Biopsy-Based Basal-Luminal Subtyping Classifier in High-Risk Prostate Cancer: A Combined Analysis of the NRG Oncology/RTOG 9202, 9413, and 9902 Phase 3 Trials

Tens of thousands of patients are diagnosed with high-risk, localized prostate cancer yearly, and many of these patients have a choice between either surgery with the possibility of requiring post operative radiotherapy and androgen deprivation therapy (ADT) or radiotherapy (RT) with long-term ADT (≥ 24 months).

Many patients elect for the former given their desire to avoid long courses of ADT. To date, there has been no patient-tailored approach to help predict which patient will benefit from long-term ADT, and the development of such an approach may help change some patient’s preferences for their initial management either with surgery or radiation therapy.

In this paper, Biopsy-Based Basal-Luminal Subtyping Classifier in High-Risk Prostate Cancer: A Combined Analysis of the NRG Oncology/RTOG 9202, 9413, and 9902 Phase III Trials (PMID: 39542826), Krishnan Patel and colleagues evaluate the utility of a 215-gene-expression-based, cell-of-origin classifier developed via machine learning called the Prostate Subtyping Classifier (PSC). This study evaluates the PSC in three prior, phase III, clinical trials (NRG/RTOG 9202, 9413, and 9902) which randomized patients with high-risk prostate cancer to short-term ADT (4 months) or long-term ADT (≥ 24 months). This study finds that the PSC serves both as a prognostic and predictive biomarker in this patient population. That is, the PSC not only may allow providers to help patients understand the likelihood they will die of prostate cancer (i.e., prostate cancer-specific mortality [PCSM]), but it also helps them understand which patients will benefit from extended courses of ADT.

Specifically, patients with luminal-subtype tumors did not appear to benefit from an extension of their ADT course from 4 to ≥ 24 months, whereas patients with basal-subtypes did appear to benefit from longer courses of ADT. The findings from this study have the potential to help personalize ADT decision making for tens of thousands of patients and may, potentially, help to reduce “over treatment” or the extension of ADT duration in some patients who are unlikely to benefit, such as those who have PSC luminal-subtype tumors.

Written by: Krishnan Patel, MD, Radiation Oncology Branch, National Cancer Institute, NIH, Bethesda, MD

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