Routine surveillance of upper urinary tract imaging for diagnosing upper urinary tract urothelial cancer recurrence in patients with non-muscle invasive bladder cancer having a tumor size ≥30 mm and carcinoma in situ.

doi:10.21203/rs.3.rs-2228861/v1

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Routine surveillance of upper urinary tract imaging for diagnosing upper urinary tract urothelial cancer recurrence in patients with non-muscle invasive bladder cancer having a tumor size ≥30 mm and carcinoma in situ.

https://doi.org/10.21203/rs.3.rs-2228861/v1

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Background

Although routine surveillance imaging to examine upper urinary tract urothelial cancer recurrence during follow-up of non-muscle invasive bladder cancer is recommended, its necessity remains invalidated. We performed a single-institute long-term follow-up cohort study to identify risk factors for upper urinary tract urothelial cancer recurrence after non-muscle invasive bladder cancer treatment, as well as the clinical impact of routine surveillance imaging.

Methods and materials

A retrospective chart review of 864 patients with primary non-muscle invasive bladder cancer who underwent initial transurethral resection of bladder tumor between 1980 and 2020 was conducted. Oncological outcomes included upper urinary tract urothelial cancer recurrence-free survival and overall survival. Moreover, we examined the opportunities to diagnose its recurrence.

Results

Of 864 patients, 19 (2.2%) experienced upper urinary tract urothelial cancer recurrence. On multivariate Fine-Gray proportional regression analyses, a tumor size ≥ 30 mm and carcinoma in situ were independently associated with short upper urinary tract urothelial cancer recurrence-free survival. Recurrence was associated with shorter overall survival. Among the aforementioned 19 patients, recurrence was detected through routine imaging in 12 (63.2%), cystoscopy in two (10.5%), urine cytology in two (10.5%), presence of gross hematuria in one (5.3%), and unknown methods in two (10.5%).

Conclusion

Most patients experiencing upper urinary tract urothelial cancer recurrence were diagnosed by routine surveillance imaging, suggesting its clinical importance, especially for patients with non-muscle invasive bladder cancer accompanied by a tumor size ≥ 30 mm and carcinoma in situ.

Upper urinary tract urothelial cancer

non-muscle invasive bladder cancer

recurrence

carcinoma in situ

routine surveillance imaging

Compared to bladder recurrence, upper urinary tract urothelial cancer (UTUC) recurrence during surveillance of non-muscle invasive bladder cancer (NMIBC) is relatively rare, with an incidence of 2.6–5.8% [1–4]. Previous reports have described high-risk NMIBC, carcinoma in situ (CIS), vesicoureteral reflux, and failed intravesical chemotherapy as prognostic factors for UTUC recurrence after treatment of NMIBC [5–6].

Each guideline mentions the need for follow-up for NMIBC with regards to the observation of the upper urinary tract. Table 1 summarizes the follow-up strategies for the diagnosis of UTUC using upper urinary tract imaging. Routine surveillance imaging, including computed tomography urography (CTU), is recommended for patients with high-risk NMIBC, but not for those with low or intermediate risk [7–11]. Although CTU has excellent diagnostic performance for UTUC, a risk of contrast nephropathy and radiation exposure exists. Sternberg et al. reported that most UTUC recurrences in patients with NMIBC were missed on routine surveillance imaging, which suggests that this method may not be efficient to diagnose UTUC recurrence [12]. The necessity of routine surveillance imaging for diagnosing UTUC after treating NMIBC remains unclear. We performed a single-institute, long-term follow-up cohort study to identify the risk factors for UTUC recurrence after NMIBC treatment and the clinical impact of routine surveillance imaging.

Patient selection and study design

The study protocol was approved by the Institutional Review Board for Clinical Studies (Medical Ethics Committee ID: 2891) at the Nara Medical University. The opt-out method was applied to obtain consent from the participants via posters and/or websites, and the study was conducted in compliance with the principles of the Declaration of Helsinki.

We conducted a retrospective chart review of 913 patients diagnosed with primary NMIBC who underwent transurethral resection of bladder tumor (TURBT) between 1980 and 2020. The inclusion criteria were as follows: 1) primary NMIBC at diagnosis at the Nara Medical University, 2) UTUC recurrence after initial TURBT, and 3) complete clinicopathological data.

The following clinicopathological variables on prognosis were evaluated: age, sex, Eastern Cooperative Oncology Group performance status (ECOG-PS), tumor size, multiplicity, clinical T category, World Health Organization (WHO) 1973 and 2004 grades, CIS, prostate-involving CIS, lymphovascular invasion (LVI), variant histology, risk classification, and intravesical recurrence after initial TURBT. The Clinical T category was determined on imaging before TURBT and through the pathological diagnosis of TURBT. After the advent of the WHO 2004 schemes, the pathologists at our hospital used the WHO 2004 grade instead of the WHO 1973 grade. The risk classification of NMIBC was defined in the Clinical Practice Guidelines for Bladder Cancer 2019 [10]. The criteria for highest-risk NMIBC are as follows:1) T1 and high grade (HG) tumors with concomitant bladder CIS, concomitant prostate-involving CIS, multiple tumors, recurrent tumors, a tumor size ≥ 30 mm, variant histology, and/or LVI; and 2) Bacillus Calmette-Guérin (BCG)-unresponsive disease. BCG-unresponsive disease was also defined in the Clinical Practice Guidelines for Bladder Cancer 2019 [10].

Follow-up

Patients were followed up after the initial TURBT according to the protocols of the Nara Medical University. Cystoscopy was performed three months after the initial TURBT. Routine cystoscopy, blood examination, and urine cytology for diagnosing intravesical recurrence were performed every three, six, or 12 months for up to ten years according to the clinicopathological factors. To diagnose the UTUC recurrence, routine radiographic imaging examinations were performed every six or 12 months after initial TURBT and further intensified by each attending physician according to the patient’s symptoms.

Outcomes

Oncological outcomes included the UTUC recurrence-free survival and overall survival (OS). UTUC recurrence-free survival was defined as the duration from initial TURBT to UTUC recurrence. The OS was examined to evaluate the impact of UTUC recurrence on the all-cause mortality. We also examined further opportunities to diagnose UTUC recurrence.

Statistical analysis

Quantitative variables are summarized as means (standard deviation [SD]), and categorical variables are presented as proportions. Student’s t-test, Fisher’s exact test, and the chi-square test were used as appropriate for the statistical analyses of patient clinicopathological characteristics. Prognostic factors for UTUC recurrence-free survival were assessed using a competing risk analysis by the Gray test for cumulative incidence. Competing events were defined as deaths without UTUC recurrence. Univariate and multivariate Fine-Gray competing risk regression analyses were used to estimate the hazard ratios for UTUC recurrence-free survival. The OS was assessed using Kaplan-Meier survival curves constructed using GraphPad Prism 7.0 (GraphPad Software, San Diego, CA, USA). Survival curves were compared using the log-rank test. A p-value < 0.05 was considered statistically significant. Statistical analyses were performed using EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan) [13].

Characteristics of patients with UTUC recurrence

Figure 1 presents the flowchart of the creation of the patient cohort dataset. Forty-four patients were excluded due to lack of data, and five patients were excluded as they were diagnosed with UTUC at the same time as primary NMIBC. Ultimately, 864 patients were included in the analysis. Table 2 shows the clinicopathological characteristics of patients and a comparison between the UTUC recurrence and non-UTUC recurrence groups. Of the 864 patients, 19 (2.2%) experienced an UTUC recurrence after initial TURBT for primary NMIBC. The mean (standard deviation) follow-up period from initial TURBT was 58.1 (46.8) months in the UTUC recurrence group and 74.7 (70.6) months in the non-UTUC recurrence group, respectively. A tumor size ≥30 mm was associated with a risk of UTUC recurrence. In the UTUC recurrence group, zero cases of cTa, four cases of cTis (21.1%), and 15 cases of cT1 (78.9%) were observed. Moreover, there were significantly more patients with WHO 1973 grade 3, WHO 2004 high grade, and CIS-positive NMIBC in the UTUC recurrence group than in the non-UTUC recurrence group. Sixteen (84.2%) of the 19 patients in the UTUC recurrence group received intravesical BCG therapy. Eight (42.1%) and 11 (57.9%) of the 19 patients in the UTUC recurrence group had high- or highest-risk NMIBC, respectively.

Prognostic factors for UTUC recurrence

Figure 2 and Supplementary Figure S1 show the cumulative incidence of UTUC recurrence-free survival after initial TURBT according to the clinicopathological variables. Figure 2 demonstrates that a tumor size ≥30 mm, high grade, CIS-positive NMIBC, cTis or cT1, and high- or highest-risk NMIBC were associated with a shorter UTUC recurrence-free survival. Table 3 shows the univariate and multivariate Fine-Gray competing risk regression analyses for UTUC recurrence-free survival. Figure 3 shows the cumulative incidence of UTUC recurrence-free survival in the four groups categorized according to tumor size and CIS status. Multivariate analyses revealed that a tumor size ≥30 mm (hazard ratio [HR], 2.53, 95% confidence interval [CI], 1.04–6.15, Fine-Gray P=0.040) and CIS-positive NMIBC (HR, 4.78, 95% CI, 1.48–15.42, Fine-Gray P=0.0089) were independently associated with a short UTUC recurrence-free survival.

OS for UTUC recurrence

Figure 4 compares the survival curves for OS after initial TURBT among patients stratified according to the number of risk factors for UTUC recurrence (A) and between those with or without UTUC recurrence (B). Prognostic factors included a tumor size ≥30 mm and CIS-positive NMIBC. Patients with both prognostic factors had significantly shorter OS (log-rank P=0.042) than those without. Moreover, UTUC recurrence was significantly associated with a shorter OS (HR, 3.95, 95% CI, 1.15–13.65, log-rank P=0.030).

Clinicopathological characteristics of 19 patients experiencing UTUC recurrence

Among the aforementioned 19 patients, UTUC was diagnosed through routine imaging in 12 (63.2%), cystoscopy in 2 (10.5%), urine cytology in 2 (10.5%), presence of gross hematuria in 1 (5.3%), and unknown methods in 2 (10.5%) patients (Figure 5).

Table 4 summarizes the opportunities for diagnosing UTUC recurrence, clinicopathological characteristics of primary NMIBC, and pathological T categories of UTUC in radical nephroureterectomy specimens or partial ureterectomy specimens. No patient with Ta NMIBC or low-/intermediate-risk NMIBC experienced a UTUC recurrence during follow-up. Of 19 patients in the UTUC recurrence group, 16 (78.9%) had a history of T1 HG NMIBC, 3 (21.1%) had a history of Tis NMIBC, 8 (42.1%) had high-risk NMIBC, and 11 (57.9%) had a highest-risk NMIBC. Sixteen patients (84.2%) received an intravesical BCG therapy after initial TURBT. Moreover, 16 patients (84.2%) underwent radical operations without neoadjuvant chemotherapy for recurrent lesions of the upper urinary tract. Of these patients, two had pathologically diagnosed pT3 (11.8%), seven had pT2 (41.2%), four had pT1 (23.5%), one had pTis (5.9%), and two had pTa (11.8%). One patient received neoadjuvant chemotherapy and was pathologically diagnosed with ypT0. Three patients were diagnosed with a UTUC recurrence more than ten years after initial TURBT.

In this retrospective study, a tumor size ≥ 30 mm and CIS-positive NMIBC increased the UTUC recurrence after initial TURBT for primary NMIBC. Moreover, high grade, cTis or cT1, and high- or highest-risk NMIBC may also be related to the recurrence rate. Previous reports have described that high-risk and CIS-positive NMIBC were prognostic factors for UTUC recurrence after treatment with NMIBC, and this study showed similar results [5, 6]. Moreover, there are reports of UTUC recurrence after radical cystectomy. Similarly, some studies demonstrate that CIS was a risk factor for UTUC recurrence [14–16].

CIS may also have an impact on OS beyond the UTUC recurrence. Figure 4 shows that a tumor size ≥ 30 mm and presence of CIS increased the all-cause mortality. Previous reports described that a history of CIS-positive NMIBC developed aggressive UTUC and increased the cancer-related mortality rate after radical nephroureterectomy for UTUC [17]. Similarly, in this study, although 17 (89.5%) of 19 patients with UTUC recurrence underwent radical operations for recurrent lesions, patients in the UTUC recurrence group had a worse prognosis. Accordingly, follow-up of the upper urinary tract in patients with CIS-positive NMIBC might be necessary to diagnose the UTUC recurrence at an early stage.

Some previous reports are skeptical about the routine surveillance imaging for diagnosing UTUC recurrence after the treatment with NMIBC [12, 18]. In contrast to previous reports, in this study, of 19 patients with UTUC recurrence, most (84.2%) were diagnosed by routine surveillance imaging, cystoscopy, or urine cytology, and only one (5.3%) was diagnosed by the presence of symptoms (Table 4). Moreover, several cases were found to present with invasive urothelial cancer, and 9 cases (47.4%) in the UTUC recurrence group had progressed to muscle invasion from non-muscle invasive disease. If routine surveillance imaging was not performed in these patients, unresectable or metastatic disease may have developed.

Sixteen (84.2%) of the 19 patients with UTUC recurrence received intravesical BCG therapy for primary NMIBC, and there were more patients who received intravesical BCG therapy in the UTUC recurrence group than those in the non-UTUC recurrence group (Tables 2 and 4). Previous reports described that the incidence of UTUC recurrence in patients who received intravesical BCG therapy for NMIBC was 7.6–8.9%, which was higher than that reported in our cohort (2.2%) [19, 20]. This could be attributed to the fact that there were more patients with CIS-positive and/or high- or highest-risk NMIBC in the cohorts of previous reports than in our retrospective cohort. Moreover, in this study, the mean period to diagnose UTUC recurrence was 58.1 months, and three patients were diagnosed with UTUC recurrence more than ten years after initial TURBT (Tables 2 and 4), suggesting that the long-term follow-up of the upper urinary tract is necessary for patients receiving intravesical BCG therapy.

In contrast, the overall incidence of UTUC after TURBT for primary NMIBC in our study was very low at 2.2%, which was almost the same as that of previous reports [1–4, 12]. Moreover, there were no patients with low- and intermediate-risk NMIBC who experienced a UTUC recurrence (Table 4). In fact, current guidelines do not recommend routine surveillance imaging for low- and intermediate-risk NMIBC [7–11]. Accordingly, routine surveillance imaging is recommended for high- or highest-risk NMIBC, especially when both tumor size ≥ 30 mm and CIS-positive NMIBC are identified. For patients with low- or intermediate-risk NMIBC, follow-up with ultrasonography and urine cytology, which are noninvasive, without radiographic imaging, such as CTU, might be sufficient.

This study has several limitations. First, data on patients were collected retrospectively, and a potential selection bias may have occurred. For example, this cohort included cases from 1980 onwards. To date, the diagnostic abilities of radiographic imaging and endoscopic techniques have advanced, and follow-up has not been uniform between cases. Second, intravesical BCG therapy mostly depends on each attending physician and is not uniformly administered for CIS-positive and high-risk NMIBC. Moreover, the number of cases with UTUC recurrence was so small that the HR of intravesical BCG therapy after TURBT could not be calculated, and its impact could not be assessed. Third, since multiple surgeons performed TURBT, prognosis might have been influenced by differences in skill. Further prospective cohort studies are required to substantiate the findings of this study.

Acknowledgment

The authors would like to thank all patients who participated in this study for their important contributions. Clinicopathological statistics are based on the results of contributions from a number of institutions in Japan. We also thank the urologists for their invaluable help in obtaining and summarizing the data used in this study.

Conflict of Interest

The authors declare no conflict of interest.

Approval of the research protocol by an Institutional Reviewer Board

The institutional review board of the Nara Medical University approved this study. The reference number is 2891.

Informed Consent

The opt-out method was applied to obtain consent from participants via posters and/or websites.

Registry and the Registration No. of the study/trial

N/A

Animal Studies

N/A

Data Availability Statements

The data underlying this article will be shared on reasonable request to the corresponding author.

Data statement

Conceptualization: Nobutaka Nishimura and Makito Miyake, Methodology: Makito Miyake, Formal analysis and investigation: Nobutaka Nishimura, Tatsuki Miyamoto, Takuto Shimizu, and Tomomi Fujii, Writing - original draft preparation: Nobutaka Nishimura, Writing - review and editing: Makito Miyake, Supervision: Yosuke Morizawa, Shunta Hori, Daisuke Gotoh, Yasushi Nakai, Kazumasa Torimoto, Nobumichi Tanaka, and Kiyohide Fujimoto.

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Table 1. Follow-up strategies for diagnosing UTUC after treatment for NMIBC by upper urinary tract imaging.
Guidelines	Risk classification of each guideline
Guidelines	Low	Intermediate	High
AUA/SUO⁷	Unnecessary	Every 1 to 2 years	Every 1 to 2 years
CUA⁸	Not mentioned	Not mentioned	Every 1 to 2 years
EAU⁹	Not mentioned	Not mentioned	Every 1 years
JUA¹⁰	As clinically indicated	As clinically indicated	Every year for up to 3 years and thereafter every 2 years
NCCN¹¹	As clinically indicated	As clinically indicated	At 12 months and therefore every 1 to 2 years
AUA/SUO, American Urological Association/Society of Urologic Oncology; CUA, Canadian Urological Association; EAU, European Association of Urology; JUA, Japanese Urological Association; NCCN, National Comprehensive Cancer Network, NMIBC, non-muscle invasive bladder cancer; UTUC, upper urinary tract urothelial cancer

Table.2Clinicopathological characteristics and comparison between UTUC recurrence group and non-UTUC recurrence group.
Variables	UTUC recurrence group n (%)	Non-UTUC recurrence group n (%)	P value
N	19 (2.2%)	845 (97.8%)
Period of follow-up from initial TURBT, mean ± SD	58.1 ± 46.8	74.7 ± 70.6	0.31
Age at initial TURBT, years, mean ± SD	71.6 ± 5.9	76.5 ± 11.9	0.078
Sex
Male	16 (84.2%)	727 (86.0%)
Female	3 (15.8%)	118 (14.0%)
ECOG-PS			1.00
0-1	19 (100.0%)	828 (98.0%)
≥ 2	0 (0.0%)	17 (2.0%)
Tumor size			0.026
< 30mm	10 (52.6%)	646 (76.4%)
≥ 30mm	9 (47.4%)	199 (23.6%)
Multiplicity			0.64
Single	12 (63.2%)	474 (56.1%)
Multiple	7 (36.8%)	371 (43.9%)
Clinical T category			< 0.001
Ta	0 (0.0%)	413 (48.9%)
Tis	4 (21.1%)	35 (4.1%)
T1	15 (78.9%)	397 (47.0%)
Grade (WHO1973)			< 0.001
Grade 1	1 (5.3%)	164 (19.4%)
Grade 2	2 (10.5%)	406 (48.0%)
Grade 3	16 (84.2%)	275 (32.5%)
Grade (WHO2004)			0.001
Low grade	3 (15.8%)	463 (54.8%)
High grade	16 (84.2%)	382 (45.2%)
CIS			< 0.001
Negative	6 (31.6%)	663 (78.5%)
Positive	13 (68.4%)	182 (21.5%)
Prostate-involving CIS			0.44
Negative	18 (94.7%)	820 (97.0%)
Positive	1 (5.3%)	25 (3.0%)
LVI			0.058
Negative	14 (73.7%)	750 (88.8%)
Positive	5 (26.3%)	95 (11.2%)
Variant histology			0.46
Negative	18 (94.7%)	819 (96.9%)
Positive	1 (5.3%)	26 (3.1%)
Intravesical therapy after TURBT			< 0.001
None	3 (15.8%)	473 (56.0%)
BCG	16 (84.2%)	239 (28.3%)
IPIC	0 (0.0%)	116 (13.7%)
BCG + IPIC	0 (0.0%)	17 (2.0%)
Risk classification^†			< 0.001
Low	0 (0.0%)	186 (22.0%)
intermidiate	0 (0.0%)	182 (21.5%)
High	8 (42.1%)	220 (26.0%)
Highest	11 (57.9%)	257 (30.4%)
BCG, Bacillus Calmette-Guérin; CIS, carcinoma in situ; ECOG-PS, Eastern Cooperative Oncology Group performance status; IPIC, immediate postoperative instillation of chemotherapy; LVI, lymphovascular invasion; SD, standard deviation; TURBT, transurethral resection of bladder tumor; UTUC, upper urinary tract urothelial carcinoma; WHO, World Health Organization † The risk was classified according to the Clinical Practice Guidelines for Bladder Cancer 2019.¹⁰

Table 3. Univariate and multivariate Fine-Gray competing risk regression analysis for UTUC recurrence-free survival in patients with primary NMIBC
Variables	Univariate			Multivariate
Variables	HRs	95% CI	P value	HRs	95% CI	P value
Age at initial TURBT, years
<70	1
≥70	0.80	0.32-2.00	0.64
Sex
Male	1
Female	1.11	0.33-3.74	0.87
Tumor size
<30mm	1			1
≥30mm	2.86	1.17-6.97	0.021	2.53	1.04-6.15	0.040
Multiplicity
Single	1
Multiple	0.85	0.33-2.14	0.72
Grade (WHO2004)
Low grade	1			1
High grade	7.07	2.05-24.43	0.002	2.28	0.48-10.78	0.30
CIS
Negative	1			1
Positive	8.02	3.09-20.81	< 0.001	4.78	1.48-15.42	0.0089
Prostate-involving CIS
Negative	1
Positive	1.56	0.21-11.61	0.66
LVI
Negative	1
Positive	2.23	0.80-6.20	0.12
Variant
Negative	1
Positive	1.68	0.24-11.99	0.60
Intravesical recurrence
Negative	1
Positive	1.83	0.69-3.83	0.26
CIS, carcinoma in situ; HR, hazard ratio; LVI, lymphovascular invasion; NMIBC, non-muscle invasive bladder cancer; PS, performance status; TURBT, transurethral resection of bladder tumor; UTUC, upper urinary tract urothelial carcinoma; WHO, World Health Organization

Table 4. A summary of the opportunities to diagnose UTUC recurrence, clinicopathological characteristics of primary NMIBC, and pathological T categories of UTUC
Patients	The opportunities of UTUC diagnosis	clinical T category of primary NMIBC	Grade (WHO2004)	CIS	Risk classification†	Intravesical therapy after initial TURBT	Treatment for UTUC	pathological T category of UTUC	Periods for UTUC recurrence
1	Routine imaging	T1	HG	Negative	Highest	BCG	Operation	pTa	171
2	Routine imaging	T1	HG	Positive	Highest	BCG	Operation	pT2	136
3	Routine imaging	T1	HG	Negative	Highest	BCG	Operation	pT2	123
4	Urine cytology	T1	HG	Positive	Highest	BCG	Operation	pT2	111
5	Cystoscopy	T1	HG	Positive	Highest	BCG	Operation	pT1	84
6	Gross hematuria	T1	LG	Negative	High	None	Operation	pTa	74
7	Unknown	T1	HG	Positive	Highest	BCG	Operation	pT1	53
8	Urine cytology	T1	HG	Positive	Highest	BCG	BCG into upper urinary tract	Unknown	48
9	Routine imaging	T1	HG	Positive	Highest	BCG	Operation	pT2	48
10	Routine imaging	T1	LG	Negative	High	None	Operation	pT1	39
11	Routine imaging	Tis	HG	Positive	High	BCG	Unknown	Unknown	39
12	Routine imaging	T1	LG	Negative	High	BCG	Operation	pT3	38
13	Routine imaging	Tis	HG	Positive	High	BCG	Operation	pT2	36
14	Routine imaging	T1	HG	Negative	High	BCG	Operation	pT2	34
15	Routine imaging	T1	HG	Positive	Highest	BCG	Operation	pT2	27
16	Unknown	T1	HG	Positive	Highest	None	Operation	pT3	18
17	Routine imaging	Tis	HG	Positive	High	BCG	Operation	pT0 after NAC	14
18	Routine imaging	Tis	HG	Positive	High	BCG	Operation	pTis	7
19	Cystoscopy	T1	HG	Positive	Highest	BCG	Operation	pT1	3
BCG, Bacillus Calmette-Guérin; CIS, carcinoma in situ; HG, high grade; LG, low grade; NAC, neoadjuvant chemotherapy; NMIBC, non-muscle invasive bladder cancer; TURBT, transurethral resection of bladder tumor; UTUC, upper urinary tract urothelial carcinoma; WHO, world health organization † The risk was classified according to the Clinical Practice Guidelines for Bladder Cancer 2019.¹⁰

SupplementaryFig.S1.tif
Supplementary Fig. S1 Cumulative incidence of UTUC recurrence-free survival after initial TURBT for primary NMIBC according to age, sex, ECOG-PS, multiplicity, prostate-involving CIS, lymphovascular invasion, variant histology, and intravesical recurrence. Survival curves of the cumulative incidence of UTUC recurrence-free survival after initial TURBT for primary NMIBC are plotted according to age (A), sex (B), ECOG-PS (C), multiplicity (D), prostate-involving CIS (E), lymphovascular invasion (F), variant histology (G), and intravesical recurrence (H).

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Routine surveillance of upper urinary tract imaging for diagnosing upper urinary tract urothelial cancer recurrence in patients with non-muscle invasive bladder cancer having a tumor size ≥30 mm and carcinoma in situ.

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