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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. 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 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 ...
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 en ...
. 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 to other areas of the body, particularly the bones 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, or pain in the pelvis or back. Benign prostatic hyperplasia 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. About 99% of cases occur after age 50. A first-degree relative with the disease increases the risk two- to three-fold. Other factors include a diet 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 pr ...
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 a ...
, while the risk from a high intake of milk products is inconclusive. An association with gonorrhea 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 dise ...
.
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 re ...
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, the ...
is present. Prostate cancer screening, including prostate-specific antigen (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 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 essential micronutrient that an organism needs in small quantities for the proper functioning of its metabolism. Essential nutrie ...
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. (2 ...
supplementation does not appear to affect risk. Many cases are managed with active surveillance or watchful waiting. 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 pa ...
,
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. Rad ...
,
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 ho ...
, 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. Chemother ...
. 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). I ...
s, bisphosphonates, and targeted therapy, 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 Continental United States, primarily located in North America. It consists of 50 U.S. state, states, a Washington, D.C., ...
five-year survival rate 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. 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 agreeme ...
. 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. These include frequent urination, nocturia (increased urination at night), difficulty starting and maintaining a steady stream of urine, hematuria (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 c ...
(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 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, a ...
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 compo ...
. Metastatic prostate cancer can cause additional symptoms. The most common symptom is bone pain, 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 characteristi ...
(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 ...
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 (zoolo ...
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 sp ...
, causing tingling, leg weakness, and urinary and fecal incontinence.


Risk factors

The primary risk factors 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 ...
, 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 tissues such as testes and prostate, as well as promoting secondary sexual characteristi ...
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 b ...
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 in
Scandinavia Scandinavia; Sámi languages: /. ( ) is a subregion in Northern Europe, with strong historical, cultural, and linguistic ties between its constituent peoples. In English usage, ''Scandinavia'' most commonly refers to Denmark, Norway, and S ...
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 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 (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 ...
'' 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 ...
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 ...
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 ...
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), microsemino ...
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 N-Acetylated Alpha-Linked Acidic Dipeptidase Like 2 (NAALADL2) is a protein, encoded by the gene ''NAALADL2'' in humans. ''NAALADL2'' shares 25%–26% sequence identity and 45% sequence similarity with the glutamate carboxypeptidase II family whic ...
'' and SNP rs35148638 nearest to '' RASA1''. A number of somatic mutations (acquired rather than inherited) have also been defined in prostate tumors that drive their growth. TMPRSS2- ETS gene family fusion, 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.


Dietary

Plant-based diets 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. ...
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 of
vitamin D Vitamin D is a group of Lipophilicity, 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 ar ...
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 a ...
supplements on risk.


Medication exposure

Some links have been established between prostate cancer and medications, medical procedures, and medical conditions. Statins may also decrease risk.


Infection

Prostatitis (
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 di ...
or
inflammation Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...
) may increase risk. In particular, infection with the sexually transmitted infections ''Chlamydia'', gonorrhea, 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, a ...
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 cohort study that follows over time a group of similar individuals (cohorts) who differ with respect to certain factors under study, to determine how these factors affect rates of a certain outcome. F ...
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 compo ...
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 t ...
s reported this benefit. An association between vasectomy and prostate cancer was found, but causality has not been established.


Pathophysiology

The prostate 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 ...
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 is ...
. 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 ente ...
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 gut in others. The adult human rectum is about long, and begins at the rectosigmoid junction (the end of the sigmoid colon) at the l ...
. 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 ...
, 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 excreted from the body through the urethra. Cellul ...
from the bladder during urination 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 compo ...
. 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. Sem ...
. 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 androgens, 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 tissues such as testes and prostate, as well as promoting secondary sexual characteristi ...
, 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 testoste ...
; dehydroepiandrosterone, 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 ...
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 characteristics 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, mitosi ...
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, o ...
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 or the rectum, or tumor cells may develop the ability to travel in the bloodstream 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 ...
. Prostate cancer is considered a malignant 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, the ...
. Prostate cancer most commonly metastasizes to the
bone 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, ...
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 includ ...
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 en ...
, and lower ureters after local progression. The route of metastasis to bone is thought to be venous, as the prostatic venous plexus 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-producing organ. Transport protein ZIP1 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 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. Pr ...
''. 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 ...
silencing is unknown. Strategies that transport zinc into transformed prostate cells effectively eliminate these cells in animals. Zinc inhibits NF-κB 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 in ...
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 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 ...
''. "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 ovari ...
and CD44 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 c ...
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 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 pr ...
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 ...
/ 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 (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 ...
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 hydrol ...
(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 may allow a doctor to detect prostate abnormalities. Cystoscopy 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 ...
.
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 anti ...
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 dise ...
, the removal of small pieces of the prostate for microscopic examination.


Imaging

Ultrasound Ultrasound is sound waves with frequencies higher than the upper audible limit of human hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hear it. This limit varies ...
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 classif ...
. 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 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. 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 which alter the cellular rate of growth and formation of new blood vessels, leading to tumours with more aggressive histological patterns, hypoxic 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 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 r ...
, tumour hypoxia 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 d ...
. The gene changes consistently observed in MRI-visible tumours include loss of tumour suppressor PTEN, increased expression of proliferation associated genes CENPF, AGR2 and growth factor GDF15 as well as a number of other genes. Changes in these pathways and genes may facilitate increased tumour growth, changes in vasculature 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 org ...
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 radiati ...
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 ...
s should be used to prevent complications such as
fever Fever, also referred to as pyrexia, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using val ...
,
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 kidne ...
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. S ...
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 Acinar adenocarcinoma is a histological subtype of gland-forming cancer that is diagnosed when cuboidal and/or columnar shaped malignant cells in the neoplastic tissue form acini and tubules. It is a common form of cancer occurring in the lung an ...
, 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 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 pr ...
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 sta ...
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 markers to determine the origin of malignant cells that have metastasized. Small cell carcinoma 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 BCL-2 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, 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 sta ...
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 includ ...
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, the ...
. 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
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, 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. 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—the reverse of what is found in many other metastatic cancers. Approved radiopharmaceutical diagnostic agents used in PET: fluciclovine (2016),
Ga 68 PSMA-11 A gallium scan is a type of nuclear medicine test that uses either a gallium-67 (67Ga) or gallium-68 (68Ga) radiopharmaceutical to obtain images of a specific type of tissue, or disease state of tissue. Gallium salts like gallium citrate and gall ...
(2020), piflufolastat (2021). After a biopsy, a
pathologist Pathology is the study of the 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 used in th ...
examines the samples under a microscope. If cancer is present, the pathologist reports the grade 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 Prostate cancer staging is the process by which physicians categorize the risk of cancer having spread beyond the prostate, or equivalently, the probability of being cured with local therapies such as surgery or radiation. Once patients are placed ...
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,
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 branche ...
, 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 o ...
intake and prostate cancer. Evidence does not support a role for omega-3 fatty acids in preventing prostate cancer. Vitamin supplements 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. Vegetariani ...
diet, lycopene, selenium
cruciferous Cruciferous vegetables are vegetables of the family Brassicaceae (also called Cruciferae) with many genera, species, and cultivars being raised for food production such as cauliflower, cabbage, kale, garden cress, bok choy, broccoli, Brussels spr ...
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 for ...
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 h ...
and dutasteride) 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), ...
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" co ...
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 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 (USPSTF) suggests the decision whether to have
PSA 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 ear ...
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, Georg ...
endorsed USPSTF's conclusion.Prostate Cancer Screening
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 Go ...
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 internationa ...
(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 ...
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, 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 effects, 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 ma ...
and urinary incontinence, 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. Rad ...
and are instead treated with hormonal therapy 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, 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 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 ear ...
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, the cost or benefit that affects a party who did not choose to incur that cost or benefit * Externals The Externals are a group of ...
,
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, pro ...
, cryosurgery, high-intensity focused ultrasound, 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 (the process of freezing the tumor), hormonal therapy, and chemotherapy may be offered if initial treatment fails and the cancer progresses. Sipuleucel-T, 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 ...
activation. The cancer chemotherapeutic docetaxel has been used as treatment for CRPC with a median survival benefit of 2 to 3 months. A second-line chemotherapy treatment is cabazitaxel. 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, ...
, docetaxel, thalidomide and prednisone appears effective in the treatment of CRPC. Immunotherapy treatment with sipuleucel-T 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 increases survival by about 4.6 months. Enzalutamide 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 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) 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 vesicles, 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 includ ...
s. It can be done by an open technique (a skin incision at the lower abdomen), or laparoscopically.
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 individuals ...
is the most commonly used open surgical technique. Robotic-assisted prostatectomy has become common. Men with localized prostate cancer, having
laparoscopic radical prostatectomy Laparoscopic radical prostatectomy (LRP) is a form of radical prostatectomy, an operation for prostate cancer. Contrasted with the original open form of the surgery, it does not make a large incision but instead uses fiber optics and miniaturiza ...
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 is the standard surgical treatment for benign enlargement of the prostate. In prostate cancer, this procedure can be used to relieve symptoms of urinary retention 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 ma ...
and urinary incontinence, 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 bladder outlet by the urethral sphincter. Pathophysiology It is the loss of sma ...
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 exercises, and the use of incontinence pads. 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, 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 co ...
. 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 a ...
, or injectable intracavernous drugs injected directly into the penis ( prostaglandin E1 and vasoactive drug mixtures). Other nonpharmacological therapy includes vacuum constriction devices and penile implants.


Psychological

Psychological interventions such as psychoeducation,
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 (suc ...
(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 List of countries and dependencies by area, seventh-largest country by area, the List of countries and dependencies by population, second-most populous ...
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. Nomograms 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 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?
American Cancer Society (2 May 2006). Retrieved on 5 April 2007
Prostate Cancer FAQs.
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 Venetian often means from or related to: * Venice, a city in Italy * Veneto, a region of Italy * Republic of Venice (697–1797), a historical nation in that area Venetian and the like may also refer to: * Venetian language, a Romance language s ...
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 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 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 ...
. Surgical removal of the testes ( orchiectomy) to treat prostate cancer was first performed in the 1890s, with limited success. Transurethral resection of the prostate (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 Physio ...
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 ac ...
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 pharm ...
" 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, accordi ...
. 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 ancestry, who was a corecipient, with Roger Guillemin and Rosalyn Sussman Yalow, o ...
and Roger Guillemin, 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 c ...
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. Rad ...
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 (rat ...
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 brachy ...
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, pro ...
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. Chemother ...
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, panc ...
was quickly joined by regimens using other systemic chemotherapy drugs. Enzalutamide 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,