RT Journal Article SR Electronic T1 Association of change in PSMA avid tumor burden during 177Lu-PSMA-617 therapy with overall survival: Should mid-point PET become standard protocol? JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 2424 OP 2424 VO 65 IS supplement 2 A1 Maufort, Natalie A1 Zipoy, Julia A1 Muniz, M.D., Miguel A1 belge bilgin, gokce A1 Navin, Patrick A1 Childs, Daniel A1 Kendi, Ayse A1 Mahmoud, Ahmed A1 Abdelrazek, Ahmad A1 Orme, Jacob A1 Andrews, M.D., Jack A1 Kase, M.D., Adam A1 Mosalem, M.B., Ch.B., Osama A1 Rodrigues Pessoa, Rodrigo A1 Nabavizadeh, Reza A1 Riaz, M.B.B.S., M.S., Irbaz A1 Johnson, Geoffrey A1 Kwon, Eugene A1 Sartor, Oliver A1 Thorpe, Matthew YR 2024 UL http://jnm.snmjournals.org/content/65/supplement_2/2424.abstract AB 2424 Introduction: Prostate specific membrane antigen (PSMA) is found on prostate cancer cells and is the basis for the theranostic pairing of PSMA-based positron imaging tomography (PET) imaging and 177Lu beta-emitting therapy for PSMA-positive metastatic castration-resistant prostate cancer (mCRPC). PET imaging using or 18F PSMA-11 is performed before treatment to establish eligibility. We aim to evaluate the utility of mid treatment PSMA PET imaging for restaging and informing treatment changes. Methods: Forty-five patients referred for 177Lu-PSMA-617 therapy who received interim PSMA PET imaging during therapy (between cycles 2 and 3 in 86% of patients) were followed for overall survival. A Medical Image Merge (MIM) post-processing workflow was used to segment tumor burden on baseline and interim PSMA PET based on an absolute standard uptake value (SUV) threshold > 4. Segmented regions of interest were categorized as physiologic or metastatic by two nuclear medicine technology students (NMTS); categorization was reviewed by a board-certified nuclear radiologist. We used conditional change Cox Regression models to evaluate the association between survival and change in SUV max, SUV mean, tumor volume, uptake volume product (UVP, mean * volume), controlled for baseline values. Tumor burden was categorized as stable with <30% change from baseline, or improved/increased with ≥30% change.Results: Tumor burden was increased in 27% and decreased in 34% of patients on interim PSMA PET. Increased tumor volume and UVP predicted shortened survival when compared to improving disease (Figure 1, p < 0.01). Change in SUV max or mean did not predict survival. When added to the same model, volume was significant (p=0.021) while mean was not (p=0.36), suggesting the effect of UVP was driven primarily by volume. Patients with stable or improving tumor burden had similar survival outcomes (p=0.17), although median survival was not reached within the currently available follow-up interval in these groups. A one standard deviation increase in tumor volume was associated with a hazard ratio of 2.2 (p=0.002); for UVP, hazard ratio was 2.0 (p=0.002).Conclusions: Our results suggest interim PSMA PET imaging after 2 cycles of 177Lu-PSMA-617 can detect treatment failure and prognosticate survival, supporting the utility of interim PSMA PET imaging during PSMA-based radionuclide therapy.We did not observe a significant difference in survival between patients with stable disease vs. partial response, although median survival has not yet been reached in our cohort. While extended follow-up is needed, this early result is encouraging for patients with stable disease.Our data also supports a growing understanding that tumor volume is more prognostic than intensity of radiotracer uptake on PSMA-based imaging. More work is needed to determine the optimal threshold for segmentation of tumor volume.