Prostate Cancer

What is Prostate? Anatomy and Functions [1]

The prostate gland is found only in males and is a part of male reproductive system. It lies below the urinary bladder and in front of the rectum. The gland surrounds the first part of the tube ‘urethra’ that carries urine from the bladder to the penis. Seminal vesicles, the glands that make the fluid for semen, are located just behind the prostate. The prostate gland is divided into 2 lobes, to the left and the right of a central groove [1,2].

The size of the gland changes with age.It grows rapidly during puberty, fueled by the rise in male hormones (called androgens) in the body.In adult men, a typical prostate is about 3 cm thick and 4 cm wide (about the size of a walnut) and weighs about 20 grams, but it can be muchlargerin older men [1].

Functions of prostate gland: [1,3]
•    Prostate gland produces a thick, clear fluid that makes the semen more fluid and protects and nourishes sperm cells in the semen.
•    It also plays a part in controlling the flow of urine.

What is Prostate cancer?
Prostate cancer forms in the cells of the prostate. Though several types of cells are found in prostate, almost all prostate cancers develop from glandular cells (adenocarcinomas). Other types of prostate cancers are very rare [2].
Prostate cancer is usually a very slow growing cancer and most patients do not have significant symptoms until the cancer reaches an advanced stage.
Most men with prostate cancer die of other unrelated causes, and many never know that they have the disease. But once prostate cancer begins to grow quickly or spreads outside the prostate, it is dangerous.

Prostate cancer that is detected early — when it’s still confined to the prostate gland — has a better chance of successful treatment.

Epidemiology

Prostate is among the top ten leading sites of cancers in India. Globocan, 2012 [4].

Incidence
Mortality
5 year Prevalence
19,095 12,231 63,818
Survival Rate [5]
• Overall 5-year survival rate – 64%
– <59 years – 55% – 60-69 years – 74% – >70 years – 52%

Indian Data

Prostate is the second leading site of cancer among males in large Indian cities like Delhi, Kolkata, Pune and Thiruvananthapuram, third leading site of cancer in cities like Bangalore and Mumbai and it is among the top ten leading sites of cancers in the rest of the PBRCs of India. The data shows that almost all regions of India are equally affected by this cancer [6].

The incidence rates of this cancer are constantly and rapidly increasing in all the PBRCs. The cancer projection data shows that the number of cases will become doubled by 2020 [7]

Risk Factors

Factors that can increase your risk of prostate cancer include:
• Age: Risk of prostate cancer increases with age. Prostate cancer is very rare in men below 40 and the risk increases rapidly after the age 50 [3, 8-10]. Out of every 10 prostate cancers, 6 are detected in men above 60 years of age [10].

• Ethnicity: Prostate cancer occurs less often in Asian-American and Hispanic/Latino men than in non-Hispanic whites. African Black men have a greater risk of prostate cancer than men of other ethnicities and these cancers are likely to be more aggressive or advanced stage at presentation. However, the reasons for these racial and ethnic differences in prostate cancer are not clear [3, 8-11].

• Family history: Prostate cancer seems to run in families which suggest a genetic or inherited factor involved in its causation. A family history of prostate cancer increases your risk of getting it [3, 8-9, 12 ].

Number of affected relatives also increases the relative risk for prostate -cancer, notably if the cancer is found in younger relatives [12].

• Genetic alterations: Inherited mutations of the BRCA1 or BRCA2 genes which are linked with familial breast and ovarian cancers may also increase prostate cancer risk in some men [13, 14].

Hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is caused by inherited gene changes that carry an increased risk for many cancers including prostate cancer [15, 16].

• Diet: Consumption of excess calcium through food (especially dairy foods) or supplements has been linked with higher risk of developing prostate cancer [17, 18].

• Obesity: Most studies have not found any causal link. However, prostate cancer in obese men is more likely to present in more advanced stages and is more difficult to treat [18].

• Inflammation of the prostate: Some studies have reported that men with prostatitis (inflammation of the prostate gland) have an increased risk for prostate cancer but other studies refute this association [10, 19].

Screening and Early Detection [20]

Prostate cancer can often be found early by testing the amount of prostate-specific antigen (PSA) in a man’s blood sample. Another way to find prostate cancer early is the digital rectal exam (DRE).

If the results of either one of these tests are abnormal, further tests are performed to see if there is a cancer. The prostate cancer found as a result of screening with the PSA test or DRE, will probably be at an earlier, more treatable stage than if no screening were done.

However, neither the PSA test nor the DRE is 100% accurate. Sometimes these tests give abnormal results even when a man does not have cancer (false-positive result), or give normal results even when a man does have cancer (false-negative result). Unclear test results can cause confusion and anxiety. False-positive results can lead some men to undergo an unnecessary prostate biopsy (with small risks of pain, infection, and bleeding). And false-negative results can give a false sense of security.

Another important issue is that even if screening detects a cancer, doctors often can’t be sure if the cancer is truly dangerous and requires immediate treatment. In fact, some prostate cancers grow so slowly that they would probably never cause problems. But these men may still be treated with either surgery or radiation which can have urinary, bowel, and/or sexual side effects that can seriously affect a man’s quality of life.

Read more

Prevention

Since the cause of prostate cancer is not known in most cases, we don’t know how to prevent it. But we can adopt certain practices to decrease the chances of getting prostate and many other types of cancer [21-23].
• Get to and stay at a healthy weight.
• Indulge in regular physical activity.
• Limit your intake of high-calorie foods and drinks.
• Eat at least 2½ cups of vegetables and fruits each day.
• Choose whole grains instead of refined grain products.
• Limit the intake of processed meat and red meat.
• Limit the alcohol intake to no more than 2 drinks per day.
• Reduce intake of dairy foods and diets rich in calcium.

Signs and Symptoms [2, 8-10]

Prostate cancer usually causes no signs or symptoms in early stages. However, advanced stage prostate cancer may cause signs and symptoms such as
• Difficulty in urination
• Urgency to pass urine
• Passing urine more often than usual, especially at night
• Decreased force in the stream of urine
• Not having a feeling of emptied bladder
• Discomfort in the pelvic area
• Blood in the semen
• Erectile dysfunction
• Bone pains
• Blood in the urine (rarely)
• Loss of bladder or bowel control due to cancer growth pressing the spinal cord.
• Weakness or numbness in the legs or feet

The urinary symptoms are caused by the enlargement of the prostate which presses upon urethra, thereby affecting the flow of urine.

These symptoms can be caused by cancerous as well as non-cancerous prostatic conditions. However, if you feel any of such symptoms consult your doctor.

The earlier a cancer is detected, the easier it is to treat it and the chances for successful treatment will be more.

Diagnosis [24]

Early prostate cancers usually don’t cause symptoms and may be detected first during screening. However, more advanced cancers often present with symptoms which prompt investigations and diagnosis of prostate cancer.

Medical history and physical exam: If your doctor suspects you might have prostate cancer, he will ask you about some specific urinary symptoms, sexual problems, bone pains etc.
The doctor would also examine you, including digital rectal examination (DRE), where a lubricated gloved finger is inserted into the rectum to feel for any hard areas on prostate.
Depending upon the findings, the doctor might advise certain tests.

PSA blood test: PSA is a substance made by the prostate.Prostate specific antigen (PSA) blood test is mainly used as a screening test to detect prostate cancer early in asymptomatic men. But it is also done in men who have symptoms suggestive of prostate cancer.
The levels of PSA are < 4nanograms/mililitre (ng/ml) in most healthy men. As PSA levels go up, the chances of having prostate cancer increase. However, a PSA level of <4 does not always guarantee exclusion of cancer; about 15% of men will still have prostate cancer on biopsy. There is about 1 in 4 chance of having prostate cancer in men with PSA between 4 and 10 ng/ml and if PSA is >10, the chance increases to 50%.
Many factors, such as age and race, can affect PSA levels. PSA levels also can be affected by—
• Certain medical procedures.
• Certain medications.
• An enlarged prostate.
• A prostate infection.
Because many factors can affect PSA levels, your doctor is the best person to interpret your PSA test result.

Transrectal ultrasound (TRUS): A small lubricated probe is placed in the rectum to provide images of prostate on a computer screen. TRUS is used to visualize prostate if the results of DRE or PSA are abnormal. It is also used to measure the size of prostate and to obtain guided biopsy of the prostate , if indicated.

Prostate Biospy: If the doctor suspects that you might have prostate cancer based on the symptoms and/or the results of early detection tests (DRE and/or PSA), he would perform a biopsy of the prostate under transrectal ultrasound guidance.
The biopsy usually takes about 10 minutes and is done in an out- patient clinic or minor OT.The biopsy is sent to the pathologist who examines it to look for any cancer cells and also to grade the cancer (Gleason’s scoring/grading) for assessing the differentiation of the tumor and for prognostication.
You may feel some soreness at site of biopsy or notice blood in urine, stool or semen for a few days after the biopsy.
Although a confirmatory diagnosis is usually made on biopsy, the biopsies may still miss a cancer even if multiple samples are taken, if the needle does not hit the cancerous area. In such cases, a repeat biopsy may be required if your doctor strongly suspects that you may have a prostate cancer.

Imaging tests: to look for spread of spread of prostate cancer.

Bone Scan: The prostate cancer often spreads to bones first, among the various sites for distant spread. This is detected by bone scan. Areas of bone damage appear as “hot spots” on the skeleton. The hot spots suggest cancer spread in the bones but may also be caused by arthritis or other bone diseases. Other investigations like CT OR MRI scans or bone biopsy may be needed to make a confirmatory diagnosis.

Computed Tomography (CT) scan: may help in detecting spread of prostate cancer to nearby lymph nodes or other organs.

Magnetic Resonance Imaging (MRI): can produce a clear picture of prostate and is useful to detect whether the cancer has spread outside the prostate into the seminal vesicles or nearby structures.

Staging of prostate cancer [25]

Stage I: Tumor is limited to prostate
• The PSA level is lower than 10
• Tumour is found in one-half or less of one lobe of the prostate.

Stage II: Tumor is limited to prostate but PSA levels are higher
• The PSA level is more than 10 but lower than 20
• Tumor is found in one-half or less of one lobe of the prostate.

Stage III: Tumor has spread beyond the outer layer of the prostate and may have spread to the seminal vesicles. The PSA can be any level.

Stage IV: Tumor has spread beyond the seminal vesicles to nearby tissue or organs, such as the rectum, bladder, lymph nodes, bones or pelvic wall. The PSA can be any level.

Treatment Protocol for Prostate Cancer [26]

A. Localized disease
(Stage I and II)
1) Surgery for prostate cancer involves removing the prostate gland (radical prostatectomy), some surrounding tissue and a few lymph nodes
: Contra-indications of surgery: Age >75 years, life expectancy <10 years 2) Radiation therapy B. Locally advance disease (Stage III) 1) Surgery 2) Radiation (external beam or brachytherapy) +/- hormonal therapy 3) Immediate vs delayed hormonal blockade – Immediate hormonal blockade has been shown to improve quality of life (decreased incidence of cord compression, ureteral obstruction, and pathologic fractures) more than delayed hormonal therapy but studies regarding overall survival benefit are conflicting. C. Metastatic Disease (Stage IV) Hormone sensitive disease • Hormone therapy is treatment to stop your body from producing the male hormone testosterone. Medications that stop the body from producing testosterone are given. • Surgery to remove the testicles (orchiectomy). Removing the testicles reduces testosterone levels in the body. Hormone Refractory Disease Chemotherapy: may be used as a treatment option for men with prostate cancer that has spread to distant areas of their bodies. It may also be an option for cancers that don’t respond to hormone therapy. i. Docetaxel plus prednisone (first line) ii. Or Mitoxantrone plus steroids iii. Bisphosphonates for bone metastases D. Increasing PSA after prostatectomy or radiation – Asymptomatic increase in PSA is a common problem. 1) Risk-Assessment – Determine the likelihood of the rising PSA being a sign of treatment failure. High risk factors – include seminal vesicle involvement, Gleason score >6, PSA >10. PSA doubling time of <6 months is also highly predictive of disease progression. 2) Local Control – Post-surgery (radical prostatectomy) radiation may provide local control, but no survival benefit has been demonstrated, and radiation-related complications may be higher. Post-radiation – salvage surgery is generally not attempted due to higher surgical complication rates. Most men are given medical therapy. Follow Up For patients with early stage disease treated with curative intent Initially every 3 months for first 2 years Then every 6 months till 5 years Then annually For patients with palliative situation: symptom based approach SUPPORTIVE CARE: Bisphosphonates Zolendronic Acid (for CrCl > 30mL/min)
Analgesics 4mg IV q 3-4 weeks (for 6-9 months then at 3 monthly interval)
For adequate pain control
TREATMENT COMPLICATIONS:

SURGERY (Radical Prostatovesiculectomy):
• Incontinence
• Impotence
• Per rectal bleeding
• Deep vein thrombosis
• Pulmonary embolism and wound infection

RADIATION:
• Impotency
• Rectal symptoms including pain, tenesmus, and diarrhea
• Bladder symptoms including cystitis, hematuria, incontinence.

HORMONE DEPRIVATION THERAPY AND ANTIANDROGENS:
• Hypogonadism, impotence, decreased libido, decreased muscle mass, increased adipose tissue, osteoporosis
• Hot flashes, sweats, and gynecomastia
• Rarely, hyperglycemia, hyperinsulinemia and insulin resistance, and dyslipidemia.

10 year Survival Rates (According to AJCC staging)
Stage I 85%
Stage II 72%
Stage III 55%
Stage IV 30%

References

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