SUO 2017: Validation of The BCG Unresponsive Definition

Washington, DC ( BCG remains the standard of care for non-muscle invasive bladder cancer, specifically high-grade disease and CIS. However, the BCG failure patient continues to be a void in clinical management – while early cystectomy is often recommended, the morbidity and recovery associated with such a procedure has made the need for additional non-invasive therapy critical. With little success in this field, the next major breakthrough awaits, though promising interventions are on the horizon.

However, not all patients with BCG failure are equivalent. Prior guidelines have differentiated BCG failure into multiple categories, including BCG refractory (HG cancer at 6 months) and BCG relapsing (relapsing HG cancer after achieving disease-free state at 6 months), after adequate BCG treatment (induction and at least one maintenance). However, more recent guidelines combined these into a “BCG unresponsive” definition. Some of these patients did not qualify for either of the original definitions due to either inadequate BCG therapy prior to recurrence (reason 1) or relapse beyond 9 months (reason 2).

In this abstract, the authors utilize their institutional data to evaluate 125 patients with HG recurrence after BCG therapy. 92 satisfied the new BCG unresponsive definition (60 BCG refractory and 32 BCG relapsing) while 33 did not (26 due to reason A or 6 patients due to reason B). Do these patients have different outcomes than patients who met the criteria? 

Recurrence free survival (RFS), progression free survival (PFS), time to cystectomy (TTC), and cancer specific survival (CSS) were compared between patients satisfying and not satisfying the BCG unresponsive definition. All patients were encouraged to undergo cystectomy as definitive therapy. As confirmation of the definition, the same comparisons were made between the BCG refractory unresponsive and the BCG relapse unresponsive patients to validate their oncologic equivalence.

There were no significant differences in patient demographics or tumor pathology between the two groups. 

Patients with BCG unresponsive disease were found to have worse 5-year RFS (66.8% vs. 89.3%) and worse 5-year PFS (93.5% vs. 100%). These patients were found on MV analysis to be independent predictors of worse RFS and cystectomy-free survival. All endpoints were similar for patients within the subgroups of BCG unresponsive disease (refractory vs relapsing) – indicating equivalence in terms of definition.

Importantly, majority of the patients who did not meet the definition had good response to repeat induction with BCG. 

As such, the authors used their smaller institutional series to validate the new definition of BCG unresponsiveness – patients outside the definition have better survival outcomes, and therefore stratification is appropriate. 

Presented by: Roger Li MD¹

Co-Authors: Michael J. Metcalfe MD², Graciela Nogueras Gonzalez MPH², Neema Navai MD², H. Barton Grossman MD², Colin P. Dinney MD² and Ashish M. Kamat MD²
Affiliation: ¹UT MD Anderson Cancer Center; ²UT MD Anderson

Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, twitter: @tchandra_uromd at the 18th Annual Meeting of the Society of Urologic Oncology, November 20-December 1, 2017 – Washington, DC