Duration of testosterone suppression and the risk of death from prostate cancer in men treated with radiation and 6 months of hormone therapy

We would like to thank Dr. D'Amico and his coauthors for elucidating a link between duration of androgen suppression after hormone therapy and risk of death from prostate cancer.1 Although all men in their study received 6 months of hormone therapy, a prolonged physiological effect from hormone therapy predicted improved prostate-cancer–specific survival. This is analogous to data from literature on breast cancer and hormone therapy. Tamoxifen is metabolized to endoxifen, which may be tamoxifen's most active metabolite, on the basis of individual cytochrome activity. In women who are prescribed equal doses of tamoxifen, individual rates of metabolism to endoxifen are predictive of relapse risk.2 In both of these studies, clinical outcome depended on individual exposure to the intended “agent” (estrogen blockade or testosterone blockade) rather than on the dose and duration of the prescription. The phenomenon of prolonged androgen suppression after cessation of hormone therapy in a cohort of patients from our institution was previously reported in Cancer.3 In that study, we demonstrated that factors associated with prolonged androgen suppression included advanced age, low baseline testosterone, and use of 3-month luteinizing-hormone–releasing hormone agonists (LHRH-a), compared to 1-month LHRH-a. In response to the current article by D'Amico et al, we analyzed outcomes—disease-specific survival and overall survival—for the same cohort that we have described previously.3 Prognostic factors including age, prostate-specific antigen (PSA), stage, Gleason score, radiotherapy dose, treatment year, hormone therapy duration, and androgen suppression duration (with recovery defined as 5 nmol/L testosterone) were examined by using Cox univariate and multivariate analyses. In the cohort as a whole, androgen-suppression duration after the end of hormone therapy was not predictive of outcomes. However, in men with Gleason scores of 8–10, androgen-suppression duration was the only predictor of disease-specific survival (hazard ratio [HR], 0.89 per month of androgen suppression; P = .035), and androgen-suppression duration showed a trend toward prediction of overall survival (HR, 0.93 per month of androgen suppression; P = .06). In contrast, hormone therapy duration did not predict either outcome. These results support findings by D'Amico and colleagues. D'Amico et al's article has drawn attention to the fact that as oncologists, we should endeavor to go beyond universally prescribed doses of hormonal agents. Further research should attempt to titrate these drugs to achieve the necessary effect in our patients, to maximize benefit, and to simultaneously minimize exposure to adverse effects. David Palma MD*, Tom Pickles MD*, * Radiation Oncology Program, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.

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