Outcome of patients with PSMA-PET/CT screen failure by VISION criteria and treated with 177Lu-PSMA therapy.

Abstract

39 Background: The VISION trial showed that 177Lu-PSMA can prolong survival and improve the quality of life of patients with advanced mCRPC. The VISION trial used PSMA-PET/CT to select patients for inclusion. Here, we evaluated the outcome of patients treated with 177Lu-PSMA who would have been screen failure (SF) by VISION-PET criteria. Methods: We conducted a retrospective cohort study in our institutional database of patients treated with ≥1 cycle of 177LuPSMA between November 2017 and July 2021 (n = 74) and a multicenter dataset published previously (n = 230) (Gafita A, Lancet Oncol 2021). One dual certified reader (M.H.) in nuclear medicine and radiology blinded for patient outcomes reviewed the baseline PSMA-PET/CT scans to define eligible (VISION-PET-E) vs SF (VISION-PET-SF) patients. VISION-PET- SF criteria were defined as:1) absence of metastatic lesion 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). Outcome measures included PSA response rates (decline of ≥50% (PSA50RR) and any decline (anyPSARR)), PSA-progression free-survival (PSA-PFS), and overall survival (OS). Results: 3/304 patients (1%) were excluded (lost to follow-up (n = 2), missing DICOM CT images (n = 1)). 272/301 (90.4%) of the analyzed patients were VISION-PET-E while 29/301 (9.6%) were VISION-PET-SF: 8/301 (2.7%) with low PSMA expression and 21/301 (7.0%) with PSMA-negative lesions, respectively. The median follow-up time was 12.6 months (IQR: 7.0-21.3, range: 0.6-62.3). VISION-PET-SF patients had a worse PSA50RR (21% vs 50%; p = 0.005), anyPSARR (41% vs 71%; p = 0.003), median PSA PFS (2.1 months (1.1-3.3) vs. 4.1 (4.0-5.8); p = 0.023)), and tended to have a shorter median OS (9.6 months (4.7-14.0) vs. 14.2 (12.6-15.9); p = 0.16) than the VISION-PET-E patients. Patients with PSMA-negative lesion (n = 21) tended to have a worse response than those with low PSMA expression (n = 8): median OS 8.2 months (4.4-11.0) vs. NA (11.1-NA) (p = 0.034), median PSA-PFS 1.8 months (1.4-3.3) vs. 2.8 (1.1-5.7) (p = 0.44), PSA50RR 19% vs 25% (p = 1.00), and any PSARR 38% vs 50% (p = 0.68). Conclusions: Some have argued that the low SF rate of 12.6% (126/1003) in the VISION trial may obviate the need for PSMA-PET eligibility screening prior to 177Lu-PSMA. Here we report that VISION-PET-SF patients had worse outcomes than VISION-PET-E patients in response to 177Lu-PSMA therapy. The best management of patients with negative or low PSMA expressing lesions is unknown. Combining 177Lu-PSMA with external-beam RT and/or with other systemic therapy may be an effective therapeutic approach. Refinements in patient selection for 177Lu-PSMA are needed to optimize patient outcomes.