EUROPEAN UROLOGY OPEN SCIENCE 48 (2023) 24–27 available at www.sciencedirect.com journal homepage: www.eu-openscience.europeanurology.com Brief Correspondence Implementing a Checklist for Transurethral Resection of Bladder Tumor to Standardize Outcome Reporting: When High-quality Resection Could Influence Oncological Outcomes Pietro Diana *, Michael Baboudjian, Andrea Gallioli, Angelo Territo, Sofia Fontanet, Paula Izquierdo, Alessandro Uleri, Paolo Verri, Óscar Rodriguez-Faba, Josep Maria Gaya, Francesco Sanguedolce, Joan Palou, Alberto Breda Article info Abstract Article history: Several randomized controlled trials (RCTs) comparing en bloc resection of bladder Accepted September 6, 2022 tumor (ERBT) to conventional transurethral resection of bladder tumor (cTURBT) have reported controversial results. In particular, the 1-yr recurrence rate ranged Associate Editor: from 5% to 40% for ERBT and from 11% to 31% for cTURBT. We provide an updated M. Carmen Mir analysis of an RCT comparing the 1-yr recurrence rate for ERBT versus cTURBT for a cohort of 219 patients comprising 123 (56.2%) in the ERBT group and 96 (43.8%) in Keywords: the cTURBT group. At 1 yr, 11 patients in the ERBT group and 12 in the cTURBT Urothelial cancer group experienced recurrence. The heterogeneity in recurrence observed in other Endoscopy Resection RCTs could be explained by the scarce and heterogeneous adoption of tools and Diagnosis techniques that have been proved to lower the recurrence rate, supporting the need Treatment for implementation of a TURBT checklist. This prompted us to create a checklist of items for RCTs to standardize how TURBT is performed in trials, facilitate compar- ison between studies, assess the applicability of results in real-life practice, and provide a push towards high-quality resections to improve oncological outcomes. The checklist could have utility as a user-friendly guide for reporting TURBT proce- dures to improve our understanding of trials involving this procedure. Patient summary: We compared the recurrence rate at 1 year for bladder cancer treated with two different approaches to remove bladder tumors in our center. The rates were comparable for the two groups. Other studies have found widely differing recurrence rates, so we propose use of a checklist to standardize these procedures and provide more consistent outcomes for patients. Ó 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY-NC-ND license (http://creative- commons.org/licenses/by-nc-nd/4.0/). Transurethral resection of bladder tumor (TURBT) is crucial resection of bladder tumor (ERBT) was introduced in an in the management of non–muscle-invasive bladder cancer attempt to provide higher-quality specimens, lower compli- (NMIBC) as it defines the ideal postoperative management cation rates, and better oncological outcomes in comparison tailored according to the patient’s risk group [1]. En bloc to conventional TURBT (cTURBT) [2]. Several randomized https://doi.org/10.1016/j.euros.2022.09.025 2666-1683/Ó 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). EUROPEAN UROLOGY OPEN SCIENCE 48 (2023) 24–27 25 controlled trials (RCTs) have reported controversial results; 56 (58.3%), 37 (38.5%), and three (3.1%) for ERBT versus in particular, the 1-yr recurrence rate ranges from 5% to 40% cTURBT, respectively. A total of 201 patients reached at least for ERBT and from 11% to 31% for cTURBT (Table 1). BC 1 yr of follow-up. The median follow-up for patients with- recurrence after TURBT is a complex and multifactorial out recurrence was 19 mo (interquartile range 14–35). Fifty event, driven mainly by patient and tumor characteristics, patients (29 in the ERBT group and 21 in the cTURBT group) but is significantly influenced by the strategy for care, and experienced BC recurrence, of which 11 for ERBT and 12 for in particular the quality of the resection and the approaches cTURBT occurred during the first year of follow-up. Kaplan- used to reduce the risk of recurrence. In our recently pub- Meier analysis revealed 1-yr recurrence-free survival rates lished RCT comparing ERBT versus cTURBT [3], we found of 90.9% (95% confidence interval 0.859–0.962) for EBRT very high rates of detrusor muscle (DM) presence in speci- and 87% (95% confidence interval 0.804–0.942) for cTURBT mens from both ERBT (95%) and cTURBT (94%). Subanalyses (p = 0.88; Supplementary Fig. 1). showed similar results in terms of oncological outcomes (3- Since a low recurrence rate was observed for both tech- mo recurrence-free survival) [3]. Here we update the onco- niques, we investigated what quality criteria could explain logic outcomes for our series by providing 1-yr results for these results. The presence of DM is widely recognized as the EBRT and cTURBT groups. the main marker of resection quality and has the potential This is an updated analysis of a single-center, prospec- to independently predict early BC recurrence [4]. In the tive, noninferiority RCT of patients undergoing ERBT or TURBT setting, several other factors decrease the risk of cTURBT for BC [3]. Participants were enrolled between April recurrence: photodynamic diagnosis [5], narrow band 2018 and June 2021. Kaplan-Meier curves were used to imaging [6], continuous saline bladder irrigation [7], post- illustrate recurrence-free survival. The log-rank test was operative single-shot instillation of mitomycin C (MMC) used to assess univariable differences in recurrence-free [8], and restaging TURBT [9]. Although there has been no survival according to the resection technique used. Statisti- clear demonstration to date, use of one, two, or more of cal analyses were performed using R v4.1.3 (R Foundation these strategies could potentially provide the highest bene- for Statistical Computing, Vienna, Austria). All tests were fit in terms of recurrence-free survival. Limitations to two-sided, with the significance level set at p < 0.05. underline, however, include the difficulty in accessing cer- A total of 248 patients were assessed for eligibility. tain technologies (eg, no reimbursement for hexaminolae- Exclusion of patients diagnosed with cT0 (n = 11) or cT2 vulinic acid) and low surgeon adherence to (n = 11) tumors or benign features (n = 5) and those with recommendations (eg, low adoption of postoperative variant histology (n = 2) left a cohort of 219 patients, 123 single-shot MMC instillation). (56.2%) in the ERBT group and 96 (43.8%) in the cTURBT Considering the RCTs on EBRT published to date, adop- group. Patients presenting with low-grade, high-grade, tion of these tools and approaches is poorly reported and CIS were 70 (56.9%), 49 (39.8%), and four (3.3%) versus (Table 2). Thus, a possible reason for the heterogeneity in Table 1 – Oncologic outcomes and inclusion/exclusion criteria for randomized controlled trials comparing ERBT versus cTURBT Study Patients High grade, n (%) RR at 12 mo (n) Inclusion/exclusion criteria ERBT cTURBT ERBT cTURBT ERBT cTURBT Liu 2013 64 56 7 (10.9) 5 (8.9) 7 6 Inclusion: papillary BC at cystoscopy with no extravesical extension, lymphatic metastasis, or invasion of adjacent organs apparent on imaging. Exclusion: urothelial papillomas, MIBC, CIS, or UTUC. Zhang 2015 149 143 G2: 8 (5.4) [G2] 8 (5.6) 46 45 Inclusion: primary single or multiple papillary BCs in the bladder with no UTUC abnormalities and absence of extravesical extension, lymph node metastasis, and adjacent organ invasion. Exclusion: biopsy-proven inverted papilloma. Cheng 2018 95 98 40 (42.1) 48 (48.9) 3 15 Inclusion: primary NMIBC and ECOG score 0–1. Exclusion: recurrent NMIBC, MIBC, CIS, and pregnancy. Balan 2018 45 45 – – 7/41 11/40 Inclusion: papillary BC between 1 and 3 cm in diameter. Exclusion: solid sessile tumors, lesions located in the bladder neck area, and tumors involving the ureteral orifice. Gakis 2020 56 59 G2: 25 (44.6) G2: 23 (38.9) 19/48 11/49 Inclusion: newly diagnosed or recurrent BC on cystoscopy. G3: 9 (16) G3: 17 (28.8) Exclusion: tumor diameter 0.5 cm; clinically apparent MIBC; >5 tumor lesions; instillation therapy within the last 8 wk; tumors too extensive to resect and retrieve in one piece. Razzaghi 2021 40 39 5 (12.5) 6 (15.4) 7 6 Inclusion: suspicious lesion on imaging. Exclusion: hydronephrosis and/or stage T3–4 BC on imaging; presence of CIS on cold-cup biopsy; UTUC; untreated urinary infection; recurrent BC; and tumor diameter >3 cm on cystoscopy. Present series 123 96 53 (43.1) 40 (41.6) 11 12 Inclusion: primary or recurrent BC located anywhere in the bladder, with a maximum of three separated lesions and/or maximum size of 3 cm for each. Exclusion: preoperative evidence of MIBC, ureteral involvement, and/or nodal/metastatic extension of the disease. ERBT = en bloc resection of bladder tumor; cTURBT = conventional transurethral resection of bladder tumor; RR = recurrence rate; BC =bladder cancer; NMIBC = non–muscle-invasive BC; MIBC = muscle-invasive BC; CIS = carcinoma in situ; UTUC = upper tract urothelial carcinoma; ECOG = Eastern Cooperative Oncology Group; CT = computed tomography. 26 EUROPEAN UROLOGY OPEN SCIENCE 48 (2023) 24–27 Table 2 – Critical assessment of checklist item reported in available randomized controlled trials comparing en bloc resection and conventional transurethral resection of bladder tumor Study Enhanced tumor Completeresection DM Single-shot Early Irrigation Second visualization presence instillation resection Liu 2013 NR NR NR NR Yes NR Zhang 2015 NR Yes Yes No Yes Yes Cheng 2018 Yes (NBI) Yes NR NR Yes Yes Balan 2018 NR NR NR NR – NR Gakis 2020 Yes (PDD) Yes Yes Yes – Yes Razzaghi 2021 NR Yes NR Yes Yes NR Present series No Yes Yes Yes Yes Yes EAU grade of Weak Strong Strong Weak Not Strong recommendation graded Yes = used; No = not used; NR =not reported; DM = detrusor muscle; NBI = narrow-band imaging; PDD = photodynamic diagnosis; EAU = European Association of Urology. BC recurrence among RCTs is the use, or not, of validated Obtaining funding: None. tools/approaches that have been proven to influence BC Administrative, technical, or material support: Breda, Palou. recurrence. Therefore, standardization for TURBT reporting Supervision: Breda. is warranted to overcome this limitation. To this end, we Other: None. propose adoption of a checklist of items comprising all the strategies that have been reported to lower the recurrence Financial disclosures: Pietro Diana certifies that all conflicts of interest, rate in NMIBC (Table 2). including specific financial interests and relationships and affiliations rel- Excellence should be encouraged even for procedures evant to the subject matter or materials discussed in the manuscript (eg, that may be perceived as trivial, such as TURBT, which employment/affiliation, grants or funding, consultancies, honoraria, stock remains the cornerstone of NMIBC management [10]. This ownership or options, expert testimony, royalties, or patents filed, checklist would be part of a larger effort to improve the received, or pending), are the following: None. reporting of various types of health research, similar to the Consolidated Standards of Reporting Trials (CONSORT) Funding/Support and role of the sponsor: None. statement, which already uses a 25-point checklist to improve the quality of research used in health care decision-making. In the past, surgical checklists have been Appendix A. Supplementary data used to prevent errors and complications that may occur during surgery. The aim of our suggested TURBT checklist Supplementary data to this article can be found online at is to provide a consistent list of items for RCTs to standard- https://doi.org/10.1016/j.euros.2022.09.025. ize how TURBT is performed, thereby facilitating compar- ison across studies, increasing the applicability of results References to real-life clinical practice, and providing a push towards high-quality resections to improve oncologic outcomes for [1] Babjuk M, Burger M, Capoun O, et al. European Association of patients. The checklist should also be used alongside con- Urology guidelines on non–muscle-invasive bladder cancer (Ta, T1, and carcinoma in situ). Eur Urol 2022;81:75–94. https://doi.org/ sideration of other parameters outside the perioperative 10.1016/j.eururo.2021.08.010. period that could also significantly influence the risk of [2] Teoh JYC, MacLennan S, Chan VWS, et al. An international recurrence, such as adjuvant instillation therapies according collaborative consensus statement on en bloc resection of bladder to the European Association of Urology risk groups (MMC tumour incorporating two systematic reviews, a two-round Delphi survey, and a consensus meeting. Eur Urol 2020;78:546–69. https:// and bacillus Calmette-Guérin). We believe that our TURBT doi.org/10.1016/j.eururo.2020.04.059. checklist is a user-friendly guide for reporting TURBT inter- [3] Gallioli A, Diana P, Fontana M, et al. En bloc versus conventional ventions that can be used alongside other checklists. We transurethral resection of bladder tumors: a single-center prospective randomized noninferiority trial. Eur Urol Oncol believe that its use will enhance the understanding of trials 2022;5:440–8. https://doi.org/10.1016/j.euo.2022.05.001. involving TURBT. [4] Mariappan P, Zachou A, Grigor KM. Detrusor muscle in the first, apparently complete transurethral resection of bladder tumour specimen is a surrogate marker of resection quality, predicts risk of Author contributions: Pietro Diana had full access to all the data in the early recurrence, and is dependent on operator experience. Eur study and takes responsibility for the integrity of the data and the accu- Urol. 2010;57:843–9. https://doi.org/10.1016/j.eururo.2009.05.047. racy of the data analysis. [5] Maisch P, Koziarz A, Vajgrt J, Narayan V, Kim MH, Dahm P. Blue vs white light for transurethral resection of non-muscle-invasive bladder cancer: an abridged Cochrane Review. BJU Int. In press. Study concept and design: Diana, Breda, Baboudjian. https://doi.org/10.1111/bju.15723. Acquisition of data: Diana, Gallioli, Fontanet, Izquierdo. [6] Lai LY, Tafuri SM, Ginier EC, et al. Narrow band imaging versus Analysis and interpretation of data: Diana, Gallioli, Verri, Sanguedolce. white light cystoscopy alone for transurethral resection of non- muscle invasive bladder cancer. Cochrane Database Syst Rev Drafting of the manuscript: Diana, Uleri, Baboudjian, Territo. 2021;2021:CD014887. https://doi.org/10.1002/14651858. Critical revision of the manuscript for important intellectual content: Galli- CD014887. oli, Rodriguez-Faba, Gaya. [7] Onishi T, Sugino Y, Shibahara T, Masui S, Yabana T, Sasaki T. Statistical analysis: Diana. Randomized controlled study of the efficacy and safety of continuous saline bladder irrigation after transurethral resection EUROPEAN UROLOGY OPEN SCIENCE 48 (2023) 24–27 27 for the treatment of non-muscle-invasive bladder cancer. BJU Int [10] Palou J, Rodríguez O, Segarra J, Rosales A. Re: Restaging 2017;119:276–82. https://doi.org/10.1111/bju.13599. transurethral resection of high risk superficial bladder cancer [8] Sylvester RJ, Oosterlinck W, Holmang S, et al. Systematic review and improves the initial response to bacillus Calmette-Guerin therapy. individual patient data meta-analysis of randomized trials J Urol 2006;176:407–8. https://doi.org/10.1016/S0022-5347(06) comparing a single immediate instillation of chemotherapy after 00593-3. transurethral resection with transurethral resection alone in patients with stage pTa–pT1 urothelial carcinoma of the bladder: Department of Urology, Fundació Puigvert, Autonomous University of which patients benefit from the instillation? Eur Urol Barcelona, Barcelona, Spain 2016;69:231–44. https://doi.org/10.1016/j.eururo.2015.05.050. [9] Cumberbatch MGK, Foerster B, Catto JWF, et al. Repeat * Corresponding author. Department of Urology, Fundació Puigvert, transurethral resection in non–muscle-invasive bladder cancer: a Autonomous University of Barcelona, Cartagena 340-350, 08025 Barce- systematic review. Eur Urol 2018;73:925–33. https://doi.org/ 10.1016/j.eururo.2018.02.014. lona, Spain. Tel. +39 392 710 4765. E-mail address: pietros.diana@gmail.com (P. Diana).