes referred to as Flemish Dutch (), Belgian Dutch ( ), or Southern Dutch (). Flemish is native to Flanders, a historical region in northern Belgium; ...
anatomist Andreas Vesalius
Andreas Vesalius (Latinized from Andries van Wezel) () was a 16th-century anatomist, physician, and author of one of the most influential books on human anatomy, ''De Humani Corporis Fabrica Libri Septem'' (''On the fabric of the human body'' '' ...
in 1538. Prostate cancer was identified in 1853. It was initially considered a rare disease, probably because of shorter life expectancies
Life expectancy is a statistical measure of the average time an organism is expected to live, based on the year of its birth, current age, and other demographic factors like sex. The most commonly used measure is life expectancy at birth ...
and poorer detection methods in the 19th century. The first treatments were surgeries to relieve urinary obstruction.
Removal of the gland was first described in 1851, and radical perineal prostatectomy
Prostatectomy (from the Ancient Greek language, Greek , "prostate" and , "excision") as a medical term refers to the surgical removal of all or part of the prostate gland. This operation is done for benignity, benign conditions that cause urina ...
was first performed in 1904 by Hugh H. Young
Hugh Hampton Young (September 18, 1870 – August 23, 1945) was an American surgery, surgeon, urologist, and medical researcher.
Biography
Hugh H. Young was born in San Antonio, Texas, San Antonio, Texas on September 18, 1870. He was the son of ...
at Johns Hopkins Hospital
The Johns Hopkins Hospital (JHH) is the teaching hospital and biomedical research facility of the Johns Hopkins School of Medicine, located in Baltimore, Maryland, U.S. It was founded in 1889 using money from a bequest of over $7 million (1873 mo ...
.
Surgical removal of the testes (orchiectomy
Orchiectomy (also named orchidectomy, and sometimes shortened as orchi or orchie) is a surgical procedure in which one or both testicles are removed. The surgery is performed as treatment for testicular cancer, as part of surgery for transgend ...
) to treat prostate cancer was first performed in the 1890s, with limited success. Transurethral resection of the prostate
Transurethral resection of the prostate (commonly known as a TURP, plural TURPs, and rarely as a transurethral prostatic resection, TUPR) is a urological operation. It is used to treat benign prostatic hyperplasia (BPH). As the name indicates, ...
(TURP) replaced radical prostatectomy for symptomatic relief of obstruction in the middle of the 20th century because it could better preserve penile erectile function. Radical retropubic prostatectomy was developed in 1983 by Patrick Walsh. This surgical approach allowed for removal of the prostate and lymph nodes with maintenance of penile function.
In 1941, Charles B. Huggins
Charles Brenton Huggins (September 22, 1901 – January 12, 1997) was a Canadian-American physician, physiologist and cancer researcher at the University of Chicago specializing in prostate cancer. He was awarded the 1966 Nobel Prize for Physi ...
published studies in which he used estrogen
Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...
to oppose testosterone production in men with metastatic prostate cancer. This discovery of "chemical castration
Castration is any action, surgical, chemical, or otherwise, by which an individual loses use of the testicles: the male gonad. Surgical castration is bilateral orchiectomy (excision of both testicles), while chemical castration uses pharmaceut ...
" won Huggins the 1966 Nobel Prize in Physiology or Medicine
The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, accord ...
. The role of the gonadotropin-releasing hormone
Gonadotropin-releasing hormone (GnRH) is a releasing hormone responsible for the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. GnRH is a tropic peptide hormone synthesized and released ...
(GnRH) in reproduction was determined by Andrzej W. Schally
Andrzej Viktor "Andrew" Schally (born 30 November 1926) is an American endocrinologistAndrew V. Schally"Andrew V. Schally" ''Encyclopædia Britannica''. of Polish Americans, Polish ancestry, who was a corecipient, with Roger Guillemin and Rosalyn ...
and Roger Guillemin
Roger Charles Louis Guillemin (born January 11, 1924) is a French-American neuroscientist. He received the National Medal of Science in 1976, and the Nobel prize for medicine in 1977 for his work on neurohormones, sharing the prize that year ...
, who shared the 1977 Nobel Prize in Physiology or Medicine for this work. GnRH receptor agonists, such as leuprorelin
Leuprorelin, also known as leuprolide, is a manufactured version of a hormone used to treat prostate cancer, breast cancer, endometriosis, uterine fibroids, as part of transgender hormone therapy, for early puberty, or to perform chemical castra ...
and goserelin
Goserelin, sold under the brand name Zoladex among others, is a medication which is used to suppress production of the sex hormones (testosterone and estrogen), particularly in the treatment of breast and prostate cancer. It is an injectable gona ...
, were subsequently developed and used to treat prostate cancer.
Radiation therapy
Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radia ...
for prostate cancer was first developed in the early 20th century and initially consisted of intraprostatic radium
Radium is a chemical element with the symbol Ra and atomic number 88. It is the sixth element in group 2 of the periodic table, also known as the alkaline earth metals. Pure radium is silvery-white, but it readily reacts with nitrogen (rather t ...
implants. External beam radiotherapy
External beam radiotherapy (EBRT) is the most common form of radiotherapy (radiation therapy). The patient sits or lies on a couch and an external source of ionizing radiation is pointed at a particular part of the body. In contrast to brachyt ...
became more popular as stronger -rayradiation sources became available in the middle of the 20th century. Brachytherapy
Brachytherapy is a form of radiation therapy where a sealed radiation source is placed inside or next to the area requiring treatment. ''Brachy'' is Greek for short. Brachytherapy is commonly used as an effective treatment for cervical, prosta ...
with implanted seeds (for prostate cancer) was first described in 1983.
Systemic chemotherapy
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
for prostate cancer was first studied in the 1970s. The initial regimen of cyclophosphamide
Cyclophosphamide (CP), also known as cytophosphane among other names, is a medication used as chemotherapy and to suppress the immune system. As chemotherapy it is used to treat lymphoma, multiple myeloma, leukemia, ovarian cancer, breast cancer ...
and 5-fluorouracil
Fluorouracil (5-FU), sold under the brand name Adrucil among others, is a cytotoxic chemotherapy medication used to treat cancer. By intravenous injection it is used for treatment of colorectal cancer, oesophageal cancer, stomach cancer, pancrea ...
was quickly joined by regimens using other systemic chemotherapy drugs.
Enzalutamide
Enzalutamide, sold under the brand name Xtandi, is a nonsteroidal antiandrogen (NSAA) medication which is used in the treatment of prostate cancer. It is indicated for use in conjunction with castration in the treatment of metastatic castrat ...
gained FDA approval in 2012 for the treatment of castration-resistant prostate cancer (CRPC). Alpharadin won FDA approval in 2013, under the priority review program.
In 2006, a previously unknown retrovirus, Xenotropic MuLV-related virus (XMRV), was associated with human prostate tumors,[ ] but ''PLOS Pathogens'' retracted the article in 2012.
Society and culture
Men with prostate cancer generally encounter significant disparities in awareness, funding, media coverage, and research—and therefore, inferior treatment and poorer outcomes—compared to other cancers of equal prevalence. In 2001, ''The Guardian
''The Guardian'' is a British daily newspaper. It was founded in 1821 as ''The Manchester Guardian'', and changed its name in 1959. Along with its sister papers ''The Observer'' and ''The Guardian Weekly'', ''The Guardian'' is part of the Gu ...
'' noted that Britain had 3,000 nurses specializing in breast cancer
Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a re ...
, compared to a single nurse for prostate cancer. Waiting time between referral and diagnosis was two weeks for breast cancer but three months for prostate cancer.
A 2007 report by the U.S.-based National Prostate Cancer Coalition stated that prostate cancer drugs were outnumbered seven to one by breast cancer drugs. ''The Times
''The Times'' is a British daily national newspaper based in London. It began in 1785 under the title ''The Daily Universal Register'', adopting its current name on 1 January 1788. ''The Times'' and its sister paper ''The Sunday Times'' (fou ...
'' also noted an "anti-male bias in cancer funding" with a four-to-one discrepancy in the United Kingdom by both the government and by cancer charities such as Cancer Research UK
Cancer Research UK (CRUK) is the world's largest independent cancer research organization. It is registered as a charity in the United Kingdom and Isle of Man, and was formed on 4 February 2002 by the merger of The Cancer Research Campaign and t ...
. Critics cite such figures when claiming that women's health is favored over men's health.
Disparities extend into detection, with governments failing to fund or mandate prostate cancer screening while fully supporting breast cancer programs. For example, a 2007 report found 49 U.S. states mandate insurance coverage for routine breast cancer screening, compared to 28 for prostate cancer.
Prostate cancer experiences significantly less media coverage than other, equally prevalent cancers, outcovered 2.6:1 by breast cancer.
Prostate Cancer Awareness Month takes place in September in a number of countries. A light blue ribbon is used to promote the cause.
Research
Castration-resistant prostate cancer
''Castration-resitant prostate cancer'' is prostate cancer that progresses despite androgen depletion therapy.
Enzalutamide
Enzalutamide, sold under the brand name Xtandi, is a nonsteroidal antiandrogen (NSAA) medication which is used in the treatment of prostate cancer. It is indicated for use in conjunction with castration in the treatment of metastatic castrat ...
is a nonsteroidal antiandrogen
A nonsteroidal antiandrogen (NSAA) is an antiandrogen with a nonsteroidal chemical structure. They are typically selective and full or silent antagonists of the androgen receptor (AR) and act by directly blocking the effects of androgens like t ...
(NSAA).
Alpharadin uses bone targeted Radium-223
Radium-223 (223Ra, Ra-223) is an Isotopes of radium#Radium-223, isotope of radium with an 11.4-day half-life. It was discovered in 1905 by T. Godlewski, a Polish chemist from Kraków, and was historically known as Decay chain#Actinium series, ac ...
isotopes to kill cancer cells by alpha radiation
Alpha decay or α-decay is a type of radioactive decay in which an atomic nucleus emits an alpha particle (helium nucleus) and thereby transforms or 'decays' into a different atomic nucleus, with a mass number that is reduced by four and an atom ...
.
PARP inhibitor
PARP inhibitors are a group of pharmacological inhibitors of the enzyme poly ADP ribose polymerase (PARP).
They are developed for multiple indications, including the treatment of heritable cancers. Several forms of cancer are more dependent on ...
olaparib
Olaparib, sold under the brand name Lynparza, is a medication for the maintenance treatment of BRCA-mutated advanced ovarian cancer in adults. It is a PARP inhibitor, inhibiting poly ADP ribose polymerase (PARP), an enzyme involved in DNA repair ...
is an approved breast/ovarian cancer drug that is undergoing clinical trials. Also in trials for CRPC are : checkpoint inhibitor
Checkpoint inhibitor therapy is a form of cancer immunotherapy. The therapy targets immune checkpoints, key regulators of the immune system that when stimulated can dampen the immune response to an immunologic stimulus. Some cancers can protect the ...
ipilimumab
Ipilimumab, sold under the brand name Yervoy, is a monoclonal antibody medication that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system.
Cytotoxic T lymphocytes (CTLs) can recognize ...
, CYP17 inhibitor galeterone (TOK-001), and immunotherapy
Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...
PROSTVAC.[
All medications for CRPC block ]androgen receptor
The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone in th ...
(AR) signaling via direct or indirect targeting of the AR ligand binding domain
In the field of molecular biology, nuclear receptors are a class of proteins responsible for sensing steroids, thyroid hormones, vitamins, and certain other molecules. These receptors work with other proteins to regulate the expression of specif ...
(LBD). AR belongs to the steroid nuclear receptor
In the field of molecular biology, nuclear receptors are a class of proteins responsible for sensing steroids, thyroid hormones, vitamins, and certain other molecules. These receptors work with other proteins to regulate the expression of speci ...
family. Development of the prostate is dependent on androgen signaling mediated through AR, and AR is also important for disease progression. Molecules that could successfully target alternative domains have emerged. Such therapies could provide an advantage; particularly in treating prostate cancers that are resistant to current therapies.
Pre-clinical
Arachidonate 5-lipoxygenase
Arachidonate 5-lipoxygenase, also known as ALOX5, 5-lipoxygenase, 5-LOX, or 5-LO, is a non-heme iron-containing enzyme (EC 1.13.11.34) that in humans is encoded by the ''ALOX5'' gene. Arachidonate 5-lipoxygenase is a member of the lipoxygenase fa ...
has been identified as playing a significant role in the survival of prostate cancer cells. Medications that target this enzyme are undergoing development. In particular, arachidonate 5-lipoxygenase inhibitors produce massive, rapid programmed cell death in prostate cancer cells.
Galectin-3
Galectin-3 is a protein that in humans is encoded by the ''LGALS3'' gene. Galectin-3 is a member of the lectin family, of which 14 mammalian galectins have been identified.
Galectin-3 is approximately 30 kDa and, like all galectins, contains a ca ...
is another potential target. Aberrant glycan profiles have been described in prostate cancer, and studies have found specific links between the galectin signature and prostate cancer.
The PIM kinase family is another potential target for selective inhibition. A number of related drugs are under development. It has been suggested the most promising approach may be to co-target this family with other pathways including PI3K
Phosphoinositide 3-kinases (PI3Ks), also called phosphatidylinositol 3-kinases, are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which i ...
.
Cancer models
Scientists have established prostate cancer cell lines
An immortalised cell line is a population of cells from a multicellular organism which would normally not proliferate indefinitely but, due to mutation, have evaded normal cellular senescence and instead can keep undergoing division. The cells ...
to investigate disease progression. LNCaP
LNCaP cells are a cell line of human cells commonly used in the field of oncology. LNCaP cells are androgen-sensitive human prostate adenocarcinoma cells derived from the left supraclavicular lymph node metastasis from a 50-year-old caucasian ma ...
, PC-3 (PC3
PC3 (PC-3) is a human prostate cancer Cell culture#Isolation of cells, cell line used in prostate cancer research and drug development. PC3 cells are useful in investigating biochemical changes in advanced prostate cancer cells and in assessing t ...
), and DU-145 (DU145
DU145 (DU-145) is a human prostate cancer cell line. DU145, PC3, and LNCaP are considered to be the standard prostate cancer cell lines used in therapeutic research.
The DU145 cell line was derived from a central nervous system metastasis, of pr ...
) are commonly used prostate cancer cell lines. The LNCaP cancer cell line was established from a human lymph node metastatic lesion of prostatic adenocarcinoma. PC-3 and DU-145 cells were established from human prostatic adenocarcinoma metastatic to bone and to brain, respectively. LNCaP cells express AR, but PC-3 and DU-145 cells express very little or no AR.
The proliferation of LNCaP cells is androgen
An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This inc ...
-dependent but the proliferation of PC-3 and DU-145 cells is androgen
An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This inc ...
-insensitive. Elevation of AR expression is often observed in advanced prostate tumor
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
s in patients. Some androgen-independent LNCaP sublines have been developed from the ATCC androgen-dependent LNCaP cells after androgen deprivation for study of prostate cancer progression. These androgen
An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This inc ...
-independent LNCaP cells have elevated AR expression and express prostate specific antigen
Prostate-specific antigen (PSA), also known as gamma-seminoprotein or kallikrein-3 (KLK3), P-30 antigen, is a glycoprotein enzyme encoded in humans by the ''KLK3'' gene. PSA is a member of the kallikrein-related peptidase family and is secreted b ...
upon androgen treatment. Paradoxically, androgens inhibit the proliferation of these androgen-independent prostate cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
cells.
Diagnosis
One active research area and non-clinically applied investigations involves non-invasive methods of tumor detection. A molecular test that detects the presence of cell-associated PCA3 mRNA in fluid obtained from the prostate and first-void urine sample is under investigation. PCA3 mRNA is expressed almost exclusively by prostate cells and has been shown to be highly over-expressed in prostate cancer cells. The test result is currently reported as a specimen ratio of PCA3 mRNA to PSA mRNA.
The PCA3 test attempts to help decide whether, in men suspected of having prostate cancer (especially if an initial biopsy fails to explain the elevated serum PSA), a biopsy/rebiopsy is needed. The higher the expression of PCA3 in the sample, the greater the likelihood of a positive biopsy. The CDC's Evaluation of Genomic Applications in Practice and Prevention Working Group discourages clinical use.
See also
*Prostate Cancer Foundation
The Prostate Cancer Foundation (PCF), headquartered in Santa Monica, California, funds research into the prevention and cure of prostate cancer.
Several important prostate cancer discoveries made in the past 30 years have been as a result of PC ...
*Testicular cancer
Testicular cancer is cancer that develops in the testicles, a part of the male reproductive system. Symptoms may include a lump in the testicle, or swelling or pain in the scrotum. Treatment may result in infertility.
Risk factors include an u ...
References
External links
*
Patient-centered information from the European Urological Association
*
{{DEFAULTSORT:Prostate Cancer
Male genital neoplasia
Neoplastic and hyperplastic prostate disorders
Histopathology
Infectious causes of cancer
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