Introduction:

There is limited data on the outcomes of initial chemotherapy followed by surgical consolidation with curative intent for patients with UTUC who have clinically node positive (cN+) disease. The purpose of this study was to assess the response of cN+ patients to chemotherapy followed by extirpative surgery and lymph node dissection.

Methods:

We queried our prospectively maintained database of 1,070 patients with UTUC for patients with cN+ disease who received chemotherapy followed by consolidative surgery with lymph node dissection. A survival analysis was performed and the Log Rank test was used to determine statistical significance. Multivariate analysis was performed using the Cox Proportional Hazards Model. Statistics were performed in Stata.

Results:

56 patients met inclusion criteria. 27 patients had cN1 disease, 21 patients had cN2 disease, and 8 patients had non-regional nodal metastasis as well as regional nodal disease, which we termed cNM. 37/56 (66%) patients had a complete response to chemotherapy with pN0 disease, including 22/27 (81%) cN1, 11/21 (52%) cN2, and 4/8 (50%) cNM patients.  Patients with a complete response to neoadjuvant chemotherapy had improved recurrence free (p = 0.0004) and overall (p < 0.0001) (Fig. 1) survival. Patients receiving MVAC as part of their chemotherapy regimen also had significantly improved recurrence free (p = 0.0471) and overall (p = 0.0457) (Fig. 2) survival. In a multivariate model of recurrence free survival adjusting for age, race, gender, BMI, ECOG, charlson, and CKD stage, the effect of MVAC chemotherapy persisted (HR 0.241, p = 0.049). For overall survival it approached but did not reach significance (HR 0.325, p = 0.053).

Conclusion:

A strong nodal response in patients with cN+ UTUC after initial chemotherapy followed by extirpative surgery with lymph node dissection results in significant improvement in recurrence free and overall survival in those who convert to pN0. Patients who received chemotherapy regimens containing MVAC also had improved overall and recurrence free survival, and this effect persisted even when accounting for potential confounders. This data contributes to the body of evidence supporting the therapeutic strategy in patients with advanced UTUC of upfront aggressive chemotherapy, ideally with an MVAC based regimen, followed by consolidative surgery in those who respond with curative intent. Limitations of our study include the retrospective nature of the data, outcomes of those who did not have consolidative surgery, and incomplete follow-up possibly leading to artificially elevated recurrence free survival and the imperfect nature of radiologic nodal staging likely leading to misattribution of some reactive nodes as cancerous.

Funding: N/A