Should there be “T” under the tree?

I love it when the great mysteries of life laugh at us mortals trying to make sense of things. Here’s one: Prostate cancer develops in 90% of men as they get old. Prostate cancer “feeds” on testosterone. Testosterone levels drop significantly as men age. Figure that one out, and I’ll chip in on your tickets to Stockholm.

Most of the fine advances (notably enzalutamide and abiraterone) made in treating advanced prostate cancer in the past 2 years have to do with what I have called “androgen receptor addiction“. It is a relatively simple idea: starve the tumor of its major growth stimulus, and just as a plant wilts when it doesn’t have enough water, the tumors shrink and die. This works so well, that unlike breast cancer where only 50% or so of women respond to anti-estrogen responses, more than 90% of men respond to ADT (androgen deprivation therapy).

Maybe we could use this to make our treatments more effective. Over and over, medical oncologists (including this one) have tried the idea of stimulating the cancer cells by giving testosterone to make the cells become active, and then hit them with one or more drugs that are most toxic to dividing cells. We tried and failed to make this work in the 1980’s as you can read here. Our colleagues at Sloan Kettering have even tried to use high doses of T alone to treat prostate cancer. Unfortunately, none of these approaches seem to work.

But what about men who (like their non-cancer brothers) have declining testosterone, weight gain, muscle loss, impotence, loss of libido, and all of the other things the ads tell us can be made better by testosterone replacement therapy? They have no prostate, or one that has been radiated, and their PSA is either low or undetectable. How safe would it be for them to take T? The truth is that we simply don’t know what the effects and risks of T replacement would be. In a current review from Medscape, the authors have presented a table of all of the very small, generally uncontrolled trials of T replacement in prostate cancer patients.

Interestingly, relatively few men experience biochemical relapse upon starting T replacement. Further, some studies show that men with the lowest levels of T prior to being diagnosed are the ones that have the highest Gleason scores. Maybe T could even be protective against developing prostate cancer or against it becoming more aggressive. As one lecturer put it, “if you give back water to the plant and it isn’t dead, it perks up and grows again, but it doesn’t keep growing to be come a tree…”

Like most oncologists, I have been very conservative in thinking about T-replacement in prostate cancer patients. In the one or two men who insisted and seemed well-informed, things are going well. So if you feel weak, down, unhappy, there is always something to ask Santa for: Testosterone. Not if you have advanced disease, and not if you are hoping for world peace however! I wish you all a Merry Christmas, Happy Holidays, and a peaceful new year.