Prostate Cancer

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.

What is Prostate? Anatomy and Functions [1]

The prostate gland is found  in males and is a part of the 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, right and left [1,2].

The size of the gland changes with age.It grows  during puberty due to the rise in male hormones (called androgens) in the body.In adult young men, a typical prostate is about 3 cm thick and 4 cm wide (about the size of a walnut) and weighs about 20 grams and starts to get larger when men reach their 40’s and early 50’s.

Functions of prostate gland: [1,3]
• Prostate gland produces prostatic fluid which contains enzymes, proteins, minerals that  protect & nourishes sperms.

•   It mixes with  fluid from seminal vesicles (present on both sides of prostate) and forms semen.

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

Burden of disease

Prostate is among the top ten leading sites of cancers in India.

Globocan, 2018 [4].

New cases: 25,696
Deaths: 17,184
5 years prevalence: 47,558

Indian Data

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 India. The cancer projection data shows that the number of cases will become doubled by 2020 [7]

Are you at risk?

Factors that can increase your risk of prostate cancer include:
• Age: Risk of prostate cancer increases with age. Prostate cancer is  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 positive 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].

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 & Inflammation of the prostate: Obesity and inflammation have been linked with prostate cancer and is are still under research for conclusive remarks

When should you consult a doctor? [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
• Obstructive/weak urination, incomplete bladder emptying
• Not having a feeling of emptied bladder
• Discomfort in the pelvic area
• Blood in the semen
• Erectile dysfunction
• Bone pains
• Blood in the urine
• 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.

How can it be prevented?

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].
• Maintain healthy body weight and avoid obesity.
• Indulge in regular physical activity.
• Limit your intake of high-calorie foods and drinks.
• Eat at least 400gm of vegetables and fruits each day.
• Choose whole grains instead of refined grain products.
• Limit the intake of processed  and red meat.
• Avoid alcohol or limit the alcohol intake to no more than 2 drinks per day.
• Limit the intake of dairy foods and diets rich in calcium.

Screening and Early Detection [20]

Prostate cancer can often be found early by testing the amount of prostate-specific antigen (PSA) in a blood. 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.

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.

How can it be diagnosed?[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 < 4micrograms/litre (microgm/lt) 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: Catheterisation of bladder, prostate biopsy, prostatic manipulation during digital rectal examination, colonoscopy etc.

DRE(Digital Rectal Examination): within 24-48 hours of a PSA test

Sternous Exercise
• 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 finally assessing the severity of the disease.
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 the 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]

Treatment

Your prostate cancer treatment options depend on several factors, such as how fast your cancer is growing,

how much it has spread, your overall health, as well as the benefits and the potential side effects of the treatment.

Immediate treatment may not be necessary

For men diagnosed with a very early stage of prostate cancer, treatment may not be necessary right away. Some men may never need treatment. Instead, doctors sometimes recommend active surveillance.

In active surveillance, regular follow-up blood tests, rectal exams and possibly biopsies may be performed to monitor progression of your cancer. If tests show your cancer is progressing, you may opt for a prostate cancer treatment such as surgery or radiation.

Active surveillance may be an option for cancer that isn’t causing symptoms, is expected to grow very slowly and is confined to a small area of the prostate. Active surveillance may also be considered for a man who has another serious health condition or an advanced age that makes cancer treatment more difficult.

Active surveillance carries a risk that the cancer may grow and spread between checkups, making it less likely to be cured.

Radiation therapy

Radiation therapy uses high-powered energy to kill cancer cells. Prostate cancer radiation therapy can be delivered in two ways:

  • Radiation that comes from outside of your body (external beam radiation). During external beam radiation therapy, you lie on a table while a machine moves around your body, directing high-powered energy beams to your prostate cancer. You typically undergo external beam radiation treatments five days a week for several weeks. External beam radiation uses X-rays or protons to deliver the radiation.
  • Radiation placed inside your body (brachytherapy). Brachytherapy involves placing many rice-sized radioactive seeds in your prostate tissue. The radioactive seeds deliver a low dose of radiation over a long period of time. Your doctor implants the radioactive seeds in your prostate using a needle guided by ultrasound images. The implanted seeds eventually stop giving off radiation and don’t need to be removed.

Side effects of radiation therapy can include painful urination, frequent urination and urgent urination, as well as rectal symptoms, such as loose stools or pain when passing stools. Erectile dysfunction can also occur.

Hormone therapy

Hormone therapy is treatment to stop your body from producing the male hormone testosterone. Prostate cancer cells rely on testosterone to help them grow. Cutting off the supply of hormones may cause cancer cells to die or to grow more slowly. Hormone therapy options include:

  • Medications that stop your body from producing testosterone. Medications known as luteinizing hormone-releasing hormone (LH-RH) agonists prevent the testicles from receiving messages to make testosterone. Drugs typically used in this type of hormone therapy include leuprolide (Lupron, Eligard), goserelin (Zoladex), triptorelin (Trelstar) and histrelin (Vantas).
  • Medications that block testosterone from reaching cancer cells. Medications known as anti-androgens prevent testosterone from reaching your cancer cells. Examples include bicalutamide (Casodex), flutamide, and nilutamide (Nilandron). These drugs typically are given along with an LH-RH agonist or given before taking an LH-RH agonist.
  • Surgery to remove the testicles (orchiectomy). Removing your testicles reduces testosterone levels in your body. The effectiveness of orchiectomy in lowering testosterone levels is similar to that of hormone therapy medications, but orchiectomy may lower testosterone levels more quickly.

Hormone therapy is used in men with advanced prostate cancer to shrink the cancer and slow the growth of tumors. In men with early-stage prostate cancer, hormone therapy may be used to shrink tumors before radiation therapy. This can make it more likely that radiation therapy will be successful.

Hormone therapy is sometimes used after surgery or radiation therapy to slow the growth of any cancer cells left behind.

Side effects of hormone therapy may include erectile dysfunction, hot flashes, loss of bone mass, reduced sex drive and weight gain.

Surgery to remove the prostate

Surgery for prostate cancer involves removing the prostate gland (radical prostatectomy), some surrounding tissue and a few lymph nodes. Ways the radical prostatectomy procedure can be performed include:

  • Using a robot to assist with surgery. During robotic laparoscopic surgery, the instruments are attached to a mechanical device (robot) and inserted into your abdomen through small incisions. The surgeon sits at a console and uses hand controls to guide the robot to move the instruments. Using a robot during laparoscopic surgery may allow the surgeon to make more precise movements with surgical tools than is possible with traditional laparoscopic surgery.
  • Making an incision in your abdomen. During retropubic surgery, the prostate gland is taken out through an incision in your lower abdomen. Compared with other types of prostate surgery, retropubic prostate surgery may carry a lower risk of nerve damage, which can lead to problems with bladder control and erections.
  • Making an incision between your anus and scrotum. Perineal surgery involves making an incision between your anus and scrotum in order to access your prostate. The perineal approach to surgery may allow for quicker recovery times, but this technique makes removing the nearby lymph nodes and avoiding nerve damage more difficult.
  • Laparoscopic prostatectomy. During a laparoscopic radical prostatectomy, the doctor performs surgery through small incisions in the abdomen with the assistance of a long, slender tube with a small camera on the end (laparoscope). This type of surgery is not commonly performed for prostate cancer in the U.S. anymore.

Discuss with your doctor which type of surgery is best for your specific situation.

Radical prostatectomy carries a risk of urinary incontinence and erectile dysfunction. Ask your doctor to explain the risks you may face based on your situation, the type of procedure you select, your age, your body type and your overall health.

Freezing prostate tissue


Cryosurgery or cryoablation involves freezing tissue to kill cancer cells. During cryosurgery for prostate cancer, small needles are inserted in the prostate using ultrasound images as guidance. A very cold gas is placed in the needles, which causes the surrounding tissue to freeze. A second gas is then placed in the needles to reheat the tissue. The cycles of freezing and thawing kill the cancer cells and some surrounding healthy tissue.

Initial attempts to use cryosurgery for prostate cancer resulted in high complication rates and unacceptable side effects. However, newer technologies have lowered complication rates, improved cancer control and made the procedure easier to tolerate. Cryosurgery may be an option for men who haven’t been helped by radiation therapy.

Heating prostate tissue using ultrasound


High-intensity focused ultrasound treatment uses powerful sound waves to heat prostate tissue, causing cancer cells to die. High-intensity focused ultrasound is done by inserting a small probe in your rectum. The probe focuses ultrasound energy at precise points in your prostate. High-intensity focused ultrasound treatments are currently only available in clinical trials in the U.S.

Chemotherapy


Chemotherapy uses drugs to kill rapidly growing cells, including cancer cells. Chemotherapy can be administered through a vein in your arm, in pill form or both.

Chemotherapy may be a treatment option for men with prostate cancer that has spread to distant areas of their bodies. Chemotherapy may also be an option for cancers that don’t respond to hormone therapy.

Multiple new chemotherapy drugs have recently been approved for treatment of progressive, metastatic prostate cancer

Immunotherapy

A form of immunotherapy (Provenge) has been developed to treat advanced, recurrent prostate cancer. This treatment takes some of your own immune cells, genetically engineers them to fight prostate cancer, then injects the cells back into your body through a vein. Some men do respond to this therapy with some improvement in their cancer, but the treatment is very expensive and requires multiple visits for the treatment.

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 Therapy:
• 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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