Upon failure of first-line ADT, should second-line hormonal manipulation without survival benefit data still be used?

Abstract

The androgen receptor (AR) is an important target in castrationresistant prostate cancer (CRPC) as the progression of the disease is still largely dependent on androgen signalling. The recommendation to continue with androgen deprivation therapy is reasonable, as cessation and restoration of testosterone levels may have an adverse impact on survival. Antiandrogen withdrawal may also be attempted in all patients, as some patients are long-term responders. In one study, 19% of patients showed no signs of progression 1 year after antiandrogen withdrawal.1 Bissada et al. reported on a case in which the duration of response was for more than 3 years after antiandrogen withdrawal.2 First-generation antiandrogens such as flutamide, bicalutamide, and nilutamide have shown to be effective against prostate cancer relapse after failure of first-line androgen deprivation therapy (ADT). Studies have indicated PSA responses of 14e48% with bicalutamide and up to 50% with nilutamide.3e9 Among patients with minimal or no bone scan involvement and low baseline prostate-specific antigen (PSA) who were started on high-dose ketoconazole, PSA levels decreased by at least 75%.10 But high doses of ketoconazole have been linked to clinically significant toxicity. Therefore, as shown in a small, retrospective study, lowdose ketoconazole may be an option for patients with biochemical failure who have failed ADT.11 With second-line hormonal manipulation using ketoconazole, response rates of between 11% and 13% were reported. There was also a marked palliation of pain in a subset of patients. Low-dose ketoconazole appears to be well