Neoadjuvant chemotherapy prior to radical nephroureterectomy: Survival outcomes and recurrence patterns by pathologic...

To evaluate survival outcomes and recurrence patterns by pathologic nodal status in upper tract urothelial carcinoma (UTUC) patients receiving neoadjuvant chemotherapy (NAC) prior to radical nephroureterectomy (RNU) and lymph node dissection (LND).

Using the international ROBUUST 2.0 database, a retrospective analysis of UTUC patients who underwent robotic/laparoscopic RNU+LND±NAC was performed. Patients were stratified by NAC and pathologic nodal status into pN0, ypN0, pN+, and ypN+ subgroups. Overall (OS), metastasis-free (MFS), and urothelial recurrence-free survivals (RFS) were compared using Kaplan-Meier curves and multivariable Cox regression modeling.

The cohort included 883 patients (15% received NAC). 212 (24%) patients had (y)pN+ disease. Median follow-up was 19 months. Compared to pN+ patients, ypN+ patients had significantly worse 1- (64% vs. 72%), 3- (40% vs. 54%), and 5-year (20% vs. 31%) OS rates. Node-negative patients had similar OS, irrespective of NAC treatment (1-year: 94%; 3-year: 77%-82%). At 1 year, all ypN+ patients had metastases, while 13% of pN+ patients remained metastasis-free. Among ypN+ patients, 89% experienced nodal/regional or distant metastases as the site of initial recurrence, compared to 39% of pN+ patients. Initial nodal/regional or distant metastases occurred in 42% and 18% of ypN0 and pN0 patients, respectively.

ypN+ patients have worse survival compared to pN+ patients. Recurrence patterns differ by nodal and NAC status, with ypN+ patients having a significantly higher incidence of nodal/regional or distant metastases as the initial site of recurrence. These survival outcomes and recurrence patterns differences may have important surveillance and treatment implications.