Predictive models of response to neoadjuvant chemotherapy in muscle-invasive bladder cancer using nuclear morphology and tissue architecture

Cell Rep Med. 2021 Aug 27;2(9):100382. doi: 10.1016/j.xcrm.2021.100382. eCollection 2021 Sep 21.

Abstract

Characterizing likelihood of response to neoadjuvant chemotherapy (NAC) in muscle-invasive bladder cancer (MIBC) is an important yet unmet challenge. In this study, a machine-learning framework is developed using imaging of biopsy pathology specimens to generate models of likelihood of NAC response. Developed using cross-validation (evaluable N = 66) and an independent validation cohort (evaluable N = 56), our models achieve promising results (65%-73% accuracy). Interestingly, one model-using features derived from hematoxylin and eosin (H&E)-stained tissues in conjunction with clinico-demographic features-is able to stratify the cohort into likely responders in cross-validation and the validation cohort (response rate of 65% for predicted responder compared with the 41% baseline response rate in the validation cohort). The results suggest that computational approaches applied to routine pathology specimens of MIBC can capture differences between responders and non-responders to NAC and should therefore be considered in the future design of precision oncology for MIBC.

Keywords: bladder cancer; chemotherapy; digital pathology; image processing; machine learning; neoadjuvant; nucleus morphology; predictive biomarkers; tissue architecture.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cell Nucleus / pathology*
  • Cohort Studies
  • Female
  • Humans
  • Image Processing, Computer-Assisted
  • Machine Learning
  • Male
  • Middle Aged
  • Models, Biological*
  • Muscles / pathology*
  • Neoadjuvant Therapy*
  • Neoplasm Invasiveness
  • Survival Analysis
  • Tumor Microenvironment
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / pathology*