Introduction:

Neoadjuvant chemotherapy prior to radical cystectomy is the standard of care for patients with localized muscle-invasive bladder cancer. The survival benefit of neoadjuvant chemotherapy appears strongly associated with pathologic downstaging at cystectomy, which is achieved by both chemotherapy and transurethral resection (TUR). In patients determined to have a visually complete TUR of muscle-invasive disease, the exact benefit of chemotherapy is unclear based on current literature. We hypothesize that chemotherapy results in equivalent pathologic and survival outcomes while allowing select patients to undergo bladder-sparing management.

Methods:

We retrospectively reviewed all patients referred to our institution for localized muscle-invasive urothelial carcinoma from 2009 to 2018. We selected patients determined to have a visually complete TUR, defined as a complete resection down to visually normal muscle as abstracted from operative reports, in addition to a negative bimanual examination and cross-sectional imaging without evidence of extravesical extension. The decision to proceed with cystectomy versus chemotherapy was at the discretion of the provider and patient. Patients with cT0 status on TUR after chemotherapy were advised that cystectomy was standard of care; those who refused cystectomy were placed on an active surveillance protocol of cytology, cystoscopy with/without biopsy, and cross-sectional imaging at 3-4 month intervals. Exclusion criteria were receipt of non-cisplatin-based chemotherapy, radiation therapy, or insufficient documentation of TUR completeness. The primary outcome of interest was pathology at cystectomy or on surveillance; secondary outcomes included metastases-free, cancer-specific, and overall survival.

Results:

Of 82 total patients, 38 (46%) patients underwent cystectomy alone, 15 (18%) patients underwent neoadjuvant chemotherapy and cystectomy, and 29 (35%) patients underwent chemotherapy with surveillance. The cohorts did not differ in patient or disease characteristics (Table 1). Rates of downstaging to ≤pT1 at cystectomy or remaining ≤cT1 on surveillance for >1 year, and rates of pT0 at cystectomy or remaining cT0 on surveillance for >1 year, were higher in patients undergoing chemotherapy and surveillance. In those who underwent surveillance after chemotherapy, 17 (59%) patients had bladder recurrence and 8 (28%) underwent cystectomy at a median of 11 months after diagnosis. In all patients who underwent cystectomy, there was no significant difference in rates of downstaging to ≤pT1, pT0, or nodal metastases at cystectomy among the cohorts. With a median follow-up of 2.5 years, metastasis-free, cancer-specific, and overall survival were not significantly different among the cohorts (Figure 1).

Conclusion:

In patients determined to have a visually complete TUR of muscle-invasive bladder cancer, chemotherapy may allow successful bladder-sparing management in select patients. Neoadjuvant chemotherapy also resulted in higher rates of pathologic downstaging at cystectomy compared to cystectomy alone, though this was not statistically significant. These findings suggest that chemotherapy may be beneficial even after a visually complete TUR of muscle-invasive disease. Further work is needed to clarify who benefits most from chemotherapy based on clinical and genetic factors.

Funding: N/A