Improving the Risk–Benefit Ratio of Endocrine Therapy in Prostate Cancer

ContextUntil very recently, it was known that endocrine therapy could improve progression-free survival but few studies could demonstrate a survival advantage in patients treated with early endocrine therapy.ObjectivesTo summarise indications and outcomes of endocrine therapy in prostate cancer and to review the different ways of reducing side-effects from this treatment modality.Evidence acquisitionSeveral randomised and nonrandomised clinical trials that deal with endocrine therapy for prostate cancer, its benefits, and its side-effects and that were published in the English literature were reviewed.Evidence synthesisAdjuvant endocrine therapy after local therapy for localised prostate cancer (T1-2 N0 M0) offers no survival advantage and has many side-effects. Treatment of locally advanced prostate cancer (T3-4 N0 M0, T1-4 N1 M0) with early androgen deprivation only has also been shown not to be superior to deferred androgen deprivation in either overall or prostate cancer-specific survival. In locally advanced prostate cancer, either radical prostatectomy or radiotherapy must be included to gain benefits from early androgen deprivation. Patients with prostate-specific antigen (PSA) relapse after local therapy for localised prostate cancer constitute a very specific group. PSA doubling time and tumour differentiation offer the opportunity to select different patient subgroups for endocrine therapy. In short-term analyses, intermittent androgen suppression seems to have fewer side-effects with equal effectiveness in cancer control; however, there are no data for either overall or prostate cancer–specific survival. Some side-effects of prolonged androgen suppression can be prevented with adjuvant medication. Biphosphonates have been demonstrated to prevent bone loss, while oestrogen receptor modulators, such as toremifene citrate, seem to alleviate side-effects such as bone metabolism, altered lipid profile, and hot flushes.ConclusionsEndocrine therapy is indicated in specific patient subgroups. Treatment strategies and adjuvant medication help to diminish treatment-associated toxicity.