Development and Validation of an Artificial Intelligence Digital Pathology Biomarker to Predict Benefit of Long-Term Hormonal Therapy and Radiotherapy in Men With High-Risk Prostate Cancer Across Multiple Phase III Trials.
Publication/Presentation Date
4-16-2025
Abstract
PURPOSE: Long-term androgen deprivation therapy (ADT) improves survival in men with high-risk localized prostate cancer (PCa) receiving radiotherapy (RT). Predictive biomarkers are needed to guide ADT duration.
METHODS: A multimodal artificial intelligence (MMAI)-derived predictive biomarker was trained for long-term (LT) versus short-term (ST) ADT using pretreatment digital prostate biopsy images and clinical data (age, prostate-specific antigen, Gleason, and T stage) from six NRG Oncology phase III randomized radiotherapy trials. The novel MMAI-derived biomarker was developed to predict the differential benefit of LT-ADT on the primary end point, distant metastasis (DM). MMAI predictive utility was validated on a seventh randomized trial, RTOG 9202 (N = 1,192), which randomly assigned men to RT + ST-ADT (4 months) versus RT + LT-ADT (28 months). Fine-Gray and cumulative incidence analyses for DM, and secondarily, death with DM, were performed. Deaths without DM were treated as competing risks.
RESULTS: In the validation cohort (median follow-up, 17.2 years), LT-ADT significantly improved DM from 26% to 17% (subdistribution hazard ratio [sHR], 0.64 [95% CI, 0.50 to 0.82],
CONCLUSION: To our knowledge, the MMAI model is the first validated predictive biomarker to guide ADT duration with RT in localized/locally advanced PCa. Approximately one third of men with high-risk PCa could safely be spared the additional 24 months of ADT and the associated morbidity.
First Page
2400365
Last Page
2400365
ISSN
1527-7755
Published In/Presented At
Armstrong, A. J., Liu, V. Y. T., Selvaraju, R. R., Chen, E., Simko, J. P., DeVries, S., Sartor, O., Sandler, H. M., Mohamad, O., Huang, H. C., Griffin, J., Yamashita, R., Esteva, A., Tran, P. T., Spratt, D. E., Carson, J. H., Peters, C., Gore, E., Lee, S. P., Monson, J. M., … Nguyen, P. L. (2025). Development and Validation of an Artificial Intelligence Digital Pathology Biomarker to Predict Benefit of Long-Term Hormonal Therapy and Radiotherapy in Men With High-Risk Prostate Cancer Across Multiple Phase III Trials. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, JCO2400365. Advance online publication. https://doi.org/10.1200/JCO.24.00365
Disciplines
Medicine and Health Sciences | Oncology
PubMedID
40239134
Department(s)
Department of Radiation Oncology
Document Type
Article