RADICAL nephroureterectomy (RNU) remains a key component in the management of upper tract urothelial carcinoma (UTUC) with lymph node involvement (cN+). However, its role within a multimodal treatment strategy remains uncertain. To clarify its impact, a systematic review and meta-analysis were conducted, evaluating data from 17 observational studies published between 2000 and 2024.
The review focused on UTUC patients with cN+ disease who underwent RNU as part of a multimodal approach, assessing oncological and postoperative outcomes. Among the studies, 15 explored the combination of chemotherapy with RNU, while two examined the addition of RNU to chemotherapy.
Findings revealed that patients receiving induction chemotherapy before RNU experienced significantly improved pathological downstaging and complete nodal response compared to those undergoing RNU alone. Specifically, induction chemotherapy was associated with a threefold increase in the likelihood of pathological downstaging and nearly threefold higher odds of achieving complete nodal response. Additionally, this approach correlated with prolonged overall survival, reducing the risk of mortality by nearly half.
Comparisons between treatment strategies further supported the superiority of induction chemotherapy plus RNU over RNU with adjuvant chemotherapy or chemotherapy alone, both of which were linked to inferior survival outcomes. Importantly, adding induction chemotherapy did not significantly increase the risk of overall or major postoperative complications, indicating its safety in appropriately selected patients.
Despite these promising results, limitations exist. The included studies were all observational in design, which may introduce potential biases. Additionally, variations in patient selection and chemotherapy regimens could affect the findings.
Overall, this analysis suggests that RNU, particularly when combined with induction chemotherapy, offers the most substantial oncological benefits without compromising patient safety. For UTUC patients with cN+ disease who are fit and have resectable tumours, this multimodal strategy may represent the optimal treatment approach. Further prospective studies are needed to confirm these findings and refine patient selection criteria.
Katie Wright, EMJ
Reference
Rai BP et al. Benefit and harms of radical nephroureterectomy as part of a multimodal treatment strategy for upper tract urothelial carcinoma patients presenting with clinical evidence of regional lymph node metastasis: a systematic review and meta-analysis by the european association of urology guidelines. Eur Urol Oncol. 2025;DOI:10.1016/j.euo.2024.12.009.
