Introduction:

For patients with muscle invasive bladder cancer (MIBC), the standard of care is platinum-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC). However, many patients refuse or are medically unfit for RC. Furthermore, between 20% and 30% of patients treated with NAC have no evidence of disease at RC. Therefore, patients who achieved a clinical complete response (cCR) to NAC and refused definitive treatment were placed on an active surveillance cCR protocol. Previous studies have reported on the long-term outcomes of this cohort. This study presents the incidence and management of non-muscle invasive bladder cancer (NMIBC) recurrence in patients while on cCR surveillance protocol.

Methods:

This was a retrospective review of a prospectively-maintained database of all patients on a cCR surveillance protocol. To enter cCR protocol, patients must have received platinum-based NAC for MIBC followed by negative cross-sectional imaging, negative cytology, and negative post-NAC maximal endoscopic resection. Patients were followed with office cystoscopy and cytology every three months and cross-sectional imaging every six months, with repeat transurethral resections (TURs) for suspicious-appearing lesions or positive cytology. Patients with MIBC recurrence or metastases within six months were deemed to be misclassified cCR and excluded from analysis. Any cCR without MIBC recurrence or metastases was considered durable, even with NMIBC recurrence. Any intravesical recurrence prompted a recommendation for definitive treatment with RC. However, patients who recurred with NMIBC and wished to continue bladder-sparing were treated, and outcomes are reported here. Outcomes of interest were number of NMIBC recurrences, grade and stage, and treatment.

Results:

A total of 61 patients had cCR, of whom 14 (23%) had history of prior NMIBC. Median time in cCR protocol was 28.3 months (IQR 10.1-58.9). Overall, 49 (80%) had durable response without MIBC recurrence or metastases. In total, 28 patients (46%) experienced a median of one NMIBC recurrence (IQR 1-2, range 0-7) with 20 (33%) having one recurrence, five (8%) having two recurrences, and three (5%) having three or more recurrences. Median time to recurrence was 11.5 months (IQR 5.2-20.3). There were 46 total recurrences; nine (20%) were LGTa, 11 (24%) were HGTa, nine (20%) were HGT1, and 17 (37%) were CIS. LGTa recurrences were all treated with TUR alone. HG recurrences were treated with BCG in 22 (59%), induction chemotherapy in one (3%), TUR alone in four (11%), and cystectomy in seven (19%). Patients with NMIBC recurrences were not more likely to recur with muscle-invasive or metastatic disease.

Conclusion:

Many patients who develop a cCR after NAC for MIBC achieve a durable response without MIBC or metastatic recurrence. However, a large proportion of these patients will experience NMIBC recurrence, primarily with HG disease. The majority of these are single recurrences managed with BCG. In this small subset, it did not appear that NMIBC recurrences resulted in higher rates of subsequent MIBC or metastatic recurrences. These data are important to appropriately counsel patients that those who achieve a cCR still have a substantial risk of NMIBC recurrence and require careful surveillance.

Funding: N/A