The SPARTAN trial demonstrated that the addition of apalutamide to androgen deprivation therapy improves outcomes among patients with nonmetastatic castration-resistant prostate cancer (nmCRPC). We applied a previously reported digital histopathology-based multimodal artificial intelligence (MMAI) algorithm to estimate clinical outcomes in SPARTAN.
Patients with available hematoxylin and eosin-stained slides from the primary tumor were included. Histopathology slides were digitized. MMAI scores ranging from 0 to 1 were generated from digital histopathology and baseline clinical parameters. Patients were categorized into MMAI non-high-risk and high-risk groups using previously validated cutoffs. Kaplan-Meier estimates were calculated for metastasis-free survival (MFS), second progression-free survival (PFS2), and overall survival (OS); comparisons were performed using Cox proportional hazards regression for treatment arms and MMAI risk. The interaction between treatment arm and risk group was evaluated using a Cox proportional hazards model.
The study included 420 evaluable patients after excluding those with missing clinical data or inadequate histopathology images. Of these, 63% (n = 266) were MMAI high risk and 37% (n = 154) were non-high risk. MMAI risk score was associated with shorter MFS (hazard ratio [HR], 1.72; P < .005), PFS2 (HR, 1.57; P < .005), and OS (HR, 1.41; P = .02). MMAI high-risk patients receiving apalutamide demonstrated significant improvement in MFS (HR, 0.19; P < .005), PFS2 (HR, 0.47; P < .005), and OS (HR, 0.6; P = .01). The interaction between MMAI risk score and treatment for MFS (P = .01) and PFS2 (P = .03) was significant, indicating greater benefit from apalutamide treatment in MMAI high-risk patients.
MMAI is a prognostic marker in nmCRPC and may serve as a predictive biomarker with high-risk patients deriving the greatest benefit from treatment with apalutamide. These results represent the first extension of an MMAI classifier to patients with castration-resistant prostate cancer, warranting additional validation.
JCO precision oncology. 2025 Jan 31 [Epub]
Felix Y Feng, Matthew R Smith, Fred Saad, Pooya Mobadersany, Shaozhou K Tian, Stephen S F Yip, Joel Greshock, Najat Khan, Margaret K Yu, Sharon McCarthy, Sabine D Brookman-May, Ariel B Bourla, Tamara Todorovic, Rikiya Yamashita, Huei-Chung Huang, Trevor J Royce, Timothy N Showalter, Jacqueline Griffin, Akinori Mitani, Andre Esteva, Eric J Small
Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA., Massachusetts General Hospital Cancer Center, Boston, MA., Centre Hospitalier de l'Université de Montréal, Université de Montréal, Montréal, QC, Canada., Janssen Research & Development, New Brunswick, NJ., Artera Inc, Los Altos, CA.