A reduction in the rate of PSA rise following chemotherapy in patients with metastatic hormone refractory prostate cancer (HRPC) predicts survival: Results of a pooled analysis of CALGB HRPC trials.
4506 Background: A prostate-specific antigen (PSA) decline of > 50% is associated with a prolongation in survival for patients with metastatic hormone refractory prostate cancer (HRPC). However, whether any reduction in the rate of PSA rise following chemotherapy prolongs survival remains unanswered. METHODS: Four pooled multi-institutional Cancer and Leukemia Group B randomized phase III trials containing a minimum of 3 pre-treatment and 3 post-treatment PSA values, and follow up information on 153 men with metastatic HRPC who received chemotherapy for progressive metastatic HRPC formed the study cohort. The ability of the ratio (R) of the post to pre-chemotherapy PSA slope and its constituents to predict time to death following chemotherapy was assessed using the proportional hazards regression model. RESULTS: At the time of this analysis, 139 men had died. When evaluated by tertiles, R was associated (pCox ≤ 0.09) with time to death following chemotherapy controlling for the value of the pre-chemotherapy PSA slope (pCox = 0.02). The median survival following chemotherapy for patients whose R-value was in the best (< - 0.8), middle (- 0.8 or more and up to - 0.3) or worse response tertile (> - 0.3) was 25 months [95% Confidence Interval (CI): 19-30], 23 months [95% CI: 18-29], and 18 months [95% CI: 14-23] respectively. The adjusted Hazard Ratio for death was 0.7 [95% CI: 0.45-1.05; pCox = 0.09] and 0.7 [95% CI: 0.45-1.04; pCox = 0.08] for patients with an R-value in the best and middle response tertile respectively as compared to the worse response tertile. CONCLUSION: A reduction in the rate of PSA rise following chemotherapy is associated with a prolongation in survival. Therefore, R may be an intermediate end point for mortality in patients with metastatic HRPC. Prospective validation is warranted. No significant financial relationships to disclose.
D'Amico, AV; Halabi, S; Vogelzang, NJ; Small, EJ
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