Gafita, Andrei

PURPOSE The continuous development of new imaging approaches, molecular phenotyping, genetic subtypes, prognosis assessments, and effective therapies across a range of disease states has created a need to redefine terminology and best practices for clinical trial conduct in patients with advanced prostate cancer. Methods We convened an international expert committee of diverse working groups, the Prostate Cancer Working Group 4 (PCWG4), between 2016 and 2025. Our objective was to formulate updated criteria based on emerging evidence and clinical trial data in a biomarker context to provide guidance for clinical trial design, eligibility, and end point assessments for patients with advanced prostate cancer. RESULTS PCWG4 redefines terminology around the disease state and previous therapies in a patient-centric context and terminology focused on androgen pathway modulation. We consider imaging, with a particular focus on positron emission tomography (PET)–defined disease. New recommendations are provided for disease state terminology, defining eligibility criteria, response and delay/prevent end points, intervals for reassessments including imaging, and patient-reported outcome determination. We provide recommendations in a biomarker-based context of use for the intended indication, reflective of patient benefit for specific interventions. We emphasize the need for development of validated PET imaging and molecular and phenotypic criteria as well as trial designs to appropriately risk stratify patients, predict and assess benefit, and measure post-treatment outcomes reliably in a trial framework. CONCLUSION PCWG4 updates recommendations on patient and tumor characterization, therapy development, and imaging criteria and extends guidance into earlier androgen pathway modulator–naïve/sensitive disease states to reflect an evolving, heterogeneous, and diverse patient population to optimize treatment benefits for all patients.

Black patients with metastatic prostate cancer have higher mortality rates compared to non-Hispanic White patients. There are no data on outcomes with [177Lu]Lu-PSMA-617 (LuPSMA) across racial groups. We evaluated the association between race and outcomes with LuPSMA in a multi-institutional cohort of consecutive patients with mCRPC treated with LuPSMA. The primary outcomes were PSA-50 rate, PSA-progression-free survival (PSA-PFS), and overall survival (OS). Statistical models were adjusted for age, number of prior therapies, sites of metastases, and baseline PSA. A total of 654 patients were included; 593 (91%) were White, 45 (7%) were Black and 16 (2%) were another non-Black minority (NBM). There were no statistically significant differences in PSA-50 rates, PSA-PFS and OS between the groups. Black and White patients treated with LuPSMA had similar clinical outcomes; efforts are needed to ensure Black and NBM patients have equal access to life prolonging therapies to narrow disparities in outcomes.

e17061 Background: ThePhase 3 VISION trial demonstrated that [177Lu]Lu-PSMA-617 prolonged overall survival (OS) in metastatic-castration resistant prostate cancer (mCRPC) patients who progressed on taxane-based chemotherapy and androgen receptor-signaling inhibitors (ARSi). The expanded access program (EAP) (NCT04825652) was opened to provide access to [177Lu]Lu-PSMA-617 for eligible patients until regulatory approval was obtained. The VISION trial required strict inclusion and exclusion criteria, which may not represent the patient population encountered in clinical practice. This study aimed to evaluate the efficacy and safety profile of [177Lu]Lu-PSMA-617 in a real-world setting within the EAP and compare the results with those from the VISION trial. Methods: Patients enrolled in the EAP between May 2021 and March 2022 at four institutions in the United States with available toxicity and outcome data were included. Outcome measures included overall survival (OS), ≥50% PSA decline rates (PSA-RR), and incidences of toxicity according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Differences in baseline characteristics, toxicity, and PSA-RR between the EAP and VISION were evaluated using a t-test of proportions. Results: 117 patients with mCRPC were eligible and included. Patients enrolled in the EAP were similarly pretreated with taxane-based chemotherapy regimens (>1 taxane: 47% vs 40%; p=0.16) and more heavily pretreated with ARSi (>1 ARSi: 70% vs 46%; p<0.001). EAP patients had similar levels of ≥3 grade anemia (18% vs 13%; p=0.15), thrombocytopenia (13% vs 8%; p=0.13), and neutropenia (3% vs 3%; p=0.85) and higher levels of ≥3 grade lymphopenia (34% vs 8%; p<0.001). Patients treated within the EAP experienced numerically shorter OS (median OS: 13.7 vs 15.3 months) and similar PSA-RR (40% vs 46%; p=0.29). Median follow-up was numerically shorter in the EAP compared with VISION (14.7 mo vs 20.3 mo). Conclusions: mCRPC patients treated with [177Lu]Lu-PSMA-617 in a real-world setting were more heavily pretreated with ARSi, had a similar safety profile, and experienced numerically shorter OS and similar PSA-RR compared with VISION trial patients. A major limitation of this study is that we did not have access to individual patient data from the VISION trial, so we were not able to assess whether differences in OS between VISION and the EAP were statistically significant.