A LARGE multicentre study has provided crucial new insights into the treatment of upper tract urothelial carcinoma (UTUC), focusing on the survival outcomes and recurrence patterns following radical nephroureterectomy (RNU) and lymph node dissection (LND), with and without neoadjuvant chemotherapy (NAC). This retrospective analysis of 883 patients, 131 of whom received NAC, sheds light on the long-debated question of how best to sequence chemotherapy in UTUC management.
While current guidelines advocate for LND at the time of RNU, particularly in high-risk patients, the precise benefits of NAC prior to surgery remain unclear. This study revealed that patients with persistent nodal disease post-NAC (ypN+) fared significantly worse than those who underwent upfront surgery (pN+), with all ypN+ patients developing distant metastases within one year of surgery.
In contrast, patients with no nodal involvement on final pathology (ypN0 or pN0) showed similar survival outcomes regardless of NAC status. However, recurrence patterns varied notably. A higher proportion of ypN0 patients experienced early regional or distant metastases compared to pN0 patients, suggesting that NAC may alter recurrence trajectories.
These findings carry important implications for post-surgical surveillance. Current guidelines do not account for NAC or nodal status when recommending follow-up strategies. The study suggests that patients with ypN0 status may benefit from more frequent early imaging, while pN0 patients – more prone to bladder recurrence – might require intensified cystoscopic monitoring.
Moreover, the lack of benefit from adjuvant immune checkpoint inhibitors in ypN+ patients, as seen in prior trials, calls into question the current adjuvant treatment options. The authors argue for a personalised approach, potentially incorporating novel agents like enfortumab vedotin plus pembrolizumab for ypN+ patients, given the high risk of early metastasis.
Although limited by retrospective design and a modest NAC cohort, this study, the largest of its kind, highlights the need to refine treatment pathways and follow-up protocols based on real-world data and individual risk profiles in UTUC management.
Reference
Sheybaee Moghaddam F et al. Neoadjuvant chemotherapy prior to radical nephroureterectomy: survival outcomes and recurrence patterns by pathologic node status. Urol Oncol. 2025;DOI:10.1016/j.urolonc.2025.03.001.
