Predictive value of extra-prostatic disease detection by pre-operative PSMA-PET for biochemical recurrence-free survival in patients treated with radical prostatectomy: Follow-up analysis of a multicenter prospective phase 3 imaging trial.

Abstract

5088 Background: To assess the predictive value of pre-operative PSMA-PET staging for biochemical recurrence (BCR) free-survival (BCR-FS) in patients treated with radical prostatectomy (RP) and pelvic lymph node dissection (PLND) with intermediate-risk (IR) to high-risk (HR) prostate cancer (PCa) included in the prospective trial used for the FDA approval of 68Ga-PSMA-11. Methods: This is a post-hoc follow-up study of the efficacy analysis cohort included in the multicenter prospective phase 3 imaging trial (n = 764; NCT03368547, NCT02611882, NCT02919111) which assessed the diagnostic accuracy of 68Ga-PSMA-11 PET for pelvic nodal metastasis detection prior to RP and PLND in patients with IR and HR PCa. Each PSMA-PET scan was read by three blinded independent readers. Readers assessed the presence of PCa (positive vs negative) by region: prostate bed (T), pelvic lymph nodes (N), extra-pelvic lymph nodes (M1a) bone (M1b) and visceral (M1c). A centralized per-region majority rule was used in case of disagreement. The surgical pathology report was used to assess the presence of pelvic lymph node metastasis by histopathology (pN0 vs pN1). The patients were followed up for biochemical progression after RP by the local investigators using electronic medical records. BCR was defined by a prostate-specific antigen (PSA) level > 0.2 ng/ml after RP or an initiation of PCa specific adjuvant/salvage therapy. Pairwise comparisons using Log-Rank test was performed to evaluate BCR-FS between the pre-operative PSMA scan reads (N0M0 vs. N+ and/or M+) and the histopathology status (pN0 vs. pN1). Results: From December 2015 to December 2019, a total of 764 patients were enrolled in the trial. 277/764 (36%) underwent RP after PSMA-PET. Clinical follow-up was obtained in 240/277 (87%) patients. The median age was 67 years (interquartile range, 61-71 years). The median follow-up time from RP was 21.4 months (IQR: 8.80 - 31.53). One hundred BCR events (41%) were observed, and 98/240 patients underwent salvage therapy or other treatment (40.6%). The BCR-FS was 24.3 (IQR: 7.8 - 48.8) in the whole cohort. 160/240 (66%), 28/240 (11.6%), 39/240 (16%), 13/240 (5.4%) patients were pN0/PSMA- (N0 and M0), pN+/PSMA+ (N+ and/or M+), pN+/PSMA-, and pN0/PSMA+, respectively. BCR-FS was higher in PSMA- than in PSMA+ patients (33 vs 7.3 months; p < 0.0001). BCR-FS was higher in pN0/PSMA- than in patients pN+/PSMA-, pN0/PSMA+ and pN+/PSMA+: 46 months vs 12.3, 11.7, and 3, respectively (p < 0.001). BCR-FS did not significantly differ between pN0/PSMA+ and pN+/PSMA- (11.7 vs 12.3; p = 0.64). Conclusions: PSMA PET staging information is predictive of BCR-FS after RP. Patients with extra-prostatic disease detected by pre-operative PSMA-PET scan have a high risk of biochemical relapse. Clinical trial information: NCT03368547.