Metastatic prostate cancer

Prof Shingai Mutambirwa gives us a better notion of what metastatic prostate cancer is and the outcomes of the various metastases.

What is metastatic prostate cancer?

When cancer cells from the prostate enter the blood and lymph vessels and travel to other parts of the body where they re-implant and grow to form secondary tumours or metastases, this is called metastatic prostate cancer or Stage IV. 

At this advanced stage, the cancer is unfortunately no longer curable but can be contained for a period on appropriate therapies. The 5-year cancer specific survival for men diagnosed with metastatic prostate cancer hovers between 30-40%. 

Various studies have shown that men who present with prostate cancer (PC) symptoms at South African public hospitals often have advanced disease. This may be due to a lack of awareness about age-appropriate screening; a lack of access to screening; or a lack of awareness of PC itself. Awareness and screening is important as early stage prostate cancer, which almost exclusively can only be found by screening, is curable in up to 95% of men.

Treatments goals

The standard initial treatment is known as androgen deprivation therapy (ADT) and involves removing testosterone from the body to slow the progression of the disease. 

Unfortunately, most advanced prostate cancers treated with ADT will eventually become resistant to the treatment after about two years and the cancer will start to progress again. This is called castrate resistant prostate cancer (CRPC). 

PC most commonly spreads to bone. Other sites that are typically affected are distant lymph nodes, liver and lungs. It can spread to any organ in the body but this is rare and occurs in <5% of patients.

Involvement of lymph nodes 

The lymphatic system consists of lymph vessels, lymph nodes and two collecting ducts and is part of the body’s immune system. The lymph vessels carry lymph fluid, which contains nutrients and other substances, which are returned via drainage into the bloodstream to circulate back to the rest of the body. Lymph vessels also remove and transport damaged cells, cancer cells, bacteria and viruses that drain from tissue. These are then filtered out when the lymph fluid travels through the lymph nodes.

PC tends to spread to regional lymph nodes in the pelvic area first. This isn’t classified as metastatic disease and has a better prognosis.

If PC spreads to lymph nodes outside the pelvic area (distant lymph nodes), it’s classified as one of the sites for distant metastases. 

Bone metastases 

PC cells have a strong affinity to spread to bone. PC cells tend to spread first to the lower spine and pelvic bone and then up the spine and to the ribs.

The cancer cells interact with the different types of bone cells. Most commonly the interaction is with the bone’s ‘builder cells’ (osteoblasts), resulting in an abnormal build-up of bone. Less commonly the interaction is with the bone’s ‘demolisher cells’ (osteoclasts), resulting in soft sections of damaged bone. Both cause bone weakness, potential fractures and pain.

Non-lymph node visceral metastases

When PC spreads to soft tissue organs other than the lymph nodes, these growths are called visceral metastases.

Men with visceral metastases generally have a worse outcome than men who only have bone metastases. Typical visceral metastatic sites are the lungs and liver which are generally affected in the late stages of PC. 

Most men (76%) that develop lung and liver metastases already have bone metastases. 

Less common visceral metastatic sites include the brain/meninges, thyroid gland, adrenal glands, peritoneum, gastrointestinal tract, urinary tract, ureter, urethra and kidneys, spleen or pancreas. 

Men with liver metastases tend to have the worst survival outcome compared to men with bone metastases or other sites of visceral metastases.

Prognosis

Though metastatic prostate cancer isn’t curable, there are numerous therapies including chemotherapy, advanced ADT, genetic therapies and targeted therapies, often involving radiation, that can contain it.

General health measures, such as exercise and not smoking, also contribute to prolongation of survival. Bone, heart and mental health also need to be addressed and should be a part of both patient and the treating team’s goals.

In addition, other first-degree family members may have an increased risk of developing cancers, particularly breast and prostate and so should be advised for earlier screening at some stage.