Pre-surgical 68Ga-PSMA-11 PET for biochemical recurrence risk assessment: A surrogate of pelvic lymph node dissection? Follow-up analysis of a multicenter prospective phase 3 imaging trial.

Abstract

285 Background: To compare the prognostic value of presurgical PSMA-PET and pelvic lymph nodes invasion (pN1) for biochemical recurrence (BCR) free-survival (FS) in patients with intermediate-risk to high-risk prostate cancer (PCa) treated with radical prostatectomy (RP) and pelvic lymph node dissection. Methods: This is a follow-up study of the surgery cohort included in the multicenter prospective phase 3 imaging trial (n=277; NCT03368547, NCT02611882, NCT02919111). Each 68Ga-PSMA-11-PET scan was read by three blinded independent readers. Local histopathology risk score (CAPRA-S (Cancer of the Prostate Risk Assessment) score without pN data), PSMA-PET extra-prostatic disease (N1/M1), and pN were used to assess risk of BCR. Patients were followed up 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 secondary treatment (>6 months after surgery). Univariate, multivariate Cox model, and c-statistic index were performed to assess the prognostic value of PSMA-PET, LNI and its added value to Local histopathology risk score. Results: From December 2015 to December 2019, 277 patients underwent surgery after PSMA-PET. Clinical follow-up was obtained in 240/277 (87%) patients. Median follow-up from surgery was 32.4 (IQR 23.3-42.9) months. Ninety-one/240 BCR events (38%) were observed. PSMA-PET N1/M1 and pN1 were found in 41/240 (17%) and 67/240 (28%) patients respectively. Local histopathology risk score, PSMA-PET and pN were significant univariate predictors of BCR. Only Local histopathology risk score and PSMA PET were significant in multivariate analysis (HR [95% CI] 1.4 (1.2-1.5) p<0.0001) and (1.7 (1-2.9) p=0.03). Prognostic value of model combining local histopathology and PSMA-PET was not significantly different than model combining local histopathology and pN (c-statistic 0.74 (0.69-0.79) vs 0.73 (0.68-0.78); p= 0.69). In patient group with low-risk Local histopathology score and PSMA-PET N0-M0 only 4/109 (5%) were pN1. In patients with high-risk local histopathology score, a PSMA-PET N1/M1 was associated with a significant lower BCR-FS than a PSMA-PET N0-M0 (median survival (95% CI) 32.7 (14.9-NR) vs 8 (3.2-15.5) p= 0.001). pN1 was found in respectively 25/34 (74%) and 34/90 (38%). Conclusions: Combination of pre-surgical PSMA-PET and Local histopathology was not statistically different than the reference standard, i.e local histopathology and pN to predict BCR-FS. Interestingly rate of discrepancy with pN was low among patient with low histopathology risk and PSMA-PET (N0-M0) and patient with high histopathology risk and PSMA-PET (N1/M1). Clinical trial information: NCT03368547 , NCT02611882 , NCT02919111 .