Highlighting Unmet Needs: Real Patients, Difficult Choices

ContextProstate cancer is a heterogeneous disease with several different stages necessitating a broad range of therapies to treat patients diagnosed at different points in the disease course. Androgen deprivation therapy (ADT) is commonly used to treat all stages of prostate cancer but is associated with toxicities that limit its use, particularly in patients with asymptomatic disease or existing comorbidities for whom such toxicity is not justified. The absence of a standard approach to ADT leads to significant variation in treatment regimens and extensive debate about timing of initiation and duration of therapy.Evidence acquisitionA nonsystematic review of the literature including PubMed and congress abstracts was performed in 2008.Evidence synthesisMost prostate cancer patients eventually progress to develop hormone-resistant prostate cancer (HRPC). Frequent prostate-specific antigen monitoring is detecting an increasing number of patients who have asymptomatic HRPC for whom the toxicity of currently available chemotherapy treatments cannot always be justified. In these cases, watchful waiting with a background of continuing castration therapy (with or without antiandrogen) is often the treatment paradigm. The majority of patients, however, receive additional second-line hormonal manipulations despite the associated toxicity and the lack of data to support the efficacy of this approach. Although there is currently no standard of care or approved treatment for nonmetastatic HRPC, docetaxel has been licensed for metastatic HRPC in many countries. The observed improvement in overall survival (2.4 mo) is considered by some to be marginal, and the toxicity profile can be problematic. Further studies are also required to address the ongoing debate regarding timing of initiation and duration of docetaxel therapy.ConclusionsEffective treatments are lacking for patients with HRPC, especially those with asymptomatic, nonmetastatic disease. The treatments that are available are limited by lack of data, suboptimal efficacy, and toxicity. There is clearly a significant requirement for new, well-tolerated, efficacious therapies for the treatment of HRPC, and extensive efforts are under way to identify new agents.