Quantifying molecular imaging patterns of treatment response or progression using a novel traffic light workflow within a prospective phase I/II trial of 177LuPSMA-617 and NOX66 (LuPIN).

166 Background: 177 Lutetium PSMA-617 (LuPSMA) is an effective therapy for metastatic castrate-resistant prostate cancer (mCRPC). However, treatment resistance may occur. We developed a quantitative workflow for serial PSMA PET/CT to optimise predictive and prognostic imaging biomarker capability for progression free (PFS) and overall survival (OS). Methods: 56 men with mCRPC previously treated with taxane chemotherapy and androgen signaling inhibitor were enrolled, receiving up to 6 doses of LuPSMA and a radiation sensitizer idronoxil (NOX66). 68 Ga-PSMA-11 PET/CT was performed at study entry and exit. Traffic Light (TL) quantification workflow was developed to track changes in both tumour volume and intensity at a total body and lesional level. Lesions were classified as responding in green (>30% decline in volume), stable in yellow (<30% change in volume/intensity), progressive in red (>30% increase in volume/intensity, or new). Overall response pattern was categorised as responding ( green/yellow), low volume red (<50% progressive disease) or high volume red (>50% progressive disease). TL workflow results were correlated with PFS and OS. Results: 37/56 men underwent both entry and exit imaging. The median PSA decline was 77% (IQR 34-92%), and 70% (26/37) achieved PSA response >50%. PSA progression occurred in 54% (20/37) at exit imaging. Median PFS was 8.6 months (95%CI 5.6-11.6) and median OS 22 months (95% CI 18.6-25.6). 95% (35/37) had reduction in PSMA SUVmax (-26.1 (IQR +11.7 to -89.4)) and SUVmean (-3.3 (+2.9 to -14.2)). PSMA total tumor volume reduced in 68% (25/37) (median -0.64 liters (range +1.44 to -1.1)). On TL workflow, 24% (9/37) had responding/stable disease ( green/ yellow), 76% (28/37) had progressive disease ( red) of whom 41% (15/37) had low volume progression and 35% (13/37) high volume progression. Men with high volume progression had worse OS compared to responders (HR 0.18 (0.05-0.59), p 0.005), and low volume progression (HR 0.30 (0.11-0.80), p 0.02). 68% (19/28) had progression on both TL workflow and PSA, while 32% (9/28) had progression on TL workflow without PSA progression. In multivariable analysis, TL workflow and PSA progression at time of exit scans were independent predictors of OS (Table). Conclusions: This study demonstrates the feasibility of characterizing lesional response on molecular imaging with a quantification TL workflow. TL workflow response independently correlated with survival outcomes, indicating serial PSMA PET has prognostic biomarker potential. Clinical trial information: ACTRN12618001073291.[Table: see text]