Upper tract urothelial carcinoma (UTUC) has an incidence of 1.2–4.7 cases per 100,000 person-years globally and the variant histology (VH) comprising approximately 7% of all UTUC cases. Due to its rarity, VH is not well understood but is generally associated with a poorer prognosis compared to conventional UTUC. This study aims to assess the impact of VH subtypes on survival outcomes in comparison with conventional UTUC.

A retrospective analysis was performed on UTUC patients with VH who underwent nephroureterectomy (NU) at our institution between 1999 and 2021, with follow-up data collected through 2023. A comparison group consisted of patients with conventional UTUC who underwent NU during the same timeframe. Clinical characteristics, including demographics, perioperative variables, and tumor factors, were evaluated using Chi-square or Student’s t-test. Overall survival (OS) and cancer-specific survival (CSS) were analyzed using the Kaplan-Meier method.

Totally, 770 UTUC cases were analyzed, comprising 66 VH cases (8.6%, VH group) and 704 conventional UTUC cases (91.4%, Conventional group). The VH group included 32 males (48.5%), while the Conventional group had 353 males (50.1%). Median age was comparable (74 years, VH group; 72 years, Conventional group), with a median follow-up of 33.5 months (IQR 10–67 months). The VH group exhibited higher pathological T stage (P < 0.05), larger tumor size (≥3 cm, P = 0.005), and higher pathological grade (P = 0.017) compared to the Conventional group. Survival analysis revealed significantly worse OS (P < 0.001) and CSS (P < 0.001) in the VH group (Figure 1). Stratification by pathological T stage (T1–T4) showed significant differences in OS and CSS only at T4 (P = 0.01 and P = 0.001, respectively). Predominant VH subtypes are squamous cell carcinoma (n = 29, 43.9%), sarcomatoid (n = 13, 19.7%), and micropapillary (n = 10, 15.2%), with no significant differences in OS (P = 0.459) or CSS (P = 0.372) among subtypes.

This study demonstrates that VH in UTUC is primarily composed of squamous cell carcinoma (SCC), sarcomatoid, and micropapillary subtypes. VH presents with more advanced pathological stages, larger tumor size, higher grade, and significantly worse survival outcomes, particularly in advanced disease. These findings underscore the distinct prognostic and therapeutic implications for VH patients, enhancing understanding of this rare UTUC’s management.