Prostate Cancer

Based on the type of cell in which cancer starts, prostate cancer can be of the following types.

1. Adenocarcinoma: Cancer that develops in the tubes (ducts) and gland cells lining the prostate gland is known as adenocarcinoma. It is the most common type of prostate cancer.

2. Transitional cell carcinoma: Transitional cell carcinoma of the prostate gland starts in the cells lining the tube carrying urine to the outside of the body (urethra). It is sometimes called as urothelial carcinoma of the prostate.

3. Squamous cell carcinoma: These cancers start in the flat cells that cover the prostate gland. They typically grow and spread more quickly than adenocarcinoma of the prostate.

4. Small cell prostate cancer: It is a type of neuroendocrine cancer. They usually grow more quickly than other types of prostate cancer.

5. Others: Other rare types of prostate cancers can develop in the prostate gland, such as sarcoma (tumour arising in tissues such as connective tissue, bone, cartilage, or striated muscle) and lymphoma (tumour of the lymphoid tissue).

Doctors may also classify prostate cancer as early-stage or advanced-stage cancer.

In early-stage prostate cancer, the cancer cells have not spread beyond the prostate gland. It usually grows very slowly. At this stage, the cancer is called localized prostate cancer. When the cancer spreads beyond the prostate gland to other areas of the body, such as liver, lungs, bones, lymph nodes, etc., it is called advanced-stage prostate cancer. This spread is called metastatic prostate cancer. Some men have already advanced-stage prostate cancer when their cancer is diagnosed, while others develop advanced-stage cancer.

The reason that some people get prostate cancer is not completely clear. In general, prostate cancer is caused by changes in the genetic material (DNA) of cells of the prostate gland. However, some factors are known to increase the chance of a person developing this disease called ‘risk factors’. Having a risk factor does not mean that you will get the disease, but the more risk factors you have can make it more likely. Some risk factors for prostate cancer are:

• Age: Age is the most important risk factor for prostate cancer. The chances of getting prostate cancer increase as you age. Most prostate cancers are detected in persons aged more than 65 years.
• Race/ Ethnicity: Prostate cancer is more common in Black men than White men and less common in Asian men.
• Family history: Men with an immediate blood relative, such as a father or a brother, who has had prostate cancer, are more likely to develop the disease.
• Hormones: People with high levels of a hormone called insulin like growth factor 1 (IGF-1), have a higher risk of developing prostate cancer.
• Genetic changes: Certain genes have been known to elevate the risk of developing prostate cancer, such as BRCA1 and BRCA2 genes.
• Diet and Obesity: A diet high in saturated fat, as well as being overweight increases the risk of prostate cancer.
• Lynch syndrome: Men with Lynch syndrome, a genetic condition, have a greater risk of developing a number of cancers, including prostate cancer.
• Chemical exposure: High level of pesticide exposure may increase the risk of prostate cancer.

If your doctor thinks you might have prostate cancer, they will ask questions about your symptoms, family history, conduct a physical exam, run certain tests, or might refer you to a urologist, a doctor who deals with cancers of the genital and urinary tract. The main tests for the diagnosis of prostate cancer include:

• Digital rectal exam (DRE): In this test, the doctor inserts a gloved, lubricated finger into your rectum and feels for any bumps or hard areas on the prostate gland that might be cancer.
• PSA Blood test: It is the primary method of testing for prostate cancer. Prostate specific antigen (PSA), a protein, is measured in the blood. PSA levels are generally higher in individuals with prostate cancer compared to those without this condition. Men with a PSA level between 4-10 ng/mL have about 25% chance of having prostate cancer. If the PSA levels are more than 10 ng/mL, the chance of having prostate cancer is >50%. Further testing needs to be done if your PSA levels are high.
• Prostate biopsy: You might need a prostate biopsy if the results of a PSA blood test, DRE, or other tests indicate that you may have prostate cancer. During a prostate biopsy, a local anaesthetic is used to numb the area around the prostate gland. Then, a thin hollow needle is inserted into the prostate gland, either through the wall of the rectum (a transrectal biopsy) or through the skin between the scrotum and the anus (transperineal biopsy), to obtain small samples of the prostate gland tissue. These samples are examined under a microscope to look for the presence of cancer cells. If cancer cells are present, a pathologist will grade the cancer using the Gleason score or Grading Group.
• Genetic testing: There are numerous known cancer-susceptibility genes that have been linked to an increased risk of developing prostate cancer, such as BRCA1, BRCA2, MLH1, MSH2, MSH6, PMS2, PALB2, HOXB13, CHEK2, NBN, BRIP1, and ATM. Your doctor might advise genetic testing for prostate cancer to look for specific hereditary gene alterations.
• Imaging tests: They are used to determine the spread of the tumour in the prostate gland, to help the doctor see the prostate gland during certain procedures, or to know the extent of spread of the cancer to other parts of the body. Most commonly used imaging tests in people with prostate cancer are transrectal ultrasound (TRUS), magnetic resonance imaging (MRI), bone scan, positron emission tomography (PET) scan, and computed tomography (CT) scan.

The stage of prostate cancer describes the size and spread of the cancer into the nearby tissues and/or around the body. This can help doctors decide how best to treat the disease and the likelihood of reaching a remission (disease-free period). The Tumour, Node, Metastasis (TNM) staging is used for the staging of the majority of cancers, including prostate cancer.

• Tumour (T): It describes the size of the cancer.
• Node (N): It describes whether the cancer has spread to the nearby lymph nodes.
• Metastasis (M): It describes whether the cancer has spread to other parts of the body.

Gleason score, also known as Grade Group, is used to grade the risk of prostate cancer getting worse and planning the treatment phase. The grade of your prostate cancer describes how quickly the cancer is likely to grow and spread around the body based on how much the cancer cells look like normal cells. There are five Grade Groups, 1 being the least aggressive and 5 being the most aggressive.

• Grade Group 1 – The cells look similar to normal prostate cells and the cancer is likely to grow very slowly, if at all.
• Grade Group 2 – Most of the cancer cells look similar to normal prostate cells and the cancer is likely to grow slowly.
• Grade Group 3 – The cells look less like normal prostate cells and the cancer is likely to grow at a moderate rate.
• Grade Group 4 – Some of the cells look abnormal and the cancer might grow quickly or at a moderate rate.
• Grade Group 5 – The cells look very abnormal. The cancer is likely to grow quickly.

Treatment of prostate cancer depends on a number of factors including the size, type, stage, and spread of cancer to other parts of the body. Persons whose cancer is detected in its early stage are more likely to live longer. Treatments for advanced-stage prostate cancer can be complex and may involve several approaches such as, hormone therapy, chemotherapy, immunotherapy, surgery, radiation therapy, and targeted therapy. Treatments for prostate cancer include:

• Observation or Active Surveillance: If your cancer is likely to grow very slowly, your doctor may not recommend any treatment. Instead, you could decide to wait to see if any symptoms appear in one of the following ways.

1. Watchful waiting (observation) is recommended for older persons who are likely to live for 10 years or less. No tests are done, but patients are told to be watchful of any changes occurring in their symptoms.

2. Active surveillance means periodic monitoring of the prostate cancer by testing the PSA levels, DRE, biopsies, and imaging tests. Active surveillance is recommended for men with low-risk prostate cancer. Cancer treatment is started only when there is a change in the test results.

• Surgery: Surgical removal of prostate cancer is advised when the cancer has not spread outside of the prostate gland. Removal of the prostate gland is known as prostatectomy. Radical prostatectomy involves removal of entire prostate gland and some surrounding tissue.
• Radiation therapy: High-energy rays or particles are used to kill or shrink cancer cells. Radiation therapy may be used as the first treatment for low grade cancers that are within the prostate gland as well as for cancers that have grown outside the gland. It is also used in cases where cancer was not completely removed or comes back after surgery. In advanced cancers, it is used to keep the cancer under control. Radiation therapy is considered less invasive than surgery. The main types of radiation therapy are

1. External beam radiation: A machine outside the body delivers radiation at the site of cancer.

2. Brachytherapy: Small seeds or pellets are surgically placed at the site of cancer that emit radiation.

3. Radiopharmaceuticals: These medicines are injected into a vein, allowing them to travel throughout the body via the bloodstream, finding and killing cancer cells.

• Hormone therapy: Male sexual hormones are called androgens and testosterone is one of the main types of androgens. Hormone therapy also called Androgen Deprivation Therapy (ADT), works by stopping the production of androgen in your body or by blocking cancer cells from using the hormones they need to grow. Lowering the levels of male hormones or preventing them from entering into the prostate cancer cells leads to shrinkage of the tumour or hampers the tumour growth. ADT can sometimes be added with corticosteroids and can be combined to chemotherapy and radiation therapy.
• Chemotherapy: It involves the use of special drugs to damage rapidly dividing cells throughout the body. They may be injected into a vein or given by mouth. These drugs travel through the bloodstream to reach cancer cells that have spread to other parts of the body. However, chemotherapy may damage even the healthy cells causing side effects.
• Targeted therapy: By identifying specific molecular biomarkers, such as BRCA1, BRCA2, and other genes, targeted drugs can be used to specifically target these biomarkers. PARP inhibitors are a class of drugs that block the PARP proteins involved in the repair of damaged DNA. By blocking the PARP proteins, these drugs make it very hard for the BRCA gene to repair damaged DNA, leading to the death of these cancer cells.
• Immunotherapy: It involves the use of drugs to stimulate the body's immune system to recognize and kill cancer cells more effectively. People whose prostate cancer cells have tested positive for specific gene changes, may be prescribed immunotherapy drugs such as checkpoint inhibitors. These drugs are used when cancer comes back even after chemotherapy, to treat cancer that cannot be removed with surgery, or has spread to other parts of the body. Cancer vaccines are another type of immunotherapy where the body’s own immune system is supercharged and stimulated to locate and destroy the cancer cells.

When prostate cancer spreads to the bone, it can cause fractures, spinal cord compression, high blood calcium levels, etc. Drugs such as bisphosphonates work by slowing down or stopping bone breakdown.

Always speak to your doctor about the various treatment options available and their associated side effects.

Clinical trials (which can also be called ‘research studies’) are designed to look at how safe experimental drugs or procedures (such as new types of surgery) are and how well they work. Researchers are working hard to learn more about prostate cancer, and the cellular and molecular mechanisms involved.

As researchers learn more about prostate cancer, clinical trials will be set up to look at potential new treatments. If you would like to know more about Roche sponsored clinical trials or are interested in taking part in a clinical trial, speak to your doctor or visit the Roche ForPatients clinical trials page link.