Abstract
Metastatic prostate cancer is a clinically and molecularly heterogeneous disease. Under the selective pressure of androgen receptor–directed (AR-directed) therapies, resistant phenotypes frequently emerge, posing significant diagnostic and therapeutic challenges. Neuroendocrine prostate cancer (NEPC) is a clinically important phenotype characterized by lineage plasticity, neuroendocrine features, visceral metastases, and poor prognosis. Accurate diagnosis of NEPC remains difficult owing to its histologic and molecular complexity but has high clinical relevance. In this study, we developed a deep learning model that leverages interpretable cellular features to improve feature extraction from H&E-stained tissue sections (NEURAL-PC). By incorporating a multiple-instance learning framework, NEURAL-PC enables robust NEPC classification solely from H&E tumor images, achieving an area under the receiver operating characteristic curve of 0.921 in independent external validation. In addition to its diagnostic utility, NEURAL-PC provides prognostic information that enables further subclassification of advanced prostate cancer across diverse datasets, supporting its strong prognostic value and generalizability. Broadly, our work highlights a hybrid approach that integrates features across different domains, offering a promising strategy for developing reliable deep learning tools in pathology. Built on this framework, NEURAL-PC represents an extensively validated diagnostic and prognostic model for advanced prostate cancer.
Authors
Zhijun Chen, Erolcan Sayar, Daniela Guevara, Helen Richards, Haoyue Zhang, Radhika A. Patel, Agnes C. Gawne, Lucas J. Liu, Ilsa Coleman, Ruth Dumpit, Colm Morrissey, Michael T. Schweizer, Ruben Raychaudhuri, Laura S. Graham, Evan Y. Yu, Heather H. Cheng, Chien-Kuang C. Ding, Yuzhuo Wang, Peter Choyke, Baris Turkbey, Chantal Chanel-Vos, Christina Fedorov, John R. Otilano, Troy Kane, Jyothi Manohar, Michael Sigouros, Jones T. Nauseef, Ana Molina, David Nanus, Scott T. Tagawa, Juan Miguel Mosquera, Himisha P. Beltran, Ruth Etzioni, Peter S. Nelson, Rama Soundararajan, Ana M. Aparicio, Cora N. Sternberg, Michael C. Haffner, Stephanie A. Harmon
NEURAL-PC classification results for UW-MATCH cohort
