Real-world Data to Assess the Applicability of Randomized Controlled Trials in Newly Metastatic Prostate Cancer

Why clinicians should know about it

• Picked for Urology (top studies of the week, 8 November 2026): Up to half of real-world mHSPC patients ineligible

Abstract

BACKGROUND: Concerns persist regarding the applicability of randomized controlled trials (RCTs) on metastatic hormone-sensitive prostate cancer (mHSPC) to real-world clinical practice. OBJECTIVE: We aimed to evaluate the generalizability of RCTs using data from PIONEER. DESIGN, SETTING AND PARTICIPANTS: Trial eligibility criteria were extracted from RCTs enrolling patients with mHSPC published between 2013 and 2023 and identified through a literature review. Patients with newly diagnosed mHSPC were identified from insurance claim databases mapped to the Observational Medical Outcomes Partnership Common Data Model. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: The proportion of patients failing to meet at least one RCT eligibility criterion was assessed for each trial. The proportion of men receiving RCT-investigated treatments who would have been ineligible for the corresponding trials was estimated. RESULTS AND LIMITATIONS: Overall, 12 trials were identified. From ∼398 000 patients with prostate cancer included in three databases, we identified 32 585 newly diagnosed mHSPC cases. The percentage of patients who would have been excluded from each RCT ranged between 8.6% and 55%. The percentage of patients who would be excluded from all trials ranged between 5.9% and 12% and increased to 26-44% when excluding the HORRAD trial. The most common reasons for exclusion were anemia (16-29%), heart failure (6.2-13%), and renal failure (3.9-19%). Between 18% and 52% of the patients receiving a drug would have been excluded from RCTs evaluating that drug. Limitations include database representativeness, incomplete clinical data, and limited generalizability to metachronous mHSPC. CONCLUSIONS: Up to half of real-world patients with newly diagnosed mHSPC would have been ineligible for RCT participation, yet many received therapies despite trial ineligibility. This highlights the need for more inclusive and representative research and a comprehensive examination of real-world data for clinical decision-making. PATIENTS SUMMARY: Up to half of real-world patients with newly diagnosed metastatic hormone-sensitive prostate cancer would have not been eligible for participation in clinical trials. A substantial proportion of patients receiving trial-tested therapies in routine clinical practice would have been excluded from the corresponding randomized controlled trials.

Abstract as published, via PubMed.