Artificial Intelligence quantified prostate specific membrane antigen imaging in metastatic castrate-resistant prostate cancer patients treated with Lutetium-177-PSMA-617

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PURPOSEThe VISION study1 found that Lutetium-177 (177Lu)-PSMA-617 ("Lu-177") improved overall survival in metastatic castrate resistant prostate cancer (mCRPC). We assessed whether artificial intelligence enhanced PSMA imaging in mCRPC patients starting Lu-177 could identify those with better treatment outcomes. PATIENTS AND METHODSWe conducted a single site, tertiary center, retrospective cohort study in 51 consecutive mCRPC patients treated 2022-2024 with Lu-177. These patients had received most standard treatments, with disease progression. Planned treatment was Lu-177 every 6 weeks while continuing androgen deprivation therapy. Before starting treatment, PSMA images were analyzed for SUVmax and quantified tumor volume using artificial intelligence software (aPROMISE, Exinni Inc.). RESULTSFifty-one mCRPC patients were treated with Lu-177; 33 (65%) received 4 or more treatment cycles and these 33 had Kaplan-Meier median overall survival (OS) of 19.3 months and 23 (70%) surviving at 24 month data analysis. At first cycle Lu-177, these 33 had significantly more favorable levels of serum albumin, alkaline phosphatase, calcium, glucose, prostate specific antigen (PSA), ECOG performance status, and F18 PSMA imaging SUV-maximum values - reflecting PSMA "target expression". In a "protocol-eligibility" analysis, 30 of the 51 patients (59%) were considered "protocol-eligible" and 21 (41%) "protocol-ineligible" based on initial clinical parameters, as defined in Methods. "Protocol-eligible" patients had OS of 14.6 mo and 63% survival at 24 months. AI-enhanced F18 PSMA quantified imaging found "protocol-eligible" tumor volume in mL to be only 39% of the volume in "ineligible" patients. CONCLUSIONIn this cohort of mCRPC patients receiving Lu-177, pre-treatment AI-assisted F18 PSMA imaging finding higher PSMA SUV / lower tumor volume associated with the patients ability to have four or more treatment cycles, protocol eligibility, and better overall survival. KEY POINTSO_ST_ABSQuestionC_ST_ABSIn mCRPC patients initiating Lu-177 therapy, can AI-assisted F18 PSMA imaging identify patients who have better treatment outomes? Findings33 (65%) of a 51 consecutive patient mCRPC cohort were able to receive 4 or more cycles Lu-177. These patients had significantly more favorable serum albumin, alkaline phosphatase, calcium, glucose, PSA, performance status, and higher AI-PSMA scan SUV-maximum values, with a trend toward lower PSMA tumor volumes in mL. They had Kaplan-Meier median OS of 19.3 months and 70% survived at 24 months. AI-enhanced PSMA tumor volumes (mL) in "protocol eligible" patients were significantly lower - only 40% - than tumor volumes of "protocol ineligible" patients. MeaningIn this cohort of mCRPC patients receiving Lu-177, pre-treatment AI-assisted F18 PSMA imaging finding higher PSMA SUV / lower tumor volume associated with the patients ability to have four or more treatment cycles, protocol eligibility, and better overall survival.

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