Radiographic paradoxical response in metastatic castrate-resistant prostate cancer (mCRPC) managed with new generation anti-androgens: a retrospective analysis.

BACKGROUND: Prostatic specific antigen (PSA) has well-recognized limitations as a marker for treatment response and disease progression. Post hoc analysis of the PREVAIL trial reported 24.5% of chemotherapy naïve metastatic castration-resistant prostate cancer (mCRPC) patients on enzalutamide had radiographic progression on conventional imaging with nonrising PSA. In this study, we sought to study the discordance of imaging with PSA kinetics in mCRPC patients on second generation anti-androgens (SGA) post-chemotherapy using combined conventional imaging, and new generation imaging in the form of C-11 choline positron emission tomography/computed tomography (C[11] choline PET/CT) scan. METHODS: We retrospectively reviewed the medical records of 123 patients with mCRPC treated with SGA (Abiraterone or Enzalutamide) after docetaxel between 2016 and 2019. Patients underwent PSA testing, and C[11] choline PET/CT scan at baseline level before starting treatment with SGA, then every 3-6 months as part of their follow up evaluation. Loss of response to SGA was defined by increase in corrected maximum standardized uptake value (SUVmax) of pretreatment lesions on C-11 Choline PET/CT, and/or development of new lesions. Suspicious new lesions were confirmed by biopsy and/or conventional imaging. RESULTS: We identified 123 mCRPC patients who received SGA (Abiraterone, n = 106; Enzalutamide, n = 17) after docetaxel. Median duration of therapy was 13.9 months (interquartile range: 8.75-21.14). Approximately 43% (n = 53) of subjects in this study exhibited an increase in choline avidity while on SGA. Of this group, 60.4% of patients experienced a parallel rise in PSA (Group-A), whereas 39.6% displayed a paradoxical response (PR) (Group-B), defined as increased choline avidity combined with stable or down-trending PSA. Median PSA at time of increase in choline avidity was 3.1 ng/ml for Group-A, and 1.3 ng/ml for Group-B (p = 0.0176). Median SUVmax was similar in both groups (4.9 for Group-A, 4.6 for Group-B; p = 0.6072). The median time for increase in choline avidity was 9.5 versus 3.9 months for Group-A versus Group-B, respectively (Log-Rank = 0.0063). CONCLUSION: Nearly 40% of mCRPC patients placed on SGA post docetaxel chemotherapy will exhibit paradoxical responses to therapy, therefore, warranting close follow up with imaging. C-11 choline PET/CT imaging is a useful tool that can help in early predication of disease progression or treatment failure.

Adding carboplatin to chemotherapy regimens for metastatic castrate-resistant prostate cancer in postsecond generation hormone therapy setting: Impact on treatment response and survival outcomes.

BACKGROUND: The clinical course in metastatic castrate-resistant prostate cancer (mCRPC) can be complicated when patients have disease progression after prior treatment with second generation hormone therapy (second HT), such as enzalutamide or abiraterone. Currently, limited data exist regarding the optimal choice of chemotherapy for mCRPC after failing second generation hormone therapy. We sought to evaluate three common chemotherapy regimens in this setting. METHODS: We retrospectively identified 150 mCRPC patients with disease progression on enzalutamide or abiraterone. Of these 150 patients, 92 patients were chemo-naïve while 58 patients had previously received docetaxel chemotherapy before being started on second HT. After failing second HT, 90 patients were assigned for docetaxel-alone (group A), 33 patients received carboplatin plus docetaxel (group B), while 27 patients received cabazitaxel-alone (Group C). A favorable response was defined by more than or equal to 50% reduction in prostate-specific antigen from the baseline level after a complete course of chemotherapy. Survival outcomes were assessed for 30-month overall survival. RESULTS: Patients in group (B) were 2.6 times as likely to have a favorable response compared to patients in group (A) (OR = 2.625, 95%CI: 1.15-5.99) and almost three times compared to patients in group (C) (OR = 2.975, 95%CI: 1.04-8.54) (P = .0442). 30-month overall survival was 70.7%, 38.9% and 30.3% for group (B), (A), and (C), respectively (P = .008). We report a Hazard Ratio of 3.1 (95% CI, 1.31-7.35; P = .0037) between patients in group (A) versus those in group (B) and a Hazard Ratio of 4.18 (95% CI, 1.58-11.06; P = .0037) between patients in group (C) compared to those in group (B) CONCLUSION: This data demonstrates improved response and overall survival in treatment-refractory mCRPC with a chemotherapy regimen of docetaxel plus carboplatin when compared to docetaxel alone or cabazitaxel alone. Further investigations are required.

Real World Experience With Pembrolizumab in Recurrent or Advanced Prostate Cancer.

INTRODUCTION: Phase II trials have shown activity with pembrolizumab against prostate cancer. However, the clinical factors predictive of a response to pembrolizumab in men with prostate cancer are unknown. PATIENTS AND METHODS: A total of 54 consecutive men with progressive, recurrent, or advanced prostate cancer were treated with 1 to 12 cycles of pembrolizumab 200 mg every 3 weeks with or without stereotactic body radiotherapy (SBRT). RESULTS: For the 31 men evaluable for response, the median age, prostate-specific antigen (PSA) level, and Gleason score were 75 years, 30 ng/mL, and 8 (4 + 4), respectively, which were similar to those for the 23 nonevaluable patients. The treatments received before pembrolizumab were enzalutamide in 26, abiraterone in 18, and sipuleucel-T in 23. All but 4 men had had castrate-resistant disease. Of the 54 men, 31 had completed ≥ 4 cycles of pembrolizumab and were evaluable for the response. Ten men had undergone SBRT to an isolated metastasis shortly before or during pembrolizumab treatment, with the goal of inducing an abscopal effect. The clinical characteristics of the 17 men with a response or stable disease were compared with those of the 14 men with progressive disease. Grade ≥ 2 toxicity occurred in 16 men (30%). PSA stabilization or a response occurred in slightly more than one half (55%) of the men treated with ≥ 4 cycles of pembrolizumab. Five patients had a notable PSA decline of > 50%, which were sustained as long as they had continued receiving pembrolizumab. A PSA response or stabilization was more common for men who had begun taking pembrolizumab with a lower PSA level, fewer bone metastases, and fewer mutations and without previous chemotherapy. A statistically nonsignificant trend toward stabilization or a response was observed in men who had undergone concomitant SBRT. CONCLUSION: Pembrolizumab showed modest anticancer activity against metastatic castrate-resistant prostate cancer. A PSA response or stabilization occurred more frequently in men with less-advanced disease.