Prostate Cancer: When the Hormonal Treatment Is No Longer Working

BackgroundThe hormone-refractory status is defined in a confirmed castrated man (who stopped any antiandrogen 6 wk earlier) by three consecutive prostate-specific antigen (PSA) increases above the nadir, reaching at least more than 50% of the nadir.Recent FindingsIt is standard of care to continue androgen-deprivation therapy (ADT) at this time. Two randomized phase 3 trials have demonstrated a survival benefit of 2 mo using a 3-wk docetaxel regimen, with a follow up of more than 50 mo. The decision for an immediate or a symptom-triggered–delayed chemotherapy must be tailored on the basis of prognostic factors such as a high PSA level, a short PSA doubling time, or multiple metastases, and otherwise on the patient's health. In symptomatic patients, docetaxel is superior to mitoxantrone for palliation with both regimens, with the weekly regimen being better tolerated.Chemotherapy is not the only possibility for symptomatic patients. Adapted modalities such as analgesic drugs, bisphosphonates, or radiotherapy must be offered.At relapse after a first-line chemotherapy, a second-line docetaxel regimen is effective. Multiple phase 2 and 3 trials are underway, using drugs such as non–taxane tubiline inhibitors, calcitriol, antiendothelin, bevacuzimab, gefitinib, Bcl2 antisense, or vaccine (GVAX®).The heterogeneity of the disease between patients and within the same patient represents the rational for an individualized treatment.ConclusionsThe use of all available modalities to maintain the best possible quality of life for as long as possible is the real objective. This goal requires a multidisciplinary approach, in which chemotherapy is only one component.