Rationale The development of consensus guidelines for interpretation of Prostate-Specific Membrane Antigen (PSMA)-Positron Emission Tomography (PET) is needed to provide more consistent reports in clinical practice. The standardization of PSMA-PET interpretation may also contribute to increasing the data reproducibility within clinical trials. Finally, guidelines in PSMA-PET interpretation are needed to communicate the exact location of findings to referring physicians, to support clinician therapeutic management decisions. Methods A panel of worldwide experts in PSMA-PET was established. Panelists were selected based on their expertise and publication record in the diagnosis or treatment of PCa, in their involvement in clinical guidelines and according to their expertise in the clinical application of radiolabeled PSMA inhibitors. Panelists were actively involved in all stages of a modified, nonanonymous, Delphi consensus process. Results According to the findings obtained by modified Delphi consensus process, panelist recommendations were implemented in a structured report for PSMA-PET. Conclusions The E-PSMA standardized reporting guidelines, a document supported by the European Association of Nuclear Medicine (EANM), provide consensus statements among a panel of experts in PSMA-PET imaging, to develop a structured report for PSMA-PET in prostate cancer and to harmonize diagnostic interpretation criteria.

The prostate-specific membrane antigen (PSMA) is highly expressed on most prostate cancer (PC) cells. Therefore, the targeting of PSMA has become increasingly important over the last decade. Glu-ureabased PSMA ligands used for both imaging and radioligand therapy are the mainstays of the current success. For PET imaging, both 68 Gaand 18 F-labeled agents have been successfully translated to clinical applications. Mainly retrospective cohort studies have shown a high value in the setting of biochemical recurrence, with high detection rates even in the presence of low prostate-specific antigen levels. Preliminary data indicated that radioguided surgery with PSMA ligands may help to further improve patient outcomes because it facilitates the removal of small tumor deposits that are otherwise difficult to detect. For primary PC, PSMA ligand PET imaging has been shown to be superior to cross-sectional imaging for the detection of metastatic lymph nodes. In addition, it promises to also provide intraprostatic tumor localization, especially when used in combination with multiparametric MRI. Increasing numbers of studies have reported considerable changes in management resulting from PSMA ligand PET imaging for both biochemical recurrence and primary disease. The use of 177 Lu-PSMA-based radioligand therapy has demonstrated a reasonable response, mainly as defined by a prostate-specific antigen response of more than 50%, comparable to other recently introduced agents. Especially given the high level of safety of 177 Lu-PSMA radioligand therapy, with only minimal grade 3 and 4 toxicities reported so far, it has the potential to expand options for metastatic castrationresistant PC. This review is intended to provide a comprehensive overview of the current literature on low-molecular-weight PSMA ligands for both PET imaging and therapeutic approaches, with a focus on agents that have been clinically adopted.

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Purpose: To evaluate the dependency of the sensitivity of [11 C]choline positron emission tomography/ computed tomography (PET/CT) for detecting and localizing primary prostate cancer (PCa) on tumor configuration in the histologic specimen. Experimental Design: Forty-three patients with biopsy-proven PCa were included. They underwent radical prostatectomy within 31 days after [11 C]choline PET/CT. The transaxial image slices and the histologic specimens were analyzed by comparing the respective slices. Maximum standardized uptake values (SUV max ) were calculated in each segment and correlated with histopathology. The tumor configuration in the histologic specimen was grouped as: I, unifocal; II, multifocal; III, rind-like shaped; IV, size <5 mm. Data analysis included the investigation of detection of PCa by SUV max , the assessment of the influence of potential contributing factors on tumor prediction, and the evaluation of whether SUV could discriminate cancer tissue from benign prostate hyperplasia (BPH), prostatitis, HGPIN (high-grade prostate intraepithelial neoplasm), or normal prostate tissue. General estimation equation models were used for statistical analysis.Results: Tumor configuration in histology was classified as I in 21 patients, as II in 9, as III in 5, and as IV in 8. The prostate segment involved by cancer is identified in 79% of the patients. SUV max was located in the same side of the prostate in 95% of patients. Tumor configuration was the only factor significantly negatively influencing tumor prediction (P < 0.001). PCa-SUV max (median SUV max ¼ 4.9) was not significantly different from BPH-SUV (median SUV max ¼ 4.5) and prostatitis-SUV (median SUV max ¼ 3.9), P ¼ 0.102 and P ¼ 0.054, respectively.Conclusions: The detection and localization of PCa in the prostate with [ 11 C]choline PET/CT is impaired by tumor configuration. Additionally, in our patient population, PCa tissue could not be distinguished from benign pathologies in the prostate.

5502 Background: To determine the accuracy of 68Ga-PSMA-11 PET for the detection of pelvic nodal metastases (N1) compared to histopathology at time of radical prostatectomy (RP). Methods: This is a prospective multicenter single-arm open-label phase 3 imaging trial. Patients with intermediate to high risk prostate cancer (PCa) considered for RP with lymph node dissection (PLND) were enrolled at the University of California, Los Angeles (UCLA) and at the San Francisco (UCSF) (NCT03368547, NCT02611882, NCT02919111), and underwent one 68Ga-PSMA-11 PET. The primary endpoint was the sensitivity (Se) and specificity (Sp) of 68Ga-PSMA-11 PET for the N1 detection compared to PLND histopathology (reference-standard) on a per patient basis using nodal region-based correlation. Each scan was read by three blinded independent central readers (BICR). Consensus was based on majority rule. Results: From December 2015 to August 2019, 633 patients underwent one 68Ga-PSMA-11 PET for primary staging, and 277/633 (44%) subsequently underwent RP and PLND. The median initial PSA was 11.1 [0.04-147]. 75/277 patients (27%) had N1 disease per histopathology. Using a regional based analysis, Se, Sp, positive predictive value (PPV) and negative predictive value (NPV) for N1 detection was 0.40 [0.34, 0.46], 0.95 [0.92, 0.97], 0.75 [0.70, 0.80], 0.81 [0.76, 0.85], respectively. Se was higher for patients with higher PSA: 0.29 [0.24, 0.35] for PSA < 11 ng/ml versus 0.48 [0.42, 0.54] for PSA > 11. Se was higher when the nodes were larger: 0.30 [0.25, 0.36] for nodes < 10 mm versus 0.68 [0.63, 0.74] for nodes > 10. The average node size in true positive patients was 10 mm versus 4 mm in false negative patients. Conclusions: In intermediate to high risk PCa patients who underwent RP and PLND, 68Ga-PSMA-11 PET detected pelvic nodal metastases with a sensitivity of 0.40 and a specificity of 0.95. Higher PSAs and larger node size correlated with increased sensitivity. Clinical trial information: NCT03368547, NCT02611882, NCT02919111 .