(UroToday.com) The 2023 American Society of Clinical Oncology (ASCO) annual meeting held in Chicago, IL between June 2nd and June 6th was host to a prostate, testicular, and penile cancers poster session. Dr. Pooya Mobadersany presented the results of an AI-enabled analysis of hematoxylin and eosin (H&E)-stained prostate cancer tissue images to assess the risk of subsequent metastasis in patients with non-metastatic castrate-resistant prostate cancer (nmCRPC) subsequently receiving apalutamide.
Apalutamide has been FDA approved for patients with nmCRPC based on overall survival benefits in the SPARTAN trial.1,2 Although the nmCRPC disease space is diminishing with the increased utilization of PSMA PET imaging, there remains a need to better risk characterize nmCRPC patients and improve our ability to predict those at increased risk of developing metastases on conventional imaging.
PATHOMIQ-PRAD is an AI-enabled prognostic algorithm that predicts the risk of metastasis from whole slide images of H&E-stained core biopsies or radical prostatectomy specimens. The objective of this study was to evaluate the rates of metastasis in nmCRPC patients, stratified by PATHOMIQ-PRAD risk grouping.
As demonstrated in the figure below, PATHOMIQ-PRAD is derived from H&E-stained pathology slides with patients assigned to a PATHOMIQ-PRAD “high” or “non-high” group.
The PATHOMIQ-PRAD model was developed and trained to predict time-to-metastasis, with metastasis defined as first evidence of radiographically detectable bone or soft tissue disease. This AI model was trained on The Cancer Genome Atlas Prostatic Adenocarcinoma whole slide images and data set to predict three-year biochemical recurrence after radical prostatectomy and was subsequently validated on whole slide images from patients with prostate cancer from the University of Wisconsin-Madison. Patients in this dataset had not received prior androgen deprivation therapy (ADT) or adjuvant radiotherapy.3
Subjects for this validation study included patients from the SPARTAN trial with available H&E-stained slides from their primary diagnosis. A PATHOMIQ-PRAD score was generated for each patient, with higher values corresponding to increased hazards of metastases. A pre-determined cut-off score of 0.55 was applied to this dataset to generate PATHOMIQ-PRAD high and low groups. Metastasis-free survival was determined using Kaplan Meier curves.
Whole slide images were collected from 467 patients (apalutamide arm: 311, placebo arm: 156). Thirty-five were excluded due to lack of tumor or poor image quality. PATHOMIQ-PRAD scores were generated for 93% of patients. The baseline patient characteristics, stratified by trial treatment arm, are summarized below:
When patients were stratified by PATHOMIQ-PRAD score (high versus non-high), an MFS benefit was observed with apalutamide, irrespective of the PATHOMIQ-PRAD risk grouping. In the non-high-risk group, use of apalutamide was associated with a significantly prolonged MFS (HR: 0.39, 95% CI: 0.17 – 0.86, p=0.02). Similarly, in the high-risk group, use of apalutamide + ADT, compared to placebo +ADT, was associated with significant MFS benefits (HR: 0.19, 95% CI: 0.1 – 0.37, p<0.005).
The investigators concluded that:
- Independent of PATHOMIQ-PRAD risk score category, all patients receiving apalutamide + ADT had improved MFS outcomes, compared to those receiving ADT alone
- Patients in the PATHOMIQ-PRAD high-risk group appear to derive a greater benefit from addition of apalutamide to ADT with a HR of 0.19 versus 0.39 in the non-high-risk group.
- These results suggest that H&E-based AI could be a tool to risk-stratify patients with nmCRPC
Presented by: Pooya Mobadersany, PhD, Janssen Research & Development
Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 2 – Tues, June 6, 2023.References:
- Smith MR, Saad F, Chowdhury S, et al. Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med 2018;378(15):1408-1418.
- Smith MR, Saad F, Chowdhury S, et al. Apalutamide and Overall Survival in Prostate Cancer. Eur Urol 2021 ;79(1):150-158.
- Huang W, Randhawa R, Jain P, et al. A Novel Artificial Intelligence–Powered Method for Prediction of Early Recurrence of Prostate Cancer After Prostatectomy and Cancer Drivers. JCO Clin Cancer Informatics 2022;6:e2100131.