Setting the Stage: ADT in Intermediate-Risk Prostate Cancer

In this segment, Amar U. Kishan, MD, of UCLA explains that short-course androgen deprivation therapy (ADT) alongside definitive radiotherapy has long been a standard of care in this setting, supported by randomized trial evidence showing improvements in outcomes such as metastasis-free survival and overall survival. ADT achieves this benefit in part by acting as a potent radiosensitizer, enhancing the curative potential of radiation. Yet that population-level benefit obscures substantial individual variation: the absolute gain a given patient receives from ADT depends heavily on that patient's underlying risk of disease progression, which is a figure that current staging tools do not reliably capture.

The National Comprehensive Cancer Network (NCCN) risk grouping system, which divides the intermediate-risk category into favorable and unfavorable subgroups based on Gleason score, prostate-specific antigen level, clinical T stage, and biopsy core data, is a useful but imprecise instrument. Kishan illustrates the problem with a concrete example: a patient whose distant metastasis risk falls from 20% to 10% with ADT gains an absolute benefit of 10 percentage points, while a patient whose risk falls from 2% to 1% gains only 1 percentage point—yet both patients experience the same relative risk reduction and would receive the same recommendation under a population-based guideline. This mismatch between population-level evidence and individual-level benefit is precisely what drives unnecessary ADT use.

The segment also introduces the evaluative framework that underlies the ArteraAI test's development. Kishan distinguishes between prognostic biomarkers, which estimate the likelihood of disease progression independent of treatment, and predictive biomarkers, which estimate the magnitude of benefit from a specific therapy. He notes that most available prostate cancer biomarkers are prognostic, not predictive, and that establishing predictive value requires the methodological rigor of a prospective randomized controlled trial.