Abstract
Objective
To describe the oncological outcomes for patients with newly diagnosed bladder cancer, as long‐term oncological outcomes and natural history of different initial subtypes of diagnoses of bladder cancer are understudied.
Patients and Methods
This was a prospective, multicentre population‐based cohort study, where newly diagnosed patients with bladder cancer from 1995 to 1996 in Stockholm County, Sweden were followed. The primary outcome was cancer‐specific mortality (CSM), separately analysed for low‐grade non‐muscle‐invasive bladder cancer (NMIBC Low), high‐grade non‐muscle‐invasive bladder cancer (NMIBC High), and muscle‐invasive bladder cancer (MIBC). We used cumulative incidence with competing risk to assess survival outcomes.
Results
In total, 526 patients were included, 396 had NMIBC. Out of 102 patients with T1, 37% died of bladder cancer during the 25‐year follow‐up. The rate of CSM for NMBIC Low was 3%, NMIBC High 26%, and MIBC 71%, respectively. For the operated patients with MIBC, the 5‐year CSM was 39%. Of the 178 patients with NMIBC High, 22% progressed to MIBC, 10% had lymph node progression, and 17% progressed to metastatic disease during the follow‐up. The main limitation of the study is that it was established 30 years ago.
Conclusion
In this population‐based study, we found that patients with NMIBC High had a persistent risk of CSM up to 25 years from the initial diagnosis, more specifically in patients with T1 tumours. The study demonstrates the importance for optimal treatment for selective high‐risk T1 patients with long life expectancy, and high risk of progression.
Keywords: bladder cancer, cancer‐specific mortality, long‐term follow‐up, progression, urothelial cancer
Abbreviations
- CSM
cancer‐specific mortality
- CSS
cancer‐specific survival
- G
grade
- NMIBC High
high‐grade NMIBC
- NMIBC Low
low‐grade NMIBC
- (N)MIBC
(non‐)muscle‐invasive bladder cancer
- PUNLMP
papillary urothelial neoplasm of low malignant potential
- RC
radical cystectomy
- TIS/CIS
carcinoma in situ
Introduction
Bladder cancer is the most common cancer of the urinary tract accounting for 3% of all diagnosed cancers worldwide [1]. Of the diagnosed bladder cancers, ~30% [2] have already grown to or beyond the detrusor muscle layer, which is associated with poor outcome. Thus, bladder cancer is divided into two major categories: muscle‐invasive bladder cancer (MIBC) and non‐MIBC (NMIBC) [2, 3, 4, 5, 6, 7]. In addition to the depth of cancer growth, tumour stage and grade are also known predictors of disease progression and death [3, 4, 5]. Previous studies have shown that the risk of recurrence and progression mainly depends on the primary tumour stage and grade [2, 6, 7], hence making accurate initial diagnosis paramount for choosing the optimal level of treatment intensity [7, 8, 9, 10].
Data from retrospective studies suggest non‐inferior survival for patients operated with radical cystectomy (RC) or BCG treatment with high‐risk NMIBC [11]. At present, the available studies present a follow‐up of 5–10 years [12, 13, 14, 15, 16, 17], and thus lacking the information on long‐term cancer outcomes. With an ageing population, and the increasing use of bladder‐sparing treatments, data on the long‐term oncological outcome of these patients becomes increasingly pivotal.
Large cohorts with long follow‐up are needed to evaluate the oncological survival of patients with bladder cancer. In this study, we used a population‐based cohort of patients with newly diagnosed bladder cancer to investigate the rate of tumour progression and the cumulative cancer‐specific mortality (CSM) by risk groups with up to 25 years of follow‐up.
Patients and Methods
Study Population
This was a prospective, observational, multicentre population‐based cohort study with an over 25‐year follow‐up of patients with bladder cancer. All patients diagnosed with bladder cancer in Stockholm County (Danderyd Hospital, Karolinska University Hospital Huddinge/Solna, Löwenströmska Hospital, Södersjukhuset, Sophiahemmet Hospital and Södertälje Hospital), Sweden during a 2‐year period (1 January 1995 to 31 December 1996) were asked to participate in the cohort. All patients underwent a primary transurethral resection for clinical and pathological staging; a second resection was performed in T1‐tumour if the initial tumour size was >3 cm. The pathology reports were reviewed and upon the re‐examination of the reports, the dataset was verified and, in a few cases, adjusted according to the original pathology report. Demographic and baseline clinical variables were collected prospectively and are described in Table 1. The data collection process has previously been described [18].
Table 1.
Baseline description of 25 years of follow‐up of patients with bladder cancer from 1995 to 1996.
| Variable | Value |
|---|---|
| Number | 526 |
| Age at diagnosis, years, mean | 70 |
| Gender, n (%) | |
| Male | 353 (67) |
| Female | 173 (33) |
| Grade WHO 1999, n (%) | |
| G1 | 210 (40) |
| G2 | 112 (21) |
| G3 | 135 (26) |
| Concomitant Carcinoma in situ, n (%) | 69 (13) |
| Grade WHO 04/16, n (%) | |
| Low | 210 (40) |
| High | 316 (60) |
| Tumour stage, n (%) | |
| Ta | 284 (54) |
| TIS | 10 (2) |
| T1 | 102 (19) |
| T2 | 87 (17) |
| ≥T3 | 43 (8) |
| Combined group/T‐stage, n (%) | |
| NMIBC Low | 208 (40) |
| NMIBC High | 188 (36) |
| MIBC | 130 (25) |
| Number of tumours at diagnosis, n (%) | |
| TIS | 10 (2) |
| 1 | 374 (71) |
| 2 | 61 (12) |
| 3 | 28 (5) |
| 4 | 25 (5) |
| 5–9 | 16 (3) |
| ≥10 | 12 (2) |
| Tumour size (cm) at diagnosis, n (%) | |
| 0–1 | 102 (19) |
| 2–3 | 249 (47) |
| 4–5 | 114 (22) |
| ≥6 | 60 (2) |
Pathology Assessment
The primary pathology assessment was done according to WHO 1973 and/or with Bergkvist classification [19, 20]. As current pathology reports are presented according to WHO 1999 and International Society of Urological Pathology (ISUP)/WHO 1998/2004/2016 (WHO 04/16), the dataset has been updated according to current classifications guidelines/standards [9].
The study population was divided into NMIBC and MIBC, and the NMIBC group was further divided into low‐risk NMIBC (low‐grade NMIBC [NMIBC Low]) and high‐risk NMIBC (high‐grade NMIBC [NMIBC High]) based on T‐stage and grade (G) according to the following: NMIBC Low comprised TaG1/Ta low grade, whilst NMIBC High comprised TaG2–G3/Ta high grade, T1, TIS (carcinoma in situ), and Ta/T1 with concomitant CIS. However, as papillary urothelial neoplasm of low malignant potential (PUNLMP), was not established in 1995–1996, patients with PUNLMP are included in the NMIBC Low group.
Follow‐Up
For the patients with NMIBC, we collected information for all recurrences and progressions after primary diagnosis until 23 June 2021. Ta low grade/TaG1 recurrences observed without collection of cytology or biopsy were counted as recurrences without progression. All grade, T‐, N‐, and M‐stage progressions were recorded with date of detection. Lymph node and metastasis progression were determined either through CT scan, MRI, or cytology. Due to histopathological and clinical differences between primary TIS and papillary carcinoma, patients with TIS were handled separately in the progression analysis.
Treatments and date of treatment were registered. Immediate RC was defined as RC with or without neoadjuvant chemotherapy within 6 months from diagnosis. RC after 6 months was defined as deferred RC and was categorised into the same group as no treatment. Neoadjuvant or induction chemotherapy prior to deferred RC was also registered. BCG treatment was given as induction course of six weekly instillations. Maintenance treatment (either monthly instillations or three weekly instillations every 3 months, for a least 1 year) was recommended.
Date and cause of death was collected from the Swedish Cause‐of‐Death Registry and electronic medical charts until end of follow‐up (23 June 2021). Patients who emigrated during follow‐up, or with unknown cause of death were excluded from the analysis of CSM (Fig. S1 and Table S1).
This study was approved by the Stockholm County Council Ethical Research Board and the Swedish Ethical Review Authority (diary numbers: 95‐368, 96‐016, 2019‐03352 and 2024‐08601‐02).
Statistical Analysis
The distribution of categorical variables is described as number of occurrences with proportions, the continuous variables are described using mean values with SDs. In the NMIBC group, grade, T‐, M‐ and N‐stage progressions were presented using Kaplan–Meier curves, divided into NMIBC Low, NMIBC High, and TIS groups. Competing risk regressions were performed to estimate the effects of tumour stage and grade on the risk of T‐progression, treating death as a competing event. Age, gender, number of tumours, and tumour size were included in the models as potential confounders. For cancer‐specific survival (CSS), we included the whole cohort and described the CSM stratified by treatment. For patients with T1 tumour, cause‐specific cumulative incidences were calculated and plotted. Additionally, stratified by NMIBC/MIBC, we described the number of CSM and any cause mortality during the follow‐up period. All the analyses were performed in Stata MP 17.0 (Stata Corp., College Station, TX, USA). The significance threshold was set to 0.05.
Results
In total, 628 patients with newly diagnosed bladder cancer were screened, of which 526 fulfilled the inclusion criteria (Fig. S1). Most patients had NMIBC (75%). In the NMIBC group, 52% of the patients had NMIBC Low. The median (range) follow‐up for the whole cohort was 93 (0.5–322) months. Detailed patient characteristics are presented in Table 1.
In the whole cohort, 147 patients (28%) died from bladder cancer with a median (range) time to death of 17 (0.5–294) months. In all, 64 patients (12%) were alive at the end of follow‐up (Fig. 1 and Table 2). Of the patients that were alive at the end of the follow‐up, 32 patients (50%) had NMBIC Low, 27 patients (42%) had NMIBC High, and five (8%) had MIBC as a primary diagnosis.
Fig. 1.
(A) Cancer‐specific cumulative incidence for the whole study population based on initial pathological T‐stage and grade after primary transurethral resection (NMIBC Low, NMIBC High, and MIBC according to WHO 04/16). (B) Cancer‐specific cumulative incidence for NMIBC Low, NMBIC High (Ta), NMIBC High (TIS), NMIBC High (T1), MIBC treated with RC <6 months, MIBC treated with RC >6 months/no treatment, and MIBC treated with radiotherapy.
Table 2.
The CSM and all‐cause mortality over the 25‐year follow‐up, divided in subgroups (NMIBC Low, NMIBC High, and MIBC).
| N | Total, n (%) | <1 year, n (%) | 1–4 years, n (%) | 5–9 years, n (%) | 10–14 years, n (%) | 15–19 years, n (%) | 20–25 years, n (%) | |
|---|---|---|---|---|---|---|---|---|
| CSM | ||||||||
| NMIBC Low | 208 | 7 (3) | 0 | 1 (1) | 4 (2) | 1 (1) | 0 | 1 (1) |
| NMIBC High | 188 | 48 (26) | 5 (3) | 26 (14) | 11 (6) | 2 (1) | 3 (2) | 1 (1) |
| TIS | 10 | 0 (0) | 0 | 0 | 0 | 0 | 0 | 0 |
| Ta | 76 | 10 (13) | 0 | 4 (5) | 5 (7) | 1 (1) | 0 | 0 |
| T1 | 102 | 38 (37) | 5 (5) | 22 (22) | 6 (6) | 1 (1) | 3 (3) | 1 (1) |
| MIBC | 130 | 92 (71) | 48 (37) | 40 (31) | 4 (3) | 0 | 0 | 0 |
| RC <6 months | 41 | 19 (46) | 6 (15) | 10 (24) | 3 (7) | 0 | 0 | 0 |
| RC >6 months | 6 | 5 (83) | 1 (17) | 4 (67) | 0 | 0 | 0 | 0 |
| No curative treatment | 68 | 57 (84) | 36 (53) | 21 (31) | 0 | 0 | 0 | 0 |
| Radiotherapy | 15 | 10 (67) | 5 (33) | 4 (27) | 1 (7) | 0 | 0 | 0 |
| Total | 526 | 147 (28) | 53 (10) | 67 (13) | 19 (4) | 3 (1) | 3 (1) | 2 (0) |
| All‐cause mortality | ||||||||
| NMIBC Low | 208 | 163 (78) | 6 (3) | 44 (21) | 38 (18) | 43 (21) | 13 (6) | 19 (9) |
| NMIBC High | 188 | 156 (83) | 16 (9) | 49 (26) | 37 (20) | 23 (12) | 19 (10) | 12 (6) |
| MIBC | 130 | 123 (95) | 52 (40) | 45 (35) | 10 (8) | 7 (5) | 8 (6) | 1 (1) |
| Total | 526 | 442 (84) | 74 (14) | 138 (26) | 85 (16) | 73 (14) | 40 (8) | 32 (6) |
In the NMIBC High group, 48 patients (26%) died from bladder cancer with a median (range) time to death of 42 (5–244) months (Table 2, Figs 1 and S3b). The cancer‐specific cumulative incidence of mortality for patients with an initial T1 tumour was 37% at 20 years after primary diagnosis (Fig. 2). When excluding patients with primary TIS from the analysis, 33 patients (32%) with T1 tumours had died within 9 years from diagnosis, and five additional patients (5%) died during the whole follow‐up period. In all, 10 patients (13%) with an initial Ta tumour in the NIMBIC High group died from bladder cancer (Table 2). In the NMIBC Low group, seven patients (3%) died from bladder cancer, where most of the deaths occurred between 5 and 9 years after diagnosis (Table 2, Figs 1 and S3a). In Fig. S2 the CSS for the NMIBC group stratified by T‐stage and grade is presented. The initial tumour stage was the most important predictor of CSM in the NMIBC group (subhazard ratio 2.09, 95% CI 1.34–3.24; P = 0.001; Table S5).
Fig. 2.
Cause‐specific cumulative incidence for patients with initial T1‐tumour.
In the MIBC group, 92 patients (71%) died from bladder cancer, of which 48 (37%) died within 1 year from the diagnosis (Table 2). Overall mortality for the MIBC group during the whole follow‐up was 95%. In all, 41 patients (32%) underwent an immediate RC, and 11 patients (27%) received neoadjuvant chemotherapy prior to RC (Tables 2 and S6). The cancer‐specific cumulative incidence of mortality in the MIBC group for patients with no treatment or deferred RC was 85% during the first 5 years, whilst the CSM for patients treated with immediate RC was 39% (Fig. 1B). There was no CSM after 7.5 years in the group of patients treated with immediate RC. In all, 15 patients (12%) were treated with radiotherapy as primary treatment for MIBC and had a 5‐year CSM of 60% (Table 2). In Table S6, we present a description of the treatment for the patients with MIBC.
Grade Progression
In the NMIBC Low group, 73 patients (35%) had grade progression (Fig. 3A), with a median (range) time to progression of 28 (1–207) months. In all, 17 of these 73 patients (23%) had an additional grade progression when using the WHO 1999 classification (Table S3).
Fig. 3.
Progression data for NMIBC according to WHO 04/16. (A) Grade progression (NMIBC High and TIS are not applicable for grade progression), (B) T‐stage progression, (C) Lymph nodes (N) progression, and (D) Progression to metastatic (M) diseases.
The T‐Stage Progression
In all, 17 patients (8%) with NMIBC Low had a T‐stage progression, with a median (range) time to progression of 49 (4–242) months. In the NMIBC High group, 52 patients (29%) progressed during the follow‐up, with a median (range) time to progression of 12 (1–234) months (Fig. 3B). Furthermore, two patients from each group had a second T‐stage progression during the follow‐up. In total, eight patients (4%) with NMIBC Low, and 41 patients (23%) with NMIBC High developed MIBC (Tables S2 and S3). Moreover, 34 patients (33%) with initial T1 tumour progressed to MIBC, of which 22 (65%) died during follow‐up (Tables 2, S2 and S3). Nine patients (26%) with initial T1 tumour, and who progressed to MIBC, had received BCG as their cancer treatment (Table 3). In both NMIBC groups (Low and High), T‐stage progressions occurred up to 20 years after primary diagnosis, with a median (range) time to progression of 15 (1–242) months. Initial tumour grade was associated with T‐stage progression (subhazard ratio 2.81, 95% CI 1.38–5.73; P = 0.005; Table S4).
Table 3.
The BCG‐treatment vs non‐BCG treatment within the NMIBC group (Low and High), according to WHO 04/16 classification.
| Categories | N (%) | CSM, n (%) | All‐cause mortality, n (%) | T‐progression, n (%) | N‐progression, n (%) | M‐progression, n (%) |
|---|---|---|---|---|---|---|
| NMIBC group | 396 | 55 (14) | 319 | 69 (17) | 20 (5) | 34 (9) |
| BCG treatment | 110 (28) | 23 (21) | 91 | 26 (24) | 10 (9) | 17 (15) |
| NMIBC Low | 16 (4) | 1 (6) | 13 | 4 (25) | 1 (6) | 1 (6) |
| NMIBC High | 94 (24) | 22 (23) | 78 | 22 (23) | 9 (10) | 16 (17) |
| TIS | 10 (3) | 9 | 0 | 0 | 0 | |
| Ta | 31 (8) | 4 (13) | 26 | 7 (23) | 2 (6) | 3 (10) |
| T1 | 53 (13) | 18 (34) | 43 | 15 (28) | 7 (13) | 13 (25) |
| RC <6 months | ||||||
| NMIBC High ‐ T1 | 3 (6) | 2 (67) | 3 | 2 (67) | 2 (67) | 0 |
| RC >6 months | ||||||
| NMIBC Low | 2 (1) | 0 | 2 | 2 (100) | 1 (50) | 0 |
| NMIBC High ‐ T1 | 8 (2) | 3 (38) | 7 | 6 (75) | 2 (25) | 2 (25) |
| No BCG treatment | 286 (72) | 32 (11) | 228 | 43 (15) | 10 (3) | 17 (6) |
| NMIBC Low | 192 (48) | 6 (3) | 150 | 13 (7) | 2 (1) | 2 (1) |
| NMIBC High | 94 (24) | 26 (28) | 78 | 30 (32) | 8 (9) | 15 (16) |
| Ta | 45 (11) | 6 (13) | 37 | 11 (24) | 2 (4) | 4 (9) |
| T1 | 49 (12) | 20 (41) | 41 | 19 (39) | 6 (12) | 11 (22) |
| RC <6 months | ||||||
| NMIBC High ‐ T1 | 9 (18) | 2 (22) | 5 | 4 (44) | 2 (22) | 1 (11) |
| RC >6 months | ||||||
| NMIBC Low | 2 (1) | 0 | 2 | 1 (50) | 1 (50) | 0 |
| NMIBC High ‐ Ta | 3 (7) | 1 (33) | 3 | 3 (100) | 2 (67) | 1 (33) |
| NMIBC High ‐ T1 | 6 (12) | 3 (50) | 5 | 6 (100) | 2 (33) | 1 (17) |
The N‐Stage and M‐Stage Progression
Metastatic progression in the lymph nodes occurred in four patients (2%) with NMIBC Low, and in 17 patients (10%) with NMIBC High (Fig. 3C). Distant metastatic progression occurred in four patients (2%) and 31 patients (17%) in the NMIBC Low and High groups, respectively (Fig. 3D).
Treatment with BCG
In total, 110 patients (28%) of the whole NMIBC group were treated with BCG (Table 3). In the NMIBC High group, 94 patients (50%) received BCG, and in this group, 53 patients (56%) had T1 as a primary diagnosis. Of the patients with NMIBC High who received BCG, 22 patients (23%) developed T‐stage, nine (10%) N‐stage, 16 (17%) M‐stage progression, and 22 patients (23%) died during follow‐up, respectively. Moreover, 18 patients (34%) in the NMIBC High group with T1 tumour, who received BCG, died during the follow‐up period. In all, 12 (67%) of these deaths occurred within 5 years from initial diagnosis. A total of 49 patients (48%) with NMIBC High with T1 tumour did not receive BCG (Table 3). Of these, 20 (41%) patients died during the follow‐up period. In all, 15 (75%) of these deaths occurred during the first 5 years of diagnosis. Nine patients (18%) with NMIBC High with T1 tumour underwent an immediate RC without prior BCG, two (22%) of which died within 4 years from surgery.
All 10 patients (3%) with solitary TIS were treated with BCG. None of them progressed or died from their cancer during follow‐up.
Discussion
In this population‐based cohort of all patients with newly diagnosed bladder cancer with a 25‐year follow‐up, we found that the cumulative CSM in patients diagnosed with initial T1 bladder cancer was 37%. For patients with primary NMIBC Low, 8% progressed in T‐stage, and 3% died from bladder cancer during the 25‐year follow‐up. Furthermore, our results demonstrates that patients with MIBC undergoing RC had no CSM after 7.5 years post‐treatment.
Our study indicates that patients with initial T1 tumours have a prolonged risk of CSM, and the risk persists 25 years after diagnosis. In fact, after 20 years of follow‐up, the CSS of T1 patients was approximately comparable to patients with T2 tumours treated with RC, highlighting the aggressive nature of some T1 tumours. Whilst RC is the standard treatment for patients with MIBC [17], the preferable treatment pathway of high‐risk NMIBC is still debated. Most of the patients with high‐risk NMIBC do not progress after bladder‐sparing treatments; however, about one third of the patients progress and develop MIBC [16]. Furthermore, when progressing from NMIBC to MIBC, the overall survival may be worse than in the patients with initially diagnosed and treated MIBC [21, 22]. Only nine patients with primary T1 underwent an immediate RC in our cohort, whilst the remaining 93 patients with an initial T1 tumour had a bladder‐sparing strategy, which could account for the prolonged bladder cancer mortality. A study [23] investigating the natural history of T1 tumours yielded similar results, revealing that 33% of patients experienced progression over a 10‐year period [23]. Moreover, among those who progressed, 40% died from bladder cancer [23]. This further highlights our findings on disease progression up to 20 years from primary diagnosis. The use of BCG instillations in our cohort varied, and a more compliant regime following the guidelines (induction + maintenance according to Southwest Oncology Group) may have improved CSS. Despite the documented effectiveness of BCG treatment in high‐risk NMIBC, about a third will progress and develop MIBC [16] or do not complete maintenance therapy [24].
Survival data for long‐term follow‐up in low‐risk NMIBC are scarce, with most of the available information focusing on recurrence and progression within this group. Progression to MIBC in this group is rare, some 3% over 10 years of follow‐up [25], and the CSM remains low [26]. In our cohort, we found an 8% risk for T‐stage progression and a 3% risk of dying from bladder cancer up to 25 years after initial diagnosis for patients with low‐risk NMIBC.
In the MIBC group, our results demonstrate that patients face a substantial risk of CSM for up to 4 years following diagnosis, whilst there was no CSM after 7.5 years after RC during the 25 years of follow‐up. These data support the notion that RC [27], and time of RC are two important factors when treating patients with MIBC [28]. The high mortality in our study reflects the lack of curative treatment for the large part of the MIBC group, which have also been presented in a separate published study based on this cohort [29].
Despite its uniquely long follow‐up time and high number of patients, our study entails several limitations. First, our prospective study was established 30 years ago, and even though the primary treatments have been the same for bladder cancer, some of the treatments such as neoadjuvant chemotherapy and bladder‐sparing treatment have evolved. Despite the guidelines, some patients with NMIBC High did not receive BCG treatment in our cohort. Additionally, only 11% of patients with MIBC in our cohort received neoadjuvant chemotherapy, which may affect the survival data of our study. Furthermore, we are not able to present high‐risk features, such as variant histology and adverse features, for patients with NMIBC High.
Conclusions
In conclusion, we found that patients diagnosed with T1 tumours have a high cumulative CSM over time. Our data also suggest that patients initially diagnosed with a NMIBC Low tumour may require an individually planned and longer follow‐up regimen as cancer‐related events can occur 20 years after diagnosis. These results underline the need of cautious follow‐up of patients with bladder cancer, especially if high‐risk features are present. Additionally, in this 25‐year follow‐up study, patients with MIBC treated with RC had no CSM after 7.5 years post‐treatment.
Disclosure of Interests
No conflicts exist.
Supporting information
Fig. S1. Flowchart for inclusion and exclusion.
Fig. S2. The CSS for Ta and TIS–T1.
Fig. S3. (A) Cause‐specific cumulative incidence for NMIBC Low, (B) Cause‐specific cumulative incidence for NMIBC High.
Table S1. Tumour and grade distribution for the entire cohort according to WHO 1999 and WHO 04/16.
Table S2. Progression data for NMIBC according to WHO 04/16.
Table S3. Specified progression distribution for NMIBC group according to WHO 1999.
Table S4. Subhazard ratio for T‐progression for the NMIBC group.
Table S5. The CSM for the NMIBC group.
Table S6. Treatment for MIBC and CSM within each subgroups.
Acknowledgement
This study was supported by Region Stockholm research grant (2019‐1137) and Signe and Olof Wallenius Stiftelse.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Fig. S1. Flowchart for inclusion and exclusion.
Fig. S2. The CSS for Ta and TIS–T1.
Fig. S3. (A) Cause‐specific cumulative incidence for NMIBC Low, (B) Cause‐specific cumulative incidence for NMIBC High.
Table S1. Tumour and grade distribution for the entire cohort according to WHO 1999 and WHO 04/16.
Table S2. Progression data for NMIBC according to WHO 04/16.
Table S3. Specified progression distribution for NMIBC group according to WHO 1999.
Table S4. Subhazard ratio for T‐progression for the NMIBC group.
Table S5. The CSM for the NMIBC group.
Table S6. Treatment for MIBC and CSM within each subgroups.