Long-term clinical impact of PSA surge in castration-resistant prostate cancer patients treated with abiraterone.

BACKGROUND: Early changes in PSA have been evaluated in association to treatment outcome. The aim of this study was to assess PSA surge phenomenon in castration-resistant prostate cancer (CRPC) patients treated with abiraterone and to correlate those variations with long-term treatment outcome. PATIENTS AND METHODS: We retrospectively evaluated 330 CRPC patients in 11 Italian hospitals, monitoring PSA levels at baseline and every 4 weeks. Other clinical, biochemical and molecular parameters were determined at baseline. We considered PSA surge as PSA increase within the first 8 weeks from starting abiraterone more than 1% from baseline followed by a PSA decline. The log-rank test was applied to compare survival between groups of patients according to PSA surge. The impact of PSA surge on survival was evaluated by Cox regression analyses. RESULTS: A total of 330 patients with CRPC, median age 74 years (range, 45-90), received abiraterone (281 chemotherapy-treated and 49 chemotherapy-naïve). PSA surge was observed in 20 (7%) post-chemotherapy and 2 (4%) chemotherapy-naïve patients. For overall patients presenting PSA surge, timing of PSA peak from baseline was 5 ± 1.8 weeks and PSA rise from baseline was 21 ± 18.4%. The overall median follow-up was 23 months (range 1-62). No significant differences in progression-free survival and overall survival were observed between patients with and without PSA surge (P = 0.16 and =0.86, respectively). In addition, uni- and multivariate analyses showed no baseline factors related to PSA surge. CONCLUSION: PSA surge occurs in both chemotherapy-treated and chemotherapy-naïve patients treated with abiraterone resulting, however, in no long-term impact on outcome. Physicians and patients should be aware of PSA surge challenge to prevent a premature discontinuation of potentially effective therapy with abiraterone. Further larger and prospective studies are warranted to investigate this not infrequent phenomenon.

Serial 18F-choline-PET imaging in patients receiving enzalutamide for metastatic castration-resistant prostate cancer: response assessment and imaging biomarkers.

AIM: High rate of non-target lesions in metastatic castration-resistant prostate cancer usually limits applicability of Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and this has led to a growing interest in using PET/computed tomography (CT). We prospectively investigated the role of (18)F-choline (FCH)-PET/CT in patients receiving enzalutamide after docetaxel. PATIENTS & METHODS: 30 patients were monitored by means of FCH-PET/CT before and during the treatment. A Cox proportional hazards regression model was used to assess the associations between metabolic parameters and clinical outcomes. RESULTS: Univariate analysis showed no significant correlation between biochemical and FCH-PET responses. Multivariate analysis showed that only baseline maximum standardized uptake value (SUVmax) significantly correlated with biochemical progression-free survival, radiological progression-free survival and overall survival. CONCLUSION: Our findings suggest that FCH-PET/CT may play a role in defining prognosis of patients receiving enzalutamide because baseline SUVmax proved to be an independent prognostic factor.

Multiple rechallenges for castration-resistant prostate cancer patients responding to first-line docetaxel: assessment of clinical outcomes and predictive factors.

OBJECTIVE: To describe the feasibility and efficacy of multiple sequential rechallenges and analyze the predictive factors that may aid in selecting patients who are more likely to respond. Several studies have demonstrated the feasibility and activity of a single docetaxel rechallenge in patients with castration-resistant prostate cancer (CRPC), thus providing an additional opportunity for treatment in docetaxel-sensitive CRPC patients in clinical practice. MATERIALS AND METHODS: CRPC patients who completed first-line docetaxel therapy without disease progression have been offered a docetaxel rechallenge, and the responders have undergone further rechallenges until the appearance of docetaxel resistance. We assessed their clinical outcomes and evaluated all the variables potentially capable of predicting the response to rechallenge by means of uni- and multivariate analysis. RESULTS: Forty-six consecutive patients underwent 92 rechallenges. The overall biochemical response rate (prostate-specific antigen [PSA] reduction >50%) was 66%. Median overall survival was 32 months with a projected 2-year overall survival from the first docetaxel administration of 77.5%. Multivariate analysis showed that the time slope-log PSA, the time from the previous cycle, and the response to the previous cycle were predictive of the response to a rechallenge. CONCLUSION: A docetaxel rechallenge may be safely repeated several times in CRPC patients and in selected patients could improve disease control. The predictive factors found in our analysis may help select the most appropriate strategy in the light of the availability of active second-line drugs.