Prostate cancer

Prostate cancer is the uncontrolled growth of cells in the prostate, a gland in the male reproductive system below the bladder. Abnormal growth of the prostate tissue is usually detected through screening tests, typically blood tests that check for prostate-specific antigen (PSA) levels. Those with high levels of PSA in their blood are at increased risk for developing prostate cancer. Diagnosis requires a biopsy of the prostate. If cancer is present, the pathologist assigns a Gleason score; a higher score represents a more dangerous tumor. Medical imaging is performed to look for cancer that has spread outside the prostate. Based on the Gleason score, PSA levels, and imaging results, a cancer case is assigned a stage 1 to 4. A higher stage signifies a more advanced, more dangerous disease.

Most prostate tumors remain small and cause no health problems. These are managed with active surveillance, monitoring the tumor with regular tests to ensure it has not grown. Tumors more likely to be dangerous can be destroyed with radiation therapy or surgically removed by radical prostatectomy. Those whose cancer spreads beyond the prostate are treated with hormone therapy which reduces levels of the androgens (masculinizing sex hormones) which prostate cells need to survive. Eventually cancer cells can grow resistant to this treatment. This most-advanced stage of the disease, called castration-resistant prostate cancer, is treated with continued hormone therapy alongside the chemotherapy drug docetaxel. Some tumors metastasize (spread) to other areas of the body, particularly the bones and lymph nodes. There, tumors cause severe bone pain, leg weakness or paralysis, and eventually death. Prostate cancer prognosis depends on how far the cancer has spread at diagnosis. Most men diagnosed have low-risk tumors confined to the prostate; 99% of them survive more than 10 years from their diagnoses. Tumors that have metastasized to distant body sites are most dangerous, with five-year survival rates of 30–40%.

The risk of developing prostate cancer increases with age; the average age of diagnosis is 67. Those with a family history of any cancer are more likely to have prostate cancer, particularly those who inherit cancer-associated variants of the BRCA2 gene. Each year 1.2 million cases of prostate cancer are diagnosed, and 350,000 die of the disease, making it the second-leading cause of cancer and cancer death in men. One in eight men are diagnosed with prostate cancer in their lifetime and one in forty die of the disease. Prostate tumors were first described in the mid-19th century, during surgeries on men with urinary obstructions. Initially, prostatectomy was the primary treatment for prostate cancer. By the mid-20th century, radiation treatments and hormone therapies were developed to improve prostate cancer treatment. The invention of hormone therapies for prostate cancer was recognized with the 1966 Nobel Prize to Charles Huggins and the 1977 Prize to Andrzej W. Schally.

Early prostate cancer usually causes no symptoms. As the cancer advances, it may cause erectile dysfunction, blood in the urine or semen, or trouble urinating – commonly including frequent urination and slow or weak urine stream. More than half of men over age 50 experience some form of urination problem, typically due to issues other than prostate cancer such as benign prostatic hyperplasia (non-cancerous enlargement of the prostate).

Advanced prostate tumors can metastasize to nearby lymph nodes and bones, particularly in the pelvis, hips, spine, ribs, head, and neck. There they can cause fatigue, unexplained weight loss, and back or bone pain that does not improve with rest. Metastases can damage the bones around them, and around a quarter of those with metastatic prostate cancer develop a bone fracture. Growing metastases can also compress the spinal cord causing weakness in the legs and feet, or limb paralysis.

Most cases of prostate cancer are diagnosed through screening tests, when tumors are too small to cause any symptoms. This is done through blood tests to measure levels of the protein prostate-specific antigen (PSA), which are elevated in those with enlarged prostates, whether due to prostate cancer or benign prostatic hyperplasia. The typical man's blood has around 1 nanogram (ng) of PSA per milliliter (mL) of blood tested. Those with PSA levels below average are very unlikely to develop dangerous prostate cancer over the next 8 to 10 years. Men with PSA levels above 4 ng/mL are at increased risk – around 1 in 4 will develop prostate cancer – and are often referred for a prostate biopsy. PSA levels over 10 ng/mL indicate an even higher risk: more than half men in this group develop prostate cancer. Men with high PSA levels are often recommended to repeat the blood test four to six weeks later, as PSA levels can fluctuate unrelated to prostate cancer. Benign prostatic hyperplasia, prostate infection, recent ejaculation, and some urological procedures can increase PSA levels; taking 5α-reductase inhibitors can decrease PSA levels.

Those with elevated PSA may undergo secondary screening blood tests that measure subtypes of PSA and other molecules to better predict the likelihood that a person will develop aggressive prostate cancer. Many measure "free PSA" – the fraction of PSA unbound to other blood proteins, usually around 10% to 30%. Men who have a lower percentage of free PSA are more likely to have prostate cancer. Several common tests more accurately detect prostate cancer cases by also measuring subtypes of free PSA, including the Prostate Health Index (measures a fragment called −2proPSA) and 4K score (measures intact free PSA). Other tests measure blood levels of additional prostate-related proteins such as kallikrein-2 (also measured by 4K score), or urine levels of mRNA molecules common to prostate tumors like PCA3 and TMPRSS2 fused to ERG.

Several large studies have found that men screened for prostate cancer have a reduced risk of dying from the disease; however, detection of cancer cases that would not have otherwise impacted health can cause anxiety, and lead to unneeded biopsies and treatments, both of which can cause unwanted complications. Major national health organizations offer differing recommendations, attempting to balance the benefits of early diagnosis with the potential harms of treating people whose tumors are unlikely to impact health. Most medical guidelines recommend that men at high risk of prostate cancer (due to age, family history, ethnicity, or prior evidence of high blood PSA levels) be counseled on the risks and benefits of PSA testing, and be offered access to screening tests. Medical guidelines generally recommend against screening for men over age 70, or with a life expectancy of less than 10 years, as a newly diagnosed prostate cancer is unlikely to impact their natural lifespan. Uptake of screening varies by geography – more than 80% of men are screened in the US and Western Europe, 20% of men in Japan, and screening is rare in regions with a low Human Development Index.