(UroToday.com) As it has been well-covered in this publication and others, the VISION trial demonstrated prolonged survival and improve quality of life for patients with advanced mCRPC who received 177Lu-PSMA as compared to a chemotherapy-free standard of care alternative. To enroll, patients must have demonstrated on PSMA PET-CT (68Ga-PSMA-11) at least one positive lesion and zero negative lesions. Positivity was defined as uptake greater than the liver parenchyma background. The authors here investigated the outcome of those patients deemed ineligible by inadequate PSMA PET imaging alone. In the phase III study, screen failure due to PSMA PET findings was 12.6% (126/1003). The authors deployed a registry compiled of patients treated with at least 1 cycle of 177Lu-PSMA, all retrospectively studied. Using a dual certified nuclear medicine and radiology reader, baseline PSMA PET-CT studies were reviewed and classified as either eligible (VISION=PET-E) or ineligible (VISION-PET-SF, i.e. Screen Failure). The mechanism of screen failure included absence of a metastatic lesion with SUV greater than liver or the presence of one or more lesion measurable by CT but with uptake less than liver background.
They described these as either PSMA low or PSMA negative, respectively. Between VISION-PET-E and VISION-PET-SF, outcomes were measured and compared including PSA response rate (PSA50RR), rate of any PSA decline (anyPSARR), PSA progression-free survival (PSA-PFS), and overall survival (OS)
With only 1% (3/304) patients missing, completeness of follow up data was excellent. Median follow up time was 22.5 months (range 3.1-62.3). Most patients were VISION-PET-E (272/301, 90.4%). The minority VISION-PET-SF group (29/301, 9.6%) included 8 (2.7%) with PSMA-low and 21 (7.0%) with PSMA negative scans.
As compared to the VISION-PET-E cohort, the VISION-PET-SF patients experienced worse PSA50RR (21% vs 50%, p = 0.005), anyPSARR (41% vs 71%, p = 0.003), median PSA PFS (2.1 months [95% CI 1.1-3.3] vs. 4.1 [95% CI 4.0-5.8], p = 0.023). Additionally, these patients displayed a trend toward shorter overall survival (9.6 months [95% CI 4.7-14.0] vs. 14.2 [95% CI 12.6-15.9]; p = 0.16).
In conclusion, the authors summed those patients who otherwise would qualify for enrollment on VISION save for insufficient PSMA imaging with those that would not meet pre-imaging criteria, estimating the total screen failure rate as approximately 20-25% of unselected populations. In addition to suggesting that further refinement of the most sensitivity population for treatment with PSMA-TRT, the authors suggest that treating without characterization of target expression may be unethical, at least for the specific PSMA agent under study in VISION.
Presented by: Masatoshi Hotta, University of California Los Angeles, Los Angeles, CA
Written by: Jones Nauseef, MD, PhD, Assistant Professor of Medicine within the Division of Hematology and Medical Oncology, Sandra and Edward Meyer Cancer Center, and Englander Institute for Precision Medicine Weill Cornell Medicine and Assistant Attending physician at NewYork-Presbyterian Hospital. @DrJonesNauseef on Twitter during the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 3 – Mon, June 7, 2022.