AUA 2024: Development and External Validation of an Artificial Intelligence-Based Tool for PROGression Risk Assessment in Non-Muscle Invasive Bladder Cancer (PROGRxN-BCa)

( The 2024 American Urological Association (AUA) Annual Meeting held in San Antonio, TX was host to a non-invasive bladder cancer podium session. Dr. Jethro Kwong presented the results of a development and external validation analysis of an artificial intelligence-based tool for PROGression Risk assessment in Non-muscle invasive Bladder Cancer (PROGRxN-BCa).

Accurate prediction of tumor progression in non-muscle invasive bladder cancer patients is essential to inform timely escalation of therapy. However, current tools to predict risk of progression in non-muscle invasive bladder cancer perform poorly and do not completely reflect current practice.


Dr. Kwong and colleagues aimed to develop and validate PROGRxN-BCa (PROGression Risk assessment in non-muscle invasive bladder cancer) – an artificial intelligence tool to better predict tumor progression. PROGRxN-BCa, based on a gradient-boosted survival forest, was trained on non-muscle invasive bladder cancer patients treated from January 2005 to June 2022 at one of three academic or community-based hospital networks: University Health Network, Sinai Health System, and Trillium Health Partners (n = 3,324) in Canada. Internal validation was then performed on patients treated from January 2016 to June 2022 at the same institutions (n = 1,321). External validation was performed on patients treated from November 2011 to June 2023 across 13 academic institutions affiliated with the Canadian Bladder Cancer Information System (n = 3,708). The primary outcome was time to progression, defined as first relapse of ≥T2 (at TURBT or cystectomy), nodal, or metastatic disease. PROGRxN-BCa was also compared to the EAU risk calculator, the most widely used clinical prediction model for non-muscle invasive bladder cancer progression.

During a median follow-up of 36 months (IQR 17-65), 1,006 out of 7,031 (14%) patients developed progression. The cohort characteristics are as follows:


PROGRxN-BCa outperformed the EAU risk calculator and LASSO Cox model, achieving a c-index between 0.76 to 0.83:


This performance benefit was consistent across clinically relevant subgroups, including age, sex, and tumor history. PROGRxN-BCa was well-calibrated for risks between 0-40%. At 5 and 10 years, PROGRxN-BCa demonstrated a higher net benefit (i.e. avoid unnecessary treatment escalation) compared to the EAU risk calculator for clinically relevant decision thresholds between 15-35%.


When applied to intermediate risk patients (n = 1,601), PROGRxN-BCa identified 19% of patients with an actual average 5-year progression risk of 32% - revealing a subset of patients who may benefit from treatment intensification. Similarly, the model identified 32% of patients with an actual average 5-year progression risk of 2.5%. This approach outperformed sub-stratification based on intermediate risk factors. As follows is the cumulative incidence of progression among intermediate-risk patients based on the EAU criteria. The blue, black, and red curves represent the lower, middle, and upper risk tertiles of patients as ranked by the PROGRxN-BCa, respectively:


Dr. Kwong concluded his presentation by discussing the development and external validation of an artificial intelligence-based tool for PROGRxN-BCa as follows:

  • In this multi-institutional study, PROGRxN-BCa consistently had better performance and higher net benefit compared to the LASSCO Cox regression and EAU NMIBC risk calculator in predicting progression in non-muscle invasive bladder cancer patients
  • It is also well-calibrated and performs well across clinically relevant subgroups
    • It can more accurately predict progression risk in contemporary patients
    • It can better sub stratify intermediate-risk NMIBC compared to current guideline recommendations
  • Ongoing work is being conducted to validate PROGRxN-BCa in additional non-muscle invasive bladder cancer cohorts

Presented by: Jethro Kwong, MD, MSc, Resident Physician, Division of Urology, University of Toronto, Toronto, ON

Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2024 American Urological Association (AUA) Annual Meeting, San Antonio, TX, Fri, May 3 – Mon, May 6, 2024.