Prostate-Specific Membrane Antigen (PSMA)-Targeted Radionuclide Therapies for Prostate Cancer.

PURPOSE OF REVIEW: Prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy (TRT) is a promising investigational treatment for metastatic castration-resistant prostate cancer (mCRPC). This review describes the available data with PSMA TRT. RECENT FINDINGS: Conjugates used for PSMA TRT include antibodies or small molecules PSMA-radiolabeled with beta (most commonly 177Lu) or alpha emitters (commonly 225Ac). 177Lu-J591 demonstrated accurate targeting of known metastatic sites, based on post-treatment scintigraphy, in study populations that were not selected for PSMA expression, with evidence of dose-response and dose-limiting myelosuppression. Early phase studies of 177Lu-PSMA-617 have demonstrated favorable adverse event profiles and signs of clinical activity as evidenced by PSA responses and other short-term outcomes. A phase II randomized study of 177Lu-PSMA-617 showed a superior PSA50 response rate (66 vs 37%) over cabazitaxel in patients with docetaxel-pretreated, progressive mCRPC selected by PSMA and FDG PET/CT scans. PSMA TRT is emerging as a promising investigational therapy for mCRPC. The first randomized data with 177Lu-PSMA-617 (phase 2) have been presented, and the first phase 3 trial has completed accrual with radiographic progression-free and overall survival as dual primary endpoints. Multiple additional phase 3 trials of PSMA-TRT are starting and studies investigating optimal patient selection and combination therapy continue.

Risk Factor Analysis Between Newly Screened and Established Hepatitis C in GI and Hepatology Clinics.

BACKGROUND: Several studies show inconsistencies in the rate of hepatitis C virus (HCV) detection among baby boomers (born 1945-1965). We conducted a cross-sectional HCV screening followed by a case-controlled comparison of the newly screened population with established HCV subjects. METHOD: Enrollment was offered to subjects aged 40-75 at our gastroenterology and hepatology clinics. Demographic data and potential risk factors were obtained, and HCV antibody test was offered to those who had never been screened and compared with a group with established HCV. Logistic regression analysis and Fisher's exact test were performed. RESULTS: Six hundred and seventy-five patients were offered participation, of whom 128 declined while 50 consented to participate but did not perform the HCV antibody test. Of 497 enrolled subjects, 252 patients had HCV, while 245 subjects (188 patients among "baby boomer") underwent screening for HCV. There were more females (62.4 vs. 41.7%) and immigrants (34.7 vs. 22.2%) among the newly screened group. Among the screened population, five patients had HCV antibody (2.04%), and two of them had positive viral load (0.82%) of whom only one fell in the baby boomer category (0.53%). Compared to HCV group, screened group had significantly lower-risk factors, such as IV drug use (1.22 vs. 43.3%), intranasal cocaine use (14.3 vs. 49.6%), and blood transfusion (18.8 vs. 32.5%). CONCLUSION: We found a slightly lower but similar prevalence of HCV antibody when screening based on birth cohort as compared to larger baby boomer studies. Future studies evaluating addition of other screening strategies or possibly universal screening may be needed.

Review of commonly used prostate specific PET tracers used in prostate cancer imaging in current clinical practice.

18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) underperforms in detecting prostate cancer (PCa) due to inherent characteristics of primary and metastatic tumors, including relatively low rate of glucose utilization. Consequently, alternate PCa PET imaging agents targeting other aspects of PCa cell biology have been developed for clinical practice. The most common dedicated PET imaging tracers include 68Ga/18F prostate-specific membrane antigen (PSMA), 11C-Choline, and 18F-fluciclovine (Axumin™). This review will describe how these agents target specific inherent characteristics of PCa and explore the current literature for these agents for both primary and recurrent PCa, comparing the advantages and limitations of each tracer. Both 11C-Choline and 18F-Fluciclovine PET have been shown to detect nodal and osseous disease at higher rates compared to FDG-PET but offer no additional benefit in detecting prostate disease, especially in primary staging. As a result, PSMA PET, specifically 68Ga-PSMA-11, has emerged as a key imaging option for both primary and recurrent cancer. PSMA PET may be more sensitive than MRI at the local level and more sensitive than 11C-Choline and 18F-Fluciclovine PET for distant disease. Furthermore, compared to 11C-Choline and 18F-Fluciclovine PET, 68Ga-PSMA-11 PET has higher detection rates at low PSA levels (<2 ng/dL). With improved delineation of disease, PSMA imaging has influenced treatment planning; radiation fields can be narrowed, and patients with isolated or oligo-metastatic disease can be spared systemic therapy. The retrospective nature of many of the studies describing these PCa imaging modalities complicates their assessment and comparison.