IMPORTANCEThe presence of pelvic nodal metastases at radical prostatectomy is associated with biochemical recurrence after prostatectomy. OBJECTIVE To assess the accuracy of prostate-specific membrane antigen (PSMA) 68 Ga-PSMA-11 positron emission tomographic (PET) imaging for the detection of pelvic nodal metastases compared with histopathology at time of radical prostatectomy and pelvic lymph node dissection. DESIGN, SETTING, AND PARTICIPANTS This investigator-initiated prospective multicenter single-arm open-label phase 3 imaging trial of diagnostic efficacy enrolled 764 patients with intermediate-to high-risk prostate cancer considered for prostatectomy at

Background Lutetium-177 (¹⁷⁷Lu) prostate-specific membrane antigen (¹⁷⁷Lu-PSMA) is a novel targeted treatment for patients with metastatic castration-resistant prostate cancer (mCRPC). Predictors of outcomes after ¹⁷⁷Lu-PSMA to enhance its clinical implementation are yet to be identified. We aimed to develop nomograms to predict outcomes after ¹⁷⁷Lu-PSMA in patients with mCRPC. MethodsIn this multicentre, retrospective study, we screened patients with mCRPC who had received ¹⁷⁷Lu-PSMA between Dec 10, 2014, and July 19, 2019, as part of the previous phase 2 trials (NCT03042312, ACTRN12615000912583) or compassionate access programmes at six hospitals and academic centres in Germany, the USA, and Australia. Eligible patients had received intravenous 6•0-8•5 GBq ¹⁷⁷Lu-PSMA once every 6-8 weeks, for a maximum of four to six cycles, and had available baseline [⁶⁸Ga]Ga-PSMA-11 PET/CT scan, clinical data, and survival outcomes. Putative predictors included 18 pretherapeutic clinicopathological and [⁶⁸Ga]Ga-PSMA-11 PET/CT variables. Data were collected locally and centralised. Primary outcomes for the nomograms were overall survival and prostate-specific antigen (PSA)-progression-free survival. Nomograms for each outcome were computed from Cox regression models with LASSO penalty for variable selection. Model performance was measured by examining discrimination (Harrell's C-index), calibration (calibration plots), and utility (patient stratification into low-risk vs high-risk groups). Models were validated internally using bootstrapping and externally by calculating their performance on a validation cohort.

The role of prostate-specific membrane antigen (PSMA)-targeted PET in comparison to mpMRI in the evaluation of intraprostatic cancer foci is not well defined. The aim of our study was to compare the diagnostic performances of PSMA PET/CT, mpMRI and PSMA PET/CT+mpMRI using 3 independent blinded readers for each modality and with histopathology as gold standard in the detection, intra-prostatic localization and local extension of primary prostate cancer.Methods: Patients with intermediate-or high-risk prostate cancer who underwent a PSMA PET/CT as part of the prospective trial (NCT03368547) and a mpMRI prior to radical prostatectomy were included. Each imaging modality was interpreted by 3 blinded independent readers unaware of the other modality result. Central majority rule was applied (2:1). Whole-mount pathology was used as the gold-standard. Imaging scans and whole-mount pathology were interpreted using the same standardized approach on a segment-and lesion-level. A "neighboring" approach was used to define imaging/pathology correlation for the detection of individual prostate cancer foci. Accuracy in determining the location, extraprostatic extension (EPE) and seminal vesicle invasion (SVI) of prostate cancer foci was assessed using receiver operating characteristic (ROC) analysis. Inter-reader agreement was calculated using inter-class coefficient (ICC) analysis. Results:The final analysis included 74 patients (14/74 -19%) intermediate risk and 60/74 -81%) high risk). Cancer detection rate (lesion-based analysis) was 85%, 83% and 87 for PSMA PET/CT, mpMRI and PSMA PET/CT+mpMRI, respectively. ΔAUC between PSMA PET/CT+mpMRI and the two imaging modalities alone for delineation of tumor localization (segment-based analysis) was statistically significant (p<0.001), but not between PSMA PET/CT and mpMRI (p=0.093). mpMRI outperformed PSMA PET/CT in detecting EPE (p=0.002) and SVI (p=0.001). On a segment-level analysis, ICC analysis showed moderate reliability among PSMA PET/CT and mpMRI readers using a 5-point Likert scale (range: 0.53 to 0.64). In the evaluation of T-staging, poor reliability was found among PSMA PET/CT readers and poor to moderate reliability was found for mpMRI readers. Conclusions: PSMA PET/CT and mpMRI have similar accuracy in the detection and intra-prostatic localization of prostate cancer foci. mpMRI performs better in identifying EPE and SVI. For the T-staging evaluation of intermediate to high-risk prostate cancer patients, mpMRI should still be considered the imaging modality of reference. Whenever available, PSMA PET/MRI or the co-registration/fusion of PSMA PET/CT and mpMRI (PSMA PET+mpMRI) should be used as it improves tumor extent delineation.