Practical RECIP: Visual assessment of Response Evaluation Criteria In PSMA-PET/CT in metastatic castration-resistant prostate cancer

Introduction: In men with metastatic castration-resistant prostate cancer (mCRPC), manual tumor segmentation for response assessment is time consuming and hence not feasible in clinical practice. The aim of this study was to evaluate the accuracy of Response Evaluation Criteria In PSMA-Imaging (RECIP) determined by visual reads for response evaluation using prostate-specific membrane antigen (PSMA)-PET/CT (PSMA-PET/CT) in men with mCRPC treated with ¹⁷⁷Lu-PSMA radioligand therapy.

Methods: In this multicenter retrospective study of men who received ¹⁷⁷Lu-PSMA and underwent PSMA-PET/CT scans at baseline (bPET) and at 12 weeks (iPET). Five nuclear medicine specialists individually interpreted each pair of PSMA-PET/CT scans for responses in PSMA-positive total tumor volume (PSMA-VOL) assessed visually and for the occurrence of new lesions. Responses in PSMA-VOL were also assessed quantitatively using semiautomatic segmentation software. The occurrence of new lesions was combined 1) with visual responses in PSMA-VOL to determine visual RECIP and 2) with quantitative responses in PSMA-VOL to determine quantitative RECIP. RECIP response classes were dichotomized in progressive (PD) vs nonprogressive disease (nPD): RECIP-PD vs RECIP-nPD. The primary outcome was the interreader reliability of visual RECIP and agreement between visual vs quantitative RECIP. The secondary outcome was the prognostic value of visual RECIP for overall survival (OS).

Results: Based on readers’ majority rule, 41/124 (33%) and 83/124 (67%) men had visual RECIP-PD and RECIP-nPD, respectively. Agreement among readers in classifying visual RECIP-PD vs RECIP-nPD was observed in 103/124 (83%) men (excellent agreement: κ=0.81). Agreement between visual vs quantitative RECIP was observed in 118/124 (95%) men (excellent agreement: κ=0.89). OS was shorter in men with visual RECIP-PD than in men with RECIP-nPD (HR 2.55; 95%CI: 1.71-3.81; p<0.001). The median OS was 8.4 months (95%CI: 7.0-9.8) for men with RECIP-PD and 16.1 months (95%CI: 13.6-18.5) for men with RECIP-nPD.

Conclusions: Visual Response Evaluation Criteria In PSMA-Imaging (RECIP) demonstrated excellent interreader reliability and excellent agreement with quantitative RECIP. Visual RECIP was prognostic for the overall survival of men undergoing 177Lu-PSMA radioligand therapy and PSMA-PET/CTVisual RECIP can be used in clinical practice for response evaluation