177Lu-PSMA-617 SPECT/CT for Early Prediction of Overall Survival in Participants with Metastatic Castration-Resistant Prostate Cancer
Details
Publication Year 2026-04,Volume 319,Issue #1,Page e252672
Journal Title
Radiology
Publication Type
Research article
Abstract
Background Lutetium 177 ((177)Lu) prostate-specific membrane antigen (PSMA)-617 SPECT/CT has demonstrated promise as a response biomarker for (177)Lu-PSMA-617 therapy. Purpose To predict overall survival (OS) after enzalutamide plus (177)Lu-PSMA-617 using quantitative parameters at (177)Lu-PSMA-617 SPECT/CT at 6 weeks, as well as prostate-specific antigen (PSA) response, in participants with metastatic castration-resistant prostate cancer. Materials and Methods This secondary analysis of the multisite prospective ENZA-p trial (August 2020-July 2022) included participants who received enzalutamide plus (177)Lu-PSMA-617 (7.5 GBq). SPECT/CT was performed 24 hours after each treatment, and total tumor volume (TTV) and mean standardized uptake value were compared between the first (baseline) and second (6-week) doses. TTV complete response (CR) at SPECT/CT was defined as TTV less than 1 mL at dose 2, and deep PSA response was defined as 90% or greater PSA reduction at dose 2. Relationships between TTV CR and deep PSA response at dose 2 and OS were examined. Results This analysis included 74 men (median age, 71 years [IQR, 66-78 years]). Median follow-up was 33 months (95% CI: 28, 37). Median OS was 31 months (95% CI: 25, 33), and the 2-year survival rate was 70% (95% CI: 58, 79). Median TTV was 236 mL (IQR, 81-688 mL) at baseline and 65 mL (IQR, 12-215 mL) at 6 weeks. Median change in TTV was -57% (IQR, -89% to -38%); 4.1% (three of 74) of participants had an increase in TTV, and 16% (12 of 74) had TTV CR. Deep PSA response was seen in 63% (45 of 71) of participants. The 2-year survival rate with TTV CR was 83% (95% CI: 48, 96), versus 67% (95% CI: 54, 77) without TTV CR (hazard ratio, 0.26 [95% CI: 0.08, 0.85]; log-rank P = .02). The 2-year survival rate was 76% (95% CI: 58, 87) with deep PSA response without TTV CR (log-rank P = .05 vs TTV CR) and 54% (95% CI: 33, 71) with neither deep PSA response nor TTV CR (log-rank P = .003 vs TTV CR). Conclusion TTV CR at (177)Lu-PSMA-617 SPECT/CT at 6 weeks was associated with improved OS and may be a valuable tool for treatment personalization with (177)Lu-PSMA-617. ClinicalTrials.gov Identifier: NCT04419402 © RSNA, 2026 Supplemental material is available for this article. See also the editorial by Galgano and Turner in this issue.
Publisher
Wiley
Keywords
Humans; Male; *Prostatic Neoplasms, Castration-Resistant/diagnostic; imaging/mortality/pathology/drug therapy/radiotherapy; Aged; *Lutetium/therapeutic use; *Heterocyclic Compounds, 1-Ring/therapeutic use; *Single Photon Emission Computed Tomography Computed Tomography/methods; *Dipeptides/therapeutic use; Prospective Studies; Prostate-Specific Antigen/blood; *Radioisotopes/therapeutic use; Nitriles/therapeutic use; Middle Aged; Radiopharmaceuticals/therapeutic use; Phenylthiohydantoin/therapeutic use/analogs & derivatives; Benzamides/therapeutic use
Department(s)
Cancer Imaging; Medical Oncology
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Creation Date: 2026-05-12 05:40:22
Last Modified: 2026-05-12 05:40:39
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