Understanding Metastatic Prostate Cancer

By Prof Shingai Mutambirwa
Head of Urology at Sefako Makgatho Health Sciences University
Chairman of the academic committee of the South African Urological Association
Head of the Medical and Scientific Advisory Board of The Prostate Cancer Foundation of South Africa.

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 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 with the 5 year cancer specific survival for men diagnosed with metastatic prostate cancer hovering between 30 – 40%.

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

Treatment for metastatic prostate cancer is aimed at slowing the progression of the disease. The standard initial treatment of metastatic prostate cancer 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 2 years and the cancer will start to progress again. This is called castrate resistant prostate cancer (CRPC).

Prostate cancer most commonly spreads (metastasises) to bone. Other sites that are typically affected are distant lymph nodes, the liver and the lungs. In reality, prostate cancer can spread to any organ in the body but this is rare and occurs in <5% of patients.

How metastatic prostate cancer is staged

The staging of cancer is a way of recording how far the cancer has progressed. The TNM staging system is used:
T describes the primary tumour and how far it has spread
N describes whether or not the cancer has spread to regional lymph nodes
M describes evidence of metastatic prostate cancer

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 blood stream 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.

Prostate cancer tends to spread to regional lymph nodes in the pelvic area first. This is indicated as N1 and it is not classified as metastatic disease and has a better prognosis.
If prostate cancer spreads to lymph nodes outside the pelvic area (distant lymph nodes) it is classified as one of the sites for distant metastases and this is indicated as M1a.

Bone Metastases

Prostate cancer cells have a strong affinity to spread to bone which is the most common metastatic site. Prostate cancer 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 types of interaction cause bone weakness and potential fractures.
The presence of bone metastases is indicated as M1b and the bone tumours can cause pain and fractures.

Non-lymph node visceral metastases

When prostate cancer spreads to soft tissue organs other than the lymph nodes these growths are called visceral metastases.
They are indicated as M1c.
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 prostate cancer. Most men (76%) that develop lung and liver metastases already have bone metastases.
Less common visceral metastatic sites include the brain/meninges, the thyroid gland, adrenal glands, peritoneum, gastrointestinal tract (stomach and intestine), 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 in not curable there are numerous therapies including chemotherapy, advanced ADT, genetic therapies and targeted therapies often involving radiation.
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 treating teams 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.

References

Coetzee L. Metastatic Prostate Cancer. Health Press Limited 2017.
Gandaglia G et al. Distribution of Metastatic Sites in Patients with Prostate Cancer: A Population-Based Analysis. Prostate 74:210–216, 2014.
Barbosa FG et al. Revisiting prostate cancer recurrence with PSMA PET: Atlas of typical and atypical patterns of spread. Radiographics 2019; 39:186-212
AJCC Cancer Staging Handbook. Seventh Edition. Springer 2010
Douketis JD. Overview of the Lymphatic System. Merck Manual. Consumer Version. Available at: https://www.merckmanuals.com/home/SearchResults?query=lymphatic+system. (Accessed on 5th July 2016).
Wong SK et al. Prostate Cancer and Bone Metastases: The Underlying Mechanisms. Int. J. Mol. Sci. 2019, 20(10), 2587
Klaassen Z., The Impact of Visceral Metastasis in Prostate Cancer Patients. Available at: https://www.urotoday.com/library-resources/mcrpc-treatment/111525-the-impact-of-visceral-metastasis-in-prostate-cancer-patients.html
Kirby RS, Patel I. Fast Facts: Prostate Cancer. Eighth edition. Health Press Limited. Jan 2014.