Target volume delineations for prostate cancer (PCa) salvage radiotherapy (SRT) after radical prostatectomy are usually drawn in the absence of visibly recurrent disease. ⁶⁸Ga-labeled prostate-specific membrane antigen (PSMA-11) PET/CT detects recurrent PCa with sensitivity superior to standard-of-care imaging at serum prostate-specific antigen (PSA) values low enough to affect target volume delineations for routine SRT. Our objective was to map the recurrence pattern of PCa early biochemical recurrence (BCR) after radical prostatectomy with ⁶⁸Ga-PSMA-11 PET/CT in patients with serum PSA levels of less than 1 ng/mL, determine how often consensus clinical target volumes (CTVs) based on the Radiation Therapy Oncology Group (RTOG) guidelines cover ⁶⁸Ga-PSMA-11 PET/CT-defined disease, and assess the potential impact of ⁶⁸Ga-PSMA-11 PET/CT on SRT. Methods: This was a post hoc analysis of an intention-to-treat population of 270 patients who underwent ⁶⁸Ga-PSMA-11 PET/CT at 4 institutions for BCR after prostatectomy without prior radiotherapy at a PSA level of less than 1 ng/mL. RTOG consensus CTVs that included both the prostate bed and the pelvic lymph nodes were contoured on the CT dataset of the PET/CT image by a radiation oncologist masked to the PET component. ⁶⁸Ga-PSMA-11 PET/CT images were analyzed by a nuclear medicine physician. ⁶⁸Ga-PSMA-11-positive lesions not covered by planning volumes based on the consensus CTVs were considered to have a potential major impact on treatment planning. Results: The median PSA level at the time of ⁶⁸Ga-PSMA-11 PET/CT was 0.48 ng/mL (range, 0.03-1 ng/mL). One hundred thirty-two of 270 patients (49%) had a positive ⁶⁸Ga-PSMA-11 PET/CT result. Fifty-two of 270 (19%) had at least one PSMA-11-positive lesion not covered by the consensus CTVs. Thirty-three of 270 (12%) had extrapelvic PSMA-11-positive lesions, and 19 of 270 (7%) had PSMA-11-positive lesions within the pelvis but not covered by the consensus CTVs. The 2 most common ⁶⁸Ga-PSMA-11-positive lesion locations outside the consensus CTVs were bone (23/52, 44%) and perirectal lymph nodes (16/52, 31%). Conclusion: Post hoc analysis of ⁶⁸Ga-PSMA-11 PET/CT implied a major impact on SRT planning in 52 of 270 patients (19%) with PCa early BCR (PSA < 1.0 ng/mL). This finding justifies a randomized imaging trial of SRT with or without ⁶⁸Ga-PSMA-11 PET/CT investigating its potential benefit on clinical outcome.

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