Response to neoadjuvant chemotherapy leads to better survival outcomes in upper tract urothelial carcinoma

Objectives: To evaluate the benefit of neoadjuvant chemotherapy (NAC) for patients with high-risk upper tract urothelial carcinoma (UTUC) using a large, well-curated multi-institutional database. Patients and Methods: This study was a multi-institutional retrospective analysis conducted by the UTUC Collaborative Network (UCAN), combining data from 2276 patients with UTUC who underwent radical nephroureterectomy at seven high-volume tertiary care centres in the United States. The UCAN data were analysed to evaluate the impact of response to NAC on survival outcomes in patients with UTUC. Results: A total of 378 patients in the UCAN database underwent NAC. On final surgical pathology, 101 patients (26.8%) had ≤ypT1N0 disease and were defined as NAC treatment responders. Patients who responded to NAC had significantly longer overall survival (OS) and progression-free survival (PFS) compared to non-responders. At 5 years post-surgery, 81.5% of responders were alive compared to 59.8% of non-responders. The median OS and PFS times among non-responders were 7.0 years (95% confidence interval [CI] 5.6–9.7) and 6.0 years (95% CI 4.6–9.3) respectively, while the median OS and PFS were not reached among responders. Limitations of this study include its retrospective design, heterogeneity in chemotherapy regimens, and the absence of clearly defined patient selection criteria for treatment. Conclusion: These data suggest that NAC can play a pivotal role in the treatment of well-selected UTUC patients who respond positively. Non-responders had clearly inferior outcomes. More work is needed to find predictors of response which can improve patient selection.