Progression of Disease after Bacillus Calmette-Guérin Therapy: Refining Patient Selection for Neoadjuvant Chemotherapy before Radical Cystectomy

Abstract

Purpose:Data from the pre-neoadjuvant chemotherapy (NAC) era suggests patients who progress on bacillus Calmette-Guérin (BCG) to muscle-invasive bladder cancer (P-MIBC) exhibit worse outcomes compared to de novo MIBC (D-MIBC). Herein, we investigate whether P-MIBC is an independent poor risk factor in the setting of contemporary NAC use.Materials and Methods:A review of patients who underwent radical cystectomy (RC) for cT2-3 MIBC from 2005 to 2018 was performed. Patients were stratified into high risk (lymphovascular invasion, variant histology, hydronephrosis, cT3b) vs low risk (no risk factors) and P-MIBC (≤pT1 treated with at least induction BCG who progressed to ≥cT2) vs D-MIBC.Results:Among 801 patients who underwent RC 20.3% had P-MIBC and 79.7% had D-MIBC. In low-risk patients treated without NAC, P-MIBC was associated with pathological upstaging (64.9% vs 42.7%, p=0.004) and worse overall (OS, p=0.006) and cancer-specific survival (CSS, p=0.001) compared to D-MIBC. P-MIBC status conferred uniformly poor survival outcomes to patients who did not receive NAC compared to D-MIBC without NAC (median OS 51.5 months [95% CI 40.0–81.0] vs 85.1 months [95% CI 62.8–96.0], p=0.040; median CSS not reached, p=0.014). However, P-MIBC status did not remain a negative prognostic factor in the setting of NAC (median OS 90.5 months [95% CI 34.0–not estimable] vs 87.8 months [95% CI 68.7–not estimable], p=0.606; median CSS not reached, p=0.448).Conclusions:P-MIBC confers a poor prognosis when managed with RC alone. Treatment with NAC results in equivalent pathological response and survival outcomes compared to D-MIBC. P-MIBC should be included in risk-stratified approaches to NAC selection.

Comparative Outcomes of Primary Versus Recurrent High-risk Non–muscle-invasive and Primary Versus Secondary Muscle-invasive Bladder Cancer After Radical Cystectomy: Results from a Retrospective Multicenter Study

“…Patients with secMIBC experienced the worst survival outcomes (RFS, CSS, and OS) and secMIBC was an independent predictor of worse CSS and OS. Previous studies reported conflicting survival outcomes for secMIBC compared to primMIBC [10] , [11] , [12] , [13] . The most recent meta-analysis, which included 16 studies with a total of 5270 patients, revealed no differences in 5- and 10-yr CSS and OS between these two groups [12] .…”

“…Previous studies showed that patients who underwent RC for recurrent HR-NMIBC had worse oncological outcomes than those with primary HR-NMIBC [7] , [8] , [9] . By contrast, data comparing oncological outcomes for patients with primary and secondary MIBC are conflicting [10] , [11] , [12] , [13] . There are no conclusive data regarding the comparative prognosis of RC for primary HR-NMIBC, recurrent HR-NMIBC, secondary MIBC, and primary MIBC.…”

This Month in Adult Urology

“…Hensley et al (page 1258) from Houston, Texas explored in a comparative study whether neoadjuvant chemotherapy (NAC) impacts these findings. 5 In a study of 801 patients, the authors again found that progression on BCG portended a worse prognosis than cystectomy in de novo patients in the absence of NAC. In the subgroup of patients with progression who were treated with NAC, the adverse implications were abrogated.…”

Predictive Biomarkers in the Management of Bladder Cancer: Perspectives in an Evolving Therapeutic Landscape

“…While guidelines support the role of NAC before radical cystectomy for MIBC, there remains a role for risk-stratified NAC patient selection. Clinicopathologic risk factors have been implemented in predicting response to cisplatin-based NAC [77,78], but efforts are underway to profile tissue-based biomarkers for this purpose. The Southwest Oncology Group (SWOG) 1314 trial prospectively profiled the ability of the COXEN tissue-based genetic classifier to predict complete pathologic response to cisplatin-based NAC (Table 2) [79].…”