Introduction:

Neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) is the standard of care for muscle-invasive bladder cancer (MIBC), with absolute increase in overall survival (OS) ranging 5-10%. In a 2014 meta-analysis, NAC was associated with a pathologic complete response (pT0) in 29% of patients, who had improved OS compared to those without a complete response. Prior studies have shown that pT0 response can be attributed not only to NAC, but also to high-quality transurethral resections (TURBT) prior to NAC. In addition, several studies on bladder preserving trimodal therapy show about a 20% higher rate of local control after a visibly complete TURBT. Therefore, we sought to assess the association between completeness of pre-NAC TURBT and subsequent response and survival outcomes.

Methods:

This was a single-institution, retrospective review of all patients who received NAC for clinically localized MIBC (≥cT2, N0) from 2000 to 2017. Patients were excluded if they received non-cisplatin-based chemotherapy or external beam radiation either concurrent to chemotherapy or as adjuvant therapy (n=15), or had insufficient documentation on completeness of TURBT (n=26). A complete TURBT was defined as tumor resection in its entirety and/or resection down to normal appearing underlying bladder muscle as described in surgical operative reports; a negative bimanual examination and cross-sectional imaging without evidence of tumor invasion were also required. If repeat restaging TURBT prior to NAC revealed clinical T0 (cT0) status, this was also considered evidence of a complete pre-NAC TURBT. The precise platinum-based NAC regimen was left to the discretion of the treating oncologist. After completion of NAC, patients either underwent a repeat TURBT or proceeded immediately to RC, as per the treating physician. Patients ultimately refusing RC were placed on a strict active surveillance and delayed intervention (ASDI) protocol of cytology, cystoscopy with or without biopsy, and cross-sectional imaging at 3-4 month intervals. Primary endpoint was durable complete response (dCR), defined as either pT0 on RC specimen or remaining cT0 on the ASDI protocol for at least 1 year. Secondary endpoints included OS and durable down-staging (dDS), defined as patients with ≤pT1 on RC specimen or remaining ≤cT1 on ASDI protocol for at least 1 year.

Results:

A total of 93 patients with MIBC met inclusion criteria. TURBT prior to NAC was described as complete in 67% (62/93) of patients. Patients with complete TURBT had lower rates of variant histology (13% vs 32%, p=0.03), had lower rates of hydronephrosis (15% vs 39%, p<0.01), and were more likely to pursue ASDI (60% vs 26%, p=0.01).  Patients with complete pre-NAC TURBT were significantly more likely to attain a dCR (37% vs 13%, OR 4.04 [95% CI 1.3-13.1), p=0.01) and dDS (60% vs. 26%, OR 4.9 [95% CI 1.8 - 12.8], p<0.01) on univariate analysis. On multivariate analysis, complete TURBT was a significant predictor of dCR and dDS; this remained true on subset analysis excluding 11 patients with ≥cT3 on restaging TUR. On Kaplan-Meier analysis, patients with complete TURBT had improved OS (5-year OS 78% vs. 46%, p<0.01). On multivariate analysis controlling for variant histology, lymphovascular invasion, and hydronephrosis, complete TURBT was the only significant predictor of OS. Complete TURBT remained a significant predictor of OS in a subset analysis excluding the 11 patients with ≥cT3 on restaging TURBT.

Conclusion:

A visibly complete TURBT prior to NAC is associated with a significant improvement in pathologic outcomes and OS in this single-institution cohort of patients with MIBC. The extent to which a complete pre-NAC TURBT represents a selection criterion for having lower clinical stage or a therapeutic advantage in response to NAC is difficult to isolate from a retrospective study. However, this report suggests a complete TURBT of muscle-invasive tumors should be pursued when feasible to potentially optimize outcomes after NAC.

Funding: N/A