Two studies coming out of Cleveland Clinic are suggesting that men who have a testosterone-related genetic abnormality would have an advantage from receiving a personalized treatment plan targeting the specific hormonal pathways.

“This is very exciting news for prostate cancer treatment and for the men who are diagnosed with this disease,” exclaimed Dr. David Samadi.  “The studies are stating that men who have inherited this particular variant would be helped a great deal by being able to personalize their treatment specifically for them helping fight their prostate cancer more aggressively.”

Both studies have been published in the October 12 issue of the Journal of the American Medical Association Oncology. 

“A reason this research was conducted is because if prostate cancer returns, a treatment can be androgen deprivation therapy (ADT),” explained Dr. Samadi.   “ADT is used to block the prostate cancer’s supply of testosterone in the testes.  In order to grow, prostate cancer cells usually require androgen hormones, such as testosterone.  ADT therapy, which could involve either the use of medications or surgery, reduces the levels of androgen hormones like testosterone to prevent the prostate cancer cells from growing.”

ADT therapy is considered a cornerstone treatment method for recurrent prostate cancer.  However, after a while, it can stop working which then can result in the cancer to pick up speed causing it to grow and spread.  But a discovery the research team made was that prostate cancer cells with a genetic abnormality survive ADT by producing their own androgens.  This genetic abnormality is HSD3B1 (1245C). 

The two studies looked at two different prostate cancer patient populations. In the first study, 213 men were analyzed whose prostate cancer had recurred after radiation therapy and then underwent ADT.  What was discovered was for the first time following radiation and ADT, prostate cancer was much more likely to spread rapidly in men who had the HSD3B1(1245C) variant. 

“The second study looked at 90 men with metastatic cancer which was no longer responding to ADT,” said Dr. Samadi.  “A drug called ketoconazole was given to these men which blocks the production of androgens outside of the testes.  This is when another discovery was made in that men with the genetic variant did better on ketoconazole then the men who did not have the genetic variant.  This led the researchers to hypothesize that the reason why men with the genetic anomaly of HSD3B1(1245C) became resistant to ADT was because they had tumors with a backup supply of androgens.   This is where ketoconazole comes in.  When ketoconazole was used to directly target the backup supply of androgens in these men, it was found to be successful at blocking these androgens from being made keeping the cancer from spreading and thus offering a better chance of survival.”

Earlier studies have also found that the use of HSD3B1(1245C) as a predictive biomarker is useful for helping doctors to make important treatment decisions.  Men who have this gene variant often have a poor outlook but these studies do offer hope for new treatment strategies for these men.

These same studies can also spur on other studies to research other next generation androgen inhibitors such as abiraterone and enzalutamide. 

“Personalized medicine is the wave of the future,” said Dr. Samadi.  “When we can make medicine specific for each individual that is when we can really see much more effective treatments for prostate cancer.  Being aware of men with specific testosterone-related genetic abnormalities can guide us as physicians to personalize their therapy to be aggressive about getting the best outcome possible for each man with prostate cancer.”

Patients newly diagnosed with prostate cancer can contact world renowned prostate cancer surgeon and urologic oncologist, Dr. David Samadi, for a free phone consultation and to learn more about prostate cancer risk, call 212-365-5000.