Prognostic Performance of RECIP 1.0 Based on [¹⁸F]PSMA-1007 PET in Prostate Cancer Patients Treated with [¹⁷⁷Lu]Lu-PSMA I&T.

Abstract

In metastatic castration-resistant prostate cancer (mCRPC) patients treated with prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT), the recently proposed criteria for evaluating response to PSMA PET (RECIP 1.0) based on ⁶⁸Ga- and ¹⁸F-labeled PET agents provided prognostic information in addition to changes in prostate-specific antigen (PSA) levels. Our aim was to evaluate the prognostic performance of this framework for overall survival (OS) in patients undergoing RLT and imaged with [¹⁸F]PSMA-1007 PET/CT and compare the prognostic performance with the PSA-based response assessment. <b>Methods:</b> In total, 73 patients with mCRPC who were scanned with [¹⁸F]PSMA-1007 PET/CT before and after 2 cycles of RLT were retrospectively analyzed. We calculated the changes in serum PSA levels (ΔPSA) and quantitative PET parameters for the whole-body tumor burden (SUV_mean, SUV_max, PSMA tumor volume, and total lesion PSMA). Men were also classified following the Prostate Cancer Working Group 3 (PCWG3) criteria for ΔPSA and RECIP 1.0 for PET imaging response. We performed univariable Cox regression analysis, followed by multivariable and Kaplan-Meier analyses. <b>Results:</b> Median OS was 15 mo with a median follow-up time of 14 mo. Univariable Cox regression analysis provided significant associations with OS for ΔPSA (per percentage, hazard ratio [HR], 1.004; 95% CI, 1.002-1.007; <i>P</i> < 0.001) and PSMA tumor volume (per unit, HR, 1.003; 95% CI, 1.000-1.005; <i>P</i> = 0.03). Multivariable Cox regression analysis confirmed ΔPSA (per percentage, HR, 1.004; 95% CI, 1.001-1.006; <i>P</i> = 0.006) as an independent prognosticator for OS. Kaplan-Meier analyses provided significant segregation between individuals with versus those without any PSA response (19 mo vs. 14 mo; HR, 2.00; 95% CI, 0.95-4.18; <i>P</i> = 0.04). Differentiation between patients with or without progressive disease (PD) was also feasible when applying PSA-based PCWG3 (19 mo vs. 9 mo for non-PD and PD, respectively; HR, 2.29; 95% CI, 1.03-5.09; <i>P</i> = 0.01) but slightly failed when applying RECIP 1.0 (<i>P</i> = 0.08). A combination of both response systems (PCWG3 and RECIP 1.0), however, yielded the best discrimination between individuals without versus those with PD (19 mo vs. 8 mo; HR, 2.78; 95% CI, 1.32-5.86; <i>P</i> = 0.002). <b>Conclusion:</b> In patients with mCRPC treated with RLT and imaged with [¹⁸F]PSMA-1007, frameworks integrating both the biochemical (PCWG3) and PET-based response (RECIP 1.0) may best assist in identifying subjects prone to disease progression.