Starting androgen deprivation therapy (ADT) to treat advanced prostate cancer is usually the start of a long treatment period that will continue for many years, actually until you die. Since our goal in cancer treatment is to make cancer a chronic illness and since prostate cancer does progress for most men in a relatively slow process it is time that we stop ignoring the sometimes horrendous side effects of ADT. The time has come for us to acknowledge these side effects and start to find ways to help mitigate them.
Currently, doctors acknowledge that these side effects exist, but they don’t do anything about them. The messages are clear, just deal with them, specifically deal with them on your own. Doctors do sometimes suggest that we exercise, using weight-bearing exercises and they do suggest that we modify our diet. But most hospitals and doctor practices do not help us accomplish these goals.
My first round of ADT brought about a weight gain of 50 pounds, when I asked my oncologist for nutrition help, specifically a referral to a nutritionist I was told that the Department did not have a nutritionist (this was Columbia University Hospital in New York City – really, no nutritionist at a major hospital center in their prostate cancer treatment department!).
Side effects of ADT should be anticipated, screened for and then mitigated. I don’t know how to do this, but it seems that we should be creating a multi-disciplinary team to deal with ADT side effects. This team should consist of an endocrinologist, a cardiologist, a geriatrician, a dietician, an exercise physiologist, and a psychologist. I know, I like to dream, but why not?
The concept of treating ADT side effects is not a foreign concept I am pulling out of my hat. A recent clinical trial by Cormie et al. is an example of successful exercise intervention in men starting ADT. In appropriately selected men who are able to tolerate a moderate intensity exercise program, the authors demonstrated improvements in lean body weight, cardiovascular fitness, muscle strength, cholesterol profile, sexual function, fatigue, and psychological status.
Positive effects on men on ADT not only include potential cardiovascular and bone health benefits, but also there is growing epidemiological and clinical trials data that associates metabolic syndrome with an adverse prostate cancer outcome. The presence of elevated C-peptide (a surrogate marker of hyper-insulinaemia) prior to treatment with ADT was associated with significantly shorter time to development of castrate resistance CRPC (16 vs 36 months).Further, men with the highest Insulin-like growth factor -1 (IGF-1)/insulin-like growth factor binding protein-1 (IGFBP-1) ratio compared to those in the lowest tertile after 3 months of ADT had a significant reduction in time to progression to CRPC in a recent retrospective study (12.4 months vs 21.9 months). It is highly ironic that while ADT remains an essential strategy in managing both localized and metastatic prostate cancer, ADT is also a potent trigger for the development and exacerbation of metabolic syndrome. In turn, such adverse effects can be the cause of cardiovascular death and potentially the early development of CRPC.
We continue ADT during the entire prostate cancer treatment journey, so why don’t we take a more active interest in helping men deal with the negative side effects they are destined to have? Not dealing with these side effects is simply cruel and unusual punishment for having prostate cancer.
1. Cormie, P., et al., Can Supervised Exercise Prevent Treatment Toxicity in Prostate Cancer Patients Initiating Androgen Deprivation Therapy: A Randomised Controlled Trial. BJU Int, 2014.
2. Flanagan, J., et al., Presence of the metabolic syndrome is associated with shorter time to castration-resistant prostate cancer.Ann Oncol, 2011. 22(4): p. 801-7.
3. Sharma, J., et al., Elevated insulin-like growth factor binding protein-1 (IGFBP-1) in men with metastatic prostate cancer starting androgen deprivation therapy (ADT) is associated with shorter time to castration resistance and overall survival.Prostate, 2014. 74(3): p. 225-34.
4. Levine, G.N., et al., Androgen-deprivation therapy in prostate cancer and cardiovascular risk: a science advisory from the American Heart Association, American Cancer Society, and American Urological Association: endorsed by the American Society for Radiation Oncology. Circulation, 2010. 121(6): p. 833-40.
Joel T. Nowak, M.A., M.S.W.