A Risk Stratification Model for Intermediate-Risk Non-Muscle-Invasive Bladder Cancer (NMIBC) - Expert Commentary

Non-muscle-invasive bladder cancers (NMIBC) represent a heterogeneous group of tumors with variable clinical outcomes. Multiple risk features are incorporated in predicting the risk of recurrence and progression to muscle-invasive bladder cancer (MIBC). Intravesical immunotherapy with Bacillus Calmette-Guerin (BCG) and chemotherapy are both considered adjuvant treatment options. However, it is challenging to define the optimum adjuvant therapy, particularly in intermediate-risk NMIBC cases. Considering the current BCG shortage, the risk-stratification tool for intermediate-risk patients is essential.

A recent study published by Soria et al. in European Urology Focus analyzed several clinicopathologic factors to develop a nomogram for predicting disease progression to MIBC in 636 patients with intermediate-risk NMIBC as defined by the European Association of Urology (EAU) guidelines. All patients received six instillations of adjuvant intravesical chemotherapy after the transurethral resection of the bladder tumor (TURBT). Maintenance was administered at the physician's discretion.

During a median follow-up time of 92.3 months, 346 (54%) patients experienced disease recurrence, and 91 (14%) developed disease progression to MIBC. Independent predictors of progression-free survival (PFS) were age (hazard ratio (HR) 1.04, p < 0.001), time to recurrence < 1 year (HR 3.41, p < 0.001), tumor size > 3 cm (HR 1.51, p = 0.006), and tumor grade 2 (HR 1.73, p = 0.01).

Using these factors, the authors developed the nomogram to predict the probability of 2-years and 5-years progression for patients receiving adjuvant chemotherapy for the intermediate-risk NMIBC. PFS was defined as the primary endpoint because it represents a clinically relevant event in the disease course and accounts for cancer-related deaths of patients. The Harrell C-index of the model was 0.75, which was higher than the C-index of 0.71 achieved by a previous model that included time to recurrence, frequency of recurrence, size, and focality.

This risk stratification model will inform the selection of patients likely to benefit from BCG because of a higher risk of disease progression.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York


  1. Soria F, D'Andrea D, Abufaraj M, Moschini M, Giordano A, Gust KM, et al. Stratification of Intermediate-risk Non–muscle-invasive Bladder Cancer Patients: Implications for Adjuvant Therapies. Eur Urol Focus. 2021;7(3):566–73. PMID: 32532704.
  2. Kamat AM, Witjes JA, Brausi M, et al. Defining and treating the spectrum of intermediate risk nonmuscle invasive bladder cancer. J Urol 2014;192:305–15. PMID: 24681333

Read the Abstract
email news signup