Lethal Metastatic Prostate Cancer May Spread from Other Sites

What You Need to Know: Multiple targeted therapies may be needed to combat metastatic prostate cancer because metastasis may be spread from multiple tumor clones according to a new study. “{The findings} are eye-opening,” said study investigator William Isaacs, PhD, who is a professor of urology at the Johns Hopkins Brady Urological Institute and a member of The Johns Hopkins Kimmel Cancer Center in Baltimore, MD. “It emphasizes the aspects that these cancers are evolving at an almost continual rate.”

The Study: Using whole-genome sequencing, Dr. Isaacs and colleagues characterized multiple metastases arising from prostate tumors in 10 men with metastatic castration-resistant prostate cancer (mCRPC). The team analyzed the subclonal architecture of prostate cancer cells and found that:

•  Metastasis-to-metastasis spread was found to be common through de novo monoclonal seeding of daughter metastases.
• Researchers found a transfer of multiple tumor clones between metastatic sites in 5 of the 10 patients.

The researchers believe that a new view of mCRPC is now emerging that tumor cells share a common heritage but subclones develop metastatic potential. The data suggest clonal diversification may occur in part as a necessity to bypass androgen deprivation therapy (ADT) and subsequently drive distinct subclones onto a convergent path of therapeutic resistance.

My Take: Whole-genome sequencing on the samples showed that even though a single cell begins the metastatic process, the disease becomes very heterogeneous as it spreads throughout the body over time. These new findings support the notion that treatments for metastatic cancers should include a combination of therapies that target a variety of genetic pathways.  The idea that metastatic tumors can seed and establish other metastatic tumors in patients is different from traditional theories that the primary tumor is solely responsible for disseminating cancer cells with metastatic potential. To me, this work is beautiful, pointing to a new way to see and manage metastatic cancer. I’m Dr. Michael Hunter.

Reference: Gundem G, Van Loo P, Kremeyer B, et al. The evolutionary history of lethal metastatic prostate cancer. Nature. 2015;520(7547):353-357.

Why Does Exercise Improve Prostate Cancer Out

In this blog, we have discussed the fact that exercise improves prostate cancer outcomes. But why?

Men who walked at a fast pace prior to a prostate cancer diagnosis had more regularly shaped blood vessels in their prostate tumors compared with men who walked slowly, providing a potential explanation for why exercise is linked to improved outcomes for men with prostate cancer. These results were presented at the American Association for Cancer Research (AACR)-Prostate Cancer Foundation Conference on Advances in Prostate Cancer Research, January 18-21, 2014, in San Diego, California.

Men who engage in higher levels of physical activity have been reported to have a lower risk of prostate cancer recurrence and mortality compared with men who participate in little or no physical activity. The biological mechanisms underlying this association are not known.

“Prior research has shown that men with prostate tumors containing more regularly shaped blood vessels have a more favorable prognosis compared with men with prostate tumors containing mostly irregularly shaped blood vessels,” said Erin Van Blarigan, ScD, of the University of California, San Francisco. “In this study, we found that men who reported walking at a brisk pace had more regularly shaped blood vessels in their prostate tumors compared with men who reported walking at a less brisk pace.

“Our findings suggest a possible mechanism by which exercise may improve outcomes in men with prostate cancer;” continued Van Blarigan. Although more data from randomized trials are needed, the study supports the growing evidence of the benefits of exercise, such as brisk walking, for men with prostate cancer.

The Health Professionals Follow-up Study, which was initiated in 1986, enables researchers to examine how nutritional and lifestyle factors affect the incidence of serious illnesses, such as cancer and heart disease. Every 2 years, participants receive questionnaires that ask about diseases and health-related topics like smoking, physical activity, and medications taken. Questionnaires that ask detailed dietary information are administered every 4 years.

Van Blarigan and colleagues investigated whether prediagnostic physical activity was associated with prostate tumor blood vessel regularity among 572 men enrolled in the Health Professionals Follow-up Study. Prediagnostic physical activity was determined through analysis of questionnaire answers. Blood vessel regularity was established by semiautomated image analysis of the tumor samples. Blood vessels that are perfect circles are considered the ideal shape.

The researchers found that men with the fastest walking pace (3.3 to 4.5 miles per hour) prior to diagnosis had 8% more regularly shaped blood vessels compared with men with the slowest walking pace (1.5 to 2.5 miles per hour).

“Our study, which provides a potential explanation by which exercise may improve outcomes in men with prostate cancer, highlights the value of multidisciplinary collaborations between laboratory, clinical, and population scientists to explore new pathways by which lifestyle factors or other exposures may affect disease,” said Van Blarigan. “It is reasonable to hypothesize that the same explanation could exist for the beneficial effects of exercise in other cancers, and it would be interesting to examine this in future studies.”

I’m Dr. Michael Hunter.

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

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