Details about Prostate Cancer

What is prostate cancer?

Prostate cancer is cancer of prostate gland. The prostate gland is a walnut-sized gland present only in men, found in the pelvis below the bladder. The prostate gland wraps around the urethra (the tube through which urine exits the body) and lies in front of the rectum. The prostate gland secretes part of the liquid portion of the semen, or seminal fluid, which carries sperm made by the testes. The fluid is essential to reproduction.

Prostate cancer is one of the most common types of cancer that develops in men and is the third leading cause of cancer deaths in American men, behind lung cancer and colorectal cancer. In 2017, the American Cancer Society estimated that 161,360 men will be newly diagnosed with prostate cancer and 26,730 men will die from the disease -- though many of them had lived with the disease for years prior to their deaths.

Prostate cancer is comprised nearly always of adenocarcinoma cells -- cells that arise from glandular tissue. Cancer cells are named according to the organ in which they originate no matter where in the body we find such cells. Thus, if prostate cancer cells spread in the body to the bones, it is not then called bone cancer. It is prostate cancer metastatic to the bones. Metastasis the process of cancer spread through the blood or lymphatic system to other organs/areas throughout the body. Prostate cancer more commonly metastasizes to lymph nodes in the pelvis and to the bones.

What causes prostate cancer?

The exact causes of prostate cancer are not known. Several risk factors for developing prostate cancer have been identified, but which of these risk factors cause a prostate cell to become cancerous is not fully known. For a cancer to develop, changes must occur in the chemicals that make up the DNA, which makes up the genes in the cell. The genes control how the cell works, for example, how quickly the cell grows, divides into new cells, and dies, as well as correcting any mistakes that occur in the DNA of the cell to keep the cell working normally. Cancer occurs when certain genes that either control the growth or death of the cell are affected, which results in abnormal cell growth and/or death. Genes are inherited (passed on from parents to their children) and thus some changes in the genes (gene mutations) that increase the risk of developing cancer may be inherited. For prostate cancer, approximately 5%-10% of prostate cancers are due to inherited gene changes. Several inherited genes have been identified that increase the risk of prostate cancer, including RNASEL, BRCA 1, and BRCA 2, DNA mismatch genes, HPC1, and HoxB13. Gene changes may also be acquired (develop during the course of your life). These changes are not passed on to children. Such changes may occur when a cell is normally undergoing growth and division. It is thought that at times during normal cell growth, risk factors may affect the DNA of the cell.

What are the risk factors for prostate cancer?

Certain risk factors may predispose a person to prostate cancer. These include the following:

• Age: Sixty percent of cases of prostate cancer arise in men over 65 years of age. The disease is rare in men under 40.
• Race or ethnicity: African-American men and Jamaican men of African ancestry are diagnosed with prostate cancer more often than are men of other races and ethnicities. Asian and Hispanic men are less likely to develop prostate cancer than are non-Hispanic white males.
• Family history: Prostate cancer can run in families. A man whose father or brother has or had prostate cancer is twice as likely to develop the disease. The younger the family member is when he is diagnosed with prostate cancer, the higher the risk is for male relatives to develop prostate cancer. The risk of developing prostate cancer also increases with the number of relatives affected.
• Nationality: Prostate cancer is more common in North America, Europe (especially northwestern countries in Europe), the Caribbean, and Australia. It is less common in Asia, Africa, and South and Central America. Multiple factors, such as diet and lifestyle, may account for this.
• Genetic factors: Mutations in a portion of the DNA called the BRCA2 gene can increase a man's risk of getting prostate cancer, as well as other cancers. This same mutation in female family members may increase their risk of developing breast or ovarian cancer. However, very few cases of prostate cancer can be directly attributed to presently identifiable genetic changes. Other inherited genes associated with an increased risk of prostate cancer include RNASEL, BRCA 1, DNA mismatch genes, HPC1, and HoxB13.
• Other factors: Diets high in red meats and fatty foods and low in fruits and vegetables appear to be associated with a higher risk of developing prostate cancer. Obesity is also linked to a higher risk of the disease. Increased calcium intake and dairy foods may increase the risk of prostate cancer.

Smoking, a history of sexually transmitted disease, a history of prostatitis (inflammation of the prostate), and a history of vasectomy have not been proven to play a role in causing prostate cancer. The role of fish oil in risk of prostate cancer remains under investigation.

What are the signs and symptoms of prostate cancer?

A patient with early prostate cancer is usually asymptomatic. However, late stage disease and sometimes early stage disease may have the following signs and symptoms:

• Frequent urination, during the day and/or at night
• Difficulty in starting (hesitancy), maintaining, or stopping the urine stream
• A weak or interrupted urine stream
• Straining to urinate
• Inability to urinate (urinary retention)
• Loss of control of urination
• Difficulty urinating when standing, requiring sitting during urination
• Pain with urination or ejaculation
• Blood in the urine or in the semen
• Abnormal rectal examination

Many symptoms of early cancer of the prostate can also be attributed to benign (noncancerous) conditions of the prostate, including benign prostatic hypertrophy (BPH), or infection in the prostate gland or urinary system.

Signs and symptoms of advanced prostate cancer (late stage prostate cancer) that has already spread from the prostate gland to elsewhere in the body (called metastatic prostate cancer) include

• a new dull, then progressively severe, pain in the bones, especially the low back;
• unexplained weight loss;
• fatigue;
• increasing shortness of breath while doing activities previously well tolerated;
• low-impact fracture of bone(s) without a lot of trauma (or broken bone[s] from minor trauma); and
• swelling of the legs related to obstruction of the lymph tissue by prostate cancer.

It is always best to find and diagnose prostate cancer at an early stage and hopefully still confined to its site of origin. At that point, treatments can cure it. When prostate cancer is widespread or metastatic, it can be treated, but it cannot be cured.

What specialists identify and treat prostate cancer?

There are several different types of specialists involved in the identification and treatment of prostate cancer.

1. The primary provider (PCP) may be the initial medical doctor to discuss prostate cancer screening and/or become concerned about the risk of prostate cancer (because of abnormal rectal examination and/or elevated PSA or family history of prostate cancer [brother or father or multiple family members diagnosed with prostate cancer at < 60 years of age]) during your routine evaluations or due to symptoms and refer you to a urologist for further evaluation.
2. Urologists are the specialists who will initially be involved in the diagnosis of prostate cancer and will perform the prostate biopsy. Depending on the grade and stage of the prostate cancer at the time of the diagnosis, additional specialists may be involved in your care. Urologists perform surgical-based treatments for prostate cancer (radical prostatectomy), minimally invasive treatments (cryotherapy, brachytherapy), and prescribe medications (hormonal therapy).
3. Medical oncologists are medical doctors who specialize in the treatment of cancer. Medical oncologists treat prostate cancer with a variety of medical therapies, including chemotherapy, immune/vaccine, and hormonal therapy.
4. Radiation oncologists are specialists who treat cancer with ionizing radiation. This radiation may be given externally (external beam radiation therapy) or internally through the placement of small radioactive pellets into the prostate (brachytherapy).
5. Often urologists, medical oncologists, and radiation oncologists work together in a multidisciplinary team to review your case and you may meet with one, two, or all of these physicians at some point during your prostate cancer treatment.

What tests do health care professionals use to diagnose prostate cancer?

The diagnosis of prostate cancer ultimately is based on the pathologist's review of tissue removed at the time of the prostate biopsy. An abnormal PSA and/or abnormal digital rectal examination often are present and are the indications for the prostate biopsy.

Digital rectal examination (DRE): As part of a physical examination, your doctor inserts a gloved and lubricated finger into your rectum and feels toward the front of your body. The prostate gland is a walnut or larger sized gland immediately in front of the rectum, and beneath your bladder. The back portion of prostate gland can be felt in this manner. Findings on this exam are compared to notes about the patient's prior digital rectal examinations.

The exam is usually brief, and most find it uncomfortable due to the pressure used to adequately examine the prostate gland. Findings such as abnormal size, lumps, or nodules (hard areas within the prostate) may indicate prostate cancer.

The national comprehensive cancer network (NCCN) notes that a DRE should not be used as a stand-alone test for detection of prostate cancer but should be performed in men with an elevated PSA. The NCCN also notes that DRE may be considered as a baseline test in all patients, as it may help identify high-grade cancers associated with a normal PSA.

Prostate specific antigen (PSA) blood test: The PSA blood test measures the level of a protein found in the blood that is produced by the prostate gland and helps keep semen in liquid form. The PSA test can indicate an increased likelihood of prostate cancer if the PSA is at an increased or elevated level or has changed significantly over time, but it does not provide a definitive diagnosis. Prostate cancer can be found in patients with a low PSA level, but this occurs less than 20% of the time.

If the PSA level is elevated (levels can depend upon your age, on the size of your prostate gland on examination, certain medications you may be taking, or recent sexual activity) or has increased significantly over time, further testing may be needed to rule out prostate cancer.

PSA measurements are often tracked over time to look for evidence of a change. The amount of time it takes for the PSA level to increase is referred to as PSA velocity. The time it takes for the PSA to double, known as the PSA doubling time, can be also tracked. PSA velocity and PSA doubling time can help your doctor determine whether prostate cancer may be present.

The presence of an abnormal result on digital rectal examination, or a new or progressive abnormality in a PSA test may lead to a referral to a physician who specializes in diseases of the urinary system (a urologist) who may perform further testing, such as a biopsy of the prostate gland.

Prostate biopsy: A biopsy refers to a procedure that involves taking of a sample of tissue from an area in the body. Prostate cancer is only definitively diagnosed by finding cancer cells on a biopsy sample taken from the prostate gland.

The urologist may have you stop medications such as blood thinners (for example, warfarin[Coumadin]), aspirin, ibuprofen [Advil, Motrin], and certain herbal supplements) before the biopsy. An antibiotic is often prescribed to help prevent an infection related to the procedure. Some urologists may actually place a small swab into your rectum a week or so prior to the procedure to determine the best antibiotic to give you (selective target antibiotic prophylaxis). You may be asked to do a cleansing enema at home before the biopsy appointment and will be instructed to take the antibiotic 30 to 60 minutes prior to the biopsy to prevent an infection. On the day of the biopsy, the doctor will apply a local anesthetic by injection or topically as a gel inside the rectum over the area of prostate gland. You will be asked to lie on your side with your knees pulled up to your chest. Sometimes you may be asked to lie on your stomach. An ultrasound probe is then placed in the rectum. This device uses sound waves to take a picture of the prostate gland and helps guide the biopsy device. The device used is a spring-loaded needle that allows the urologist to remove tiny cores of tissue from the prostate gland. Usually, 12 cores are obtained, six from each side. Two cores are taken from the upper, middle, and lower portions of each side of the prostate gland. The cores are examined under the microscope by a pathologist (a doctor who specializes in examining tissues to make a diagnosis). Results may take several days.

If you do not have an anus (due to previous surgery), then transperineal prostate biopsy is performed. During this procedure, which is often performed under sedation, the biopsy needle is inserted through the perineum (area between the scrotum and the anus) into the prostate.

A biopsy procedure is usually uncomplicated, with just some numbness, pain, or tenderness in the area for a short time afterward. Occasionally, a patient has some blood in the urine, stool, or the ejaculate after the procedure. Rarely, the patient may develop an infection after a biopsy procedure (urinary tract infection, prostate infection, testis infection) or be unable to urinate. If one develops a fever after the procedure, has continued blood in the urine or ejaculate, or has troubles urinating, further evaluation by the performing doctor is needed.

Prostate cancer biopsy results

The result of the pathologist's analysis of the biopsy cores under the microscope is the only way to diagnose prostate cancer. The prostate biopsy technique samples many areas of the prostate but rarely the biopsy can miss small areas of prostate cancer in the prostate. Thus, if the initial biopsy results are negative but the urologist is still suspicious based on the results of the examination, the ultrasound images seen during the procedure, or the PSA, additional biopsies or tests may be recommended.

The pathologist's report on the biopsy sample showing prostate cancer will contain much detailed information. The size of the biopsy core and the percentage of involvement of each core will be reported. Most importantly the prostate cancer present will be assigned a numerical score, which is usually expressed as a sum of two numbers (for example, 3 + 4) and is referred to as the Gleason Score. This characterizes the appearance of the cancer cells and helps predict its likely level of aggressiveness in the body. It is often also referred to as the grade of the prostate cancer.

A new prostate cancer grading system was developed in 2014 to help assess risk and assign a Gleason grade group. This grade group is particularly useful in Gleason score 7, where the predominant cell type could be a 4 or a 3, which may impact prostate cancer risk.

• Gleason grade group 1: Gleason score < 6
• Gleason grade group 2: Gleason score 3+4= 7
• Gleason grade group 3: Gleason score 4+3 = 7
• Gleason grade group 4: Gleason 4+4 =8, 3+5 = 8 and 5+3 = 8
• Gleason grade group 5: Gleason score 9 and 10

The Gleason score and the extent of involvement of the biopsy core expressed as a percentage, as well as the PSA level as well as your general state of health and otherwise estimated life expectancy, all help to allow doctors to make their best recommendations for you regarding how your cancer should be treated.