Clinical characteristics of typical UC and atypical subtypes

In total, 8915 patients were enrolled, of which 8220 (92.2%) exhibited typical UC, while 695 (7.8%) presented as atypical subtypes. Clinical parameters of patients with typical carcinoma and atypical subtypes are detailed in Table 1. N-stage and M-stage of atypical subtypes were higher than typical UC (all p < 0.001). Figure 1 presents the statistical data concerning histological types. Non-papillary urothelial carcinoma accounted for 53.30% of cases, while papillary urothelial carcinoma represented 46.70%. Among atypical subtypes, other types of ureter carcinoma was the most prevalent, accounting for 64.03%.

Table 1 Clinical characteristics of typical UC and atypical subtypesFig. 1

Summary of histological type and prognosis analysis of different groups of histological types. A Truncate histogram of histological type statistics B Pie chart of histological type statistics C Prognosis analysis of all patients D Prognosis analysis of patients with typical UC E Prognosis analysis of patients with atypical subtype

Effects of histological types on prognosis

Kaplan–Meier curves revealed that all atypical subtypes had worse CSS and OS than typical urothelial carcinoma (all p < 0.001; Fig. 1C). In addition, we divided all patients into distinct histological type groups. Kaplan–Meier curves illustrated that papillary urothelial carcinoma had better CSS and OS than non-papillary urothelial carcinoma (all p < 0.001; Fig. 1D). Among all the atypical subtypes, papillary carcinoma demonstrated the most favorable CSS and OS outcomes (CSS: p = 0.05, OS: p = 0.005; Fig. 1E). Multivariate analysis showed histological subtype as an independent risk factor for an unfavorable prognosis (HR = 1.602, 95% CI 1.371–1.872, p < 0.001; Table 2).

Table 2 Cox regression analysis evaluating variables associated with overall survival of all UC patientsEffects of chemotherapy on prognosis of different histological types

We divided all patients into chemotherapy and nonchemotherapy group. Kaplan–Meier curves demonstrated that the non-chemotherapy group exhibited superior OS and CSS (all p < 0.001; Fig. 2A). However, multivariate analysis indicated that chemotherapy had no statistically significant impact on the prognosis of all patients (HR = 0.931, 95% CI 0.850–1.019, p = 0.121; Table 2).

Fig. 2

Effects of chemotherapy on prognosis of different histological types A Effects of chemotherapy on all patients B Effects of chemotherapy on patients with T1 UC C Effects of chemotherapy on patients with T2 UC D Effects of chemotherapy on patients with T3/T4 UC

To investigate the impact of chemotherapy on various histological type of UC, we categorized the patients into distinct histological type groups. Records of papillary urothelial carcinoma and non-papillary urothelial carcinoma were sufficient for multivariate Cox analysis, while others (atypical subtypes) were of insufficient quantity. Therefore we divided all the rest of the patients with atypical UC into one group for multivariate Cox analysis. We also constructed Kaplan–Meier curves to evaluate the impact of chemotherapy within each group of atypical subtypes.

Multivariate Cox analysis revealed that chemotherapy had no statistically significant effect on the prognosis of patients with papillary urothelial carcinoma (HR = 1.055, 95% CI 0.906–1.228, p = 0.493; Supplementary Table 3). However, chemotherapy demonstrated a statistically significant positive impact on the prognosis of patients with non-papillary urothelial carcinoma (HR = 0.860, 95% CI 0.764–0.966, p = 0.011; Supplementary Table 2).

The multivariate Cox analysis on all patients with atypical UC indicated that chemotherapy had no statistically significant effect on the prognosis (HR = 0.997, 95% CI 0.675–1.473, p = 0.987; Supplementary Table 4). Chemotherapy group of patients with small cell carcinoma exhibited improved OS and CSS than non-chemotherapy group (OS: p = 0.003, CSS: p = 0.014; Supplementary Fig. 1B). However, Kaplan–Meier curves revealed that chemotherapy group had worse CSS than non-chemotherapy group among patients with squamous cell carcinoma or papillary carcinoma (Squamous cell carcinoma: p = 0.03; Papillary carcinoma: p = 0.002; Supplementary Fig. 1).

Effects of chemotherapy on prognosis of different T stages

Stratified analysis of T1, T2, T3/T4 was performed for typical UC and atypical subtypes. Patients with lower T-stage were shown to have better prognosis (all p < 0.001; Fig. 3A–C). Kaplan–Meier curves revealed that all atypical subtypes had worse CSS and OS than typical urothelial carcinoma among patients with T1 UC, T2 UC, and T3/T4 UC (all p < 0.001; Fig. 3D–F).

Fig. 3

Stratified analysis of T-stage effects on prognosis of different histological types A Effects of T-stage on all patients B Effects of T-stage on patients with atypical subtypes C Effects of T-stage on patients with typical UC D Effects of histological types on patients with T1 UC E Effects of histological types on patients with T2 UC F Effects of histological types on patients with T3/T4 UC

Kaplan–Meier curves demonstrated that nonchemotherapy group of patients in T1 group had better OS and CSS (OS: p < 0.001, CSS: p < 0.001; Fig. 2B), while nonchemotherapy group of patients in T3/T4 group exhibited poorer OS and CSS (OS: p < 0.001, CSS: p = 0.026; Fig. 2D). In T2 group, nonchemotherapy group of patients had better CSS while chemotherapy had no statistically significant effect on OS (OS: p = 0.237, CSS: p < 0.001; Fig. 2C).

The multivariate analysis on patients in T1 group revealed that chemotherapy had statistically significant negative effect on prognosis (HR = 1.235, 95% CI 1.016–1.502, p = 0.034; Supplementary Table 5). However, chemotherapy had no statistically significant effect on the prognosis of patients in T2 group (HR = 1.103, 95% CI 0.916–1.329, p = 0.3; Supplementary Table 6). Chemotherapy had statistically significant positive effect on the prognosis of patients in T3/T4 group (HR = 0.739, 95% CI 0.654–0.835, p < 0.001; Supplementary Table 7).