Prognostic Value of Concomitant Carcinoma In Situ in the Radical Cystectomy Specimen: A Systematic Review and Meta-Analysis
2018; Lippincott Williams & Wilkins; Volume: 201; Issue: 1 Linguagem: Inglês
10.1016/j.juro.2018.05.162
ISSN1527-3792
AutoresShoji Kimura, Andrea Mari, Beat Foerster, Mohammad Abufaraj, Mihai Dorin Vartolomei, Judith Stangl‐Kremser, Pierre I. Karakiewicz, Shin Egawa, Shahrokh F. Shariat,
Tópico(s)Urinary and Genital Oncology Studies
ResumoOpen AccessJournal of UrologyReview Article1 Jan 2019Prognostic Value of Concomitant Carcinoma In Situ in the Radical Cystectomy Specimen: A Systematic Review and Meta-Analysis Shoji Kimura, Andrea Mari, Beat Foerster, Mohammad Abufaraj, Mihai D. Vartolomei, Judith Stangl-Kremser, Pierre I. Karakiewicz, Shin Egawa, and Shahrokh F. Shariat Shoji KimuraShoji Kimura Department of Urology, Medical University of Vienna, Vienna, Austria Departments of Urology, Jikei University School of Medicine, Tokyo, Japan , Andrea MariAndrea Mari Department of Urology, Medical University of Vienna, Vienna, Austria Careggi Hospital, University of Florence, Florence, Italy , Beat FoersterBeat Foerster Department of Urology, Medical University of Vienna, Vienna, Austria Kantonsspital Winterthur, Winterthur, Switzerland , Mohammad AbufarajMohammad Abufaraj Department of Urology, Medical University of Vienna, Vienna, Austria Department of Special Surgery, Jordan University Hospital, University of Jordan, Amman, Jordan , Mihai D. VartolomeiMihai D. Vartolomei Department of Urology, Medical University of Vienna, Vienna, Austria Department of Cell and Molecular Biology, University of Medicine and Pharmacy, Tirgu Mures, Romania , Judith Stangl-KremserJudith Stangl-Kremser Department of Urology, Medical University of Vienna, Vienna, Austria , Pierre I. KarakiewiczPierre I. Karakiewicz Division of Urology, University of Montreal Health Center, Montreal, Quebec, Canada , Shin EgawaShin Egawa Departments of Urology, Jikei University School of Medicine, Tokyo, Japan , and Shahrokh F. ShariatShahrokh F. Shariat †Correspondence: Department of Urology and Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, A-1090Vienna, Austria (telephone: +4314040026150; FAX: +4314040023320; e-mail: E-mail Address: [email protected]). Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria Weill Cornell Medical College, New York, New York University of Texas Southwestern Medical Center, Dallas, Texas View All Author Informationhttps://doi.org/10.1016/j.juro.2018.05.162AboutAbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Abstract Purpose: We investigated the prognostic impact of concomitant carcinoma in situ in radical cystectomy specimens. Materials and Methods: We performed a systematic review and meta-analysis using MEDLINE®, Scopus®, Web of Science™ and The Cochrane Library to identify eligible studies published until October 2017. Studies were eligible for analysis if they compared patients with concomitant carcinoma in situ in radical cystectomy specimens for bladder cancer to patients without concomitant carcinoma in situ to determine its value to prognosticate overall mortality, recurrence-free survival, cancer specific mortality and ureteral involvement using multivariable analysis. The protocol for this systematic review was registered in PROSPERO (Prospective Register of Systematic Reviews, CRD42018086539) and is available in full on the University of York website. Results: Overall 23 studies published between 2006 and 2017 including a total of 20,647 patients were selected for the systematic review and meta-analysis. Concomitant carcinoma in situ was reported in 39.4% of radical cystectomy specimens. In studies analyzing all patients the presence of concomitant carcinoma in situ was not associated with overall mortality (pooled HR 0.92, 0.77–1.10), recurrence-free survival (pooled HR 1.06, 0.99–1.13) or cancer specific mortality (pooled HR 1.00, 0.93–1.07). It was associated with ureteral involvement (pooled OR 4.51, 2.59–7.84). On subanalysis of studies restricted to patients with organ confined bladder cancer at radical cystectomy concomitant carcinoma in situ was associated with worse recurrence-free survival (pooled HR 1.57, 1.12–2.21) and cancer specific mortality (pooled HR 1.51, 1.001–2.280). Conclusions: Concomitant carcinoma in situ is significantly associated with ureteral involvement in patients treated with radical cystectomy. In patients with organ confined disease concomitant carcinoma in situ in the radical cystectomy specimen is a prognosticator of recurrence-free survival and cancer specific mortality. Abbreviations and Acronyms BC bladder cancer BCG bacillus Calmette-Guérin CIS carcinoma in situ CSM cancer specific mortality MIBC muscle invasive BC NOS Newcastle-Ottawa Scale OM overall mortality RC radical cystectomy RFS recurrence-free survival RoB risk of bias TUR transurethral resection UUT upper urinary tract Radical cystectomy with pelvic lymph node dissection is standard treatment of patients with MIBC and patients with very high risk nonMIBC.1–3 Despite radical treatment up to 50% of patients experience disease recurrence and eventually death.4 CIS is a flat, high grade manifestation of BC which can present in isolation or concomitantly with papillary lesions. CIS can spread along the surface of the bladder focally or in a diffuse pattern.5 The presence of concomitant CIS in TUR specimens increases the risk of disease recurrence and progression to MIBC if left untreated.6 While the aggressiveness of concomitant CIS in nonMIBC TUR specimens is well known, its prognostic impact at the time of RC remains controversial. Concomitant CIS in RC specimens was not found to be associated with worse oncologic outcomes in some large retrospective studies.7–9 On the other hand, other reports showed that concomitant CIS portends an unfavorable prognosis in patients with organ confined BC.10 Moreover, concomitant CIS in the RC specimen has been associated with an increased risk of ureteral involvement and, therefore, of UUT recurrence.11–13 In recent years various studies have provided further evidence of the prognostic value of concomitant CIS in patients treated with RC for BC. Identifying the histological features associated with a worse prognosis is of paramount importance to improve patient counseling and treatment decision making regarding followup and adjuvant therapy. In this systematic review and meta-analysis, we investigated the clinical impact of the presence of concomitant CIS in RC specimens on the oncologic outcomes in patients with BC. Materials and Methods The protocol has been registered in the international PROSPERO database (CRD42018086539) and is available in full on the University of York website. Literature Search This systematic review and meta-analysis was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement14 and the Cochrane Handbook for Systematic Reviews of Interventions.15 We performed a comprehensive literature search of electronic databases, including MEDLINE, Web of Science, Scopus and The Cochrane Library, on October 10, 2017 to identify studies published until October 2017 of the impact of concomitant CIS in the RC specimen on the oncologic outcome. All full text papers were assessed and excluded when found to be inappropriate after screening based on the study title and abstract. Two reviewers (SK and AM) performed this process independently. Disagreement was resolved by a third party (BF). The string terms used were ((("bladder cancer" OR "bladder carcinoma" OR" lower urinary tract cancer" OR "bladder tumor") AND ("radical cystectomy" OR "RC")) AND (("concomitant cis" OR "carcinoma in situ" OR "cis only" OR "Tis")). OM, RFS, CSM and predictive ureteral involvement were our primary outcomes of interest. Eligibility Criteria According to the PRISMA guidelines we referred to the population, intervention, comparator, outcome and study design approach to specify inclusion criteria.14 The studies were considered eligible if patients with concomitant CIS (population) in RC (intervention) specimens for BC were compared to patients without concomitant CIS (comparator) to determine independent predictors of the mentioned primary outcomes (outcome) using multivariate Cox regression or logistic regression analysis (study design) in nonrandomized observational or cohort studies. Studies were excluded based on certain criteria, including review articles, editorials, commentaries, written in a nonEnglish language, meeting abstracts, reply by author or case reports. If multiple articles were written by the same group based on similar patient cohorts, only the largest or most recently published study was included in analysis. Data Extraction Two authors (SK and AM) independently extracted the required data from all eligible studies. Baseline clinicopathological characteristics and data on perioperative chemotherapy were collected. Subsequently the HR or OR and the 95% CI of concomitant CIS associated with each outcome were retrieved. Furthermore, we searched for methods and important confounders to establish comparability. Study quality was evaluated by the NOS for cohort studies.16 The NOS assesses the quality of studies using a star system based on 3 domains, including cohort selection, cohort comparability and outcome assessment. The NOS ranges from 0 to 9. A threshold of 7 or greater was identified to distinguish higher quality studies. All discrepancies in data extraction were generally resolved by consensus or finally decided by one of us (SFS). Statistical Analysis Due to the observational nature of included studies, we extracted adjusted HRs or ORs and 95% CIs for cumulative effect size calculation. Studies with Kaplan-Meier log rank tests, univariable Cox proportional hazard regression or logistic regression analyses were not considered for meta-analysis. Effect summary estimation methods were not used in these cases as a high level of additional selection bias would have been introduced. Statistical pooling of effect measures was based on the level of heterogeneity among studies, which was assessed with the Cochrane Q test and the I2 statistic. Significant heterogeneity was considered at p <0.05 using the Cochrane Q test and a ratio greater than 50% for I2 statistics, which led to the use of random effect models according to the DerSimonian and Laird method.17–19 When these tests were negative for heterogeneity, fixed effect models were chosen to calculate pooled HRs by the inverse variance method. Publication bias, including the small study effect, was evaluated by visual inspection of funnel plots for all assessed comparisons. Statistical analyses were performed with STATA/MP™, version 14.2. Bias Risk The RoB evaluation of each study was assessed according to the Cochrane Handbook for Systematic Reviews of Interventions15 for including nonrandomized studies.20 Due to only nonrandomized comparative studies the RoB was determined using the pragmatic approach by examining the risk of preassigned confounders. The main confounding factors were identified as the most important prognostic factors of OM, disease recurrence, CSM and ureteral involvement after RC. Therefore, we reviewed the studies, adjusting for the effects of patient age, gender, pathological tumor stage, tumor grade, pathological node status, number of positive nodes, number of nodes removed, neoadjuvant chemotherapy and adjuvant chemotherapy in the Cox regression or logistic regression analysis applied in the studies. The presence of confounders was determined by consensus. Results Study Selection and Characteristics Overall 2,092 articles were identified for initial assessment (fig. 1). Of these articles 875 duplicates were removed. Another 824 and 375 articles were then excluded after title and abstract assessment, and a full text reading, respectively. Finally, 23 studies of the impact of concomitant CIS on oncologic outcomes in a total of 20,647 patients treated with RC were included for qualitative and quantitative analyses.7–13,21–35 Figure 1. Flow chart of article selection process to analyze prognostic significance of concomitant CIS in RC specimens of patients with bladder cancer. UC, urothelial carcinoma. The supplementary table (http://jurology.com/) lists the general characteristics of eligible studies.7–13,21–35 All studies had a retrospective design and were published between 2006 and 2017. Patients were enrolled from Europe in 10 studies, from North America in 7 and from Asia in 3 while 3 were international collaborations. Overall 8,142 of the 20,647 patients (39.4%) treated with RC had concomitant CIS in the RC specimen. The rate of concomitant CIS in patients with organ confined and locally advanced disease was 41.7% and 35.7%, respectively. Concomitant CIS was defined in only 4 studies.7,29,33,34 The table summarizes pathological characteristics.7–9,11–13,21–35 Organ confined disease was reported in 10,322 of 20,532 patients (50.3%) and lymph node involvement was reported in 5,136 of 19,202 (26.7%). The studies had a median NOS of 6 (IQR 4–8). Table. Clinical features of patients in eligible studies included in systematic review References No. Pts % Stage % Chemotherapy pT1 or Less pT2 pT3 pT4 pN+ Neoadjuvant Adjuvant Karakiewicz et al21 728 36.4 22.4 29.5 11.7 23.6 4.9 25.5 Lee et al22 115 Not reported Not reported Raj et al13 1,330 35 19 45 Not reported Not reported Dotan et al23 1,589 54 46 24 11 17 Karam et al24 226 18.6 28.8 36.7 15.9 28.8 7 27 Shariat et al10 713 26.5 26.4 34.4 12.8 24.9 6 29 Isbarn et al25 208 43.3 56.7 0 0 0 Not reported Shariat et al26 692 1.3 6.1 65.5 27.2 47.5 Excluded 38.3 May et al27 607 68.9 14.9 12.4 3.6 11.4 Excluded 4.3 Nuhn et al7 3,973 23.9 26.8 34.8 14.4 27.8 Not reported 24.5 Otto et al8 2,483 28.5 27 33.9 10.7 25.8 Excluded 13.9 da Silva et al28 1,502 31.7 26.6 30.6 11.2 22 Excluded 21.4 May et al29 228 0 0 0 100 52.2 Excluded 32.9 Yafi et al9 1,968 48.2 51.8 26.18 3.4 19.8 Gaisa et al30 121 20.7 29.8 39.7 9.9 22.3 Not reported 16.5 Gakis et al31 297 40.4 59.6 20.2 Not reported Kim et al11 402 41.5 18.9 39.6 20.7 10.2 28.1 Kwon et al32 746 51.7 48.7 25.5 Excluded 23.6 Soave et al33 485 30.2 22.9 27.6 18.1 28.5 Excluded 20.4 Vallo et al34 358 0 0 0 100 52.8 Not reported 32.7 Moschini et al35 1,128 23.9 16.6 38.8 20.7 36.5 Excluded 14.4 Masson-Locomte et al12 441 19.3 21.5 37.2 20.9 26.1 Not reported Masson-Locomte et al12 307 30.9 26.9 34.9 17.3 26.7 Not reported Concomitant Carcinoma In Situ Meta-Analysis (pT0-4 Group) Association with Overall Mortality The impact of concomitant CIS on OM was investigated in 5 studies in a total of 4,182 patients with pT0-4 in the RC specimens. Forest plots showed that concomitant CIS was not significantly associated with OM (pooled HR 0.92, 95% CI 0.77–1.10, z = 0.90, fig. 2, A). The Cochrane Q test (chi-square 3.24, p = 0.518) and the I2 test (I2 = 0.0%) were not significantly heterogeneous. Funnel plots did not identify any study over the pseudo 95% CI (fig. 2, A). Part A of the supplementary figure (http://jurology.com/) shows the OM RoB table. Figure 2. Forest and funnel plots show association of concomitant CIS in RC specimens with oncologic outcome in pT0-4 group. A, OM. B, disease recurrence (rec). C, CSM. D, ureteral involvement (UI). Association with Recurrence-Free Survival The impact of concomitant CIS on RFS was investigated in 12 studies in a total of 14,047 patients with pT0-4 in the RC specimens. Forest plots showed that concomitant CIS was not significantly associated with RFS (pooled HR 1.06, 95% CI 0.99–1.13, z = 1.57, fig. 2, B). The Cochrane Q test (chi-square 10.81, p = 0.459) and the I2 test (I2 = 0.0%) were not significantly heterogeneous. Funnel plots did not identify any study over the pseudo 95% CI (fig. 2, B). Part B of the supplementary figure (http://jurology.com/) shows the RFS RoB table. Association with Cancer Specific Mortality The impact of concomitant CIS on CSM was investigated in 15 studies in a total of 16,813 patients with pT0-4 in the RC specimens. Forest plots revealed that concomitant CIS was not significantly associated with CSM (pooled HR 1.00, 95% CI 0.93–1.07, z = 0.09, fig. 2, C). The Cochrane Q test (chi-square 14.97, p = 0.380) and the I2 test (I2 = 6.5%) were not significantly heterogeneous. The funnel plots identified 1 study over the pseudo 95% CI (fig. 2, C). Part C of the supplementary figure (http://jurology.com/) shows the CSM RoB table. Correlation with Ureteral Involvement The impact of concomitant CIS on ureteral involvement was investigated in 4 studies in a total of 2,480 patients with pT0-4 in the RC specimens. Forest plots demonstrated that concomitant CIS was significantly associated with ureteral involvement (pooled OR 4.51, 95% CI, 2.59–7.84, z = 5.33, fig. 2, D). The Cochrane Q test (chi-square 1.43, p = 0.699) and the I2 test (I2 = 0.0%) were not significantly heterogeneous. Funnel plots did not demonstrate any study over the pseudo 95% CI (fig. 2, D). Part D of the supplementary figure (http://jurology.com/) shows the ureteral involvement RoB table. Subgroup Analysis The impact of concomitant CIS in RC specimens on RFS and CSM was also investigated in cohorts of patients with organ confined disease (pT0-2). Overall 3 studies in a total of 1,041 patients were identified and concomitant CIS was reported in 41.7%. Forest plots showed that concomitant CIS was associated with RFS (pooled HR 1.57, 1.12–2.21, z = 2.61) and CSM (pooled HR 1.51, 1.001–2.280, z = 1.96). The Cochrane Q test (chi-square 1.11, p = 0.575, chi-square 0.78, p = 0.678) and the I2 test (I2 = 0.0% and 0.0%) of RFS and CSM, respectively, were not significantly heterogeneous. Funnel plots identified no study over the pseudo 95% CI (fig. 3). Figure 3. Forest and funnel plots show association of concomitant CIS in RC specimens with oncologic outcome in organ confined disease group. A, disease recurrence (rec). B, CSM. Discussion CIS is a flat and often multifocal high grade bladder lesion. Patients with primary or concomitant CIS with papillary urothelial BC have an increased probability of a concomitant lesion in the UUT, the prostatic ducts and the urethra.36,37 Intravesical BCG is the standard treatment in patients with primary or concomitant CIS in the nonMIBC setting.2,38 Approximately 54% and 34% of patients who have CIS and are not treated with BCG after TUR experience progression to MIBC39 and eventually BC related death,6 respectively. Therefore, early RC has been advocated in patients who are BCG unresponsive or have frequent recurrences, or when there is a BCG shortage.5 Conversely the prognostic role of concomitant CIS in RC specimens is still controversial. In this systematic review and meta-analysis we analyzed 23 studies enrolling a total of 20,647 patients treated with RC for BC. To our knowledge this is the first meta-analysis to elucidate the impact of concomitant CIS in RC specimens. In this systematic review and meta-analysis 39.4% of patients had concomitant CIS in the pathological specimens. Concomitant CIS was not associated with OM, RFS or CSM but it was significantly associated with ureteral involvement. Conversely we found that in the subgroup of patients with organ confined disease concomitant CIS was significantly associated with RFS and CSM. We confirmed that concomitant CIS in the RC specimen is a strong predictor of ureteral involvement regardless of tumor stage. Indeed, patients harboring primary or concomitant CIS are at an increased risk for UUT recurrence. This suggests the need for more intensive UUT followup in patients who harbor concomitant CIS in RC specimens.40 To our knowledge whether earlier recognition of UUT recurrence improves survival or lowers the burden of care after RC remains to be proved. However, as BCG therapy is effective for CIS, one could consider this as an approach. A risk adapted followup would enable decreased intensity of followup in some patients and selection of the type of followup (imaging and/or cytology).41 This further suggests the need for clear reporting of concomitant CIS in all pathological reports since this has an impact on the intensity and type of followup. Although concomitant CIS was not associated with worse oncologic outcomes in all patients treated with RC, it was a prognostic factor in patients with organ confined disease. This finding is consistent with the current literature. In fact, some investigators found several genetic similarities between CIS and MIBC, such as chromosome 9 alterations and chromosome arm 17p losses, which may accelerate progression to more aggressive biology and to panurothelial disease.42–44 CIS is also characterized by the loss of intercellular cohesiveness and adherence, which might lead to invasive disease evolution and worse prognosis.45,46 This meta-analysis highlights that patients with organ confined disease and CIS are less likely to be cured by radical surgery alone. They should undergo close followup or be considered for adjuvant therapies. Other pathological features such as variant histology and lymphovascular invasion are also considered drivers of aggressive biology and prognosis.47,48 In a systematic review Gakis et al found that concomitant CIS was one of the strongest predictors of UUT recurrence after RC and patients with UUT recurrence experienced high CSM, mandating strict followup scheduling.49 Current guidelines recommend that proper followup should be based on the natural timing of recurrence.1 Generally disease recurs relatively late after RC in patients with early stage disease at RC and UUT recurrence. Our opinion in this review is that patients with concomitant CIS should be followed for a long duration, even longer than 5 years after RC. This meta-analysis has several limitations. 1) Only retrospective cohort studies were included in this review. Therefore, patients for whom it was not possible to obtain complete information were excluded from analysis, possibly creating selection bias. Notably the patients with clinical T1 disease and concomitant CIS who underwent early RC were not considered in our meta-analysis and they might have had a good prognosis. Further studies are needed to elucidate the association of concomitant CIS with oncologic outcomes in cT1 cohorts. 2) There may be reporting bias related to the fact that studies that do not identify independent predictors of outcomes are less likely to be published. 3) Several studies did not provide the rate of neoadjuvant chemotherapy. This might have influenced pathological results, including CIS and adjuvant chemotherapy, which may influence oncologic outcomes. Conclusions Concomitant CIS in the RC specimen is not associated with worse OM, RFS or CSM in all patients with BC. In fact, it predicts a higher likelihood of recurrence with ureteral involvement in pT0-4 cases. Conversely concomitant CIS in the RC specimen is significantly associated with RFS and CSM in patients with organ confined disease at RC. These data support the meticulous histological assessment and reporting of CIS in RC specimens and its integration into predictive tools for patient counseling, followup scheduling and clinical decision making regarding adjuvant therapies. References 1. : Updated 2016 EAU Guidelines on muscle-invasive and metastatic bladder cancer. Eur Urol 2017; 71: 462. Google Scholar 2. : EAU Guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2016. Eur Urol 2017; 71: 447. Google Scholar 3. : ICUD-EAU International Consultation on Bladder Cancer 2012: screening, diagnosis, and molecular markers. Eur Urol 2013; 63: 4. Google Scholar 4. : Outcomes of radical cystectomy for transitional cell carcinoma of the bladder: a contemporary series from the Bladder Cancer Research Consortium. J Urol 2006; 176: 2414. Link, Google Scholar 5. : Diagnosis and management of urothelial carcinoma in situ of the lower urinary tract: a systematic review. Eur Urol 2015; 67: 876. Google Scholar 6. : Prognostic factors and risk groups in T1G3 non-muscle-invasive bladder cancer patients initially treated with bacillus Calmette-Guérin: results of a retrospective multicenter study of 2451 patients. Eur Urol 2015; 67: 74. Google Scholar 7. : Concomitant carcinoma in situ in cystectomy specimens is not associated with clinical outcomes after surgery. Urol Int 2011; 87: 42. Google Scholar 8. : Analysis of sex differences in cancer-specific survival and perioperative mortality following radical cystectomy: results of a large German multicenter study of nearly 2500 patients with urothelial carcinoma of the bladder. Gend Med 2012; 9: 481. Google Scholar 9. : Impact of concomitant carcinoma in situ on upstaging and outcome following radical cystectomy for bladder cancer. World J Urol 2014; 32: 1295. Google Scholar 10. : Concomitant carcinoma in situ is a feature of aggressive disease in patients with organ-confined TCC at radical cystectomy. Eur Urol 2007; 51: 152. Google Scholar 11. : The clinical significance of intra-operative ureteral frozen section analysis at radical cystectomy for urothelial carcinoma of the bladder. World J Urol 2015; 33: 359. Google Scholar 12. : Predictive factors for final pathologic ureteral sections on 700 radical cystectomy specimens: implications for intraoperative frozen section decision-making. Urol Oncol 2017; 35: 659.e1. Google Scholar 13. : Significance of intraoperative ureteral evaluation at radical cystectomy for urothelial cancer. Cancer 2006; 107: 2167. Google Scholar 14. : The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol 2009; 62: e1. Google Scholar 15. : Cochrane Handbook for Systematic Reviews of Interventions, Version 5.1.0, updated March 2011. Baltimore: The Cochrane Collaboration® 2011. Available at http://handbook-5-1.cochrane.org/. Accessed May 6, 2018. Google Scholar 16. : The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa: The Ottawa Hospital Research Institute 2011. Available at http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed May 6, 2018. Google Scholar 17. : Random-effects model for meta-analysis of clinical trials: an update. Contemp Clin Trials 2007; 28: 105. Google Scholar 18. : Meta-analysis in clinical trials. Control Clin Trials 1986; 7: 177. Google Scholar 19. : Measuring inconsistency in meta-analyses. BMJ 2003; 327: 557. Google Scholar 20. : Evaluating non-randomized intervention studies. Health Technol Assess 2003; 7: 1. Google Scholar 21. : Nomogram for predicting disease recurrence after radical cystectomy for transitional cell carcinoma of the bladder. J Urol 2006; 176: 1354. Link, Google Scholar 22. : Significance of cancer involvement at the ureteral margin detected on routine frozen section analysis during radical cystectomy. Urol Int 2006; 77: 13. Google Scholar 23. : Positive surgical margins in soft tissue following radical cystectomy for bladder cancer and cancer specific survival. J Urol 2007; 178: 2308. Link, Google Scholar 24. : Use of combined apoptosis biomarkers for prediction of bladder cancer recurrence and mortality after radical cystectomy. Lancet Oncol 2007; 8: 128. Google Scholar 25. : Residual pathological stage at radical cystectomy significantly impacts outcomes for initial T2N0 bladder cancer. J Urol 2009; 182: 459. Link, Google Scholar 26. : Combination of multiple molecular markers can improve prognostication in patients with locally advanced and lymph node positive bladder cancer. J Urol 2010; 183: 68. Link, Google Scholar 27. : Pathological upstaging detected in radical cystectomy procedures is associated with a significantly worse tumour-specific survival rate for patients with clinical T1 urothelial carcinoma of the urinary bladder. Scand J Urol Nephrol 2011; 45: 251. Google Scholar 28. : Impact of statin use on oncologic outcomes in patients with urothelial carcinoma of the bladder treated with radical cystectomy. J Urol 2013; 190: 487. Link, Google Scholar 29. : Gender-specific differences in cancer-specific survival after radical cystectomy for patients with urothelial carcinoma of the urinary bladder in pathologic tumor stage T4a. Urol Oncol 2013; 31: 1141. Google Scholar 30. : In cystectomy specimens with bladder cancer whole organ embedding increases the detection rate of histopathological parameters, but not of those with prognostic significance. Virchows Archiv 2015; 466: 423. Google Scholar 31. : Urethral recurrence in women with orthotopic bladder substitutes: a multi-institutional study. Urol Oncol 2015; 33: 204.e17. Google Scholar 32. : Adjuvant chemotherapy after radical cystectomy for bladder cancer: a comparative study using inverse-probability-of-treatment weighting. J Cancer Res Clin Oncol 2015; 141: 169. Google Scholar 33. : Does the extent of variant histology affect oncological outcomes in patients with urothelial carcinoma of the bladder treated with radical cystectomy?Urol Oncol 2015; 33: 21.e1. Google Scholar 34. : Comparative analysis of the effect of prostatic invasion patterns on cancer-specific mortality after radical cystectomy in pT4a urothelial carcinoma of the bladder. Urol Oncol 2016; 34: 432.e1. Google Scholar 35. : The presence of carcinoma in situ at radical cystectomy increases the risk of urothelial recurrence: implications for follow-up schemes. Urol Oncol 2017; 35: 151.e17. Google Scholar 36. : Upper urinary tract recurrence after radical cystectomy for bladder cancer: incidence and risk factors. Int J Urol 2012; 19: 229. Google Scholar 37. : Incidental prostate cancer in Asian men: high prevalence of incidental prostatic adenocarcinoma in Chinese patients undergoing radical cystoprostatectomy for treatment of bladder cancer and selection of candidates for prostate-sparing cystectomy. Prostate 2015; 75: 845. Google Scholar 38. : Characteristics and outcomes of patients with clinical T1 grade 3 urothelial carcinoma treated with radical cystectomy: results from an international cohort. Eur Urol 2010; 57: 300. Google Scholar 39. : Carcinoma in situ. Urol Clin North Am 1992; 19: 499. Medline, Google Scholar 40. : Combining imaging and ureteroscopy variables in a preoperative multivariable model for prediction of muscle-invasive and non-organ confined disease in patients with upper tract urothelial carcinoma. BJU Int 2012; 109: 77. Google Scholar 41. : Urinary cytology has a poor performance for predicting invasive or high-grade upper-tract urothelial carcinoma. BJU Int 2011; 108: 701. Google Scholar 42. : Occurrence of chromosome 9 and p53 alterations in multifocal dysplasia and carcinoma in situ of human urinary bladder. Cancer Res 2002; 62: 809. Google Scholar 43. : The bladder cancer genome; chromosomal changes as prognostic makers, opportunities, and obstacles. Urol Oncol 2012; 30: 533. Google Scholar 44. : Consistent genomic alterations in carcinoma in situ of the urinary bladder confirm the presence of two major pathways in bladder cancer development. Int J Cancer 2009; 125: 2095. Google Scholar 45. : E-cadherin immunostaining of bladder transitional cell carcinoma, carcinoma in situ and lymph node metastases with long-term followup. J Urol 2001; 165: 1473. Link, Google Scholar 46. : E-cadherin expression predicts clinical outcome in carcinoma in situ of the urinary bladder. Urology 2001; 57: 60. Google Scholar 47. : Clinical outcomes following radical cystectomy for primary nontransitional cell carcinoma of the bladder compared to transitional cell carcinoma of the bladder. J Urol 2006; 175: 2048. Link, Google Scholar 48. : International validation of the prognostic value of lymphovascular invasion in patients treated with radical cystectomy. BJU Int 2010; 105: 1402. Google Scholar 49. : Systematic review on the fate of the remnant urothelium after radical cystectomy. Eur Urol 2017; 71: 545. Google Scholar No direct or indirect commercial incentive associated with publishing this article. The corresponding author certifies that, when applicable, a statement(s) has been included in the manuscript documenting institutional review board, ethics committee or ethical review board study approval; principles of Helsinki Declaration were followed in lieu of formal ethics committee approval; institutional animal care and use committee approval; all human subjects provided written informed consent with guarantees of confidentiality; IRB approved protocol number; animal approved project number. © 2019 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byChang S (2019) Re: Prognostic Significance of Lymphatic, Vascular and Perineural Invasion for Bladder Cancer Patients Treated by Radical CystectomyJournal of Urology, VOL. 202, NO. 6, (1097-1097), Online publication date: 1-Dec-2019. Volume 201Issue 1January 2019Page: 46-55Supplementary Materials Advertisement Copyright & Permissions© 2019 by American Urological Association Education and Research, Inc.Keywordsmortalityprognosiscystectomyurinary bladder neoplasmscarcinoma in situMetricsAuthor Information Shoji Kimura Department of Urology, Medical University of Vienna, Vienna, Austria Departments of Urology, Jikei University School of Medicine, Tokyo, Japan Equal study contribution. More articles by this author Andrea Mari Department of Urology, Medical University of Vienna, Vienna, Austria Careggi Hospital, University of Florence, Florence, Italy Equal study contribution. More articles by this author Beat Foerster Department of Urology, Medical University of Vienna, Vienna, Austria Kantonsspital Winterthur, Winterthur, Switzerland More articles by this author Mohammad Abufaraj Department of Urology, Medical University of Vienna, Vienna, Austria Department of Special Surgery, Jordan University Hospital, University of Jordan, Amman, Jordan More articles by this author Mihai D. Vartolomei Department of Urology, Medical University of Vienna, Vienna, Austria Department of Cell and Molecular Biology, University of Medicine and Pharmacy, Tirgu Mures, Romania More articles by this author Judith Stangl-Kremser Department of Urology, Medical University of Vienna, Vienna, Austria More articles by this author Pierre I. Karakiewicz Division of Urology, University of Montreal Health Center, Montreal, Quebec, Canada More articles by this author Shin Egawa Departments of Urology, Jikei University School of Medicine, Tokyo, Japan More articles by this author Shahrokh F. Shariat Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria Weill Cornell Medical College, New York, New York University of Texas Southwestern Medical Center, Dallas, Texas †Correspondence: Department of Urology and Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, A-1090Vienna, Austria (telephone: +4314040026150; FAX: +4314040023320; e-mail: E-mail Address: [email protected]). More articles by this author Expand All No direct or indirect commercial incentive associated with publishing this article. The corresponding author certifies that, when applicable, a statement(s) has been included in the manuscript documenting institutional review board, ethics committee or ethical review board study approval; principles of Helsinki Declaration were followed in lieu of formal ethics committee approval; institutional animal care and use committee approval; all human subjects provided written informed consent with guarantees of confidentiality; IRB approved protocol number; animal approved project number. Advertisement Advertisement PDF downloadLoading ...
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