Prostate cancer and genetics

ALSO KNOWN AS: Prostatic carcinoma

DEFINITION Prostate cancer is a disease in which cancer cells grow in the prostate gland. The prostate is a walnut-sized gland in men. The prostate makes a fluid that is part of semen.

Cancer occurs when cells in the body (in this case, prostate cells) divide without control or order. Normally, cells divide in a regulated manner. If cells keep dividing uncontrollably when new cells are not needed, a mass of tissue forms, called a growth or tumor. The term “cancer” refers to malignant tumors, which can invade nearby tissue and spread to other parts of the body. A benign tumor does not invade or spread. The sooner prostate cancer is treated, the better the outcome. Men should contact their doctors right away if they think they have this condition.

Risk Factors

Men should tell their doctors if they have any of the risk factors for prostate cancer. As of 2024, the American Cancer Society reported that men who are fifty years of age or older and Black men are at increased risk for the disease, with six out of ten cases found in men over the age of sixty-five. Other risk factors include having a family history of prostate cancer, especially in a father or brother; having a family history of prostate cancer diagnosed at a young age; and eating a high-fat diet.

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Etiology and Genetics

Prostate cancer is a complex condition that may involve both genetic and environmental determinants. Most cases are sporadic, with no known underlying genetic basis. According to Corewell Health in 2024, approximately 5 to 10 percent of cases are termed “familial” because they run in families, and these probably result from a combination of shared genes and shared lifestyles. Few cases are specifically termed “hereditary,” yet mutations in a dozen or more genes have been identified that may increase an individual’s susceptibility to prostate cancer. Mutations in susceptibility genes for hereditary prostate cancer probably account for about half of the cases of disease in patients aged fifty years or younger. In these cases, the vast majority show an autosomal dominant pattern of transmission, meaning that a single copy of the mutation is sufficient to cause the increased susceptibility. An affected individual has a 50 percent chance of transmitting the mutation to each of his or her children. Other cases of hereditary prostate cancer, however, result from a spontaneous new mutation, so in these instances, affected individuals will have an unaffected father.

Genes known to be associated with increased susceptibility to prostate cancer are HPC1 (found on chromosome 1 at position 1q25), HPC2 (located on chromosome 17 at position 17p11), HPCX (at position 11p11.22), CAPB (at position 1p36.1-p35), PCA3 (at position 9q21-q22), and TMPRSS2 (at position 21q22.3). Additionally, mutations in the BRCA1 and BRCA2 genes, most commonly associated with hereditary breast and ovarian cancer, also confer an increased risk for prostate cancer. One study suggests that men with BRCA1 mutations have a slightly increased risk while men with BRCA2 mutations may have as much as a 20 percent risk of developing prostate cancer, according to the American Society of Clinical Oncology. Studies also indicate that a mutation in the HOXB13 gene is linked to prostate cancer.

Symptoms

Men who have any of these symptoms should not assume they are due to prostate cancer. These symptoms may also be caused by other, less serious health conditions, such as benign prostatic hyperplasia (BPH) or an infection.

Men should tell their doctors if they have any of the symptoms, which include a need to urinate frequently, especially at night; difficulty starting urination or holding back urine; an inability to urinate; a weak or interrupted urine flow; and painful or burning urination. Additional symptoms include difficulty having an erection, painful ejaculation, blood in urine or semen, and frequent pain or stiffness in the lower back, hips, or upper thighs.

Screening and Diagnosis

The doctor will ask about symptoms and medical history and will perform a physical exam. Tests include a digital rectal exam, in which the doctor will insert a gloved finger into the rectum in order to examine it; urine tests to check for blood or infection; and blood tests to measure prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP).

Other tests to learn more about the cause of a patient’s symptoms include transrectal ultrasonography, a test that uses sound waves and a inserted into the rectum to find tumors; intravenous pyelogram, a series of X-rays of the organs of the urinary tract; cystoscopy, in which the doctor looks into the urethra and bladder through a thin, lighted tube; and biopsy, the removal of a sample of prostate tissue to test for cancer cells.

Treatment and Therapy

Once prostate cancer is found, tests are done to find out if the cancer has spread and, if so, to what extent. Treatment depends on how far the cancer has spread. Patients should talk to a radiation oncologist and urologist, who can help decide the best treatment plan. Patients should also discuss the benefits and risks of each treatment option.

Standard options include watchful waiting. There is no treatment with watchful waiting. The doctor will do tests to see if the cancer is growing. Watchful waiting is used for early-stage prostate cancer that seems to be growing slowly, for older prostate cancer patients, and for those with serious medical problems that may make the treatment risks outweigh the possible benefits.

Surgery involves removing the cancerous tumor, nearby tissues, and possibly the nearby lymph nodes. Surgery is offered to patients who are in good health and are younger than seventy years old.

Types of surgery include pelvic lymphadenectomy, the removal of lymph nodes in the pelvis to determine if they contain cancer. If they do, removal of the prostate and other treatment may be recommended. Radical retropubic prostatectomy is the removal of the entire prostate and nearby lymph nodes through an incision in the abdomen. Radical perineal prostatectomy is the removal of the entire prostate through an incision between the scrotum and the anus; nearby lymph nodes are sometimes removed through a separate incision in the abdomen.

Transurethral resection of the prostate (TURP) is the removal of part of the prostate with an instrument inserted through the urethra. TURP is not a cancer surgery, but it can be used to relieve the symptoms of patients who have either prostate cancer or an enlarged gland due to other reasons.

Prostate cancer surgery can cause impotence, and it can also cause urine leakage from the bladder or stool from the rectum. Nerve-sparing surgery may reduce these risks. However, this surgery may not treat very large tumors or tumors that are very close to nerves.

Robotic surgery and laparoscopic surgery may be other options. These minimally invasive techniques can reduce side effects, blood loss, and recovery time.

Radiation therapy involves the use of radiation to kill cancer cells and shrink tumors. Radiation may be external radiation therapy, in which radiation is directed at the tumor from a source outside the body, or internal radiation therapy, in which radioactive materials are placed into the body near the cancer cells. Internal radiation therapy is often used for treating earlier-stage cancers. Radiation therapy for prostate cancer may cause impotence and urinary problems. However, most studies show that impotence rates are less for radiation therapy than for standard prostatectomy and slightly less than rates for nerve-sparing procedures. Incontinence also occurs less frequently following radiation therapy than it does following prostatectomy. However, there is a slightly increased risk of cystitis due to radiation.

Hormone therapy is used for patients whose prostate cancer has spread beyond the prostate or has recurred after treatment. The goal of hormone therapy is to lower levels of the male hormones, called androgens. The main androgen is testosterone. Lowering androgen levels can cause prostate cancers to shrink or grow more slowly, but it does not cure cancer.

Methods of hormone therapy include orchiectomy, a surgical procedure to remove one or both of the testicles, which are the main source of male hormones. Orchiectomy decreases hormone production, which can shrink or slow the growth of most prostate cancers. Luteinizing hormone-releasing hormone (LHRH) agonists are injections that can decrease the amount of testosterone made by the testicles. Antiandrogens, such as flutamide or bicalutamide, are medications that can block the action of androgens. These medications are used in combination with orchiectomy or LHRH agonists, a combination called total androgen blockade. Other forms of hormone therapy include the use of drugs, such as ketoconazole or aminoglutethimide, that prevent the adrenal glands from making androgens and estrogens, drugs that prevent the production of testosterone in the testicles. Estrogens are rarely used today because of the risk of serious side effects. Hormone therapy for prostate cancer may cause hot flashes, impaired sexual function, loss of sexual desire, and weakened bones.

Prostate cancer can also be treated using ablative therapies such as cryoablation or high-intensity focused ultrasound (HIFU). Cryoablation, or cryotherapy, is a method in which prostate tissue is frozen using very cold gas in order to kill cancer cells and some of the surrounding tissue. HIFU kills cancerous prostate tissue through the application of heat in the form of concentrated ultrasound energy. Other treatments are being tested. Patients may want to consider taking part in a when weighing their treatment options.

Chemotherapy is the use of drugs to kill cancer cells. It may be given in many forms, including pill, injection, and via a catheter. The drugs enter the bloodstream and travel through the body, killing mostly cancer cells but also some healthy cells. One type of chemotherapy is the use of docetaxel (Taxotere). This drug was found to prolong life in men with hormone-refractory prostate cancer (HRPC). In HRPC, PSA levels continue to rise or the tumor continues to grow despite hormone therapy.

Biological therapy is the use of medications or substances made by the body to increase or restore the body’s natural defenses against cancer. It is also called biological response modifier (BRM) therapy. High-intensity focused ultrasound is a treatment that uses an endorectal probe to make ultrasound (high-energy sound waves). This can destroy cancer cells. Conformal radiation therapy uses three-dimensional radiation beams that are conformed into the shape of the diseased prostate. This treatment spares nearby tissue from the damaging effects of radiation. Intensity-modulated radiation therapy (IMRT) uses radiation beams of different intensities to deliver higher doses of radiation therapy to the tumor and lower doses to nearby tissues at the same time.

Prevention and Outcomes

Beginning at age fifty, men should be offered a digital rectal exam and PSA blood test to screen for prostate cancer. Many, but not all, professional organizations recommend a yearly PSA blood test for men older than fifty. Black men and men with close family members who have had prostate cancer diagnosed at a young age should begin screening when they are forty-five years old. All men should discuss PSA testing with their doctors.

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