Concomitant carcinoma in situ may not be a prognostic factor for patients with bladder cancer following radical cystectomy: a PRISMA-compliant systematic review and meta-analysis



Numerous recent studies have shown that concomitant carcinoma in situ (CIS) can be closely associated with the prognosis of patients with bladder cancer (BCa). However, the prognostic value of CIS in BCa is still not conclusive. Hence, we performed a systematic review and meta-analysis to explore the association between CIS and clinicopathological features and the prognostic value for BCa following radical cystectomy.


We performed this study in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Relevant studies were systematically collected from PubMed, EMBASE, and Web of Science, with an expiration date of August 2018. Hazard ratios and 95% confidence intervals (CIs) were pooled to assess the intensity of association. All data were analyzed by Stata 12.0. Moreover, heterogeneity and publication bias were determined, and sensitivity analysis was performed to examine whether the findings of the meta-analysis were robust.


A total of 18,845 patients from 24 studies were included in the analysis. Our results indicated that CIS has no significant correlation with cancer-specific mortality (CSM) (pooled HR = 0.97, 95% CI 0.93–1.00, p = 0.059), overall mortality (OM) (pooled HR = 0.93, 95% CI 0.85–1.01, p = 0.076), overall survival (OS) (pooled HR = 1.04, 95% CI 0.96–1.12, p = 0.386), cancer-specific survival (CSS) (pooled HR = 1.06, 95% CI 0.97–1.16, p = 0.186), recurrence-free survival (RFS) (HR = 1.05, 95% CI 0.99–1.11, p = 0.098) or recurrence (pooled HR = 1.04, 95% CI 0.98–1.11, p = 0.212) in BCa patients. In addition, CIS was not correlated with gender (male vs. female, OR = 1.00, 95% CI 0.74–1.34, p = 0.978), pathological stage (III/IV vs. I/II: OR = 0.74, 95% CI 0.50–1.10, p = 0.132), tumor grade (1/2 vs. 3: OR = 3.38, 95% CI 0.73–15.65, p = 0.119), soft tissue surgical margin (STSM) (+ vs. − : OR = 1.20, 95% CI 0.97–1.48, p = 0.093) or lymphovascular invasion (LVI) (+ vs. − : OR = 0.92, 95% CI 0.62–1.38, p = 0.702),but was closely related to adjuvant chemotherapy (ACT) (yes vs. no, OR = 1.17, 95% CI 1.03–1.32, p = 0.019). Furthermore, these findings were demonstrated to be reliable by our sensitivity and subgroup analysis.


The prognostic value of CIS in BCa remains inconclusive in patients submitted to RC. Our data indicated that CIS may have no significant correlation with the prognosis and clinicopathological parameters of BCa patients, and also may not be applied to risk stratification or individualized therapy in BCa patients. Further research should be conducted to confirm our findings.

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Fig. 1
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Fig. 4



Concomitant carcinoma in situ


Bladder cancer


Radical cystectomy


Preferred reporting items for systematic reviews and meta-analyses


Newcastle Ottawa scale


Hazard ratios


Corresponding 95% confidence intervals


Cancer-specific mortality


Overall mortality


Overall survival


Cancer-specific survival


Recurrence-free survival


Soft tissue surgical margin


Lymphovascular invasion


Adjuvant chemotherapy


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Conceptualization: LZ, BW. Literature search: ZZ, HZ. Data analysis: JY, YJ. Writing—original draft: LZ. Writing—review and editing: BW. All authors approved the final manuscript.

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Correspondence to Lijin Zhang.

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Supplementary Figure S1. Forest plots of the association between concomitant carcinoma in situ and clinicopathological features of BCa: (A) gender, (B) pathological stage, (C) tumor grade, (D) STSM, (E) LVI, and (F) ACT.

Supplementary Figure S2. Sensitivity analysis under the specific model: (A) effect of individual studies on the pooled HR for CSM; (B) effect of individual studies on the pooled HR for OM; (C) effect of individual studies on the pooled HR for CSS; (D) effect of individual studies on the pooled HR for OS; (E) effect of individual studies on the pooled HR for RFS; and (F) effect of individual studies on the pooled HR for recurrence.

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Zhang, L., Wu, B., Zha, Z. et al. Concomitant carcinoma in situ may not be a prognostic factor for patients with bladder cancer following radical cystectomy: a PRISMA-compliant systematic review and meta-analysis. World J Urol 38, 129–142 (2020).

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  • Carcinoma in situ
  • Bladder cancer
  • Radical cystectomy
  • Prognosis
  • Meta-analysis