Prospectİve Evaluatİon of Surgİcal Margİns İn Non-Muscle Invasİve Bladder Cancer Followİng Prİmary Transurethral Resectİon

Prospectİve Evaluatİon of Surgİcal Margİns İn Non-Muscle Invasİve Bladder Cancer Followİng Prİmary Transurethral Resectİon | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Prospectİve Evaluatİon of Surgİcal Margİns İn Non-Muscle Invasİve Bladder Cancer Followİng Prİmary Transurethral Resectİon Çağatay Özsoy, Yiğit Demir, Kayhan Yılmaz, Mahmut Taha Ölçücü, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4009445/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose: Non-muscle invasive bladder cancers (NMIBC) constitute approximately 75% of bladder cancer cases. Primary transurethral resection (TUR) plays a pivotal role in both diagnosis and treatment. However, despite initial resection, tumors are often missed, leaving behind microscopic residual tumors. This study aims to prospectively investigate the surgical margins of tumors, which may serve as a potential source of residual tumors. Methods: Seventy patients diagnosed with NMIBC who underwent primary TUR were enrolled in this study. Following initial resection, samples were collected from the normal-looking mucosa extending 1 cm beyond the surgical margins. Lesions were categorized as 'no tumor' for benign lesions, 'TCC' for urothelial cancer, and 'UD' for dysplasia. Clinical and pathological features of these groups were compared, and risk factors for detecting TCC in the normal-looking mucosa were analyzed. Results: The TCC group showed a significantly higher rate of T1 stage tumors compared to the no tumor group, and a significantly higher rate of high-grade (HG) stage tumors compared to the UD group. Moreover, the TCC group had a significantly higher proportion of high-risk patients (85.7%) compared to the other groups, while the no tumor group had a significantly higher proportion of low-risk patients (35.3%) compared to the TCC group (0.0%). Additionally, the TCC group demonstrated a significantly higher rate of carcinoma in situ (CIS) compared to the no tumor group (35.7% vs. 5.9%). TCC formation was associated with T1 stage, HG stage, and the presence of CIS based on univariate analyses. Conclusion: To minimize residual tumors and prevent recurrence in patients undergoing primary TUR, we advocate for resection of macroscopically visible tumors with at least 2 cm of intact bladder mucosa, thereby enhancing the quality of TUR. TCC bladder cancer surgical margin INTRODUCTION Bladder cancer (BC), pathologically characterized mostly by urothelial carcinoma, is the tenth most common malignancy worldwide and the 13th leading cause of cancer-related deaths [1]. Approximately 75% of BC patients presents as non-muscle-invasive bladder cancer (NMIBC: CIS, Ta, or T1)[2]. NMIBC is typically managed with transurethral resection (TUR) and/or intravesical use of chemotherapeutic agents or bacillus BCG. Transurethral resection (TUR) is the initial and critical step in the management of BC. The aim of the procedure is complete resection of non-invasive papillary tumors and characterization of the tumor's histopathology[3]. Although TUR is a procedure that urologists are familiar with and perform often, the intended diagnostic and therapeutic results are not always achieved, and outcomes frequently fall short of optimal levels. Within five years, 15–61% of NMIBC cases recur as non-invasive cancers, and 1–45% of cases progress to muscle-invasive BC [4]. It is clear that tumors are frequently overlooked during the initial resection, which results in microscopic residual tumors. In T1 NMIBC cases, ReTUR procedures reveal 0–32% T2 disease and 20–71% residual cancer [5]. In a study investigating tumor recurrence at the first surveillance cystoscopy, it was observed that half of the recurrences occurred at the site of the primary tumor [6]. In another study, when patients with NMIBC underwent repeat surveillance cystoscopies, recurrences were observed in 33% of patients, with 18% occurring within the first year. Of the recurrences in the first year, 81% originated from the primary tumor site [7]. In this study, we aimed to investigate the surgical margins of tumors that we believe could be the source of tumor recurrences and progression in NMIBC. MATERİALS AND METHODS Prior to the study, ethical approval was received from the ethics committee of Antalya Training and Research Hospital on May 7, 2020, with protocol number 6/27. The study was designed as a prospective observational study. Patients who underwent transurethral resection (TUR) for a primary bladder mass between May 8, 2020, and October 8, 2021, and who agreed to participate in the study, were included in the research. Patients with extravesical organ metastases to the bladder, bladder cancer subtypes other than transitional cell carcinoma (TCC), patients diagnosed with upper urinary system TCC, patients who had previously received pelvic radiotherapy or systemic chemotherapy, and patients diagnosed with muscle-invasive bladder cancer were excluded from the study. Initially, 81 patients were included in the study. Nine patients who met the exclusion criteria based on histopathological diagnosis at the first TUR (6 muscle invasive, 1 prostate carcinoma invasion, 1 inverted papilloma, and 1 carcinosarcoma) and two patients diagnosed with muscle invasion at ReTUR and were excluded. As a result, the study population consisted of 70 patients. Surgical Technique All surgeries were performed by experienced surgeons who had performed TUR at least 300 times (MA, KY). After macroscopic visualization of the tumor and mapping of the bladder, the tumors were resected with a 1 cm safe surgical margin using a 26 F bipolar resectoscope and 30° optical lens while the bladder was half full. The tumors was taken into the first pathology container. The tumor base was also resected and taken into the second pathology container. After the resection, 1 cm outside the resected area was considered a safe surgical margin, and biopsies were taken from the normal-looking mucosa at the safe surgical margin. Two biopsies were taken for tumors up to 3 cm, and 5–8 biopsies for tumors larger than 3 cm, and placed into the third pathology container. When there were multiple tumors present, the largest tumor was identified as the reference tumor, and the same protocol was followed. The region surrounding the tumor's surgical margin was coagulated for tumor control and bleeding control following resection biopsies. Patients meeting the indications for ReTUR according to the 2019 EAU Guidelines underwent ReTUR 2–6 weeks later, and patients diagnosed with muscle-invasive bladder cancer were excluded from the study. Histopathological Evaluation Macroscopic tumor and biopsy materials were sent to our hospital's pathology unit in separate containers. All histopathological evaluations were performed by a single pathologist experienced in uropathology (AS). The TNM staging of the primary tumor, histopathological stage, and the presence of CIS were recorded from the pathology results. Histopathological evaluation of biopsies taken from the surgical margins of the tumor was also recorded. All benign lesions in biopsies were recorded as "no tumor," urothelial cancer cases were recorded as "TCC," and cases with dysplasia were recorded as "UD" according to the 2021 EAU bladder cancer guidelines. Patients were classified according to their risk classification. Data Analysis Descriptive statistics were presented as frequency (n) and percentage (%) for categorical variables, mean ± standard deviation (SD) if the normal distribution assumption was met, and median (min-max) values if it was not. The normality assumption was checked with the Shapiro-Wilk test. Fisher's Exact Test, Fisher Freeman Halton Exact test, or Pearson chi-square test were used to analyze relationships between categorical variables. Mann-Whitney U test was used for non-parametric comparison of continuous variables between independent two groups, and Student's t-test was used for parametric comparison. Kruskal Wallis test was used for non-parametric comparison of continuous variables between independent more than two groups, and One Way ANOVA test was used for parametric comparison, with post-hoc tests performed with LSD correction for significant cases. Logistic regression analysis, both univariate and multivariate, was performed to determine independent risk factors associated with dependent variables in patients. Variables with p < 0.2 in univariate analysis were included in the multivariate model. The results were presented with odds ratio (OR) and 95% confidence intervals. All analyses were conducted using IBM SPSS 23.0 (IBM Corp., Armonk, NY) software, and p-values less than 0.05 were considered statistically significant. RESULTS Demographic data, as well as preoperative and postoperative data of the patients, are presented in Table 1 . A total of 70 patients were included in the study, with an average age of 64.9 ± 11.6 years, and 84.9% (n = 58) of them were male. Among the 70 patients, 34 patients had no tumor, 14 had TCC (7 CIS, 4 Ta, 1 T1, 2 HG), and 22 had dysplasian at the surgical margin. There were no significant differences in age and cigarette usage among patients classified by biopsy categories. It was observed that 82.4% of patients in the no tumor group, 92.9% in the TCC group, and 77.3% in the dysplasia group were male, but this difference was not statistically significant (p = 0.590). Table 1 Demographic Characteristics and Operative Data of the Patients Variables All Patients (n:70) Age (Year) 64,9 ± 11,6 Gender Male 58(82,9) Female 12(17,1) Smoking (package/year) 27,5(0–82) Tumor diameter (cm) 3(1–6) 3 39(55,7) Tumor mutlifocality Single 50(71,4) Mutlifocal 20(28,6) TNM Ta 29(41,4) T1 41(58,6) Grade LG 37(52,9) HG 33(47,1) Risk classification Low 16(22,9) Intermediate 15(21,4) High 35(50,0) Very high 4(5,7) CIS 12(17,1) The findings are presented as mean ± standard deviation (SD), median (minimum-maximum), or as percentages (n %) in the table. Findings regarding demographic characteristics and preoperative and postoperative data based on biopsy classifications are presented in Table 2 . There were no significant differences in tumor size and tumor mutlifocality among the groups. T1 stage rate was significantly higher in the TCC group compared to the tumor-free group (85.7% vs. 47.1%, p = 0.047). TCC group had a significantly higher rate of high-grade (HG) tumors compared to the UD group (78.6% vs. 36.4%, p = 0.029). The proportion of low-risk patients in the tumor-free group (35.3%) was significantly lower than in the TCC group (0.0%), and the proportion of high-risk patients in the TCC group (85.7%) was significantly higher than in the other two groups (tumor-free: 44.1%, dysplasia: 36.4%) (p = 0.016). The rate of CIS in TCC group (35.7%) was significantly higher than no tumor group (5.9%) (p = 0.025). Table 2 Demographic Characteristics, Preoperative and Postoperative Data Based on Biopsy Classifications of Patients Variables No tumor (n:34) TCC (n:14) UD (n:22) p Age (year) 62,79 ± 13,82 65,71 ± 7,15 67,82 ± 9,73 0,280 Gender Male 28(82,4) 13(92,9) 17(77,3) 0,590 Female 6(17,6) 1(7,1) 5(22,7) Smoking (package/year) 22,5(0–60) 20(0–50) 35(0–82) 0,254 Tumor diameter (cm) 2(1–2) 2(1–2) 1,5(1–2) 0,449 3 18(52,9) 10(71,4) 11(50,0) Tumor mutlifocality Single 22(64,7) 10(71,4) 18(81,8) 0,384 Mutlifocal 12(35,3) 4(28,6) 4(18,2) TNM Ta 18(52,9) a 2(14,3) b 9(40,9) a,b 0,047 T1 16(47,1) a 12(85,7) b 13(59,1) a,b Grade LG 20(58,8) a,b 3(21,4) b 14(63,6) a 0,029 HG 14(41,2) a,b 11(78,6) b 8(36,4) a Risk classification Low 12(35,3) a 0(0,0) b 4(18,2) a,b 0,016 Intermediate 5(14,7) 2(14,3) 8(36,4) High 15(44,1) a 12(85,7) b 8(36,4) a Very high 2(5,9) 0(0,0) 2(9,1) CIS 2(5,9) a 5(35,7) b 5(22,7) a,b 0,025 The findings are presented as mean ± standard deviation (SD), median (minimum-maximum), or as percentages (n %). Statistically significant differences in post-hoc pairwise comparisons are indicated by different lowercase letters. Statistical analyses included One Way ANOVA with post hoc LSD test, Kruskal Wallis test, and Chi-square test. Univariate and multivariate logistic regression analysis was used to evaluate factors that independently affected the occurrence of TCC at surgical margins in included patients, as indicated in Table 3 . In the univariate analysis, it was found that being in T1 stage (OR: 5.586; 95% CI: 1.144–27.286; p = 0.034), being in HG stage (OR: 5.667; 95% CI: 1.419–22.630; p = 0.014), and the presence of CIS (OR: 3.889; 95% CI: 1.008-15.000; p = 0.049) were associated with the occurence of TCC. Variables with p < 0.2 in the univariate analysis were included in the multivariate model. Multivariate analysis did not reveal statistically significant results observed in univariate analysis. Table 3 Factors Influencing the Occurence of TCC Factor affecting TCC occurence Univariate Multivariate Variables OR (%95 GA) p OR (%95 GA) p Age (Year) 1,007(0,957-1,060) 0,784 Female Gender 0,315(0,037 − 2,670) 0,289 Smoking (package/year) 0,980(0,950-1,011) 0,193 Tumor diameter (cm) 1,319(0,842-2,066) 0,227 Multifocality Single Reference - Multifocal 1,000(0,274-3,656) 0,999 TNM Ta Reference - T1 5,586(1,144 − 27,286) 0,034 G stage LG Reference - Reference - HG 5,667(1,419 − 22,630) 0,014 2,300(0,357 − 14,808) 0,381 CIS 3,889(1,008–15,000) 0,049 3,940(0,555 − 27,950) 0,170 The variables with p < 0.2 in the univariate analysis were included in the multivariate analysis (Nagelkerke R Square: 0.421). DISCUSSION In this study, we collected samples at the surgical margins of patients who had undergone primary transurethral resection (TUR) for non-muscle-invasive bladder cancer (NMIBC). We found that 34 (48.5%) patients had no malignant or premalignant lesion at the surgical margin, while 14 (20%) patients had transitional cell carcinoma (TCC) (7 carcinoma in situ [CIS], 4 Ta, 1 T1, 2 high-grade [HG]) and 22 (31.5%) patients had premalignant lesions called urothelial dysplasia (UD). By classifying the patients according to the biopsy findings, we found that TCC detection at the surgical margins was connected to T1 disease, HG disease, high-risk disease, and CIS (Table 3 ). In univariate logistic regression analysis, we also found a positive correlation between the detection of TCC at the surgical margin and T1 disease, HG disease, and CIS. However, multivariate analysis did not reveal this association. Bladder cancer is the most common cancer of the urinary system, with approximately 75% of cases being non-muscle-invasive bladder cancer (NMIBC) (Ta, T1, CIS) [2]. Transurethral resection (TUR) is the most important step in the diagnosis and treatment of NMIBC. However, about 15% of patients who undergo TUR, experience recurrence and progression, which can lead to muscle invasion, metastasis, and death. This rate is even higher for T1 bladder cancer. Research findings indicate that among patients with T1 bladder cancer, progression rates range from 14–54% and morbidity rates from 5–30%[8,7,9]. Although complete resection of all visible tumor is crucial in the treatment of NMIBC, achieving complete resection of multifocal lesions, especially T1 tumors associated with CIS, is often difficult during primary TUR. During a cystoscopy, it might be difficult to identify tumor extension to the surgical margin or lamina propria invasion since tumors often expand across a much wider region than their outward appearance suggests. Achieving distinct negative surgical margins becomes more challenging when there is mucosal edema, bladder spasms, or bleeding during resection. These factors can make it harder to differentiate between healthy mucosa and mucosa bearing malignancies[10]. In patients with T1 bladder cancer, repeat TUR (ReTUR) improves local tumor control, particularly if the first TUR was insufficient or incomplete[11]. Recurrence rates of 38% have been recorded in individuals who received ReTUR, compared to roughly 53% in patients who underwent primary TUR[7]. According to Divrik et al., 40% of patients who had ReTUR experienced tumor recurrence, compared to 70% of patients who had only primary TUR[11]. Herr et al. Reported that, residual T1 cancer was identified following ReTUR in 92 out of 352 patients with T1 bladder cancer, and 82% of these patients experienced progression (muscle invasion) within 5 years[10]. According to the EAU guidelines, ReTUR is strongly recommended for the management of high-grade T1 bladder cancer because it can reveal residual tumors or incorrect staging[2]. Koie et al. reported that the 5-year recurrence-free survival rate was 77.1% and the progression-free survival rate was 97.6% in patients who underwent substantial resection followed by immediate intravesical therapy following first TUR [12]. This study concluded that well-performed primary TUR and intravesical treatment can achieve good oncological outcomes in some patients without the need for ReTUR. A procedure that may not always be feasible due to factors such as patient compliance with follow-up schedules, early access to pathology results after primary TUR, and timely performance of ReTUR. Therefore, the quality of primary TUR is crucial in diseases like bladder cancer that require frequent follow-up and treatment. Tumors are frequently overlooked during primary TUR. Residual cancer can be detected in 20–71% of cases during repeat TUR (ReTUR) for T1 NMIBC. A systematic review that evaluated the results of ReTUR in 8,403 NMIBC patients found that residual tumor remained after primary TUR in 51% of cases [5]. Several retrospective large-scale studies have shown that the absence of detrusor muscle in the primary TUR specimen is associated with a higher risk of residual disease [13,14]. ). Leaving residual tumor during primary TUR not only increases the likelihood of early recurrence and progression but also reduces the response to BCG therapy [15]. There are studies suggesting that techniques such as narrow-band imaging [16], fluorescent imaging [17], the use of lasers during resection, and en-bloc resection [18] can reduce the possibility of microscopic residual tumors. However, despite advances in technology and techniques in the literature, a significant rate of residual tumor is still reported after primary TUR [5]. In our study, we investigated tumors that could potentially be overlooked in the normal-looking mucosa surrounding the macroscopically visible tumor tissue, independent of muscle tissue. We found that 20% of patients had TCC and 35.7% had premalignant lesions called UD at the surgical margins. Herr and Donat discussed two types of bladder tumors: "tentacular" and "broad-front" [19]. In the broad-front type, the macroscopic tumor protrudes into the bladder but remains within the layers of the bladder, and the macroscopic tumor field is located in an area that does not extend beyond a certain point. In the tentacular type, the macroscopic tumor protrudes into the bladder and is frond-like within the layers of the bladder, extending up to 2 to 3 cm beyond the macroscopic tumor. In a study where Kolosy Z. assessed the quality of his own TUR, after completing the TUR, he performed additional resections 1 cm beyond the tumor base and the macroscopically visible tumor, resulting in a 35% rate of residual tumor detection [20]. In our study, the detection of TCC in biopsy results obtained from surgical margins at a rate of 20% supports the 'tentacular' tumor type. The prognosis of bladder cancer is associated with various factors, including age, gender, tumor multifocality, tumor growth pattern, pathological stage, lamina propria infiltration, the presence of muscle in the specimen, and CIS [21]. Some of these factors that affect prognosis may also be risk factors for residual disease. Cao et al. reported that T1 disease, HG disease, and multifocality during primary TUR were independent risk factors for residual disease [22]. In another study involving 288 NMIBC patients, having a tumor larger than 3 cm, multifocality, and concomitant CIS during primary TUR were identified as risk factors for HG residual disease [23]. However, in our study, T1 disease and HG disease were identified as risk factors for residual tumors while multifocality and tumor size were not. UD represents early morphological changes between normal urothelium and CIS. It is recognized as cells with homogeneous cytoplasm, abnormal polarity, and a slightly increased nucleus-cytoplasm ratio [24]. UD is a flat lesion that does not resemble CIS [25]. In the EAU Bladder Cancer Guidelines, UD is recognized as the only premalignant lesion for NMIBC [2]. The high risk of progression in UD has been associated with abnormal expression of cell adhesion molecules such as E-cadherin and β-catenin and the abnormal expression of p53 [26]. Similarly, p53 pathway dysregulation is seen in CIS and invasive bladder cancers [27]. Impaired synthesis of E-cadherin has been found to increase the risk of bladder cancer recurrence [28]. In a study by Liu et al., abnormal expression of p53 and E-cadherin was identified as independent risk factors for residual tumors after primary TUR [29]. In our study, samples obtained from the surgical margins of the tumors showed a significant incidence of UD (35.7%). UD, which carries a risk of progression to invasive carcinoma due to the dysregulation of the p53 and E-cadherin pathways, may be responsible for some of the possible tumor recurrences. Limitations of our study include the small number of patients, the lack of follow-up duration, and the inclusion of ReTUR results in the analysis. We believe that conducting prospective randomized studies with a larger number of patients and longer follow-up periods will make significant contributions to the literature. In conclusion, with this study, we demonstrated that the quality of resection in patients undergoing primary TUR is generally associated with the depth of resection and the presence of muscle. However, our study showed that a significant amount of residual tumor could still be detected at the surgical margins. Additionally, we identified a significant amount of UD at the surgical margins, which could potentially progress to invasive TCC in the future and serve as a source of recurrences. Based on the results of our study, we recommend resecting the macroscopically visible tumor along with at least 2 cm of healthy bladder mucosa to minimize residual tumors and clear UD areas that could contribute to recurrences in patients undergoing primary TUR. Declarations Competing Interests: No competing financial or non-financial interests that are directly or indirectly related to the work exist. Author Contribution Ç.Ö. and Ş.K. wrote the main manuscript,Y.D. and M.T.Ö. collected the data,K.Y. conceived and designed the analysis,M.A. supervised References IARC, Cancer Today. Estimated number of new cases in 2020, worldwide, both sexes, all ages. 2021. Babjuk M, Burger M, Capoun O, Cohen D, Compérat EM, Escrig JLD, Gontero P, Liedberg F, Masson-Lecomte A, Mostafid AHJEU (2021) European Association of Urology Guidelines on Non–muscle-invasive Bladder Cancer (Ta, T1, and Carcinoma in Situ). Hall RJPU (1992) Transurethral resection for transitional cell carcinoma. 6:460-471 Sylvester RJ, Van Der Meijden AP, Oosterlinck W, Witjes JA, Bouffioux C, Denis L, Newling DW, Kurth KJEu (2006) Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials. 49 (3):466-477 Cumberbatch MG, Foerster B, Catto JW, Kamat AM, Kassouf W, Jubber I, Shariat SF, Sylvester RJ, Gontero PJEu (2018) Repeat transurethral resection in non–muscle-invasive bladder cancer: a systematic review. 73 (6):925-933 Wolf H, Iversen H, Rosenkilde P, Schrøder TJSjou, Supplementum n (1987) Transurethral surgery in the treatment of invasive bladder cancer (T1 and T2). 104:127-132 Grimm M-O, Steinhoff C, Simon X, Spiegelhalder P, Ackermann R, VÖGELI TAJTJou (2003) Effect of routine repeat transurethral resection for superficial bladder cancer: a long-term observational study. 170 (2):433-437 Kulkarni GS, Hakenberg OW, Gschwend JE, Thalmann G, Kassouf W, Kamat A, Zlotta AJEu (2010) An updated critical analysis of the treatment strategy for newly diagnosed high-grade T1 (previously T1G3) bladder cancer. 57 (1):60-70 Cookson MS, Herr HW, Zhang Z-F, Soloway S, Sogani PC, Fair WRJTJou (1997) The treated natural history of high risk superficial bladder cancer: 15-year outcome. 158 (1):62-67 Herr HWJT (2011) Role of re-resection in non–muscle-invasive bladder cancer. 11:283-288 Divrik RT, Şahin AF, Yildirim Ü, Altok M, Zorlu FJEu (2010) Impact of routine second transurethral resection on the long-term outcome of patients with newly diagnosed pT1 urothelial carcinoma with respect to recurrence, progression rate, and disease-specific survival: a prospective randomised clinical trial. 58 (2):185-190 Koie T, Ohyama C, Hosogoe S, Yamamoto H, Imai A, Hatakeyama S, Yoneyama T, Hashimoto Y, Yoneyama T, Tobisawa YJIu, nephrology (2015) Oncological outcomes of a single but extensive transurethral resection followed by appropriate intra-vesical instillation therapy for newly diagnosed non-muscle-invasive bladder cancer. 47 (9):1509-1514 Gontero P, Sylvester R, Pisano F, Joniau S, Oderda M, Serretta V, Larré S, Di Stasi S, Van Rhijn B, Witjes AJJBi (2016) The impact of re-TUR on clinical outcomes in a large multi-centre cohort of T1-HG/G3 patients treated with BCG. 118 (1):44 Mariappan P, Zachou A, Grigor KM (2010) Detrusor muscle in the first, apparently complete transurethral resection of bladder tumour specimen is a surrogate marker of resection quality, predicts risk of early recurrence, and is dependent on operator experience. European urology 57 (5):843-849. doi:10.1016/j.eururo.2009.05.047 Herr HWJTJou (2005) Restaging transurethral resection of high risk superficial bladder cancer improves the initial response to bacillus Calmette-Guerin therapy. 174 (6):2134-2137 Naito S, Algaba F, Babjuk M, Bryan RT, Sun Y-H, Valiquette L, de la Rosette J, urology CNBIGSGJE (2016) The clinical research office of the endourological society (CROES) multicentre randomised trial of narrow band imaging–assisted transurethral resection of bladder tumour (TURBT) versus conventional white light imaging–assisted TURBT in primary non–muscle-invasive bladder cancer patients: trial protocol and 1-year results. 70 (3):506-515 Grossman HB, Stenzl A, Fradet Y, Mynderse LA, Kriegmair M, Witjes JA, Soloway MS, Karl A, Burger MJTJou (2012) Long-term decrease in bladder cancer recurrence with hexaminolevulinate enabled fluorescence cystoscopy. 188 (1):58-62 Hurle R, Casale P, Lazzeri M, Paciotti M, Saita A, Colombo P, Morenghi E, Oswald D, Colleselli D, Mitterberger MJWjou (2020) En bloc re-resection of high-risk NMIBC after en bloc resection: results of a multicenter observational study. 38 (3):703-708 Herr HW, Donat SM (2008) Quality control in transurethral resection of bladder tumours. BJU international 102 (9 Pt B):1242-1246. doi:10.1111/j.1464-410X.2008.07966.x Kolozsy ZJBjou (1991) Histopathological “self control” in transurethral resection of bladder tumours. 67 (2):162-164 Serretta V (2009) T1HG bladder tumours: so many papers, do we need them? Yes, we do! Cao M, Yang G, Pan J, Sun J, Chen Q, Chen Y, Chen H, Xue WJIjoc, medicine e (2015) Repeated transurethral resection for non-muscle invasive bladder cancer. 8 (1):1416 Ferro M, Di Lorenzo G, Buonerba C, Lucarelli G, Russo GI, Cantiello F, Farhan ARA, Di Stasi S, Musi G, Hurle RJJoC (2018) Predictors of residual T1 high grade on re-transurethral resection in a large multi-institutional cohort of patients with primary T1 high-grade/grade 3 bladder cancer. 9 (22):4250 Lopez-Beltran A, Montironi R, Vidal A, Scarpelli M, Cheng L (2013) Urothelial dysplasia of the bladder: diagnostic features and clinical significance. Analytical and quantitative cytopathology and histopathology 35 (3):121-129 Jones TD, Cheng L (2006) Papillary Urothelial Neoplasm of Low Malignant Potential: Evolving Terminology and Concepts. 175 (6):1995-2003. doi:doi:10.1016/S0022-5347(06)00267-9 Pan Q, Yang GL, Yang JH, Lin SL, Liu N, Liu SS, Liu MY, Zhang LH, Huang YR, Shen RL, Liu Q, Gao JX, Bo JJ (2015) Metformin can block precancerous progression to invasive tumors of bladder through inhibiting STAT3-mediated signaling pathways. Journal of experimental & clinical cancer research : CR 34 (1):77. doi:10.1186/s13046-015-0183-0 Mitra AP, Datar RH, Cote RJJJoCO (2006) Molecular pathways in invasive bladder cancer: new insights into mechanisms, progression, and target identification. 24 (35):5552-5564 Jankowski JA, Bruton R, Shepherd N, Sanders DJMP (1997) Cadherin and catenin biology represent a global mechanism for epithelial cancer progression. 50 (6):289 Liu W, Qi L, Zu X, Li Y, He W, Tong S, Chen M A preoperative marker panel for the prediction of residual tumor and the decision making for repeat transurethral resection. In: Urologic Oncology: Seminars and Original Investigations, 2015. vol 4. Elsevier, pp 165. e169-165. e114 Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4009445","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":276162830,"identity":"8254f33d-7176-4742-963b-570a356bd597","order_by":0,"name":"Çağatay Özsoy","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABEUlEQVRIiWNgGAWjYNCDDxU2QJKx8QBBlTAVjDPOpIGoBuK1MPO2HUYRwAr4249f/Pyh5rCcfP/hY5Iz287brW0/DLSlxiYalxaJMznFEgeOHTZmnJGWJvHh3O3kbWcSgVqOpeU24NBiwJCTIHGA7XBiswSPmeSMstvJZgeAWhgbDuPWwv8m+ceBf4cT2/jPmEnzsJ1LNjv/kIAWifRjEgfbDif2MOQAtbQdsDO7QcAWiRtv2CzO9qUbS0ikJVvOOJOcYHYDaEsCHr/w96c/vlHxzRoUYgdvfKiwszc7n/7wwYcaG5xaGBh4DIBEM4jFIgEkEsEqE3AqBwH2B0CiDsRi/gAk7PEqHgWjYBSMghEJAH5cazRX82EgAAAAAElFTkSuQmCC","orcid":"","institution":"Adnan Menderes University Medical Faculty","correspondingAuthor":true,"prefix":"","firstName":"Çağatay","middleName":"","lastName":"Özsoy","suffix":""},{"id":276162831,"identity":"1636098d-615a-4f2b-93e8-7183dffbec2b","order_by":1,"name":"Yiğit Demir","email":"","orcid":"","institution":"Antalya Training and Research Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yiğit","middleName":"","lastName":"Demir","suffix":""},{"id":276162832,"identity":"1c16760e-c3b9-47c4-9aa8-0441e3af0a1b","order_by":2,"name":"Kayhan Yılmaz","email":"","orcid":"","institution":"Antalya Training and Research Hospital","correspondingAuthor":false,"prefix":"","firstName":"Kayhan","middleName":"","lastName":"Yılmaz","suffix":""},{"id":276162833,"identity":"daf3cedc-f638-4c6f-9867-ee7f0b5edc71","order_by":3,"name":"Mahmut Taha Ölçücü","email":"","orcid":"","institution":"Antalya Training and Research Hospital","correspondingAuthor":false,"prefix":"","firstName":"Mahmut","middleName":"Taha","lastName":"Ölçücü","suffix":""},{"id":276162834,"identity":"435472c8-9a2f-4e29-8167-1be740ed9219","order_by":4,"name":"Şahin Kılıç","email":"","orcid":"","institution":"Antalya Training and Research Hospital","correspondingAuthor":false,"prefix":"","firstName":"Şahin","middleName":"","lastName":"Kılıç","suffix":""},{"id":276162835,"identity":"3c8bb7ef-7890-4435-93f9-800b6a8605bf","order_by":5,"name":"Mutlu Ateş","email":"","orcid":"","institution":"Antalya Training and Research Hospital","correspondingAuthor":false,"prefix":"","firstName":"Mutlu","middleName":"","lastName":"Ateş","suffix":""}],"badges":[],"createdAt":"2024-03-03 18:36:23","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-4009445/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4009445/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":52274817,"identity":"0a3bc83d-b4c3-42a8-886d-6073de02f5e3","added_by":"auto","created_at":"2024-03-08 13:36:16","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":259043,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4009445/v1/474d8531-e151-426b-90f0-7d2f8c6da99f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eProspectİve Evaluatİon of Surgİcal Margİns İn Non-Muscle Invasİve Bladder Cancer Followİng Prİmary Transurethral Resectİon\u003c/p\u003e","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eBladder cancer (BC), pathologically characterized mostly by urothelial carcinoma, is the tenth most common malignancy worldwide and the 13th leading cause of cancer-related deaths [1]. Approximately 75% of BC patients presents as non-muscle-invasive bladder cancer (NMIBC: CIS, Ta, or T1)[2]. NMIBC is typically managed with transurethral resection (TUR) and/or intravesical use of chemotherapeutic agents or bacillus BCG.\u003c/p\u003e \u003cp\u003eTransurethral resection (TUR) is the initial and critical step in the management of BC. The aim of the procedure is complete resection of non-invasive papillary tumors and characterization of the tumor's histopathology[3]. Although TUR is a procedure that urologists are familiar with and perform often, the intended diagnostic and therapeutic results are not always achieved, and outcomes frequently fall short of optimal levels. Within five years, 15\u0026ndash;61% of NMIBC cases recur as non-invasive cancers, and 1\u0026ndash;45% of cases progress to muscle-invasive BC [4].\u003c/p\u003e \u003cp\u003eIt is clear that tumors are frequently overlooked during the initial resection, which results in microscopic residual tumors. In T1 NMIBC cases, ReTUR procedures reveal 0\u0026ndash;32% T2 disease and 20\u0026ndash;71% residual cancer [5]. In a study investigating tumor recurrence at the first surveillance cystoscopy, it was observed that half of the recurrences occurred at the site of the primary tumor [6]. In another study, when patients with NMIBC underwent repeat surveillance cystoscopies, recurrences were observed in 33% of patients, with 18% occurring within the first year. Of the recurrences in the first year, 81% originated from the primary tumor site [7].\u003c/p\u003e \u003cp\u003eIn this study, we aimed to investigate the surgical margins of tumors that we believe could be the source of tumor recurrences and progression in NMIBC.\u003c/p\u003e"},{"header":"MATERİALS AND METHODS","content":"\u003cp\u003e Prior to the study, ethical approval was received from the ethics committee of Antalya Training and Research Hospital on May 7, 2020, with protocol number 6/27.\u003c/p\u003e \u003cp\u003eThe study was designed as a prospective observational study. Patients who underwent transurethral resection (TUR) for a primary bladder mass between May 8, 2020, and October 8, 2021, and who agreed to participate in the study, were included in the research. Patients with extravesical organ metastases to the bladder, bladder cancer subtypes other than transitional cell carcinoma (TCC), patients diagnosed with upper urinary system TCC, patients who had previously received pelvic radiotherapy or systemic chemotherapy, and patients diagnosed with muscle-invasive bladder cancer were excluded from the study. Initially, 81 patients were included in the study. Nine patients who met the exclusion criteria based on histopathological diagnosis at the first TUR (6 muscle invasive, 1 prostate carcinoma invasion, 1 inverted papilloma, and 1 carcinosarcoma) and two patients diagnosed with muscle invasion at ReTUR and were excluded. As a result, the study population consisted of 70 patients.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eSurgical Technique\u003c/strong\u003e \u003cp\u003eAll surgeries were performed by experienced surgeons who had performed TUR at least 300 times (MA, KY). After macroscopic visualization of the tumor and mapping of the bladder, the tumors were resected with a 1 cm safe surgical margin using a 26 F bipolar resectoscope and 30\u0026deg; optical lens while the bladder was half full. The tumors was taken into the first pathology container. The tumor base was also resected and taken into the second pathology container. After the resection, 1 cm outside the resected area was considered a safe surgical margin, and biopsies were taken from the normal-looking mucosa at the safe surgical margin. Two biopsies were taken for tumors up to 3 cm, and 5\u0026ndash;8 biopsies for tumors larger than 3 cm, and placed into the third pathology container. When there were multiple tumors present, the largest tumor was identified as the reference tumor, and the same protocol was followed. The region surrounding the tumor's surgical margin was coagulated for tumor control and bleeding control following resection biopsies. Patients meeting the indications for ReTUR according to the 2019 EAU Guidelines underwent ReTUR 2\u0026ndash;6 weeks later, and patients diagnosed with muscle-invasive bladder cancer were excluded from the study.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eHistopathological Evaluation\u003c/strong\u003e \u003cp\u003eMacroscopic tumor and biopsy materials were sent to our hospital's pathology unit in separate containers. All histopathological evaluations were performed by a single pathologist experienced in uropathology (AS). The TNM staging of the primary tumor, histopathological stage, and the presence of CIS were recorded from the pathology results. Histopathological evaluation of biopsies taken from the surgical margins of the tumor was also recorded. All benign lesions in biopsies were recorded as \"no tumor,\" urothelial cancer cases were recorded as \"TCC,\" and cases with dysplasia were recorded as \"UD\" according to the 2021 EAU bladder cancer guidelines. Patients were classified according to their risk classification.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eData Analysis\u003c/strong\u003e \u003cp\u003eDescriptive statistics were presented as frequency (n) and percentage (%) for categorical variables, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) if the normal distribution assumption was met, and median (min-max) values if it was not. The normality assumption was checked with the Shapiro-Wilk test. Fisher's Exact Test, Fisher Freeman Halton Exact test, or Pearson chi-square test were used to analyze relationships between categorical variables. Mann-Whitney U test was used for non-parametric comparison of continuous variables between independent two groups, and Student's t-test was used for parametric comparison. Kruskal Wallis test was used for non-parametric comparison of continuous variables between independent more than two groups, and One Way ANOVA test was used for parametric comparison, with post-hoc tests performed with LSD correction for significant cases. Logistic regression analysis, both univariate and multivariate, was performed to determine independent risk factors associated with dependent variables in patients. Variables with p\u0026thinsp;\u0026lt;\u0026thinsp;0.2 in univariate analysis were included in the multivariate model. The results were presented with odds ratio (OR) and 95% confidence intervals. All analyses were conducted using IBM SPSS 23.0 (IBM Corp., Armonk, NY) software, and p-values less than 0.05 were considered statistically significant.\u003c/p\u003e \u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eDemographic data, as well as preoperative and postoperative data of the patients, are presented in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. A total of 70 patients were included in the study, with an average age of 64.9\u0026thinsp;\u0026plusmn;\u0026thinsp;11.6 years, and 84.9% (n\u0026thinsp;=\u0026thinsp;58) of them were male. Among the 70 patients, 34 patients had no tumor, 14 had TCC (7 CIS, 4 Ta, 1 T1, 2 HG), and 22 had dysplasian at the surgical margin. There were no significant differences in age and cigarette usage among patients classified by biopsy categories. It was observed that 82.4% of patients in the no tumor group, 92.9% in the TCC group, and 77.3% in the dysplasia group were male, but this difference was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.590).\u003c/p\u003e\n\u003ctable\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eDemographic Characteristics and Operative Data of the Patients\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"5\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" style=\"width: 66.0232%;\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 33.9768%;\"\u003e\n \u003cp\u003eAll Patients\u003c/p\u003e\n \u003cp\u003e(n:70)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 66.0232%;\"\u003e\n \u003cp\u003eAge (Year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 33.9768%;\"\u003e\n \u003cp\u003e64,9\u0026thinsp;\u0026plusmn;\u0026thinsp;11,6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 66.0232%;\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 33.9768%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 66.0232%;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 33.9768%;\"\u003e\n \u003cp\u003e58(82,9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 66.0232%;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 33.9768%;\"\u003e\n \u003cp\u003e12(17,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 66.0232%;\"\u003e\n \u003cp\u003eSmoking (package/year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 33.9768%;\"\u003e\n \u003cp\u003e27,5(0\u0026ndash;82)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 66.0232%;\"\u003e\n \u003cp\u003eTumor diameter (cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 33.9768%;\"\u003e\n \u003cp\u003e3(1\u0026ndash;6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 66.0232%;\"\u003e\n \u003cp\u003e\u0026lt;3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 33.9768%;\"\u003e\n \u003cp\u003e31(44,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 66.0232%;\"\u003e\n \u003cp\u003e\u0026gt;3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 33.9768%;\"\u003e\n \u003cp\u003e39(55,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 66.0232%;\"\u003e\n \u003cp\u003eTumor mutlifocality\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 33.9768%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 66.0232%;\"\u003e\n \u003cp\u003eSingle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 33.9768%;\"\u003e\n \u003cp\u003e50(71,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 66.0232%;\"\u003e\n \u003cp\u003eMutlifocal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 33.9768%;\"\u003e\n \u003cp\u003e20(28,6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 66.0232%;\"\u003e\n \u003cp\u003eTNM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 33.9768%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 66.0232%;\"\u003e\n \u003cp\u003eTa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 33.9768%;\"\u003e\n \u003cp\u003e29(41,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 66.0232%;\"\u003e\n \u003cp\u003eT1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 33.9768%;\"\u003e\n \u003cp\u003e41(58,6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 66.0232%;\"\u003e\n \u003cp\u003eGrade\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 33.9768%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 66.0232%;\"\u003e\n \u003cp\u003eLG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 33.9768%;\"\u003e\n \u003cp\u003e37(52,9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 66.0232%;\"\u003e\n \u003cp\u003eHG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 33.9768%;\"\u003e\n \u003cp\u003e33(47,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 66.0232%;\"\u003e\n \u003cp\u003eRisk classification\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 33.9768%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 66.0232%;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 33.9768%;\"\u003e\n \u003cp\u003e16(22,9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 66.0232%;\"\u003e\n \u003cp\u003eIntermediate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 33.9768%;\"\u003e\n \u003cp\u003e15(21,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 66.0232%;\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 33.9768%;\"\u003e\n \u003cp\u003e35(50,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 66.0232%;\"\u003e\n \u003cp\u003eVery high\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 33.9768%;\"\u003e\n \u003cp\u003e4(5,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 66.0232%;\"\u003e\n \u003cp\u003eCIS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 33.9768%;\"\u003e\n \u003cp\u003e12(17,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eThe findings are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD), median (minimum-maximum), or as percentages (n %) in the table.\u003c/p\u003e\n\u003cp\u003eFindings regarding demographic characteristics and preoperative and postoperative data based on biopsy classifications are presented in Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. There were no significant differences in tumor size and tumor mutlifocality among the groups. T1 stage rate was significantly higher in the TCC group compared to the tumor-free group (85.7% vs. 47.1%, p\u0026thinsp;=\u0026thinsp;0.047). TCC group had a significantly higher rate of high-grade (HG) tumors compared to the UD group (78.6% vs. 36.4%, p\u0026thinsp;=\u0026thinsp;0.029). The proportion of low-risk patients in the tumor-free group (35.3%) was significantly lower than in the TCC group (0.0%), and the proportion of high-risk patients in the TCC group (85.7%) was significantly higher than in the other two groups (tumor-free: 44.1%, dysplasia: 36.4%) (p\u0026thinsp;=\u0026thinsp;0.016). The rate of CIS in TCC group (35.7%) was significantly higher than no tumor group (5.9%) (p\u0026thinsp;=\u0026thinsp;0.025).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eDemographic Characteristics, Preoperative and Postoperative Data Based on Biopsy Classifications of Patients\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"5\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNo tumor\u003c/p\u003e\n \u003cp\u003e(n:34)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTCC\u003c/p\u003e\n \u003cp\u003e(n:14)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eUD\u003c/p\u003e\n \u003cp\u003e(n:22)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge (year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e62,79\u0026thinsp;\u0026plusmn;\u0026thinsp;13,82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e65,71\u0026thinsp;\u0026plusmn;\u0026thinsp;7,15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67,82\u0026thinsp;\u0026plusmn;\u0026thinsp;9,73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,280\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28(82,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13(92,9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17(77,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,590\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6(17,6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(7,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(22,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking (package/year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22,5(0\u0026ndash;60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20(0\u0026ndash;50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e35(0\u0026ndash;82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,254\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTumor diameter (cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(1\u0026ndash;2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(1\u0026ndash;2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1,5(1\u0026ndash;2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,449\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16(47,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(28,6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11(50,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,407\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18(52,9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10(71,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11(50,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTumor mutlifocality\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSingle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22(64,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10(71,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18(81,8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0,384\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMutlifocal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12(35,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(28,6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(18,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTNM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18(52,9)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(14,3)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9(40,9)\u003csup\u003ea,b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,047\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eT1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16(47,1)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12(85,7)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13(59,1)\u003csup\u003ea,b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGrade\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20(58,8)\u003csup\u003ea,b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(21,4)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14(63,6)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,029\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14(41,2)\u003csup\u003ea,b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11(78,6)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8(36,4)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRisk classification\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12(35,3)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0(0,0)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(18,2)\u003csup\u003ea,b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,016\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIntermediate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(14,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(14,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8(36,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15(44,1)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12(85,7)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8(36,4)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVery high\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(5,9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0(0,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(9,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCIS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(5,9)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(35,7)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(22,7)\u003csup\u003ea,b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,025\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eThe findings are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD), median (minimum-maximum), or as percentages (n %). Statistically significant differences in post-hoc pairwise comparisons are indicated by different lowercase letters. Statistical analyses included One Way ANOVA with post hoc LSD test, Kruskal Wallis test, and Chi-square test.\u003c/p\u003e\n\u003cp\u003eUnivariate and multivariate logistic regression analysis was used to evaluate factors that independently affected the occurrence of TCC at surgical margins in included patients, as indicated in Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e. In the univariate analysis, it was found that being in T1 stage (OR: 5.586; 95% CI: 1.144\u0026ndash;27.286; p\u0026thinsp;=\u0026thinsp;0.034), being in HG stage (OR: 5.667; 95% CI: 1.419\u0026ndash;22.630; p\u0026thinsp;=\u0026thinsp;0.014), and the presence of CIS (OR: 3.889; 95% CI: 1.008-15.000; p\u0026thinsp;=\u0026thinsp;0.049) were associated with the occurence of TCC. Variables with p\u0026thinsp;\u0026lt;\u0026thinsp;0.2 in the univariate analysis were included in the multivariate model. Multivariate analysis did not reveal statistically significant results observed in univariate analysis.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eFactors Influencing the Occurence of TCC\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"6\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" style=\"width: 36.2153%;\"\u003e\n \u003cp\u003eFactor affecting TCC occurence\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\" style=\"width: 30.0163%;\"\u003e\n \u003cp\u003eUnivariate\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\" style=\"width: 30.0163%;\"\u003e\n \u003cp\u003eMultivariate\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" style=\"width: 36.2153%;\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 23.6542%;\"\u003e\n \u003cp\u003eOR (%95 GA)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 6.3622%;\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 23.6542%;\"\u003e\n \u003cp\u003eOR (%95 GA)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 6.3622%;\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 36.2153%;\"\u003e\n \u003cp\u003eAge (Year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.6542%;\"\u003e\n \u003cp\u003e1,007(0,957-1,060)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.3622%;\"\u003e\n \u003cp\u003e0,784\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.6542%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.3622%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 36.2153%;\"\u003e\n \u003cp\u003eFemale Gender\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.6542%;\"\u003e\n \u003cp\u003e0,315(0,037\u0026thinsp;\u0026minus;\u0026thinsp;2,670)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.3622%;\"\u003e\n \u003cp\u003e0,289\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.6542%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.3622%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 36.2153%;\"\u003e\n \u003cp\u003eSmoking (package/year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.6542%;\"\u003e\n \u003cp\u003e0,980(0,950-1,011)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.3622%;\"\u003e\n \u003cp\u003e0,193\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.6542%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.3622%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 36.2153%;\"\u003e\n \u003cp\u003eTumor diameter (cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.6542%;\"\u003e\n \u003cp\u003e1,319(0,842-2,066)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.3622%;\"\u003e\n \u003cp\u003e0,227\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.6542%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.3622%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 36.2153%;\"\u003e\n \u003cp\u003eMultifocality\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.6542%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.3622%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.6542%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.3622%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 36.2153%;\"\u003e\n \u003cp\u003eSingle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.6542%;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.3622%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.6542%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.3622%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 36.2153%;\"\u003e\n \u003cp\u003eMultifocal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.6542%;\"\u003e\n \u003cp\u003e1,000(0,274-3,656)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.3622%;\"\u003e\n \u003cp\u003e0,999\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.6542%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.3622%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 36.2153%;\"\u003e\n \u003cp\u003eTNM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.6542%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.3622%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.6542%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.3622%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 36.2153%;\"\u003e\n \u003cp\u003eTa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.6542%;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.3622%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.6542%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.3622%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 36.2153%;\"\u003e\n \u003cp\u003eT1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.6542%;\"\u003e\n \u003cp\u003e5,586(1,144\u0026thinsp;\u0026minus;\u0026thinsp;27,286)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.3622%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,034\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.6542%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.3622%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 36.2153%;\"\u003e\n \u003cp\u003eG stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.6542%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.3622%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.6542%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.3622%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 36.2153%;\"\u003e\n \u003cp\u003eLG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.6542%;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.3622%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.6542%;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.3622%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 36.2153%;\"\u003e\n \u003cp\u003eHG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.6542%;\"\u003e\n \u003cp\u003e5,667(1,419\u0026thinsp;\u0026minus;\u0026thinsp;22,630)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.3622%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,014\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.6542%;\"\u003e\n \u003cp\u003e2,300(0,357\u0026thinsp;\u0026minus;\u0026thinsp;14,808)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.3622%;\"\u003e\n \u003cp\u003e0,381\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 36.2153%;\"\u003e\n \u003cp\u003eCIS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.6542%;\"\u003e\n \u003cp\u003e3,889(1,008\u0026ndash;15,000)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.3622%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,049\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.6542%;\"\u003e\n \u003cp\u003e3,940(0,555\u0026thinsp;\u0026minus;\u0026thinsp;27,950)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.3622%;\"\u003e\n \u003cp\u003e0,170\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eThe variables with p\u0026thinsp;\u0026lt;\u0026thinsp;0.2 in the univariate analysis were included in the multivariate analysis (Nagelkerke R Square: 0.421).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eIn this study, we collected samples at the surgical margins of patients who had undergone primary transurethral resection (TUR) for non-muscle-invasive bladder cancer (NMIBC). We found that 34 (48.5%) patients had no malignant or premalignant lesion at the surgical margin, while 14 (20%) patients had transitional cell carcinoma (TCC) (7 carcinoma in situ [CIS], 4 Ta, 1 T1, 2 high-grade [HG]) and 22 (31.5%) patients had premalignant lesions called urothelial dysplasia (UD). By classifying the patients according to the biopsy findings, we found that TCC detection at the surgical margins was connected to T1 disease, HG disease, high-risk disease, and CIS (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). In univariate logistic regression analysis, we also found a positive correlation between the detection of TCC at the surgical margin and T1 disease, HG disease, and CIS. However, multivariate analysis did not reveal this association. Bladder cancer is the most common cancer of the urinary system, with approximately 75% of cases being non-muscle-invasive bladder cancer (NMIBC) (Ta, T1, CIS) [2].\u003c/p\u003e \u003cp\u003eTransurethral resection (TUR) is the most important step in the diagnosis and treatment of NMIBC. However, about 15% of patients who undergo TUR, experience recurrence and progression, which can lead to muscle invasion, metastasis, and death. This rate is even higher for T1 bladder cancer. Research findings indicate that among patients with T1 bladder cancer, progression rates range from 14\u0026ndash;54% and morbidity rates from 5\u0026ndash;30%[8,7,9]. Although complete resection of all visible tumor is crucial in the treatment of NMIBC, achieving complete resection of multifocal lesions, especially T1 tumors associated with CIS, is often difficult during primary TUR. During a cystoscopy, it might be difficult to identify tumor extension to the surgical margin or lamina propria invasion since tumors often expand across a much wider region than their outward appearance suggests. Achieving distinct negative surgical margins becomes more challenging when there is mucosal edema, bladder spasms, or bleeding during resection. These factors can make it harder to differentiate between healthy mucosa and mucosa bearing malignancies[10].\u003c/p\u003e \u003cp\u003eIn patients with T1 bladder cancer, repeat TUR (ReTUR) improves local tumor control, particularly if the first TUR was insufficient or incomplete[11]. Recurrence rates of 38% have been recorded in individuals who received ReTUR, compared to roughly 53% in patients who underwent primary TUR[7]. According to Divrik et al., 40% of patients who had ReTUR experienced tumor recurrence, compared to 70% of patients who had only primary TUR[11]. Herr et al. Reported that, residual T1 cancer was identified following ReTUR in 92 out of 352 patients with T1 bladder cancer, and 82% of these patients experienced progression (muscle invasion) within 5 years[10]. According to the EAU guidelines, ReTUR is strongly recommended for the management of high-grade T1 bladder cancer because it can reveal residual tumors or incorrect staging[2]. Koie et al. reported that the 5-year recurrence-free survival rate was 77.1% and the progression-free survival rate was 97.6% in patients who underwent substantial resection followed by immediate intravesical therapy following first TUR [12]. This study concluded that well-performed primary TUR and intravesical treatment can achieve good oncological outcomes in some patients without the need for ReTUR. A procedure that may not always be feasible due to factors such as patient compliance with follow-up schedules, early access to pathology results after primary TUR, and timely performance of ReTUR. Therefore, the quality of primary TUR is crucial in diseases like bladder cancer that require frequent follow-up and treatment.\u003c/p\u003e \u003cp\u003eTumors are frequently overlooked during primary TUR. Residual cancer can be detected in 20\u0026ndash;71% of cases during repeat TUR (ReTUR) for T1 NMIBC. A systematic review that evaluated the results of ReTUR in 8,403 NMIBC patients found that residual tumor remained after primary TUR in 51% of cases [5]. Several retrospective large-scale studies have shown that the absence of detrusor muscle in the primary TUR specimen is associated with a higher risk of residual disease [13,14]. ). Leaving residual tumor during primary TUR not only increases the likelihood of early recurrence and progression but also reduces the response to BCG therapy [15]. There are studies suggesting that techniques such as narrow-band imaging [16], fluorescent imaging [17], the use of lasers during resection, and en-bloc resection [18] can reduce the possibility of microscopic residual tumors. However, despite advances in technology and techniques in the literature, a significant rate of residual tumor is still reported after primary TUR [5]. In our study, we investigated tumors that could potentially be overlooked in the normal-looking mucosa surrounding the macroscopically visible tumor tissue, independent of muscle tissue. We found that 20% of patients had TCC and 35.7% had premalignant lesions called UD at the surgical margins.\u003c/p\u003e \u003cp\u003eHerr and Donat discussed two types of bladder tumors: \"tentacular\" and \"broad-front\" [19]. In the broad-front type, the macroscopic tumor protrudes into the bladder but remains within the layers of the bladder, and the macroscopic tumor field is located in an area that does not extend beyond a certain point. In the tentacular type, the macroscopic tumor protrudes into the bladder and is frond-like within the layers of the bladder, extending up to 2 to 3 cm beyond the macroscopic tumor. In a study where Kolosy Z. assessed the quality of his own TUR, after completing the TUR, he performed additional resections 1 cm beyond the tumor base and the macroscopically visible tumor, resulting in a 35% rate of residual tumor detection [20]. In our study, the detection of TCC in biopsy results obtained from surgical margins at a rate of 20% supports the 'tentacular' tumor type.\u003c/p\u003e \u003cp\u003eThe prognosis of bladder cancer is associated with various factors, including age, gender, tumor multifocality, tumor growth pattern, pathological stage, lamina propria infiltration, the presence of muscle in the specimen, and CIS [21]. Some of these factors that affect prognosis may also be risk factors for residual disease. Cao et al. reported that T1 disease, HG disease, and multifocality during primary TUR were independent risk factors for residual disease [22]. In another study involving 288 NMIBC patients, having a tumor larger than 3 cm, multifocality, and concomitant CIS during primary TUR were identified as risk factors for HG residual disease [23]. However, in our study, T1 disease and HG disease were identified as risk factors for residual tumors while multifocality and tumor size were not.\u003c/p\u003e \u003cp\u003eUD represents early morphological changes between normal urothelium and CIS. It is recognized as cells with homogeneous cytoplasm, abnormal polarity, and a slightly increased nucleus-cytoplasm ratio [24]. UD is a flat lesion that does not resemble CIS [25]. In the EAU Bladder Cancer Guidelines, UD is recognized as the only premalignant lesion for NMIBC [2]. The high risk of progression in UD has been associated with abnormal expression of cell adhesion molecules such as E-cadherin and β-catenin and the abnormal expression of p53 [26]. Similarly, p53 pathway dysregulation is seen in CIS and invasive bladder cancers [27]. Impaired synthesis of E-cadherin has been found to increase the risk of bladder cancer recurrence [28]. In a study by Liu et al., abnormal expression of p53 and E-cadherin was identified as independent risk factors for residual tumors after primary TUR [29].\u003c/p\u003e \u003cp\u003e In our study, samples obtained from the surgical margins of the tumors showed a significant incidence of UD (35.7%). UD, which carries a risk of progression to invasive carcinoma due to the dysregulation of the p53 and E-cadherin pathways, may be responsible for some of the possible tumor recurrences.\u003c/p\u003e \u003cp\u003eLimitations of our study include the small number of patients, the lack of follow-up duration, and the inclusion of ReTUR results in the analysis. We believe that conducting prospective randomized studies with a larger number of patients and longer follow-up periods will make significant contributions to the literature.\u003c/p\u003e \u003cp\u003eIn conclusion, with this study, we demonstrated that the quality of resection in patients undergoing primary TUR is generally associated with the depth of resection and the presence of muscle. However, our study showed that a significant amount of residual tumor could still be detected at the surgical margins. Additionally, we identified a significant amount of UD at the surgical margins, which could potentially progress to invasive TCC in the future and serve as a source of recurrences. Based on the results of our study, we recommend resecting the macroscopically visible tumor along with at least 2 cm of healthy bladder mucosa to minimize residual tumors and clear UD areas that could contribute to recurrences in patients undergoing primary TUR.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCompeting Interests:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo competing financial or non-financial interests that are directly or indirectly related to the work exist.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026Ccedil;.\u0026Ouml;. and Ş.K. wrote the main manuscript,Y.D. and M.T.\u0026Ouml;. collected the data,K.Y. conceived and designed the analysis,M.A. supervised\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eIARC, Cancer Today. Estimated number of new cases in 2020, worldwide, both sexes, all ages. 2021. \u003c/li\u003e\n\u003cli\u003eBabjuk M, Burger M, Capoun O, Cohen D, Comp\u0026eacute;rat EM, Escrig JLD, Gontero P, Liedberg F, Masson-Lecomte A, Mostafid AHJEU (2021) European Association of Urology Guidelines on Non\u0026ndash;muscle-invasive Bladder Cancer (Ta, T1, and Carcinoma in Situ). \u003c/li\u003e\n\u003cli\u003eHall RJPU (1992) Transurethral resection for transitional cell carcinoma. 6:460-471\u003c/li\u003e\n\u003cli\u003eSylvester RJ, Van Der Meijden AP, Oosterlinck W, Witjes JA, Bouffioux C, Denis L, Newling DW, Kurth KJEu (2006) Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials. 49 (3):466-477\u003c/li\u003e\n\u003cli\u003eCumberbatch MG, Foerster B, Catto JW, Kamat AM, Kassouf W, Jubber I, Shariat SF, Sylvester RJ, Gontero PJEu (2018) Repeat transurethral resection in non\u0026ndash;muscle-invasive bladder cancer: a systematic review. 73 (6):925-933\u003c/li\u003e\n\u003cli\u003eWolf H, Iversen H, Rosenkilde P, Schr\u0026oslash;der TJSjou, Supplementum n (1987) Transurethral surgery in the treatment of invasive bladder cancer (T1 and T2). 104:127-132\u003c/li\u003e\n\u003cli\u003eGrimm M-O, Steinhoff C, Simon X, Spiegelhalder P, Ackermann R, V\u0026Ouml;GELI TAJTJou (2003) Effect of routine repeat transurethral resection for superficial bladder cancer: a long-term observational study. 170 (2):433-437\u003c/li\u003e\n\u003cli\u003eKulkarni GS, Hakenberg OW, Gschwend JE, Thalmann G, Kassouf W, Kamat A, Zlotta AJEu (2010) An updated critical analysis of the treatment strategy for newly diagnosed high-grade T1 (previously T1G3) bladder cancer. 57 (1):60-70\u003c/li\u003e\n\u003cli\u003eCookson MS, Herr HW, Zhang Z-F, Soloway S, Sogani PC, Fair WRJTJou (1997) The treated natural history of high risk superficial bladder cancer: 15-year outcome. 158 (1):62-67\u003c/li\u003e\n\u003cli\u003eHerr HWJT (2011) Role of re-resection in non\u0026ndash;muscle-invasive bladder cancer. 11:283-288\u003c/li\u003e\n\u003cli\u003eDivrik RT, Şahin AF, Yildirim \u0026Uuml;, Altok M, Zorlu FJEu (2010) Impact of routine second transurethral resection on the long-term outcome of patients with newly diagnosed pT1 urothelial carcinoma with respect to recurrence, progression rate, and disease-specific survival: a prospective randomised clinical trial. 58 (2):185-190\u003c/li\u003e\n\u003cli\u003eKoie T, Ohyama C, Hosogoe S, Yamamoto H, Imai A, Hatakeyama S, Yoneyama T, Hashimoto Y, Yoneyama T, Tobisawa YJIu, nephrology (2015) Oncological outcomes of a single but extensive transurethral resection followed by appropriate intra-vesical instillation therapy for newly diagnosed non-muscle-invasive bladder cancer. 47 (9):1509-1514\u003c/li\u003e\n\u003cli\u003eGontero P, Sylvester R, Pisano F, Joniau S, Oderda M, Serretta V, Larr\u0026eacute; S, Di Stasi S, Van Rhijn B, Witjes AJJBi (2016) The impact of re-TUR on clinical outcomes in a large multi-centre cohort of T1-HG/G3 patients treated with BCG. 118 (1):44\u003c/li\u003e\n\u003cli\u003eMariappan P, Zachou A, Grigor KM (2010) Detrusor muscle in the first, apparently complete transurethral resection of bladder tumour specimen is a surrogate marker of resection quality, predicts risk of early recurrence, and is dependent on operator experience. European urology 57 (5):843-849. doi:10.1016/j.eururo.2009.05.047\u003c/li\u003e\n\u003cli\u003eHerr HWJTJou (2005) Restaging transurethral resection of high risk superficial bladder cancer improves the initial response to bacillus Calmette-Guerin therapy. 174 (6):2134-2137\u003c/li\u003e\n\u003cli\u003eNaito S, Algaba F, Babjuk M, Bryan RT, Sun Y-H, Valiquette L, de la Rosette J, urology CNBIGSGJE (2016) The clinical research office of the endourological society (CROES) multicentre randomised trial of narrow band imaging\u0026ndash;assisted transurethral resection of bladder tumour (TURBT) versus conventional white light imaging\u0026ndash;assisted TURBT in primary non\u0026ndash;muscle-invasive bladder cancer patients: trial protocol and 1-year results. 70 (3):506-515\u003c/li\u003e\n\u003cli\u003eGrossman HB, Stenzl A, Fradet Y, Mynderse LA, Kriegmair M, Witjes JA, Soloway MS, Karl A, Burger MJTJou (2012) Long-term decrease in bladder cancer recurrence with hexaminolevulinate enabled fluorescence cystoscopy. 188 (1):58-62\u003c/li\u003e\n\u003cli\u003eHurle R, Casale P, Lazzeri M, Paciotti M, Saita A, Colombo P, Morenghi E, Oswald D, Colleselli D, Mitterberger MJWjou (2020) En bloc re-resection of high-risk NMIBC after en bloc resection: results of a multicenter observational study. 38 (3):703-708\u003c/li\u003e\n\u003cli\u003eHerr HW, Donat SM (2008) Quality control in transurethral resection of bladder tumours. BJU international 102 (9 Pt B):1242-1246. doi:10.1111/j.1464-410X.2008.07966.x\u003c/li\u003e\n\u003cli\u003eKolozsy ZJBjou (1991) Histopathological \u0026ldquo;self control\u0026rdquo; in transurethral resection of bladder tumours. 67 (2):162-164\u003c/li\u003e\n\u003cli\u003eSerretta V (2009) T1HG bladder tumours: so many papers, do we need them? Yes, we do! \u003c/li\u003e\n\u003cli\u003eCao M, Yang G, Pan J, Sun J, Chen Q, Chen Y, Chen H, Xue WJIjoc, medicine e (2015) Repeated transurethral resection for non-muscle invasive bladder cancer. 8 (1):1416\u003c/li\u003e\n\u003cli\u003eFerro M, Di Lorenzo G, Buonerba C, Lucarelli G, Russo GI, Cantiello F, Farhan ARA, Di Stasi S, Musi G, Hurle RJJoC (2018) Predictors of residual T1 high grade on re-transurethral resection in a large multi-institutional cohort of patients with primary T1 high-grade/grade 3 bladder cancer. 9 (22):4250\u003c/li\u003e\n\u003cli\u003eLopez-Beltran A, Montironi R, Vidal A, Scarpelli M, Cheng L (2013) Urothelial dysplasia of the bladder: diagnostic features and clinical significance. Analytical and quantitative cytopathology and histopathology 35 (3):121-129\u003c/li\u003e\n\u003cli\u003eJones TD, Cheng L (2006) Papillary Urothelial Neoplasm of Low Malignant Potential: Evolving Terminology and Concepts. 175 (6):1995-2003. doi:doi:10.1016/S0022-5347(06)00267-9\u003c/li\u003e\n\u003cli\u003ePan Q, Yang GL, Yang JH, Lin SL, Liu N, Liu SS, Liu MY, Zhang LH, Huang YR, Shen RL, Liu Q, Gao JX, Bo JJ (2015) Metformin can block precancerous progression to invasive tumors of bladder through inhibiting STAT3-mediated signaling pathways. Journal of experimental \u0026amp; clinical cancer research : CR 34 (1):77. doi:10.1186/s13046-015-0183-0\u003c/li\u003e\n\u003cli\u003eMitra AP, Datar RH, Cote RJJJoCO (2006) Molecular pathways in invasive bladder cancer: new insights into mechanisms, progression, and target identification. 24 (35):5552-5564\u003c/li\u003e\n\u003cli\u003eJankowski JA, Bruton R, Shepherd N, Sanders DJMP (1997) Cadherin and catenin biology represent a global mechanism for epithelial cancer progression. 50 (6):289\u003c/li\u003e\n\u003cli\u003eLiu W, Qi L, Zu X, Li Y, He W, Tong S, Chen M A preoperative marker panel for the prediction of residual tumor and the decision making for repeat transurethral resection. In: Urologic Oncology: Seminars and Original Investigations, 2015. vol 4. Elsevier, pp 165. e169-165. e114\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"TCC, bladder, cancer, surgical, margin","lastPublishedDoi":"10.21203/rs.3.rs-4009445/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4009445/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose:\u003c/strong\u003e Non-muscle invasive bladder cancers (NMIBC) constitute approximately 75% of bladder cancer cases. Primary transurethral resection (TUR) plays a pivotal role in both diagnosis and treatment. However, despite initial resection, tumors are often missed, leaving behind microscopic residual tumors. This study aims to prospectively investigate the surgical margins of tumors, which may serve as a potential source of residual tumors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e Seventy patients diagnosed with NMIBC who underwent primary TUR were enrolled in this study. Following initial resection, samples were collected from the normal-looking mucosa extending 1 cm beyond the surgical margins. Lesions were categorized as 'no tumor' for benign lesions, 'TCC' for urothelial cancer, and 'UD' for dysplasia. Clinical and pathological features of these groups were compared, and risk factors for detecting TCC in the normal-looking mucosa were analyzed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e The TCC group showed a significantly higher rate of T1 stage tumors compared to the no tumor group, and a significantly higher rate of high-grade (HG) stage tumors compared to the UD group. Moreover, the TCC group had a significantly higher proportion of high-risk patients (85.7%) compared to the other groups, while the no tumor group had a significantly higher proportion of low-risk patients (35.3%) compared to the TCC group (0.0%). Additionally, the TCC group demonstrated a significantly higher rate of carcinoma in situ (CIS) compared to the no tumor group (35.7% vs. 5.9%). TCC formation was associated with T1 stage, HG stage, and the presence of CIS based on univariate analyses.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e To minimize residual tumors and prevent recurrence in patients undergoing primary TUR, we advocate for resection of macroscopically visible tumors with at least 2 cm of intact bladder mucosa, thereby enhancing the quality of TUR.\u003c/p\u003e","manuscriptTitle":"Prospectİve Evaluatİon of Surgİcal Margİns İn Non-Muscle Invasİve Bladder Cancer Followİng Prİmary Transurethral Resectİon","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-06 03:50:28","doi":"10.21203/rs.3.rs-4009445/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8687bcaf-ef1a-4d1d-b0c0-3ad3f2d3b035","owner":[],"postedDate":"March 6th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-03-08T13:35:06+00:00","versionOfRecord":[],"versionCreatedAt":"2024-03-06 03:50:28","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4009445","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4009445","identity":"rs-4009445","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}