Multiple Docetaxel Retreatments Without Prednisone for Metastatic Castration-Resistant Prostate Cancer in the Docetaxel-Only Era: Effects on PSA Kinetics and Survival

INTRODUCTION: This study aimed to assess the effects of multiple docetaxel (DOC) treatments on prostate-specific antigen (PSA) kinetics and survival among patients with metastatic castration-resistant prostate cancer (mCRPC) who were sensitive to first-line DOC and received no other life-prolonging agents. To eliminate the effect of cortisone on serum PSA, only patients who were treated without prednisone were included. METHODS: This IRB-approved retrospective study evaluated 52 patients with mCRPC who were retreated using DOC after first-line DOC (without prednisone in both cases), based on a PSA response of > 50% and no radiographic progression. Twenty-three PSA-based factors, including static and kinetic PSA measures, were evaluate for their ability to predict overall survival (OS) RESULTS: The patients received 688 cycles of DOC in 143 series, including 91 courses of retreatments (1 cycle: 28 patients, 2 cycles: 14 patients, 3 cycles: 8 patients, 4 cycles: 1 patient, and 7 cycles: 1 patient). The median overall number of cycles per patient was 12 (range: 7–31). The median durations of the first, second, and third holidays were 18 weeks (6–60 weeks), 16 weeks (3–44 weeks), and 17 weeks (8–51 weeks), respectively. The median OSs were 22 months (10.5–70 months) after the first DOC treatment and 14 months (3–65 months) after the second DOC treatment. The > 50% PSA decline rate was 48% after retreatment. Short treatment holidays (< 3 months) were associated with shortened OS (p = 0.01). In the multivariate analysis, a 25% PSA increase over the nadir was the strongest predictor of survival (HR: 3.20, 95% CI: 1.47–6.99, p = 0.003). CONCLUSIONS: DOC retreatment without prednisone had anti-tumor activity in a considerable proportion of mCRPC cases that were initially sensitive to first-line DOC. A 25% PSA increase over the nadir might predict acquired DOC resistance.