ASCO 2022: Outcome of Patients With PSMA PET/CT Screen Failure by VISION Criteria and Treated With 177Lu-PSMA Therapy: A Multicenter Retrospective Analysis

( At the 2022 American Society of Clinical Oncology Annual Meeting held in Chicago and virtually, the poster session focused on Prostate, Testicular, and Penile cancers on Monday afternoon included a presentation from Dr. Masatoshi Hotta discussing outcomes of theranostic treatment with 177Lu-PSMA, among patients who would be deemed ineligible for therapy according to criteria used for inclusion in the VISION trial.

There has been significant interest recently in the field of theranostics for prostate cancer. The phase II TheraP and phase III VISION trials demonstrated the benefit of 177Lu-PSMA-617 in patients with heavily pre-treated mCRPC with evidence that it PSMA prolongs survival and improves the quality of life. However, each of these trials used (somewhat different) imaging based inclusion criteria to select patients for therapy. In VISION, the screen failure rate associated with these imaging requirements was 12.6% (126/1003) and some have argued that the trial could have been positive even in an unselected population.

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To address the question of whether the VISION-PET criteria were appropriate to stratify patients into likely responders versus non-responders to177Lu-PSMA, the authors evaluated the outcome of patients who would have been excluded by the VISION-PET criteria and were nevertheless treated with 177Lu-PSMA.

To do so, they identified patients in their institutional database (n = 74) and those enrolled in a multicenter dataset published previously (n = 230) who were treated with at least one cycle of 177Lu-PSMA between 11/2017 and 07/2021. One dual certified nuclear medicine and radiology reader reviewed baseline PSMA PET/CT studies and classified the patients as eligible (VISION-PET-E) or screen failure (VISION-PET-SF) based on the VISION-PET criteria which are as follows:
 1) absence of metastatic lesion(s) with uptake > liver background (i.e., low PSMA expression) or 2) presence of ≥ 1 metastatic lesion measurable by CT (≥ 1 cm for bone lesions with soft-tissue component (M1b) and solid/visceral organs lesions (M1c); ≥ 2.5 cm for lymph nodes lesions (N1-M1a)) with uptake ≤ liver background (i.e., PSMA-negative lesions).

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In this study, the outcome measures were PSA response rates (decline of ≥50% (PSA50RR), any decline (anyPSARR)), PSA-progression free-survival (PSA-PFS), and overall survival (OS).

Among 304 potentially eligible patients, 3 (1%) were excluded due to lost to follow-up (n = 2) and missing CT data (n = 1). Among the eligible patients, 272 (90.4%) were VISION-PET-E, while 29 (9.6%) were VISION-PET-SF. In terms of the screen failures, 8 (2.7%) and 21 (7.0%) patients with low PSMA expression and PSMA-negative lesions, respectively.

Among included patients, the median follow-up time was 22.5 (range: 2.1-62.3) months. The VISION-PET-SF patients had worse PSA50RR (21% vs 50%; p = 0.005), any PSARR (41% vs 71%; p = 0.003), median PSA PFS (2.1 months (95%CI: 1.1-3.3) vs. 4.1 (4.0-5.8); p = 0.023)), and tended to have a shorter OS (9.6 months (95%CI: 4.7-14.0) vs. 14.2 (12.6-15.9); p = 0.16) than the VISION-PET-E patients.

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Thus, the authors conclude that, among patients receiving 177Lu-PSMA, those who do not meet the VISION PET inclusion criteria have significantly worse outcomes. Refinements in patient selection for 177Lu-PSMA are needed to optimize outcomes.

Presented by: Masatoshi Hotta, MD, PhD, University of California Los Angeles, Los Angeles, CA

Written by: Christopher J.D. Wallis, University of Toronto, Twitter: @WallisCJD during the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 3 – Mon, June 7, 2022.