Prostate Cancer

As in any cancer, prostate cancers are divided into 4 stages. Stage 1 & 2 are localized cancer, stage 3 is locally advanced cancer and stage 4 is advanced. Another factor is the grade of the disease called Gleason grade – this is seen in the biopsy report to grade the aggressiveness of cancer. Gleason grade can be graded from 1-5 and clubbed into groups

• Stage 1: In the first stage of prostate cancer, the cancer is only in the prostate. Your doctor might feel the cancer growth during the digital rectal exam; usually on a part of one side of the prostate. Else, your doctor can find cancer through needle biopsy that was done due to high PSA levels, or during transurethral resection of prostate surgery. In stage 1, PSA levels are below 10 and the Grade Group is 1.
• Stage 2: In the second stage, the cancer is relatively advanced but is still limited to the prostate. This stage is further divided into three stages; stage 2A, 2B, and 2C.

  Stage 2A is when the PSA level is 10 or more but below 20 and cancer found is a part of a side of your prostate and the Grade Group is 1. Otherwise, it is when both sides of the prostate or more than one half of one side of your prostate has cancer and the Grade Group is

  Stage 2B is when the cancer is on either one side of the prostate or both sides of your prostate. In this stage, the Grade Group is 2 and the PSA level is less than 20.

  Stage 2C is when the cancer is on both sides of the prostate or one side of the prostate. The Grade Group is 3 or 4 and the PSA level is less than 20.

• Stage 3: In the third stage of prostate cancer, cancer may be in the prostate only or may have spread to other parts of your body. This stage is further divided into three sub-stages.

  Stage 3A is when the cancer is still in the prostate only. Cancer can be on both sides of your prostate or only on one side. The PSA level is below 20 and the Grade Group can be 1, 2, 3, or 4.

  Stage 3B is when cancer has advanced and spread to the seminal vesicles. It may have spread to nearby organs or tissues. The PSA level can be anything and the Grade Group is 1, 2, 3, or 4.

  Stage 3C is when the cancer is in one or both sides of your prostate and has spread to nearby organs such as the rectum and bladder. The PSA level can be anything and the Grade Group of this stage is 5.

• Stage 4: In this stage, prostate cancer has advanced further. This stage is divided into two sub-stages.

  Stage 4A is when the cancer is on one or both sides of your prostate has spread to nearby organs, and has spread to lymph nodes too. The PSA can be any level and the Grade Group is anything from 1 to 5.

  Stage 4B is when cancer has spread to other parts of your body. This can be lymph nodes that are further away or bones.

When diagnosed with prostate cancer, your doctor will also make a series of estimates to decide the stage of the disease which will help to decide the correct treatment protocol. Factors include:

• PSA level
• Gleason score
• Clinical stage, which is based on findings of the digital rectal exam (DR.E) and/or an imaging exam.

There are three main risk groups, each of which has its own set of treatment options.

Low risk:

• Less than 10% chance of having spread to other parts of the body
• Low risk of progressing if not treated
• PSA less than 10 ng/mL
• Gleason score of 6 or lower
• No tumor felt on DR.E or feels contained within the prostate gland with only a small abnormal area

Intermediate risk:

• 10% to 15% chance of having spread
• Higher chance (up to 70% over 15 years) of progressing if not treated
• PSA of 10 to 20 ng/mL
• Gleason score of 7
• Tumour can be felt on one or both sides of the prostate on DR.E, but it seems to be contained within the gland

High risk:

• Aggressive features that increase the chance of spreading now or in the future
• PSA over 20 ng/mL
• Gleason score of 8 to 10
• Tumour can be felt on DR.E and seems to have spread outside the gland

Almost all prostate cancers begin in the gland cells of the prostate and thereby are known as adenocarcinomas.

There are also rare variants of the prostate cancers:

• Sarcoma
• Transitional cell carcinomas
• Small cell carcinomas
• Neuroendocrine tumors

Pre-cancerous changes of the prostate: By age 50, about half of all men have small changes in the size and shape of the cells in the prostate. This is called prostatic intraepithelial neoplasia (PIN).

High-grade PIN needs surveillance as the chances of developing cancers are high.

Prostate is intimately involved in the sexual process of the male and any disease of the prostate can affect the male sexually. However, patients may not have major issues in sexual intercourse whilst having CaP. Sometimes prostate cancer patients may present with blood in semen or painful ejaculation.

Most of the prostate cancers are caused by genetic mutations – either acquired or inherited.

Inherited Gene Mutations

Some gene mutations can be passed from generation to generation (inherited) and are found in all cells in the body. Inherited gene changes are thought to play a role in about 10% of prostate cancers. Cancer caused by inherited genes is called hereditary cancer. Several inherited mutated genes have been linked to hereditary prostate cancer, including:

• BRCA1 and BRCA2: These tumor suppressor genes normally help repair mistakes in a cell’s DNA (or cause the cell to die if the mistake can’t be fixed). Inherited mutations in these genes more commonly cause breast and ovarian cancer in women. But changes in these genes (especially BRCA2) also account for a small number of prostate cancers.
• CHEK2, ATM, PALB2, and RAD51D: Mutations in these other DNA repair genes might also be responsible for some hereditary prostate cancers.
• DNA mismatch repair genes (such as MSH2, MSH6, MLH1, and PMS2): These genes normally help fix mistakes (mismatches) in DNA that can be made when a cell is preparing to divide into 2 new cells. (Cells must make a new copy of their DNA each time they divide.) Men with inherited mutations in one of these genes have a condition known as Lynch syndrome (also known as hereditary non-polyposis colorectal cancer, or HNPCC), and are at increased risk of colorectal, prostate, and some other cancers.
• RNASEL (formerly HPC1): The normal function of this tumor suppressor gene is to help cells die when something goes wrong inside them. Inherited mutations in this gene might let abnormal cells live longer than they should, which can lead to an increased risk of prostate cancer.
• HOXB13: This gene is important in the development of the prostate gland. Mutations in this gene have been linked to early-onset prostate cancer (prostate cancer diagnosed at a young age) that runs in some families. Fortunately, this mutation is rare.

ther inherited gene mutations may account for some hereditary prostate cancers, and research is being done to find these genes.

Acquired Gene Mutations

Some genes mutate during a person’s lifetime, and the mutation is not passed on to children. These changes are found only in cells that come from the original mutated cell. These are called acquired mutations. Most gene mutations related to prostate cancer seem to develop during a man’s life rather than having been inherited.

Every time a cell prepares to divide into 2 new cells, it must copy its DNA. This process isn’t perfect, and sometimes errors occur, leaving defective DNA in the new cell. It’s not clear how often these DNA changes might be random events, and how often they are influenced by other factors (such as diet, hormone levels, etc.). In general, the more quickly prostate cells grow and divide, the more chances there are for mutations to occur. Therefore, anything that speeds up this process may make prostate cancer more likely.

For example, androgens (male hormones), such as testosterone, promote prostate cell growth. Having higher levels of androgens might contribute to prostate cancer risk in some men.

Some research has found that men with high levels of another hormone, insulin-like growth factor-1 (IGF-1), are more likely to get prostate cancer. However, other studies have not found such a link. Further research is needed to make sense of these findings.

Can Prostate Cancer Be Prevented?

There is no sure way to prevent prostate cancer. Many risk factors such as age, race, and family history can’t be controlled.

Bodyweight, physical activity, and diet

The effects of body weight, physical activity, and diet on prostate cancer risk aren’t completely clear, but there are things you can do that might lower your risk.

Some studies have found that men who are overweight or obese have a higher risk of developing advanced prostate cancer or prostate cancer that is more likely to be fatal.

Although not all studies agree, several have found a higher risk of prostate cancer in men whose diets are high in dairy products and calcium.

For now, the best advice about diet and activity to possibly reduce the risk of prostate cancer is to:

• Get to and stay at a healthy weight.
• Keep physically active.
• Follow a healthy eating pattern, which includes a variety of colorful fruits and vegetables and whole grains, and avoids or limits red and processed meats, sugar-sweetened beverages, and highly processed foods.

It may also be sensible to limit calcium supplements and to not get too much calcium in the diet. (This does not mean that men who are being treated for prostate cancer should not take calcium supplements if their doctor recommends them.)

Vitamin, mineral, and other supplements

Vitamin, mineral, and other supplements

Vitamin E and selenium: Some early studies suggested that taking vitamin E or selenium supplements might lower prostate cancer risk.

But in a large study known as the Selenium and Vitamin E Cancer Prevention Trial (SELECT), neither vitamin E nor selenium supplements were found to lower prostate cancer risk. Men in the study taking the vitamin E supplements were later found to have a slightly higher risk of prostate cancer.

Soy and isoflavones: Some early research has suggested possible benefits from soy proteins (called isoflavones) in lowering prostate cancer risk. Several studies are now looking more closely at the possible effects of these proteins.

Taking any supplements can have both risks and benefits. Before starting vitamins or other supplements, talk with your doctor.

Medicines

Some drugs might help reduce the risk of prostate cancer.

5-alpha reductase inhibitors

5-alpha reductase is an enzyme in the body that changes testosterone into dihydrotestosterone (DHT), the main hormone that causes the prostate to grow. Drugs called 5-alpha reductase inhibitors, such as finasteride and dutasteride (block this enzyme from making DHT.

These drugs are used to treat benign prostatic hyperplasia (BPH), non-cancerous growth of the prostate.

Large studies of both of these drugs have been done to see if they might also be useful in lowering prostate cancer risk. In these studies, men taking either drug were less likely to develop prostate cancer after several years than men getting an inactive placebo.

When the results were looked at more closely, the men who took these drugs had fewer low-grade prostate cancers, but they had about the same (or a slightly higher) risk of higher-grade prostate cancers, which are more likely to grow and spread. Long term, it’s not clear if these drugs affect death rates, as men in these studies had similar survival whether or not they took one of these drugs.

These drugs can cause sexual side effects such as lowered sexual desire and erectile dysfunction (impotence), as well as the growth of breast tissue in some men. But they can help with urinary problems from BPH such as trouble urinating and leaking urine (incontinence).

Aspirin

Some research suggests that men who take a daily aspirin might have a lower risk of getting and dying from prostate cancer. But more research is needed to show if the possible benefits outweigh the risks. Long-term aspirin use can have side effects, including an increased risk of bleeding in the digestive tract. While aspirin can also have other health benefits, at this time most doctors don’t recommend taking it just to try to lower prostate cancer risk.

Spread to bones are very common in cases of prostate cancer. It is an advanced stage disease but all is not lost. The latest hormone manipulations and theranostics can take care of the metastases and help the patients lead a pain-free life. A five-year survival rate of 35