Perioperative Chemotherapy in Bladder and Upper Tract Urothelial Carcinoma: Outcomes by Nodal Status and Lymphovascular Invasion.

Background/

Objectives

Optimal selection for perioperative therapy in urothelial carcinoma (UC) remains uncertain. We evaluated the efficacy of neoadjuvant and/or adjuvant chemotherapy (NAC/AC) for patients with bladder cancer (BC) and upper tract UC (UTUC), examined the role of lymphovascular invasion (LVI), and considered the implications for adjuvant nivolumab.

Methods

We retrospectively analyzed consecutive patients who underwent radical cystectomy or radical nephroureterectomy at a single center (July 1998-April 2021; observation to 31 March 2025). After exclusions, 252 BC and 153 UTUC patients were included. Endpoints were cancer-specific survival, progression-free survival (PFS; BC), non-urinary-tract recurrence-free survival (NUTRFS; UTUC), and overall survival (OS). Survival was estimated by Kaplan-Meier analysis and compared by log-rank tests.

Results

For BC, AC did not improve the PFS or OS in the overall pT ≥ 2 population, whereas node-positive (pN+) disease derived significant benefits in both endpoints among NAC-naïve patients (PFS and OS, p = 0.002 and p = 0.008). For UTUC, AC conferred no advantage in NUTRFS or OS for the overall pT ≥ 2 population. However, NUTRFS benefits emerged in the pN+ subset (p = 0.049), although the OS was not improved. Among NAC-treated BC, the outcomes were poorest for ≥ypT3 and ypN+, whereas ypT ≤ 2 fared better. LVI was associated with adverse outcomes and was borderline higher in pN+ versus pT ≥ 2/pN- for BC (p = 0.056) and significantly higher for UTUC (p = 0.012).

Conclusions

In this retrospective, single-center cohort, our exploratory analyses suggest that perioperative benefit is largely node-dependent, supporting prioritizing systemic therapy for pN+ disease and cautioning against routine AC for pT2/ypT2 without nodal involvement. After NAC, adjuvant therapy appeared most justified for ≥ypT3/ypN+. Prospective biomarker-integrated validation is warranted and, given the small and underpowered subgroups and the potential for selection and immortal time biases, these observations should be interpreted as hypothesis-generating rather than causal.