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 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 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 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.
Signs and symptoms
Early prostate cancer usually causes no symptoms. As the cancer advances, it may cause erectile dysfunction, blood in the urine or semen, or trouble urinatingcommonly 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.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.
Screening
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, 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 of PSA per milliliter 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 4ng/mL are at increased riskaround 1 in 4 will develop prostate cancerand are often referred for a prostate biopsy. PSA levels over 10ng/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 and 4K score. Other tests measure blood levels of additional prostate-related proteins such as kallikrein-2, 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 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 geographymore 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.
Diagnosis
Men suspected of having prostate cancer may undergo several tests to assess the prostate. One common procedure is the digital rectal examination, in which a doctor inserts a lubricated finger into the rectum to feel the nearby prostate. Tumors feel like stiff, irregularly shaped lumps against the rest of the prostate. Hardening of the prostate can also be due to benign prostatic hyperplasia; around 20–25% of those with abnormal findings on their rectal exams have prostate cancer. Several urological societies' guidelines recommend magnetic resonance imaging to evaluate the prostate for potential tumors in men with high PSA levels. MRI results can help distinguish those who have potentially dangerous tumors from those who do not.A definitive diagnosis of prostate cancer requires a biopsy of the prostate. Prostate biopsies are typically taken by a needle passing through the rectum or perineum, guided by transrectal ultrasonography, MRI, or a combination of the two. Ten to twelve samples are taken from several regions of the prostate to improve the chances of finding any tumors. Biopsies are sent for a histopathologic diagnosis of prostate cancer, wherein they are examined under a microscope by a pathologist, who determines the type and extent of cancerous cells present. Cancers are first classified based on their appearance under a microscope. More than 95% of prostate cancers are classified as adenocarcinomas, with the rest largely squamous-cell carcinoma and transitional cell carcinoma.
File:Gallium PSMA PET scan.png|thumb|alt=Medical images of a man's torso. Arrows indicate tumor metastases, visible as dots in the man's spine and pelvis, in both scans.|CT scan and PSMA scan showing prostate cancer metastases in the bone. The dye used for PSMA scans is also absorbed by the kidneys, liver, and spleen.
Next, tumor samples are graded based on how much the tumor tissue differs from normal prostate tissue; the more different the tumor appears, the faster the tumor is likely to grow. The Gleason grading system is commonly used, where the pathologist assigns numbers ranging from 3 to 5 to different regions of the biopsied tissue. They then calculate a "Gleason score" by adding the two numbers that represent the largest areas of the biopsy sample. The lowest possible Gleason score of 6 represents a biopsy most similar to healthy prostate; the highest Gleason score of 10 represents the most severely cancerous. Gleason scores are commonly grouped into "Gleason grade groups", which predict disease prognosis: a Gleason score of 6 is Gleason grade group 1. A score of 7 can be grade group 2 or 3; it is grade group 2 if the less severe Gleason score covered more area; grade group 3 if the more severe Gleason score covered more area. A score of 8 is grade group 4. A score of 9 or 10 is grade group 5.
The extent of cancer spread is assessed by MRI or PSMA scan – a positron emission tomography imaging technique where a radioactive label that binds the prostate protein prostate-specific membrane antigen is used to detect metastases distant from the prostate. CT scans may also be used, but are less able to detect spread outside the prostate than MRI. Bone scintigraphy is used to test for spread of cancer to bones.