68Gallium prostate-specific membrane antigen (PSMA) ligand 68Ga-HBED-CC-PSMA (68Ga-PSMA) is a promising radiotracer for positron emission tomography (PET)/computed tomography (CT) of prostate cancer. To conduct a meta-analysis to evaluate detection rate, diagnostic test accuracy, and adverse effects of 68Ga-PSMA PET/CT or PET/magnetic resonance imaging (MRI) for staging of prostate cancer and for restaging of rising prostate-specific antigen (PSA) after initial treatment. Following the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines, our systematic review searched for articles in PubMed and EMBASE databases from 2012 to July 2016. The reference standard was pathology after biopsy or surgery. The analyses used a random effect model and a hierarchical summary receiver operating characteristic model. Fifteen 68Ga-PSMA PET/CT studies with 1256 patients met the inclusion criteria. Seven studies of staging PET/CT or PET/MRI detected a regional site of cancer for 203 of 273 patients (74%). Nine studies of restaging PET/CT detected sites of recurrence in 799 of 983 patients (81%) with a 50% detection rate (74 of 147 patients) for restaging PSA of 0.2-0.49 ng/ml and a 53% detection rate (56 of 195 patients) for restaging PSA of 0.50-0.99 ng/ml. Staging 68Ga-PSMA PET/CT in the studies had higher detection rates of sites in the prostate bed than restaging 68Ga-PSMA PET/CT (mean 57% vs 14%, p=0.031, t test). Both staging and restaging 68Ga-PSMA PET/CT found that a subgroup of the patients had metastatic sites in pelvic lymph nodes or distant organs. Eight studies of staging PET/CT undertook histologic correlations. We performed prostate-segment-based analysis specifically regarding the primary cancer lesion for four of these studies, and patient-based analysis specifically regarding pelvic lymph node metastases for four other studies. The pooled sensitivities for staging in the two groups of studies were 70% and 61%, and the pooled specificities were 84% and 97%. None of the studies reported complications from the PET/CT imaging. 68Ga-PSMA PET/CT has clinical relevance to detect sites of recurrence for patients with PSA recurrence after radical prostatectomy (RP) with PSA levels less than 1.0 ng/ml. Choline positron emission tomography (PET)/computed tomography (CT) can detect sites of recurrent prostate cancer in an earlier phase of prostate-specific antigen (PSA) recurrence than bone scans and CT scans, but choline PET/CT is rarely positive for patients with restaging PSA levels under 1 ng/ml. A new radiotracer called 68Ga-PSMA for PET/CT was able to detect sites of recurring cancer in up to 50% of patients who had an early rise in PSA exceeding 0.5 ng/ml after initial radical prostatectomy. The published studies did not report adverse effects of 68Ga-PSMA PET/CT imaging.

Aims There is a controversy as to the relative efficacy of ¹⁷⁷Lu prostate specific membrane antigen (PSMA) radioligand therapy (RLT) and third-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC). The aim of our systematic review was to elucidate whether ¹⁷⁷Lu-PSMA RLT and third-line treatment have similar effects and adverse effects (PROSPERO ID CRD42017067743). Methods The review followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Searches in Pubmed and Embase selected articles up to September 2017. A search in ClinicalTrials.gov indicated ongoing studies. The meta-analysis used the random-effects model. Results Twelve studies including 669 patients reported ¹⁷⁷Lu-PSMA RLT. Overall, 43% of the patients had a maximum decline of PSA of ≥50% following treatment with ¹⁷⁷Lu-PSMA RLT. The treatment with ¹⁷⁷Lu-PSMA-617 and ¹⁷⁷Lu-PSMA for imaging and therapy (I&T) had mainly transient adverse effects. Sixteen studies including 1338 patients reported third-line treatment. Overall, 21% of the patients had a best decline of PSA of ≥50% following third-line treatment. After third-line treatment with enzalutamide and cabazitaxel, adverse effects caused discontinuation of treatment for 10% to 23% of the patients. ¹⁷⁷Lu-PSMA RLT gave a best PSA decline ≥50% more often than third-line treatment (mean 44% versus 22%, p = 0.0002, t test). ¹⁷⁷Lu-PSMA RLT gave objective remission more often than third-line treatment (overall 31 of 109 patients versus 43 of 275 patients, p = 0.004, χ² test). Median survival was longer after ¹⁷⁷Lu-PSMA RLT than after third-line treatment, but the difference was not statistically significant (mean 14 months versus 12 months, p = 0.32, t test). Adverse effects caused discontinuation of treatment more often for third-line treatment than for ¹⁷⁷Lu-PSMA RLT (22 of 66 patients versus 0 of 469 patients, p < 0.001, χ² test). Conclusions As for patients with mCRPC, treatment with ¹⁷⁷Lu-PSMA-617 RTL and ¹⁷⁷Lu-PSMA I&T gave better effects and caused fewer adverse effects than third-line treatment.

177 Lu-PSMA radioligand therapy of predominant lymph node metastatic prostate cancer 177Lu-PSMA radioligand therapy of predominant lymph node metastatic prostate cancer

This study aimed to compare the diagnostic performance of [¹⁸F]PSMA-1007 positron emission tomography/computed tomography (PET/CT) (¹⁸F-PSMA) and [⁶⁸Ga]Ga-PSMA-11 PET/CT (⁶⁸Ga-PSMA) by identifying prostate-specific antigen (PSA) threshold levels for optimal detecting recurrent prostate cancer (PC) and to compare both methods. Retrospectively, the study included 264 patients. The performances of ¹⁸F-PSMA and ⁶⁸Ga-PSMA in relation to the pre-scan PSA were assessed by receiver operating characteristic (ROC) curve. ¹⁸F-PSMA showed PC-lesions in 87.5% (112/128 patients), while ⁶⁸Ga-PSMA identified them in 88.9% (121/136). For ¹⁸F-PSMA biochemical recurrent (BCR) patients treated with radical prostatectomy (78/128, patient group: F-RP), a PSA of 1.08 ng/mL was found to be the optimal cut-off level for predicting positive and negative scans (AUC = 0.821; 95%, CI: 0.710–0.932), while for prostatectomized ⁶⁸Ga-PSMA BCR-patients (89/136, patient group: Ga-RP), the cut-off was 1.84 ng/mL (AUC = 0.588; 95%, CI: 0.410–0.766). In patients with PSA < 1.08 ng/mL (F-RP) 76.3% and <1.84 ng/mL (Ga-RP) 78.6% scans were positive, whereas patients with PSA ≥ 1.08 ng/mL (F-RP) or 1.84 ng/mL (Ga-RP) had positive scan results in 100% and 91.5% (p < 0.001/p = 0.085). The identified PSA thresholds for PSMA-mappable PC lesions in BCR-patients (RP) showed a better separation for ¹⁸F-PSMA with regard to the distinguishing of positive and negative PC-lesions compared to ⁶⁸Ga-PSMA. However, the two PSMA PET/CT tracers gave similar overall findings.