Stress testing deep learning models for prostate cancer detection on biopsies and surgical specimens.

Journal: The Journal of pathology
PMID:

Abstract

The presence, location, and extent of prostate cancer is assessed by pathologists using H&E-stained tissue slides. Machine learning approaches can accomplish these tasks for both biopsies and radical prostatectomies. Deep learning approaches using convolutional neural networks (CNNs) have been shown to identify cancer in pathologic slides, some securing regulatory approval for clinical use. However, differences in sample processing can subtly alter the morphology between sample types, making it unclear whether deep learning algorithms will consistently work on both types of slide images. Our goal was to investigate whether morphological differences between sample types affected the performance of biopsy-trained cancer detection CNN models when applied to radical prostatectomies and vice versa using multiple cohorts (N = 1,000). Radical prostatectomies (N = 100) and biopsies (N = 50) were acquired from The University of Pennsylvania to train (80%) and validate (20%) a DenseNet CNN for biopsies (M), radical prostatectomies (M), and a combined dataset (M). On a tile level, M and M achieved F1 scores greater than 0.88 when applied to their own sample type but less than 0.65 when applied across sample types. On a whole-slide level, models achieved significantly better performance on their own sample type compared to the alternative model (p < 0.05) for all metrics. This was confirmed by external validation using digitized biopsy slide images from a clinical trial [NRG Radiation Therapy Oncology Group (RTOG)] (NRG/RTOG 0521, N = 750) via both qualitative and quantitative analyses (p < 0.05). A comprehensive review of model outputs revealed morphologically driven decision making that adversely affected model performance. M appeared to be challenged with the analysis of open gland structures, whereas M appeared to be challenged with closed gland structures, indicating potential morphological variation between the training sets. These findings suggest that differences in morphology and heterogeneity necessitate the need for more tailored, sample-specific (i.e. biopsy and surgical) machine learning models. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Authors

  • Brennan T Flannery
    Case Western Reserve University, Cleveland, OH, USA.
  • Howard M Sandler
    Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Priti Lal
    Department of Pathology, University of Pennsylvania, Philadelphia, Pennsylvania.
  • Michael D Feldman
    Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.
  • Juan C Santa-Rosario
    CorePlus, Carolina, Puerto Rico.
  • Tilak Pathak
    Emory Winship Cancer Institute, Atlanta, GA, USA.
  • Tuomas Mirtti
    Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
  • Xavier Farré
    Department of Health, Public Health Agency of Catalonia, Lleida, Catalonia, Spain.
  • Rohann Correa
    Department of Oncology, London Health Sciences Centre, London, ON, Canada.
  • Susan Chafe
    Cross Cancer Institute, Edmonton, AB, Canada.
  • Amit Shah
  • Jason A Efstathiou
    Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts. Electronic address: jefstathiou@partners.org.
  • Karen Hoffman
    The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Mark A Hallman
    Fox Chase Cancer Center, Philadelphia, PA, USA.
  • Michael Straza
    Medical College of Wisconsin, Milwaukee, WI, USA.
  • Richard Jordan
    NRG Oncology Biospecimen Bank, San Francisco, CA, USA.
  • Stephanie L Pugh
    NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania.
  • Felix Feng
    University of California San Francisco, San Francisco, CA, USA.
  • Anant Madabhushi
    Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio.