Abstract
73
Introduction: 177Lu-PSMA radioligand therapy (RLT) is a novel therapeutic agent that has shown promising results in phase 2 trials in patients with metastatic castration-resistant prostate cancer (mCRPC). 177Lu-PSMA RLT typically involves a baseline PSMA PET imaging to define eligible patients for the treatment. Interim FDG-PET showed high predictive value for survival rate in lymphoma patients. This concept has not been explored for 177Lu-PSMA RLT. The aim of this retrospective analysis was to evaluate the predictive value of tumor response on interim PSMA PET after 2 cycles of 177Lu-PSMA RLT for overall survival (OS). M&M: Patients who underwent a 68Ga-PSMA11 PET/CT at baseline and after two cycles of 177Lu-PSMA at our institution were included in the analysis. qPSMA was used for tumor burden assessment, using a fixed SUV-threshold of 3 for bone lesions segmentation and a liver-based SUV-threshold for soft-tissue lesions delineation. PSMA-avid tumor volume (PSMA-TV) was used as output parameter. Tumor response was assessed by the changes in PSMA-TV from baseline to the second PSMA PET. Three classification methods were explored. In the first one based on the volume response (PSMA-ONE), patients were divided into three categories: responders (PSMA-TV >30%decline), stable disease (PSMA-TV <30%increase and <30%decline) and progressive disease (PSMA-TV increase>30%). In this classification, new lesions did not define progressive disease per se. For the second definition (PSMA-TWO) patients were divided in: responders (PSMA-TV>30%), stable disease (PSMA-TV <30%decline and <30%increase) and progressive disease (PSMA-TV >30%increase and/or progress by new lesions). For the third definition (PSMA-THREE) patients were divided in: responders (PSMA-TV>30%decline), non-responders (PSMA-TV <30%decline and any PSMA-TV progress) and new lesions (occurrence of new lesions). The correlation between tumor response according to the three definitions and OS was evaluated.
Results: Median PSMA-TV decline was -9.13% (IQR:-44.2% to 38.2%). Median OS was 11.3 (95%CI: 8.7-13.9) months. PSMA-ONE was correlated with survival (HR=1.48, 95%CI: 1.06-2.07, p=0.01) with a median survival of 15.7 (95%CI:10.0-21.3) vs 7.4 (95%CI: 3.7-10.5) vs 7.4 (95CI%: 4.7-10.1) months for responders vs. stable disease vs. progressive disease, respectively. PSMA-TWO was correlated with survival (HR=1.56, 95%CI: 1.13-2.14, p=0.006) with a median OS of 16.5 (95%CI: 13.0-20.0), 9.0 (95%CI: 5.7-12.3) and 7.4 (95%CI: 5.1-9.8) months for responders vs. stable disease vs. progressive disease, respectively. PSMA-THREE was correlated with survival (HR=1.61, 95%CI: 1.15-2.24; p=0.005), with a median OS of 16.5 (95%CI: 13.0-20.0), 9.8 (95%CI: 6.1-13.5) and 6.2 (95%CI: 4.1-8.4) months for responders vs. non-responders vs. new lesions, respectively. The Gönen-Haller concordance indices for the correlation with OS were 0.58, 0.60 and 0.60 for PSMA-ONE, PSMA-TWO and PSMA-THREE, respectively.
Conclusions: In patients with mCRPC treated with 177Lu-PSMA, tumor response assessed on interim PSMA PET after 2 RLT cycles was associated with OS. Occurrence of new lesions in PSMA PET is a prognostic factor for progressive disease and should be included in defining tumor response based on PSMA PET Imaging. Further analyses involving biochemical and clinical parameters are warranted. This analysis paves the way towards the use of interim PSMA PET in a prospective setting during 177Lu-PSMA radioligand therapy.
