A rapid PSA half-life following docetaxel chemotherapy is associated with improved survival in hormone refractory prostate cancer.
BACKGROUND
Docetaxel chemotherapy prolongs survival in metastatic hormone-refractory prostate cancer (mHRPC), but many patients fail to respond to this therapy and there is potential for serious toxicity. Patients differ in their percent prostate-specific antigen (PSA) decline and rate of PSA decline following treatment. We propose that patients who achieve a rapid rate of PSA decline, measured as a shorter PSA half-life (PSAHL), may experience a longer overall survival (OS) than those who achieve a slower rate of PSA decline.


METHODS
A chart review of patients treated with docetaxel for mHRPC in Alberta from January 2000 to May 2006 was performed. At 42 days (after 2 cycles) and 84 days (after 4 cycles) following chemotherapy, PSA response and PSAHL were determined. PSAHL could only be determined in patients with a PSA drop from baseline. Optimal PSAHL values for OS stratification were determined using the log-rank chi-square statistic. Survival analysis was carried out using Kaplan-Meier curves and regression analysis.


RESULTS
There were 154 patients who fulfilled the inclusion criteria. Using 42-day postdocetaxel data, no associations with OS could be demonstrated. Using 84-day postdocetaxel data, patients stratified by PSAHL demonstrated a significant difference in OS (15 months vs. 25 months) and this relationship remained following multivariate analysis (hazard ratio 0.08 [0.021-0.34]).


CONCLUSIONS
A more rapid rate of PSA decline (PSAHL <70 days) measured after 4 cycles of chemotherapy was associated with a longer OS. This result was independent of other known markers of survival and allowed for a greater survival differentiation than PSA response.
Hanninen
Mikael
M
Department of Internal Medicine, University of Alberta, Edmonton, AB;
Venner
Peter
P
North
Scott
S