Prostate Cancer – Causes, Symptoms, Diagnosis, Treatment

Prostate cancer is one of the most common cancers in men and the global burden of this disease is rising. Lifestyle modifications like smoking cessation, exercise and weight control offer opportunities to decrease the risk of developing prostate cancer. Early detection of prostate cancer by PSA screening remains controversial; yet, changes in PSA threshold, the frequency of screening, and the addition of other biomarkers have the potential to minimize overdiagnosis associated with PSA screening. Several new biomarkers appear promising in individuals with elevated PSA levels or those diagnosed with prostate cancer, these are likely to guide in separating individuals who can be spared of aggressive treatment from those who need it. Several pharmacological agents like 5α-reductase inhibitors, aspirin etc. have the potential to prevent the development of prostate cancer. In this review, we discuss the current evidence and research questions regarding prevention, early detection of prostate cancer and management of men either at high risk of prostate cancer or diagnosed with low-grade prostate cancer.

Causes of Prostate Cancer

The exact causes of prostate cancer aren’t known. But some factors are known to increase the risk. These are the main risk factors:

  • Age – The risk of prostate cancer increases with age.
  • Ethnicity –  Black men are somewhat more likely to develop prostate cancer.
  • Close relatives – Men who have a father or brother who developed prostate cancer are at somewhat higher risk themselves. If your father and several brothers have (had) prostate cancer, your risk is even higher.
  • High doses of vitamin E – Dietary supplements that have a lot of vitamin E in them have been proven to increase the risk of prostate cancer if taken over many years.
  • Dietary – Consuming fruits and vegetables has been found to be of little benefit in preventing prostate cancer.[rx] Evidence supports little role for dietary fruits and vegetables in prostate cancer occurrence.[rx] Red meat and processed meat also appear to have little effect in human studies.[rx] Higher meat consumption has been associated with a higher risk in some studies.[rx] Lower blood levels of vitamin D may increase the risk of developing prostate cancer.[rx] Folic acid supplements have no effect on the risk of developing prostate cancer.[rx]
  • Medication exposure – There are also some links between prostate cancer and medications, medical procedures, and medical conditions.[rx] Use of the cholesterol-lowering medications known as statins may also decrease prostate cancer risk.[rx]
  • Infection – Infection or inflammation of the prostate (prostatitis) may increase the chance for prostate cancer while another study shows infection may help prevent prostate cancer by increasing blood flow to the area. In particular, infection with the sexually transmitted infections chlamydia, gonorrhea, or syphilis seems to increase risk.[rx][rx]
  • Papillomavirus – has been proposed in several studies to have a potential role in prostate cancer, but as of 2015 the evidence was inconclusive.[rx] A review in 2018 suggested there may be an increased risk but noted that this increased risk was still debatable.[rx]
  • Environmental – Research released in May 2007 found that US war veterans who had been exposed to Agent Orange had a 48% increased risk of prostate cancer recurrence following surgery.[rx]
  • Sexual – Although there is some evidence from prospective cohort studies that frequent ejaculation may reduce prostate cancer risk,[rx] there are no results from randomized controlled trials concluding that this benefit exists.[rx] There is an association between vasectomy and prostate cancer, but more research is needed to determine if this is a causal relationship.[rx] 
  • Certain types of food – such as red meat or tomatoes, are often associated with cancer – some are thought to cause cancer and some are believed to prevent it. But research has not proven that men can lower their risk of developing prostate cancer by eating a specific diet.

Symptoms of Prostate Cancer

These and other signs and symptoms may be caused by prostate cancer or by other conditions. Check with your doctor if you have any of the following:

  • Weak or interrupted (“stop-and-go”) flow of urine.
  • Sudden urge to urinate.
  • Frequent urination (especially at night).
  • Trouble starting the flow of urine.
  • Trouble emptying the bladder completely.
  • A pain in the back, hips, or pelvis that doesn’t go away.
  • Shortness of breath, feeling very tired, fast heartbeat, dizziness, or pale skin caused by anemia.

The Grade Group and PSA level are used to stage prostate cancer

  • The stage of the cancer is based on the results of the staging and diagnostic tests, including the prostate-specific antigen (PSA) test  and the Grade Group. The tissue samples removed during the biopsy are used to find out the Gleason score. The Gleason score ranges from 2 to 10 and describes how different the cancer cells look from normal cells under a microscope and how likely it is that the tumor will spread. The lower the number, the more cancer cells look like normal cells and are likely to grow and spread slowly.

The Grade Group depends on the Gleason score.

  • Grade Group 1 is a Gleason score of 6 or less.
  • Grade Group 2 or 3 is a Gleason score of 7.
  • Grade Group 4 is a Gleason score 8.
  • Grade Group 5 is a Gleason score of 9 or 10.

The PSA test measures the level of PSA in the blood. PSA is a substance made by the prostate that may be found in an increased amount in the blood of men who have prostate cancer.

Stages are used for prostate cancer

Stage I

Two panel drawing of stage I prostate cancer; the top panel shows cancer in less than one-half of the right side of the prostate found by needle biopsy. The bottom panel shows cancer in less than one-half of the left side of the prostate found by digital rectal exam. In both panels, the PSA level is less than 10 and the Grade Group is 1. The bladder, rectum, and urethra are also shown.

Stage I prostate cancer – Cancer is found in the prostate only. The cancer is not felt during a digital rectal exam and is found by needle biopsy done for high prostate-specific antigen (PSA) level or in a sample of tissue removed during surgery for other reasons. The PSA level is less than 10 and the Grade Group is 1; OR the cancer is felt during a digital rectal exam and is found in one-half or less of one side of the prostate. The PSA level is less than 10 and the Grade Group is 1.

In stage I

  • cancer is found in the prostate only. Cancer is not felt during a digital rectal exam and is found by needle biopsy[ (done for a high PSA level) or in a sample of tissue removed during surgery for other reasons (such as benign prostatic hyperplasia).
  • The PSA level is lower than 10 and the Grade Group is 1, or is felt during a digital rectal exam and is found in one-half or less of one side of the prostate. The PSA level is lower than 10 and the Grade Group is 1.

Stage II

  • In stage II, cancer is more advanced than in stage I but has not spread outside the prostate. Stage II is divided into stages IIA, IIB, and IIC.

Two-panel drawing of stage IIA prostate cancer; the top panel shows cancer in one-half or less of one side of the prostate. The PSA level is at least 10 but less than 20 and the Grade Group is 1. The bottom panel shows cancer in more than one-half of one side of the prostate. The PSA level is less than 20 and the Grade Group is 1. In both panels, the bladder, rectum, and urethra are also shown.

  • Stage IIA prostate cancer – Cancer is found in the prostate only. Cancer is found in one-half or less of one side of the prostate. The prostate-specific antigen (PSA) level is at least 10 but less than 20 and the Grade Group is 1; OR cancer is found in more than one-half of one side of the prostate or in both sides of the prostate. The PSA level is less than 20 and the Grade Group is 1.
  • In stage IIA, cancer is found in one-half or less of one side of the prostate. The PSA level is at least 10 but lower than 20 and the Grade Group is 1 or found in more than one-half of one side of the prostate or in both sides of the prostate. The PSA level is lower than 20 and the Grade Group is 1.

Stage IIB prostate cancer; drawing shows cancer in one side of the prostate. The PSA level is less than 20 and the Grade Group is 2. Also shown are the bladder, rectum, and urethra.

Stage IIB prostate cancer. Cancer is found in the prostate only. Cancer is found in one or both sides of the prostate. The prostate-specific antigen level is less than 20 and the Grade Group is 2.

In stage IIB, cancer

  • is found in one or both sides of the prostate. The PSA level is lower than 20 and the Grade Group is 2.

Stage IIC prostate cancer; drawing shows cancer in both sides of the prostate. The PSA level is less than 20 and the Grade Group is 3 or 4. Also shown are the bladder, rectum, and urethra.

Stage IIC prostate cancer. Cancer is found in the prostate only. Cancer is found in one or both sides of the prostate. The prostate-specific antigen level is less than 20 and the Grade Group is 3 or 4.

In stage IIC, cancer

  • is found in one or both sides of the prostate. The PSA level is lower than 20 and the Grade Group is 3 or 4.

Stage III

Stage III is divided into stages IIIA, IIIB, and IIIC.

Stage IIIA prostate cancer; drawing shows cancer in one side of the prostate. The PSA level is at least 20 and the Grade Group is 1, 2, 3, or 4. Also shown are the bladder, rectum, and urethra.

Stage IIIA prostate cancer – Cancer is found in the prostate only. Cancer is found in one or both sides of the prostate. The prostate-specific antigen level is at least 20 and the Grade Group is 1, 2, 3, or 4.

In stage IIIA, canceris found in one or both sides of the prostate. The PSA level is at least 20 and the Grade Group is 1, 2, 3, or 4.

Stage IIIB prostate cancer; drawing shows cancer that has spread from the prostate to the seminal vesicles and to nearby tissue. The PSA can be any level and the Grade Group is 1, 2, 3, or 4. Also shown are the pelvic wall, bladder, and rectum.

Stage IIIB prostate cancer – Cancer has spread from the prostate to the seminal vesicles or to nearby tissue or organs, such as the rectum, bladder, or pelvic wall. The prostate-specific antigen can be any level and the Grade Group is 1, 2, 3, or 4.

In stage IIIB – cancer has spread from the prostate to the seminal vesicles or to nearby tissue or organs, such as the rectum, bladder, or pelvic wall. The PSA can be any level and the Grade Group is 1, 2, 3, or 4.

Stage IIIC prostate cancer; drawing shows cancer in one side of the prostate. The PSA can be any level and the Grade Group is 5. Also shown are the bladder, rectum, and urethra.

Stage IIIC prostate cancer – Cancer is found in one or both sides of the prostate and may have spread to the seminal vesicles or to nearby tissue or organs, such as the rectum, bladder, or pelvic wall. The prostate-specific antigen can be any level and the Grade Group is 5.

In stage IIIC – cancer is found in one or both sides of the prostate and may have spread to the seminal vesicles or to nearby tissue or organs, such as the rectum, bladder, or pelvic wall. The PSA can be any level and the Grade Group is 5.

Stage IV

Stage IV is divided into stages IVA and IVB.

Stage IVA prostate cancer; drawing shows cancer in one side of the prostate and in nearby lymph nodes. The PSA can be any level and the Grade Group is 1 ,2, 3, 4, or 5. Also shown are the bladder, rectum, and urethra.

Stage IVA prostate cancer – Cancer is found in one or both sides of the prostate and may have spread to the seminal vesicles or to nearby tissue or organs, such as the rectum, bladder, or pelvic wall. Cancer has spread to nearby lymph nodes. The prostate-specific antigen can be any level and the Grade Group is 1, 2, 3, 4, or 5.

In stage IVA – cancer is found in one or both sides of the prostate and may have spread to the seminal vesicles or to nearby tissue or organs, such as the rectum, bladder, or pelvic wall. Cancer has spread to nearby lymph nodes.

Stage IVB prostate cancer; drawing shows other parts of the body where prostate cancer may spread, including the distant lymph nodes and bones. An inset shows cancer cells spreading from the prostate, through the blood and lymph system, to another part of the body where metastatic cancer has formed.

Stage IVB prostate cancer – Cancer has spread to other parts of the body, such as the bones or distant lymph nodes. In stage IVB, cancer has spread to other parts of the body, such as the bones or distant lymph nodes. Prostate cancer often spreads to the bones.

Diagnosis

If it’s thought that a man might have prostate cancer, the doctor will first ask about the symptoms to get a rough idea of the problem and figure out what might be causing it (anamnesis). After that, one or more of the following examinations may be done:

  • Palpation (feeling): Here the doctor gently inserts a finger into the anus to feel the size, hardness and surface of the prostate. This test is also known as a digital rectal exam (from the Latin word digitus, meaning “finger”). Although some men find it uncomfortable, it’s usually not painful.
  • Physical exam and historyAn exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.
  • Digital rectal exam (DRE): An exam of the rectum. The doctor or nurse inserts a lubricated, gloved finger into the rectum and feels the prostate through the rectal wall for lumps or abnormal areas.

    Digital rectal exam; drawing shows a side view of the male reproductive anatomy and the urinary anatomy, including the prostate, rectum, and bladder. Also shown is a gloved, lubricated finger inserted into the rectum to feel the rectum, anus, and prostate.

    Digital rectal exam (DRE). The doctor inserts a gloved, lubricated finger into the rectum and feels the rectum, anus, and prostate (in males) to check for anything abnormal.

  • Prostate-specific antigen (PSA) test: A test that measures the level of PSA in the blood. PSA is a substance made by the prostate that may be found in higher than normal amounts in the blood of men who have prostate cancer. PSA levels may also be high in men who have an infection or inflammation of the prostate or BPH (an enlarged, but noncancerous, prostate).
  • Transrectal ultrasound: A procedure in which a probe that is about the size of a finger is inserted into the rectum to check the prostate. The probe is used to bounce high-energy sound waves (ultrasound[) off internal tissues or organs and make echoes. The echoes form a picture of body tissues called a sonogram. Transrectal ultrasound may be used during a biopsy procedure. This is called a transrectal ultrasound-guided biopsy.

    Transrectal ultrasound; drawing shows a side view of the male reproductive and urinary anatomy including the prostate, anus, rectum, and bladder; also shows an ultrasound probe inserted into the rectum to check the prostate. Inset shows patient lying on back on a table having a transrectal ultrasound procedure.

    Transrectal ultrasound – An ultrasound probe is inserted into the rectum to check the prostate. The probe bounces sound waves off body tissues to make echoes that form a sonogram (computer picture) of the prostate.

  • Transrectal magnetic resonance imaging (MRI) – A procedure that uses a strong magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. A probe that gives off radio waves is inserted into the rectum near the prostate. This helps the MRI machine make clearer pictures of the prostate and nearby tissue. A transrectal MRI is done to find out if cancer has spread outside the prostate into nearby tissues. This procedure is also called nuclear magnetic resonance imaging (NMRI). Transrectal MRI may be used during a biopsy procedure. This is called a transrectal MRI guided biopsy.
  • Biopsy – The removal of cells or tissues so they can be viewed under a microscope by a pathologist. The pathologist will check the tissue sample to see if there are cancer cells and find out the Gleason scor. The Gleason score ranges from 2-10 and describes how likely it is that a tumor will spread. The lower the number, the less likely the tumor is to spread.
  • A transrectal biopsy – is used to diagnose prostate cancer. A transrectal biopsy is the removal of tissue from the prostate by inserting a thin needle through the rectum and into the prostate. This procedure may be done using transrectal ultrasound or transrectal MRI to help guide where samples of tissue are taken from. A pathologist views the tissue under a microscope to look for cancer cells.

    Transrectal biopsy; drawing shows a side view of the prostate, bladder, and rectum. Drawing also shows an ultrasound probe with a needle inserted into the rectum to remove a tissue sample from the prostate.

    Transrectal biopsy. An ultrasound probe is inserted into the rectum to show where the tumor is. Then a needle is inserted through the rectum into the prostate to remove tissue from the prostate.

    Sometimes a biopsy is done using a sample of tissue that was removed during transurethral resection of the prostate (TURP) to treat BPH.
  • PSA test – The PSA test is a blood test that looks for a certain protein known as “prostate-specific antigen.” This protein is produced inside the prostate. Small amounts of it enter the bloodstream. Having high levels of PSA might – but doesn’t necessarily – mean that someone has prostate cancer. Other things can lead to an increase in PSA levels too.
  • Transrectal ultrasound (TRUS) – Ultrasound is used to check the size and shape of the prostate gland. This involves gently inserting an ultrasound device about as wide as a finger into the rectum (the end part of the bowel).
  • The tissue sample (biopsy) – The only way to find out whether there actually is cancerous tissue in the prostate is by taking a tissue sample. Ten to twelve tissue samples are usually taken to be examined under a microscope, where they can be checked for cancer. The most commonly used approach is called fine needle aspiration. Like TRUS, this involves gently inserting an ultrasound device into the rectum. There is a fine needle inside the device. The needle is pushed through the wall of the rectum and into the prostate, where it is used to remove samples of tissue. The ultrasound helps guide the needle to the right place. This procedure is done using local anesthetic, or – in some rare cases – brief general anesthetic

Gleason Pattern 4 (left of image) and Gleason Pattern 5 stain[rx].

A pathologist microscopically examines the biopsy specimen for certain “Gleason” patterns. These Gleason patterns are associated with the following features:

  • Pattern 1 – The cancerous prostate closely resembles normal prostate tissue. The glands are small, well-formed, and closely packed. This corresponds to a well-differentiated carcinoma.
  • Pattern 2 – The tissue still has well-formed glands, but they are larger and have more tissue between them, implying that the stroma has increased. This also corresponds to a moderately differentiated carcinoma.
  • Pattern 3 – The tissue still has recognizable glands, but the cells are darker. At high magnification[rx], some of these cells have left the glands and are beginning to invade the surrounding tissue or having an infiltrative pattern. This corresponds to a moderately differentiated carcinoma.
  • Pattern 4 – The tissue has few recognizable glands. Many cells are invading the surrounding tissue in neoplastic clumps. This corresponds to a poorly differentiated carcinoma.
  • Pattern 5 – The tissue does not have any or only a few recognizable glands. There are often just sheets of cells throughout the surrounding tissue. This corresponds to anaplastic carcinoma.

In the present form of the Gleason system, prostate cancer of Gleason patterns 1 and 2 are rarely seen. Gleason pattern 3 is by far the most common.

Primary, secondary and tertiary grades

After analyzing the tissue samples, the pathologist then assigns a grade to the observed patterns of the tumor specimen.

  • Primary grade – assigned to the dominant pattern of the tumor (has to be greater than 50% of the total pattern seen).
  • Secondary grade – assigned to the next-most-frequent pattern (has to be less than 50%, but at least 5%, of the pattern of total cancer, observed).
  • Tertiary grade – increasingly, pathologists provide details of the “tertiary” component. This is where there is a small component of a third (generally more aggressive) pattern.

Treatment

There are different types of treatment for patients with prostate cancer.

Different types of treatment are available for patients with prostate cancer. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research studymeant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.

Seven types of standard treatment are used:

Watchful waiting or active surveillance

Watchful waiting and active surveillance are treatments used for older men who do not have signs or symptoms or have other medical conditions and for men whose prostate cancer is found during a screening test.

Watchful waiting is closely monitoring a patient’s condition without giving any treatment until signs or symptoms appear or change. Treatment is given to relieve symptoms and improve quality of life.

Active surveillance is closely following a patient’s condition without giving any treatment unless there are changes in test results. It is used to find early signs that the condition is getting worse. Inactive surveillance, patients are given certain exams and tests, including digital rectal exam, PSA test, transrectal ultrasound, and transrectal needle biopsy, to check if the cancer is growing. When cancer begins to grow, treatment is given to cure the cancer.

Other terms that are used to describe not giving treatment to cure prostate cancer right after diagnosis are observation, watch and wait, and expectant management.

Surgery

Patients in good health whose tumor is in the prostate gland only may be treated with surgery to remove the tumor. The following types of surgery are used:

  • Radical prostatectomy: A surgical procedure to remove the prostate, surrounding tissue, and seminal vesicles. There are two types of radical prostatectomy:
  • Retropubic prostatectomy: A surgical procedure to remove the prostate through an incision (cut) in the abdominal wall. Removal of nearby lymph nodes may be done at the same time.
  • Perineal prostatectomy: A surgical procedure to remove the prostate through an incision (cut) made in the perineum (area between the scrotum and anus). Nearby lymph nodes may also be removed through a separate incision in the abdomen.

    Two panel drawing showing two ways of doing a radical prostatectomy; in the first panel, dotted line shows where incision is made through the wall of the abdomen for a retropubic prostatectomy; in the second panel, dotted line shows where incision is made in area between the scrotum and the anus for a perineal prostatectomy.

    Two types of radical prostatectomy. In a retropubic prostatectomy, the prostate is removed through an incision in the wall of the abdomen. In a perineal prostatectomy, the prostate is removed through an incision in the area between the scrotum and the anus.

  • Pelvic lymphadenectomy – A surgical procedure to remove the lymph nodes in the pelvis. A pathologist views the tissue under a microscope to look for cancer cells. If the lymph nodes contain cancer, the doctor will not remove the prostate and may recommend other treatment.
  • Transurethral resection of the prostate (TURP): A surgical procedure to remove tissue from the prostate using a resectoscope (a thin, lighted tube with a cutting tool) inserted through the urethra. This procedure is done to treat benign prostatic hypertrophy and it is sometimes done to relieve symptoms caused by a tumor before other cancer treatment is given. TURP may also be done in men whose tumor is in the prostate only and who cannot have a radical prostatectomy.

    Transurethral resection of the prostate; drawing shows removal of tissue from the prostate using a resectoscope (a thin, lighted tube with a cutting tool at the end) inserted through the urethra.

    Transurethral resection of the prostate (TURP). Tissue is removed from the prostate using a resectoscope (a thin, lighted tube with a cutting tool at the end) inserted through the urethra. Prostate tissue that is blocking the urethra is cut away and removed through the resectoscope.

In some cases, nerve-sparing surgery can be done. This type of surgery may save the nerves that control erection. However, men with large tumors or tumors that are very close to the nerves may not be able to have this surgery.

Possible problems after prostate cancer surgery include the following:

  • Impotence.
  • Leakage of urine from the bladder or stool from the rectum.
  • Shortening of the penis (1 to 2 centimeters). The exact reason for this is not known.
  • Inguinal hernia (bulging of fat or part of the small intestine through weak muscles into the groin). Inguinal hernia may occur more often in men treated with radical prostatectomy than in men who have some other types of prostate surgery, radiation therapy, or prostate biopsy alone. It is most likely to occur within the first 2 years after radical prostatectomy.

Radiation therapy and radiopharmaceutical therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are different types of radiation therapy:

  • External radiation therapy –  uses a machine outside the body to send radiation toward the cancer. Conformal radiation is a type of external radiation therapy that uses a computer to make a 3-dimensional (3-D) picture of the tumor and shapes the radiation beams to fit the tumor. This allows a high dose of radiation to reach the tumor and causes less damage to nearby healthy tissue.
    Hypofractionated radiation therapy – may be given because it has a more convenient treatment schedule. Hypofractionated radiation therapy is radiation treatment in which a larger than usual total dose of radiation is given once a day over a shorter period of time (fewer days) compared to standard radiation therapy. Hypofractionated radiation therapy may have worse side effects than standard radiation therapy, depending on the schedules used.
  • Internal radiation therapy – uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. In early-stage prostate cancer, the radioactive seeds are placed in the prostate using needles that are inserted through the skin between the scrotum and rectum. The placement of the radioactive seeds in the prostate is guided by images from transrectal ultrasound or computed tomography (CT). The needles are removed after the radioactive seeds are placed in the prostatate

Radiopharmaceutical therapy – uses a radioactive substance to treat cancer. Radiopharmaceutical therapy includes the following:

  • Alpha emitter radiation therapy uses a radioactive substance to treat prostate cancer that has spread to the bone. A radioactive substance called radium-223 is injected into a vein and travels through the bloodstream. The radium-223 collects in areas of bone with cancer and kills the cancer cells.
  • The way radiation therapy is given depends on the type and stage of the cancer being treated. External radiation therapy, internal radiation therapy, and radiopharmaceutical therapy are used to treat prostate cancer.
  • Men treated with radiation therapy for prostate cancer have an increased risk of having bladder and/or gastrointestinalcancer.
  • Radiation therapy can cause impotence and urinary problems that may get worse with age.

Hormone therapy

Hormone therapy is a cancer treatment that removes hormones[ or blocks their action and stops cancer cells from growing. Hormones are substances made by glands in the body and circulated in the bloodstream. In prostate cancer, male sex hormones can cause prostate cancer to grow. Drugs, surgery, or other hormones are used to reduce the number of male hormones or block them from working.

Hormone therapy for prostate cancer may include the following:

  • Abiraterone acetate can prevent prostate cancer cells from making androgens. It is used in men with advanced prostate cancer that has not gotten better with other hormone therapy.
  • Orchiectomy is a surgical procedure to remove one or both testicles, the main source of male hormones, such as testosterone, to decrease the amount of hormone being made.
  • Estrogens (hormones that promote female sex characteristics) can prevent the testicles from making testosterone. However, estrogens are seldom used today in the treatment of prostate cancer because of the risk of serious side effects.
  • Luteinizing hormone-releasing hormone agonists can stop the testicles from making testosterone. Examples are leuprolide, goserelin, and buserelin.
  • Antiandrogens can block the action of androgens (hormones that promote male sex characteristics), such as testosterone. Examples are flutamide,[, enzalutamide, nilutamide, and nilutamide.
  • Drugs that can prevent the adrenal glands from making androgens include ketoconazole and aminoglutethimide.

Hot flashes, impaired sexual function, loss of desire for sex, and weakened bones may occur in men treated with hormone therapy. Other side effects include diarrhea, nausea, and itching.

Hormonal Therapy

  • Hormonal therapy in prostate cancer. Diagram shows the different organs (purple text), hormones (black text and arrows), and treatments (red text and arrows) important in hormonal therapy.

Androgen Deprivation Therapy

  • Hormonal therapy  – uses medications or surgery to block prostate cancer cells from getting dihydrotestosterone[rx] (DHT), a hormone produced in the prostate and required for the growth and spread of most prostate cancer cells. Blocking DHT often causes prostate cancer to stop growing and even shrink. However, hormonal therapy rarely cures prostate cancer because cancers that initially respond to hormonal therapy typically become resistant after one to two years. Hormonal therapy is, therefore, usually used when cancer has spread from the prostate. It may also be given to certain men undergoing radiation therapy or surgery to help prevent the return of their cancer.[rx]
  • Hormonal Therapy – for prostate cancer targets the pathways the body uses to produce DHT. A feedback loop involving the testicles, the hypothalamus, and the pituitary, adrenal, and prostate glands controls the blood levels of DHT. First, low blood levels of DHT stimulate the hypothalamus[rx] to produce gonadotropin-releasing hormone[rx](GnRH). GnRH then stimulates the pituitary gland to produce luteinizing hormone[rx] (LH), and LH stimulates the testicles to produce testosterone. Finally, testosterone from the testicles and dehydroepiandrosterone from the adrenal glands][rx] stimulate the prostate to produce more DHT. Hormonal therapy can decrease levels of DHT by interrupting this pathway at any point. There are several forms of hormonal therapy:
  • Orchiectomy – also called “castration,” is surgery to remove the testicles. Because the testicles make most of the body’s testosterone after orchiectomy testosterone levels drop. Now the prostate not only lacks the testosterone stimulus to produce DHT but also does not have enough testosterone to transform into DHT. Orchiectomy is considered the gold standard of treatment.[rx]
  • Antiandrogens – are medications such as flutamide, nilutamide, bicalutamide, enzalutamide, apalutamide, and cyproterone acetate that directly block the actions of testosterone and DHT within prostate cancer cells.
  • Medications – that block the production of adrenal androgens such as DHEA include ketoconazole and aminoglutethimide. Because the adrenal glands make only about 5% of the body’s androgens, these medications are, in general, used only in combination with other methods that can block the 95% of androgens made by the testicles. These combined methods are called total androgen blockade (TAB). TAB can also be achieved using antiandrogens.
  • GnRH action can be interrupted in one of two ways – GnRH antagonists such as abarelix[rx] and degarelix suppress the production of LH directly by acting on the anterior pituitary. GnRH agonists[rx] such as leuprorelin[rx] and goserelin suppress LH through the process of downregulation[rx] after an initial stimulation effect which can cause initial tumor flare. In order to prevent stimulation of tumor growth during the initial LH surge, an antiandrogen such as cyproterone acetate is prescribed a week before and three weeks after GnRH agonists are given. Abarelix and degarelix[rx] are examples of GnRH antagonists, whereas the GnRH agonists include leuprolide, goserelin, triptorelin[rx], and buserelin. Initially, GnRH agonists increase the production of LH. However, because the constant supply of the medication does not match the body’s natural production rhythm, production of both LH and GnRH decreases after a few weeks.[rx]
  • Abiraterone acetate – [rx] was FDA approved in April 2011 for the treatment of castration-resistant prostate cancer for patients who have failed docetaxel therapy. Abiraterone acetate inhibits an enzyme known as CYP17, which is used in the body to produce testosterone.[rx][rx]

Drugs Approved for Prostate Cancer for more information.

Chemotherapy

  • Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy).
  • When chemotherapy is placed directly into the cerebrospinal fluid, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). The way the chemotherapy is given depends on the type and stage of the cancer being treated. Drugs Approved for Prostate Cancer[rx]

Biologic Therapy

  • Biologic therapy is a treatment that uses the patient’s immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body’s natural defenses against cancer. Sipuleucel-T is a type of biologic therapy used to treat prostate cancer that has metastasized (spread to other parts of the body). Drugs Approved for Prostate Cancer

Bisphosphonate Therapy

  • Bisphosphonate drugs, such as clodronate or zoledronater, reduce bone disease when cancer has spread to the bone. Men who are treated with antiandrogen therapy or orchiectomy are at an increased risk of bone loss. In these men, bisphosphonate drugs lessen the risk of bone fracture (breaks). The use of bisphosphonate drugs to prevent or slow the growth of bone metastases is being studied in clinical trials.

There are treatments for bone pain caused by bone metastases or hormone therapy.

Prostate cancer that has spread to the bone and certain types of hormone therapy can weaken bones and lead to bone pain. Treatments for bone pain include the following:

  • Pain medicine.
  • External radiation therapy.
  • Strontium-89 (a radioisotope).
  • Targeted therapy with a monoclonal antibody, such as denosumab.
  • Bisphosphonate therapy.
  • Corticosteroids.

New types of treatment are being tested in clinical trials.

  • This summary section describes treatments that are being studied in clinical trials. It may not mention every new treatment being studied. Information about clinical trials is available from the NCI website.

Cryosurgery

  • Cryosurgery is a treatment that uses an instrument to freeze and destroy prostate cancer cells. Ultrasound is used to find the area that will be treated. This type of treatment is also called cryotherapy. Cryosurgery can cause impotence and leakage of urine from the bladder or stool from the rectum.

High-Intensity–Focused Ultrasound Therapy

  • High-intensity–focused ultrasound therapy is a treatment that uses ultrasound (high-energy sound waves) to destroy cancer cells. To treat prostate cancer, an endorectal problm is used to make the sound waves.

Proton Beam Radiation Therapy

  • Proton beam radiation therapy is a type of high-energy, external radiation therapy that targets tumors with streams of protons (small, positively charged particles). This type of radiation therapy is being studied in the treatment of prostate cancer.

Photodynamic Therapy

  • A cancer treatment that uses a drug and a certain type of laser light to kill cancer cells. A drug that is not active until it is exposed to light is injected into a vein. The drug collects more in cancer cells than in normal cells. Fiberoptic tubes are then used to carry the laser light to the cancer cells, where the drug becomes active and kills the cells. Photodynamic therapy causes little damage to healthy tissue. It is used mainly to treat tumors on or just under the skin or in the lining of internal organs.

Treatment for prostate cancer may cause side effects

  • For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.
  • Many of today’s standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.
  • Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Patients can enter clinical trials before, during, or after starting their cancer treatment

  • Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring(coming back) or reduce the side effects of cancer treatment.
  • Clinical trials are taking place in many parts of the country. Information about clinical trials supported by NCI can be found on NCI’s clinical trials search webpage. Clinical trials supported by other organizations can be found on the ClinicalTrials.gov website.

Follow-up tests may be needed

  • Some of the tests that were done to diagnose cancer or to find out the stage of cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change or stop treatment may be based on the results of these tests.
  • Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.

Treatment Options by Stage

For information about the treatments listed below, see the Treatment Option Overview[rx] section.

Stage I Prostate Cancer

Standard treatment of stage I prostate cancer may include the following:

  • Watchful waiting.
  • Active surveillance. If cancer begins to grow, hormone therapy may be given.
  • Radical prostatectomy, usually with pelvic lymphadenectomy. Radiation therapy may be given after surgery.
  • External radiation therapy. Hormone therapy may be given after radiation therapy.
  • Internal radiation therapy with radioactive seeds .
  • A clinical trial of high-intensity–focused ultrasound therapy.
  • A clinical trial of photodynamic therapy.
  • A clinical trial of cryosurgery.

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General informationabout clinical trials is also available.

Stage II Prostate Cancer

 of  may include the following:

  • Watchful waiting.
  • Active surveillance  If cancer begins to grow, hormone therapy may be given.
  • Radical prostatectomy, usually with pelvic lymphadenectomy. Radiation therapy may be given after surgery.
  • External radiation therapy. Hormone therapy may be given after radiation therapy.
  • Internal radiation therapy with radioactive seeds.
  • A clinical trial of cryosurgery.
  • A clinical trial of high-intensity–focused ultrasound therapy.
  • A clinical trial of proton beam radiation therapy.
  • A clinical trial of photodynamic therapy.
  • Clinical trials of new types of treatment, such as hormone therapy followed by radical prostatectomy.

Use our clinical trial search[rx] to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General informationabout clinical trials is also available.

Stage III Prostate Cancer

Standard treatment of stage III prostate cancer may include the following:

  • External radiation therapy. Hormone therapy may be given after radiation therapy.
  • Hormone therapy. Radiation therapy may be given after hormone therapy.
  • Radical prostatectomy. Radiation therapy may be given after surgery.
  • Watchful waiting.
  • Active surveillance. If cancer begins to grow, hormone therapy may be given.

Treatment to control cancer that is in the prostate and lessen urinary symptoms may include the following:

  • External radiation therapy.
  • Internal radiation therapy with radioactive seeds.
  • Hormone therapy.
  • Transurethral resection of the prostate (TURP).
  • A clinical trial of new types of radiation therapy.
  • A clinical trial of cryosurgery.

Use our clinical trial search[rx] to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done.

Stage IV Prostate Cancer

Standard treatment of stage IV prostate cancer may include the following:

  • Hormone therapy.
  • Hormone therapy combined with chemotherapy.
  • Bisphosphonate therapy.
  • External radiation therapy. Hormone therapy may be given after radiation therapy.
  • Alpha emitter radiation therapy.
  • Watchful waiting.
  • Active surveillance. If cancer begins to grow, hormone therapy may be given.
  • A clinical trial of radical prostatectomy with orchiectomy.

Treatment to control cancer that is in the prostate and lessen urinary symptoms may include the following:

  • Transurethral resection of the prostate (TURP).
  • Radiation therapy.

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done.

Treatment Options for Recurrent or Hormone-Resistant Prostate Cancer

For information about the treatments listed below, see the Treatment Option Overview[rx] section.

Standard treatment of recurrent or hormone-resistant prostate cancer may include the following:

  • Hormone therapy.
  • Chemotherapy for patients already treated with hormone therapy.
  • iologic therapy with sipuleucel-T for patients already treated with hormone therapy.
  • External radiation therapy.
  • Prostatectomy for patients already treated with radiation therapy.
  • Alpha emitter radiation therapy.

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients.

If the tumor is small, only inside the prostate, and not aggressive (low-risk prostate cancer), the following treatments are also possible:

  • Active surveillance: Here the prostate cancer is simply monitored, and not treated, at first. This strategy is based on the fact that low-risk prostate cancer usually grows very slowly or doesn’t grow at all. It is often found that cancer has still not advanced even years after it was diagnosed. Instead of having treatment, the prostate is checked regularly. Treatment attempting to get rid of cancer (curative treatment) is only started if the tumor starts growing. The advantage of this approach is that the side effects of surgery or radiotherapy can be avoided as long as cancer does not grow. One possible disadvantage: If cancer does progress, that is sometimes discovered too late. It may have already spread to other parts of the body by then (metastasis). Knowing that you have cancer in your body can be distressing too.
  • Watchful waiting: This strategy also starts by only monitoring prostate cancer at first. But if the tumor starts growing, only the symptoms are treated, not the tumor itself (this is known as “palliative” care). This approach is mainly considered in older men, who may also have other medical problems. The risks and stress of surgery or radiotherapy could outweigh the possible benefits of this treatment.

References

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Prostate cancer

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