METRADS-P vs. RECIST/PCWG criteria to detect disease progression in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Tunariu Nina , Avesani Giacomo , Russo Luca , Porta Nuria , Withey Sam , Abramowicz Katarzina , Biscombe Katie , Bottazzi Silvia , Hujairi Nabil , Ribeiro Ana Sofia , Taha Tarek , Longoria-Lozano Ossian , Jacobs Tiaan , Emsley Robby , Vit Sharon , Sala Evis , Messiou Christina , Koh Dow-Mu , Sharp Adam , De Bono Johann S. 
Published: June 2024

5070 Background: Radiographic Progression-free survival (rPFS) derived from Computer Tomography (CT) and Bone Scan (BS) using Prostate Cancer Working Group (PCWG) criteria is utilized as an intermediate clinical endpoint for overall survival (OS) benefit in mCRPC. Whole Body MRI (WBMRI) is emerging as a potentially superior response biomarker, allowing a more accurate assessment of bone marrow and soft tissue disease. We have now compared the performance of previously reported WBMRI criteria (MET-RADS-P) with PCWG criteria as a response biomarker for mCRPC, and this with overall survival (OS). Methods: We retrospectively analysed imaging data from mCRPC patients that 1) discontinued therapy based on PCWG criteria; 2) had contemporaneous WBMRI, CT, and BS at time-points according to PCWG. Soft tissue lesions were classified according to RECIST1.1 both on CT and WBMRI; bone lesions were classified on BS using PCWG criteria as non-PD (non-progressive disease), PD-U (PD unknown) & PD (progressive disease) and on WBMRI using MET-RADS-P as non–PD (subclassified as partial response-PR & stable disease-SD) & PD, for each imaging time-point. We calculated % agreement between MET-RADS-P and PCWG across all time-points. Median PFS as per PCWG (rPFS) and METRADS-P (mPFS) and median OS according to METRADS-P response at 12 weeks was estimated by Kaplan Meier. Results: 100 cases (91 subjects received 100 lines of treatment, 100 baseline imaging & 216 follow-up imaging assessments). For soft tissue disease, RECIST 1.1 and WBMRI assessments were concordant at 201 of 216 time-points (93.1%); the discordance was related to superior detection of local disease and liver metastases on WBMRI. Bone metastases assessments showed agreement in 37.5% time-points, with details as follows (% over BS category): 1) Negative BS (13 time-points): WBMRI 69.2% negative, 15.4% PR, 15.4% as PD; 2) Non-PD BS (154 time-points): WBMRI non-PD 51% (34.4% PR, 17.5% SD), 48.1% PD; 3) PD-U BS (40 time-points): WBMRI PD 90%; Non-PD 10% (1pt FLARE & 3pt with subsequent concordant PD). At time of PD-U, 30 out of 40 pt (75%) discontinued treatment due to RECIST PD (24/40) & clinical progression (6/40). 4) PD confirmatory BS (9 time-points) : WBMRI 100%PD. Median rPFS by PCWG was 4.9 months (m) (95%CI: 3.8-5.7); the median mPFS by MET-RADS-P was 2.8 months (2.6-3.9), with overall progression rate of 70% and 94% respectively. Non-PD by WBMRI at 12-weeks associated with longer OS when compared with PD by MRI (median OS: 17.9m (14.2-22.6) vs 14.4m (9.6-17.0) (crude log-rank test 0.0059). Conclusions: Regarding soft-tissue disease, MET-RADS-P detects progression earlier than RECIST in 4.2% time-points, while for bone metastases it detects progression earlier than PCWG at 51.9% of timepoints. WBMRI can better classify BS non-PD patients in PR, SD and PD. Response evaluation based on WBMRI is a prognostic factor in mCRPC.