AUA 2018: Accurate Prediction of Progression to Muscle Invasive Disease in Patients with T1G3 Bladder Cancer: A Clinical Decision-Making Tool

San Francisco, CA ( NMIBC represents approximately 70% of all bladder cancer diagnoses. While low-grade disease has high rates of recurrence and low rates of progression, patients with CIS and high-grade (HG) disease have high rates of progression to muscle-invasive bladder cancer. Early definitive therapy and more aggressive interventions may help alter the natural history of the disease and provide curative options for these patients. However, as the treatment for MIBC has significant quality of life impacts, overtreatment is also a concern – these treatments should not be taken lightly. Yet, at this time, beyond histopathology, we don’t have accurate methods to predict progression and, as a result, cannot best select patients for more invasive interventions. Certain pathologic features may help modify risk, including presence of lymphovascular invasion (LVI) and variant histology (VH). 

To help address this, the authors of this multi-institutional study pooled data from 1,289 patients with high-grade (WHO 1973 Grade 3) pT1 (lamina propria invasion) bladder cancer who were treated with transurethral resection of bladder (TURB) and adjuvant intravesical bacillus Calmette-Guérin (BCG). Based on clinical and pathologic variables, they were able to develop a nomogram to predict an individual patient’s 2 and 5-year probability of disease progression after TURB. The cohort was split into a development (n=645) and validation cohort (n=644), both of which were similar. 

This cohort of patients had a median follow-up of 56.6 months (IQR 19.3-92.5). Other demographics included median age 68, 80% male, 68.3% had tumor size < 3 cm, and 64% unifocal tumor.

In terms of clinical outcomes, disease progression occurred in 89 patients (13.8%). Indeed, this seems relatively low! ***

Of the cohort, 157 (12.2%) patients were found to have VH (types and percentage unknown) and 115 (8.9%) had LVI at the time of TURB; 34 patients (2.6%) had both. Cumulative incidence graph for disease progression demonstrates the additive effect.

UroToday AUA2018 Cumulative Incidence graph 

Both factors were independently associated with disease progression on multivariable competing risk analysis (HR: 4.4, 95%CI: 2.8-6.9, p <0.001 and HR: 3.5, 95%CI: 2.1–5.8, p <0.001, respectively). Other independent predictors were concomitant cis, tumor size, and multifocality.

UroToday AUA2018 Progression to Muscle Invasive Disease

Key variables included variant histology and LVI (both contributed the most), concomitant CIS, tumor size, and multifocality.

Decision curve analysis showed that the proposed nomogram superior was superior to current models within a threshold probability of progression between 5-55%. As risk of progression is usually within this range, this seems to be a reasonable model to help predict progression.

Yet, would this change clinical management? I don’t think most physicians would feel comfortable skipping BCG therapy and going to early cystectomy based on this alone!

Limitations / Discussion Points:
1. It does not take into account BCG response. Hence, they ignore the impact of the primary non-invasive treatment for this disease state. Yet, response to BCG is an important predictor of progression.
2. Limitations are inherent to the retrospective design
3. Pathology review was not commented on – were all these patients truly HG pT1
4. Most recent WHO classification recommends HG and LG – not Grade 1-3. How does this work with the current classification system? Most pathologists no longer reported Grade 1-3.

Presented by: David D'Andrea
Co-Authors: Mohammad Abufaraj, Martin Susani, Robin Ristl, Beat Foerster, Shoji Kimura, Andrea Mari, Alberto Briganti, Pierre Karakiewicz, Kilian Gust, Morgan Roupret, Shahrokh Shariat

Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, @tchandra_uromd at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA
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