Matthias Eiber

68Ga-PSMA PET/CT: Joint EANM and SNMMI procedure guideline for prostate cancer imaging: version 1.0

The aim of this guideline is to provide standards for the recommendation, performance, interpretation and reporting of 68Ga-PSMA PET/CT for prostate cancer imaging. These recommendations will help to improve accuracy, precision, and repeatability of 68Ga-PSMA PET/CT for prostate cancer essentially needed for implementation of this modality in science and routine clinical practice.

Impact of 68Ga-PSMA PET/CT on salvage radiotherapy planning in patients with prostate cancer and persisting PSA values or biochemical relapse after prostatectomy

BackgroundSalvage radiotherapy (SRT) is clinically established in prostate cancer (PC) patients with PSA persistence or biochemical relapse (BCR) after prior radical surgery. PET/CT imaging prior to SRT may be performed to localize disease recurrence. The recently introduced 68Ga-PSMA outperforms other PET tracers for detection of recurrence and is therefore expected also to impact radiation planning.Forty-five patients with PSA persistence (16xa0pts) or BCR (29xa0pts) after prior prostatectomy, scheduled to undergo SRT of the prostate bed, underwent 68Ga-PSMA PET/CT. The median PSA level was 0.67xa0ng/ml. The impact of 68Ga-PSMA PET/CT on the treatment decision was assessed. Patients with oligometastatic (≤5 lesions) PC underwent radiotherapy (RT), with the extent of the RT area and dose escalation being based on PET positivity.ResultsSuspicious lesions were detected in 24/45 (53.3xa0%) patients. In 62.5xa0% of patients, lesions were only detected by 68Ga-PSMA PET. Treatment was changed in 19/45 (42.2xa0%) patients, e.g., extending SRT to metastases (9/19), administering dose escalation in patients with morphological local recurrence (6/19), or replacing SRT by systemic therapy (2/19). 38/45 (84.4xa0%) followed the treatment recommendation, with data on clinical follow-up being available in 21 patients treated with SRT. All but one showed biochemical response (mean PSA decline 78u2009±u200919xa0%) within a mean follow-up of 8.12u2009±u20095.23xa0months.Conclusions68Ga-PSMA PET/CT impacts treatment planning in more than 40xa0% of patients scheduled to undergo SRT. Future prospective studies are needed to confirm this significant therapeutic impact on patients prior to SRT.

68Ga-PSMA-PET for radiation treatment planning in prostate cancer recurrences after surgery: Individualized medicine or new standard in salvage treatment

68Ga‐PSMA‐PET imaging is a novel promising diagnostic tool to locate early biochemical failure after radical prostatectomy (RP) in prostate cancer (PC) patients. Exact knowledge of the relapse location may result in changes of the therapy concept aside from changes to the TNM stage. To gain data for this approach, we evaluated PC patients receiving 68Ga‐PSMA‐PET imaging before salvage radiotherapy (RT).

Pearls and pitfalls in clinical interpretation of prostate-specific membrane antigen (PSMA)-targeted PET imaging

BackgroundThe rapidly expanding clinical adaptation of prostate-specific membrane antigen (PSMA)-targeted PET imaging in the evaluation of patients with prostate cancer has placed an increasing onus on understanding both the potential pearls of interpretation as well as limitations of this new technique. As with any new molecular imaging modality, accurate characterization of abnormalities on PSMA-targeted PET imaging can be accomplished only if one is aware of the normal distribution pattern, physiological variants of radiotracer uptake, and potential sources of false-positive and false-negative imaging findings. In recent years, a growing number of reports have come to light describing incidental non-prostatic benign or malignant pathologies with high uptake on PSMA-targeted PET imaging. In this review, we have summarized the published literature regarding the potential pearls and technical and interpretive pitfalls of this imaging modality. Knowledge of these limitations can increase the confidence of interpreting physicians and thus improve patient care.ConclusionsAs PSMA-targeted PET is expected to be evaluated in larger prospective trials, the dissemination of potential diagnostic pitfalls and the biologic underpinning of those findings will be of increased importance.

The Impact of Somatostatin Receptor–Directed PET/CT on the Management of Patients with Neuroendocrine Tumor: A Systematic Review and Meta-Analysis

Somatostatin receptor (SSTR) imaging is widely used for guiding the management of neuroendocrine tumor (NET) patients. 68Ga-DOTATATE approval by the U.S. Food and Drug Administration has triggered widespread clinical interest in SSTR PET/CT throughout the United States. Here, we performed a systematic review and meta-analysis to evaluate the impact of SSTR PET/CT on the management of patients with NETs. Methods: A comprehensive literature search was performed using The National Center for Biotechnology Information PubMed online database, applying the following key words: “management” AND “PET” AND “neuroendocrine”. Fourteen of 190 studies were deemed suitable based on the following inclusion criteria: original research, cohort study, number of patients 10 or more, and reported change in management after SSTR PET/CT. Change in management across studies was determined by a random-effects model. Results: A total of 1,561 patients were included. Overall, change in management occurred in 44% (range, 16%–71%) of NET patients after SSTR PET/CT. In 4 of 14 studies, SSTR PET/CT was performed after an 111In-Octreotide scan. In this subgroup, additional information by SSTR PET/CT led to a change in management in 39% (range, 16%–71%) of patients. Seven of 14 studies differentiated between inter- and intramodality changes, with most changes being intermodality (77%; intramodality, 23%). Conclusion: The management was changed in more than one third of patients undergoing SSTR PET/CT even when performed after an 111In-Octreotide scan. Intermodality changes were 3 times more likely than intramodality changes, underlining the clinical impact of SSTR PET/CT.

68Ga-PSMA-11 PET/CT interobserver agreement for prostate cancer assessments: an international multicenter prospective study

The interobserver agreement for 68Ga-PSMA-11 PET/CT study interpretations in patients with prostate cancer is unknown. Methods: 68Ga-PSMA-11 PET/CT was performed in 50 patients with prostate cancer for biochemical recurrence (n = 25), primary diagnosis (n = 10), biochemical persistence after primary therapy (n = 5), or staging of known metastatic disease (n = 10). Images were reviewed by 16 observers who used a standardized approach for interpretation of local (T), nodal (N), bone (Mb), or visceral (Mc) involvement. Observers were classified as having a low (<30 prior 68Ga-PSMA-11 PET/CT studies; n = 5), intermediate (30–300 studies; n = 5), or high level of experience (>300 studies; n = 6). Histopathology (n = 25, 50%), post–external-beam radiation therapy prostate-specific antigen response (n = 15, 30%), or follow-up PET/CT (n = 10, 20%) served as a standard of reference. Observer groups were compared by overall agreement (% patients matching the standard of reference) and Fleiss κ with mean and corresponding 95% confidence interval (CI). Results: Agreement among all observers was substantial for T (κ = 0.62; 95% CI, 0.59–0.64) and N (κ = 0.74; 95% CI, 0.71–0.76) staging and almost perfect for Mb (κ = 0.88; 95% CI, 0.86–0.91) staging. Level of experience positively correlated with agreement for T (κ = 0.73/0.66/0.50 for high/intermediate/low experience, respectively), N (κ = 0.80/0.76/0.64, respectively), and Mc staging (κ = 0.61/0.46/0.36, respectively). Interobserver agreement for Mb was almost perfect irrespective of prior experience (κ = 0.87/0.91/0.88, respectively). Observers with low experience, when compared with intermediate and high experience, demonstrated significantly lower median overall agreement (54% vs. 66% and 76%, P = 0.041) and specificity for T staging (73% vs. 88% and 93%, P = 0.032). Conclusion: The interpretation of 68Ga-PSMA-11 PET/CT for prostate cancer staging is highly consistent among observers with high levels of experience, especially for nodal and bone assessments. Initial training on at least 30 patient cases is recommended to ensure acceptable performance.

68Ga-PSMA-11 PET/CT Mapping of Prostate Cancer Biochemical Recurrence After Radical Prostatectomy in 270 Patients with a PSA Level of Less Than 1.0 ng/mL: Impact on Salvage Radiotherapy Planning

Target volume delineations for prostate cancer (PCa) salvage radiotherapy (SRT) after radical prostatectomy are usually drawn in the absence of visibly recurrent disease. 68Ga-labeled prostate-specific membrane antigen (PSMA-11) PET/CT detects recurrent PCa with sensitivity superior to standard-of-care imaging at serum prostate-specific antigen (PSA) values low enough to affect target volume delineations for routine SRT. Our objective was to map the recurrence pattern of PCa early biochemical recurrence (BCR) after radical prostatectomy with 68Ga-PSMA-11 PET/CT in patients with serum PSA levels of less than 1 ng/mL, determine how often consensus clinical target volumes (CTVs) based on the Radiation Therapy Oncology Group (RTOG) guidelines cover 68Ga-PSMA-11 PET/CT-defined disease, and assess the potential impact of 68Ga-PSMA-11 PET/CT on SRT. Methods: This was a post hoc analysis of an intention-to-treat population of 270 patients who underwent 68Ga-PSMA-11 PET/CT at 4 institutions for BCR after prostatectomy without prior radiotherapy at a PSA level of less than 1 ng/mL. RTOG consensus CTVs that included both the prostate bed and the pelvic lymph nodes were contoured on the CT dataset of the PET/CT image by a radiation oncologist masked to the PET component. 68Ga-PSMA-11 PET/CT images were analyzed by a nuclear medicine physician. 68Ga-PSMA-11–positive lesions not covered by planning volumes based on the consensus CTVs were considered to have a potential major impact on treatment planning. Results: The median PSA level at the time of 68Ga-PSMA-11 PET/CT was 0.48 ng/mL (range, 0.03–1 ng/mL). One hundred thirty-two of 270 patients (49%) had a positive 68Ga-PSMA-11 PET/CT result. Fifty-two of 270 (19%) had at least one PSMA-11–positive lesion not covered by the consensus CTVs. Thirty-three of 270 (12%) had extrapelvic PSMA-11–positive lesions, and 19 of 270 (7%) had PSMA-11–positive lesions within the pelvis but not covered by the consensus CTVs. The 2 most common 68Ga-PSMA-11–positive lesion locations outside the consensus CTVs were bone (23/52, 44%) and perirectal lymph nodes (16/52, 31%). Conclusion: Post hoc analysis of 68Ga-PSMA-11 PET/CT implied a major impact on SRT planning in 52 of 270 patients (19%) with PCa early BCR (PSA < 1.0 ng/mL). This finding justifies a randomized imaging trial of SRT with or without 68Ga-PSMA-11 PET/CT investigating its potential benefit on clinical outcome.

177Lu-PSMA radioligand therapy for prostate cancer

177Lu-prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) using inhibitors of PSMA is a novel therapeutic option in patients with metastatic castration-resistant prostate cancer. The current literature suggests that this therapy is well tolerated and effective. On the basis of clinical need and current evidence, the therapy is being implemented in a growing number of centers worldwide. Here, we review important aspects of 177Lu-PSMA RLT, including patient stratification, the therapy protocol, concomitant medication, and follow-up, to inform medical staff involved in the RLT and care of patients with metastatic castration-resistant prostate cancer.

Prostate-Specific Membrane Antigen Ligands for Imaging and Therapy

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-urea–based PSMA ligands used for both imaging and radioligand therapy are the mainstays of the current success. For PET imaging, both 68Ga- and 18F-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 177Lu-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 177Lu-PSMA radioligand therapy, with only minimal grade 3 and 4 toxicities reported so far, it has the potential to expand options for metastatic castration-resistant 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.

Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE): Proposed miTNM Classification for the Interpretation of PSMA-Ligand PET/CT

Prostate-specific membrane antigen (PSMA)–ligand PET imaging provides unprecedented accuracy for whole-body staging of prostate cancer. As PSMA-ligand PET/CT is increasingly adopted in clinical trials and routine practice worldwide, a unified language for image reporting is urgently needed. We propose a molecular imaging TNM system (miTNM, version 1.0) as a standardized reporting framework for PSMA-ligand PET/CT or PET/MRI. miTNM is designed to organize findings in comprehensible categories to promote the exchange of information among physicians and institutions. Additionally, flowcharts integrating findings of PSMA-ligand PET and morphologic imaging have been designed to guide image interpretation. Specific applications, such as assessment of prognosis or impact on management, should be evaluated in future trials. miTNM is a living framework that evolves with clinical experience and scientific data.