Use of speed and extent of PSA response during the first three cycles of docetaxel chemotherapy in metastatic castrate-resistant prostate cancer to predict overall survival.

Abstract

48 Background: Docetaxel chemotherapy has an established role in the management of metastatic castrate-resistant prostate carcinoma (CRPC). With an overall survival benefit demonstrated with second line agents, identifying non-responders to docetaxel at an early stage would allow timely consideration of therapy change.We wished to assess PSA response rates to sequential cycles of docetaxel chemotherapy to determine after which cycle men should be considered nonresponders.We also wished to assess if previous therapy with diethylstilbestrol (DES) influenced subsequent response to docetaxel. Methods: Retrospective case review of all men with CRPC receiving docetaxel chemotherapy between January 2007 and April 2010 at our institution was performed. PSA immediately prior to cycle 1 (baseline) and subsequent cycles were noted and evaluated for response compared to baseline PSA. Results: 86 men with a median age of 65 years (47-81) received an average of 5 cycles (1-10) of docetaxel chemotherapy. 67 (77%) had a documented fall in PSA below baseline during chemotherapy with 56 (65%) and 43 (50%) having a PSA response of >30% and >50% respectively. A PSA level lower than baseline was seen in 54%, 63% and 72% of men after cycles 1, 2 and 3 respectively. Limited PSA falls below baseline were seen in 3 (3.4%) and 2 (2.3%) men after cycles 4 and 5 respectively. All PSA responses of >50% had occurred by the start of cycle 4. Of the 14 men who had received DES prior to starting docetaxel, only 3 (21%) had >50% reduction in PSA. The median overall survival for men achieving a PSA response >50% below baseline was 20 mths and was significantly better than the median overall survival of 10mths for those with no PSA response >50% (p<0.0001). Site of metastatic disease also correlated with survival. Conclusions: In our population, men who fail to document a PSA response to the first 3 cycles of docetaxel chemotherapy are highly unlikely to do so after this time. Response defined as a fall below baseline and the extent of PSA decline below baseline are all correlated with survival. More modest PSA responses are seen in men pre-treated with DES than those who have not received DES. No significant financial relationships to disclose.