Artificial Intelligence Predictive Model for Hormone Therapy Use in Prostate Cancer.

Background Androgen deprivation therapy (ADT) with radiotherapy can benefit patients with localized prostate cancer. However, ADT can negatively impact quality of life and there remain no validated predictive models to guide its use. Methods Digital pathology image and clinical data from pre-treatment prostate tissue from 5,727 patients enrolled on five phase III randomized trials treated with radiotherapy +/- ADT were used to develop and validate an artificial intelligence (AI)-derived predictive model to assess ADT benefit with the primary endpoint of distant metastasis. After the model was locked, validation was performed on NRG/RTOG 9408 (n = 1,594) that randomized men to radiotherapy +/- 4 months of ADT. Fine-Gray regression and restricted mean survival times were used to assess the interaction between treatment and predictive model and within predictive model positive and negative subgroup treatment effects. Results In the NRG/RTOG 9408 validation cohort (14.9 years of median follow-up), ADT significantly improved time to distant metastasis (subdistribution hazard ratio [sHR] = 0.64, 95%CI [0.45-0.90], p = 0.01). The predictive model-treatment interaction was significant (p-interaction = 0.01). In predictive model positive patients (n = 543, 34%), ADT significantly reduced the risk of distant metastasis compared to radiotherapy alone (sHR = 0.34, 95%CI [0.19-0.63], p < 0.001). There were no significant differences between treatment arms in the predictive model negative subgroup (n = 1,051, 66%; sHR = 0.92, 95%CI [0.59-1.43], p = 0.71). Conclusions Our data, derived and validated from completed randomized phase III trials, show that an AI-based predictive model was able to identify prostate cancer patients, with predominately intermediate-risk disease, who are likely to benefit from short-term ADT.

Research square. 2023 Apr 21*** epublish ***

Daniel E Spratt, Siyi Tang, Yilun Sun, Huei-Chung Huang, Emmalyn Chen, Osama Mohamad, Andrew J Armstrong, Jonathan D Tward, Paul L Nguyen, Joshua M Lang, Jingbin Zhang, Akinori Mitani, Jeffry P Simko, Sandy DeVries, Douwe van der Wal, Hans Pinckaers, Jedidiah M Monson, Holly A Campbell, James Wallace, Michelle J Ferguson, Jean-Paul Bahary, Edward M Schaeffer, Nrg Prostate Cancer Ai Consortium, Howard M Sandler, Phuoc T Tran, Joseph P Rodgers, Andre Esteva, Rikiya Yamashita, Felix Y Feng