Locally advanced prostate cancer: effective treatments, but many adverse effects.

Locally advanced prostate tumours, i.e. those that extend beyond the prostate gland but are not metastatic, often carry a poor prognosis: between 10% and 40% of patients die within 5 years after diagnosis. Various treatments are proposed to improve their prognosis. Which treatments have a proven survival benefit, and what are their adverse effects? To answer these questions, we reviewed the literature using the standard Prescrire methodology. Prostatectomy has not been evaluated in controlled trials versus either watchful waiting or radiation therapy alone. Prostatectomy is mainly proposed to patients who are in good general health. Five years after prostatectomy, mortality from prostate cancer is between 2% and 16%, depending on the study.Three-quarters of patients who have surgery at this stage experience erectile dysfunction, and at least 20% of patients develop urinary incontinence. External beam radiation therapy alone has not been compared with watchful waiting or prostatectomy. External beam radiation therapy has documented benefits in patients with locally advanced prostate cancer treated with gonadorelin agonists, preventing 8 to 10 deaths from all causes after 7 to 10 years of follow-up among 100 treated patients. However, about 60% of patients experience erectile dysfunction, about 15% symptomatic radiation proctitis, and about 5% urinary incontinence. When combined with prostatectomy, radiation therapy did not affect the 5-year survival rate but prolonged survival by about 2 years in a trial with more than 10 years of follow-up. When used without concomitant androgen suppression, antiandrogens have no proven impact on overall survival in patients with locally advanced prostate cancer. In the absence of radical prostatectomy or radiation therapy, androgen suppression, by means of orchiectomy or gonadorelin agonist, has a minimal impact on overall survival among patients with locally advanced cancer. In one randomised trial, androgen suppression in combination with prostatectomy prolonged median survival by about 2.5 years among patients with lymph node involvement. In another randomised trial, treatment with a gonadorelin agonist and flutamide for 6 months, started before radiation therapy, reduced the 10-year overall mortality rate to 29%, versus 43% after radiation therapy alone. Androgen suppression for at least 3 years after radiation therapy prevented 10 to 18 deaths from all causes per 100 patients during 10 to 15 years of follow-up in three randomised trials that provided similar results. Shorter durations of treatment appeared to be less effective in 3 other randomised controlled trials. The adverse effects of gonadorelin agonists often undermine patients' quality of life, due to hot flushes, loss of libido, erectile dysfunction, gynaecomastia, osteoporosis, weight gain, cardiovascular events, and diabetes. In mid-2012, European clinical practice guidelines recommend a combination of radiation therapy and androgen suppression for 2 to 3 years for most patients with locally advanced prostate cancer. Before choosing between therapeutic options, it is crucial to take into account the patient's priorities in terms of treatment efficacy and adverse effects, and reversibility of adverse effects.