68Ga-PSMA PET/CT for response assessment and outcome prediction in metastatic prostate cancer patients treated with taxane-based chemotherapy

Aim: We aimed to evaluate the role of Positron Emission Tomography (PET) targeting the Prostate-Specific Membrane Antigen (PSMA) for response assessment in metastatic prostate cancer (mPCa) patients treated with taxane-based chemotherapy (docetaxel or cabazitaxel) and its predictive value on patient outcome. Methods: We retrospectively evaluated 37 patients with metastatic hormone-sensitive or castration-resistant prostate cancer (mHSPC or mCRPC) who underwent ⁶⁸Ga-PSMA-11 PET/CT at baseline and after the last cycle of taxane-based chemotherapy (docetaxel or cabazitaxel) without treatment modification between scans. Biochemical response (BR) was defined as an undetectable or decreased prostate-specific antigen (PSA) by ≥50% compared to baseline. Association between BR and different PET parameters were tested. A cut-off of ≥30% change in PSMA total tumor volume (PSMA-TV) was used to define PSMA responders (PSMA-R) vs PSMA non-responders (PSMA-NR). Correlation between PSMA-PET/CT response and BR was evaluated using the Phi coefficient. Association between PET-response and overall survival (OS) was performed using Cox regression and Kaplan-Meier method. Results: Our cohort was composed of 8 (22%) mHSPC and 29 (78%) mCRPC patients. Twenty-one patients received docetaxel, and 16 received cabazitaxel treatment (median: 6 cycles, interquartile (IQR):5-8). BR was found in 18/37 patients. Using PSMA-TV, PSMA-PET/CT response was concordant with BR in 35/37 patients (Phi=0.89, p<0.0001). There were 18/37 PSMA-R (6 complete response and 12 partial response) and 19/37 PSMA-NR (17 progressive disease and 2 stable disease). After a median follow-up of 23 months there was a statistically significant longer overall survival (OS) for PSMA-R compared to PSMA-NR (median OS not reached vs 12 months, respectively, HR 0.10; 95%CI: 0.03–0.39, P = 0.001) for the entire population. Among the mCRPC subgroup, differences in OS were also observed (median 22 vs 12 months respectively, HR 0.22, 95%CI: 0.06–0.82, P = 0.023) with a 12-month OS rate of 100% for PSMA-R and 52% for PSMA-NR (P = 0.011). Conclusion: This retrospective analysis suggests that ⁶⁸Ga-PSMA-11 PET/CT is a promising imaging modality for assessing response to taxane-based chemotherapy in mPCa. PSMA-expression changes might be used as a predictive biomarker for OS which might help tailor individual therapy and select eligible patients for clinical trials.