5090 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 68 Ga-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 .

To assess the added prognostic value of pre-surgical PSMA PET for early biochemical recurrence (BCR) progression free-survival (BCR-PFS) compared to pre-surgical CAPRA (Cancer of the Prostate Risk Assessment) and post-surgical CAPRA-S scores in patients treated with radical prostatectomy (RP) and Pelvic Lymph Node Dissection (PLND) with intermediate-risk (IR) to high-risk (HR) prostate cancer (PCa). This is a follow-up study of the surgery cohort included in the multicenter prospective phase 3 imaging trial (n = 277; 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. PSMA PET prostate uptake (low vs. high), PSMA PET extra-prostatic disease (N/M), CAPRA and CAPRA-S score 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 and to compare with CAPRA and CAPRA-S scores. From December 2015 to December 2019, a total of 277 patients underwent RP after PSMA-PET. Clinical follow-up was obtained in 240/277 (87%) patients. The median follow-up from surgery was 32.4 months. Ninety-one/240 BCR events (38%) were observed. PSMA extra-prostatic disease was found in 41/240 (17%) patients. PSMA PET high prostate uptake PSMA extra-prostatic disease, pre-surgical CAPRA score and post-surgical CAPRA-S score were significant univariate predictors of BCR. Only addition of PSMA extra-prostatic disease to CAPRA score significantly improved risk assessment compared to CAPRA score alone (c-statistic 0.70 (0.64–0.75) vs. 0.63 (0.57–0.69); P < 0.001). Post-surgical model with CAPRA-S did not demonstrate a higher prognostic value compared to pre-surgical combining pre-surgical PSMA PET and CAPRA score. Pre-surgical PSMA PET significantly improved early BCR-PFS risk assessment and presented an added prognostic value for pre-surgical CAPRA-score. The combination of PSMA PET and CAPRA score was not statistically different with the reference standard, i.e. the post-surgical CAPRA-S score.

BACKGROUND:In the initial staging of patients with high-risk prostate cancer (PCa), prostate-specific membrane antigen positron emission tomography (PSMA-PET) has been established as a front-line imaging modality. The increasing number of PSMA-PET scans performed in the primary staging setting might be associated with decreases in biochemical recurrence (BCR)-free survival (BCR-FS). OBJECTIVE:To assess the added prognostic value of presurgical PSMA-PET for BCR-FS compared with the presurgical Cancer of the Prostate Risk Assessment (CAPRA) and postsurgical CAPRA-Surgery (CAPRA-S) scores in patients with intermediate- to high-risk PCa treated with radical prostatectomy (RP) and pelvic lymph node dissection. DESIGN, SETTING, AND PARTICIPANTS:This is a follow-up study of the surgical cohort evaluated in the multicenter prospective phase 3 imaging trial (n = 277; NCT03368547, NCT02611882, and NCT02919111). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:Each 68Ga-PSMA-11-PET scan was read by three blinded independent readers. PSMA-PET prostate uptake (low vs high), PSMA-PET extraprostatic disease (N1/M1), and CAPRA and CAPRA-S scores were used to assess the risk of BCR. Patients were followed after RP by local investigators using electronic medical records. BCR was defined by a prostate-specific antigen (PSA) level increasing to ≥0.2 ng/ml after RP or initiation of PCa-specific secondary treatment (>6 mo after surgery). Univariate and multivariable Cox models, and c-statistic index were performed to assess the prognostic value of PSMA-PET and for a comparison with the CAPRA and CAPRA-S scores. RESULTS AND LIMITATIONS:From December 2015 to December 2019, 277 patients underwent surgery after PSMA-PET. Clinical follow-up was obtained in 240/277 (87%) patients. The median follow-up after surgery was 32.4 (interquartile range 23.3-42.9) mo. Of 240 BCR events, 91 (38%) were observed. PSMA-PET N1/M1 was found in 41/240 (17%) patients. PSMA-PET prostate uptake, PSMA-PET N1/M1, and CAPRA and CAPRA-S scores were significant univariate predictors of BCR. The addition of PSMA-PET N1/M1 status to the presurgical CAPRA score improved the risk assessment for BCR significantly in comparison with the presurgical CAPRA score alone (c-statistic 0.70 [0.64-0.75] vs 0.63 [0.57-0.69]; p < 0.001). The C-index of the postsurgical model utilizing the postsurgical CAPRA-S score alone was not significantly different from the presurgical model combining the presurgical CAPRA score and PSMA-PET N1/M1 status (p = 0.19). CONCLUSIONS:Presurgical PSMA-PET was a strong prognostic biomarker improving BCR-FS risk assessment. Its implementation in the presurgical risk assessment with the CAPRA score improved the performance and reduced the difference with the reference standard (postsurgical CAPRA-S score). PATIENT SUMMARY:The use prostate-specific membrane antigen positron emission tomography improved the assessment of biochemical recurrence risk in patients with intermediate- and high-risk prostate cancer who were treated with radical prostatectomy and pelvic lymph node dissection.

5011 Background: PSMA positron emission tomography (PET) has a higher accuracy than computed tomography (CT) and bone scans to stage patients with prostate cancer. However, we do not understand how to apply clinical trial data based on conventional imaging to patients staged using PSMA PET. Therefore, we aim to evaluate the ability of bone scans to detect osseous metastases using PSMA PET as a reference standard. Methods: In this multicenter retrospective diagnostic study, 167 patients with prostate cancer, who were imaged with bone scan and PSMA PET performed within 100 days were included for analysis. Each study was interpreted by three blinded readers, and the results of the PSMA PET were used as the reference standard. Endpoints were positive predictive value (PPV), negative predictive value (NPV) and specificity for bone scans. Additionally, inter-reader reproducibility, positivity rate, uptake on PSMA PET, and number of lesions were evaluated. Results: 167 patients were included in the study, with 77 at initial staging, 60 in the BCR/CSPC setting and 30 in the CRPC setting. BS findings for metastatic disease validated by PSMA PET were tabulated. In all patients, the PPV, NPV and specificity for bone scans were 0.73 [0.61,0.82], 0.82 [0.74,0.88] and 0.82 [0.74,0.88]. In patients at initial staging, the PPV, NPV and specificity for bone scans were 0.43 [0.26,0.63], 0.94 [0.85,0.98], and 0.80 [0.68,0.88]. At initial staging 13/23 (57%) of positive bone scans were false positive. Inter-reader agreement for bone disease was moderate for bone scans (Fleiss k, 0.51) and substantial for the PSMA PET reference standard (Fleiss k, 0.80). Conclusions: In this multicenter retrospective study, the PPV of bone scans was low in patients at initial staging with majority of positive bone scans being false positives. This suggests that a large proportion of patients considered low volume metastatic by bone scan actually have localized disease. [Table: see text]

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.

The purpose of this prospective study was to determine the correct localization rate (CLR) of 18F-fluorocholine PET for the detection of parathyroid adenomas in comparison to 99mTc-sestamibi imaging. Methods: This was a single-arm prospective trial. Ninety-eight patients with biochemical evidence of primary hyperparathyroidism were imaged before parathyroidectomy using 18F-fluorocholine PET/MRI. 99mTc-sestamibi imaging performed separately from the study was evaluated for comparison. The primary endpoint of the study was the CLR on a patient level. Each imaging study was interpreted by 3 masked readers on a per-region basis. Lesions were validated by histopathologic analysis of surgical specimens. Results: Of the 98 patients who underwent 18F-fluorocholine PET, 77 subsequently underwent parathyroidectomy and 60 of those had 99mTc-sestamibi imaging. For 18F-fluorocholine PET in patients who underwent parathyroidectomy, the CLR based on the masked reader consensus was 75% (95% CI, 0.63-0.82). In patients who underwent surgery and had an available 99mTc-sestamibi study, the CLR increased from 17% (95% CI, 0.10-0.27) for 99mTc-sestamibi imaging to 70% (95% CI, 0.59-0.79) for 18F-fluorocholine PET. Conclusion: In this prospective study using masked readers, the CLR for 18F-fluorocholine PET was 75%. In patients with a paired 99mTc-sestamibi study, the use of 18F-fluorocholine PET increased the CLR from 17% to 70%. 18F-fluorocholine PET is a superior imaging modality for the localization of parathyroid adenomas.