Steven Stone, PhD, presents “UroVision Interview – Simon Criteria for Biomarkers in Urologic Oncology.”
How to cite: Stone, Steven. “UroVision Interview – Simon Criteria for Biomarkers in Urologic Oncology.” February 19, 2025. Accessed Nov 2025. https://grandroundsinurology.com/urovision-interview-simon-criteria-for-biomarkers-in-urologic-oncology/
UroVision Interview – Simon Criteria for Biomarkers in Urologic Oncology – Summary
E. David Crawford, MD, Editor in Chief of Grand Rounds in Urology and Professor of Urology at the University of California, San Diego, introduces Steven Stone, PhD, EVP of Research and Development at Envision Sciences, Salt Lake City, Utah. In this 12-minute discussion, Dr. Steven Stone addresses the utility of the Simon criteria as a framework for validating prognostic and predictive biomarkers, particularly in urologic oncology. He emphasizes that while randomized clinical trials (RCTs) are considered the gold standard for assessing medical utility, especially for predictive biomarkers, their role in validating prognostic markers is more nuanced.
Stone begins by affirming the value of RCTs in therapeutic contexts: randomization balances known and unknown confounders, enabling reliable attribution of outcome differences to the intervention. This rationale extends naturally to predictive biomarkers. However, he argues that prognostic biomarkers that stratify risk independent of therapy do not necessarily require validation within RCTs. He contends that if prospectively assembled with prespecified endpoints and rigorous tissue/sample collection protocols, real-world observational cohorts may provide stronger external validity. Prognostic tests are often intended for heterogeneous populations with varied clinical courses and treatments, which RCT populations typically do not reflect.
Stone also critiques rigid adherence to the Simon criteria in clinical guideline inclusion. He calls for guideline committees to adopt a more holistic, case-by-case evaluation of biomarker evidence, similar to FDA review practices, accounting for prospective design, statistical planning, and clinical relevance of endpoints such as metastasis or disease-specific mortality.
Dr. Stone acknowledges the role of RCTs in late-stage biomarker development, particularly in demonstrating that risk stratification based on biomarkers improves outcomes, reduces morbidity, or optimizes resource utilization. However, he emphasizes that initial validation of prognostic biomarkers does not require randomization if robust real-world methodologies are employed.
