Concomitant Concomitant Carcinoma In Situ Research Articles

Prognosis of Primary Papillary Ta Grade 3 Bladder Cancer in the Non–muscle-invasive Spectrum

BackgroundTa grade 3 (G3) non–muscle-invasive bladder cancer (NMIBC) is a relatively rare diagnosis with an ambiguous character owing to the presence of an aggressive G3 component together with the lower malignant potential of the Ta component. The European Association of Urology (EAU) NMIBC guidelines recently changed the risk stratification for Ta G3 from high risk to intermediate, high, or very high risk. However, prognostic studies on Ta G3 carcinomas are limited and inconclusive. ObjectiveTo evaluate the prognostic value of categorizing Ta G3 compared to Ta G2 and T1 G3 carcinomas. Design, setting, and participantsIndividual patient data for 5170 primary Ta–T1 bladder tumors from 17 hospitals were analyzed. Transurethral resection of the tumor was performed between 1990 and 2018. Outcome measurements and statistical analysisTime to recurrence and time to progression were analyzed using cumulative incidence functions, log-rank tests, and multivariable Cox-regression models with interaction terms stratified by institution. Results and limitationsTa G3 represented 7.5% (387/5170) of Ta–T1 carcinomas of which 42% were classified as intermediate risk. Time to recurrence did not differ between Ta G3 and Ta G2 (p = 0.9) or T1 G3 (p = 0.4). Progression at 5 yr occurred for 3.6% (95% confidence interval [CI] 2.7–4.8%) of Ta G2, 13% (95% CI 9.3–17%) of Ta G3, and 20% (95% CI 17–23%) of T1 G3 carcinomas. Time to progression for Ta G3 was shorter than for Ta G2 (p < 0.001) and longer than for T1 G3 (p = 0.002). Patients with Ta G3 NMIBC with concomitant carcinoma in situ (CIS) had worse prognosis and a similar time to progression as for patients with T1 G3 NMIBC with CIS (p = 0.5). Multivariable analyses for recurrence and progression showed similar results. ConclusionsThe prognosis of Ta G3 tumors in terms of progression appears to be in between that of Ta G2 and T1 G3. However, patients with Ta G3 NMIBC with concomitant CIS have worse prognosis that is comparable to that of T1 G3 with CIS. Our results support the recent EAU NMIBC guideline changes for more refined risk stratification of Ta G3 tumors because many of these patients have better prognosis than previously thought. Patient summaryWe used data from 17 centers in Europe and Canada to assess the prognosis for patients with stage Ta grade 3 (G3) non–muscle-invasive bladder cancer (NMIBC). Time to cancer progression for Ta G3 cancer differed from both Ta G2 and T1 G3 tumors. Our results support the recent change in the European Association of Urology guidelines for more refined risk stratification of Ta G3 NMIBC because many patients with this tumor have better prognosis than previously thought.

The probability of residual tumor detection in the second transurethral resection of pT1 urothelial bladder cancer according to the risk factors

ObjectiveTo analyze the predictive factors for residual tumors in the second resection after the initial transurethral resection of bladder tumor (TUR-BT) in patients with pT1 tumors and to develop a simple method to predict the probability of residual tumor detection. Material and MethodsPatients with pT1 bladder cancer who underwent a second resection within two to six weeks after the initial TUR-BT were included in our retrospective study. The patients’ demographics and the tumor characteristics of the initial and second resections were recorded. ResultsA total of 144 patients were included in our analysis with a 53-month follow-up. In the univariate logistic regression analysis, tumor grade, concomitant carcinoma in situ (CIS), macroscopic appearance of the tumor (solid vs papillary), and presence of a variant histology, were significant risk factors for residual tumor. In the multivariate analysis, tumor grade was the only independent predictor of residual tumor at second TUR (OR: 5.62, 95% CI: 1.228–25.708, p = 0.026). According to our findings, the patients with the highest risk have a 90.9% residual tumor detection probability at the second resection, and the patients with the lowest risk have 25.4%. ConclusionsTumor grade, macroscopic appearance of the tumor (solid vs papillary), and concomitant CIS, were important predictors of residual tumors at second resection of primary pT1 NMIBC patients. We were able to calculate the probability of residual tumor which helped us determine risk adapted strategies according to these probabilities.

MP50-20 SURGICAL MANAGEMENT AND OUTCOMES OF NATIVE UPPER URINARY TRACT UROTHELIAL CARCINOMA AFTER KIDNEY TRANSPLANTATION

You have accessJournal of UrologyCME1 May 2022MP50-20 SURGICAL MANAGEMENT AND OUTCOMES OF NATIVE UPPER URINARY TRACT UROTHELIAL CARCINOMA AFTER KIDNEY TRANSPLANTATION Shi-Jie Tsai, Eric Yi-Hsiu Huang, Tzu-Hao Huang, Tzu-Chun Wei, Chih-Chieh Lin, Tzu-Ping Lin, Hsiao-Jen Chung, William J.S. Huang, and Yen-Hwa Chang Shi-Jie TsaiShi-Jie Tsai More articles by this author , Eric Yi-Hsiu HuangEric Yi-Hsiu Huang More articles by this author , Tzu-Hao HuangTzu-Hao Huang More articles by this author , Tzu-Chun WeiTzu-Chun Wei More articles by this author , Chih-Chieh LinChih-Chieh Lin More articles by this author , Tzu-Ping LinTzu-Ping Lin More articles by this author , Hsiao-Jen ChungHsiao-Jen Chung More articles by this author , William J.S. HuangWilliam J.S. Huang More articles by this author , and Yen-Hwa ChangYen-Hwa Chang More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002625.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Kidney transplant (KT) recipients were associated with increased incidence of malignancy due to use of immunosuppressant. Urothelial carcinoma (UC) was one of the leading de novo malignancies following KT. For UC arising from native upper urinary tract after KT, radical nephroureterectomy (RNU) was the gold standard of treatment. We aim to analyze the surgical and oncological outcomes of KT recipients with native upper urinary tract UC underwent RNU. METHODS: We retrospectively reviewed KT patients underwent RNU due to upper tract urothelial carcinoma (UTUC) at our institute from 2005 to 2016. Demographic data and oncologic outcomes were collected from medical records. RESULTS: A total of 26 patients were included in this study. The average age at RNU was 59.4±12.2 years (range 22-73), and the time interval from KT to RNU was 10.7±5.6 years (range 1.5-20). Five patients (19%) received unilateral RNU. Twenty-one patients (81%) received simultaneous bilateral radical nephroureterectomy (SBRNU). The methods of surgical approach were open in 13 (50%) cases, laparoscopy in 10 (38%) cases, and robotic-assisted in 3 (12%) cases. The perioperative complication rate was 30%, and 11% was ≥ grade III Clavien-Dindo classification. Function loss of the graft kidney was not observed in all cases.The histopathology results showed 11 (42%) cases were locally advanced stage (pT3/4 or node positive). Twenty-two (85%) patients had multifocal tumors, and 13 (50%) patients had concomitant carcinoma in situ (CIS) lesions. Among 21 patients received SBRNU, synchronous UC in bilateral upper urinary tracts were identified in 11 (52%) patients, while only three of them (27%) had pre-operative image or pathology suspicion of bilateral lesions. Two out of five patients received unilateral RNU eventually experienced contralateral recurrence with mean interval of 5.5 years. The mean follow-up period of our cohort was 46 months (range 2-138). Local recurrence and/or metastasis were observed in 9 (35%) patients. Intravesical recurrences were noted in 14 (54%) patients, with a median time of 8.5 months from surgery to recurrence. The cancer-specific and overall survival rate was 67% and 62%, respectively. CONCLUSIONS: Native UTUC after KT is a unique patient cohort that is commonly associated with multifocal tumors, concomitant CIS lesions, and locally advanced stage, thus warranted timely surgical intervention and further therapy. SBRNU should be performed if possible due to high prevalence of synchronous bilateral UTUC and high contralateral recurrence rate. Source of Funding: Nil © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e874 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Shi-Jie Tsai More articles by this author Eric Yi-Hsiu Huang More articles by this author Tzu-Hao Huang More articles by this author Tzu-Chun Wei More articles by this author Chih-Chieh Lin More articles by this author Tzu-Ping Lin More articles by this author Hsiao-Jen Chung More articles by this author William J.S. Huang More articles by this author Yen-Hwa Chang More articles by this author Expand All Advertisement PDF DownloadLoading ...

Urinary pH is an independent predictor of upper tract recurrence in non-muscle-invasive bladder cancer patients with a smoking history

Limited information is currently available on predictors of upper tract urothelial carcinoma (UTUC) recurrence in non-muscle-invasive bladder cancer (NMIBC) patients according to smoking history, although smoking probably contributes to urothelial carcinogenesis. Therefore, the present study aimed to identify independent predictors of UTUC recurrence in all patients and those with a smoking history. Our study population comprised 1190 NMIBC patients who underwent transurethral resection of bladder tumor. UTUC developed in 43 patients during the follow-up. A history of bacillus Calmette-Guérin (BCG) therapy was independently associated with a lower incidence of UTUC (HR = 0.43; P = 0.011). In a subgroup of NMIBC patients with a smoking history, concomitant carcinoma in situ (CIS) and a lower urinary pH (< 6) were independently associated with a higher incidence of UTUC recurrence (HR = 3.34, P = 0.006 and HR = 3.73, P = 0.008, respectively). Among patients with a longer smoking duration (≥ 20 years) or larger smoking intensity (≥ 20 cigarettes per day), those with lower urinary pH (< 6) had a significantly higher UTUC recurrence rate than their counterparts. These results suggest that BCG instillation may prevent UTUC recurrence in NMIBC patients, while a lower urinary pH and concomitant CIS increase the risk of UTUC recurrence in those with a smoking history.

Prognostic Significance of the Neutrophil-to-Lymphocyte Ratio in Patients with Non-Muscle Invasive Bladder Cancer treated with Intravesical Bacillus Calmette-Guérin and the Relationship with the CUETO Scoring Model.

In this study, we evaluated the predictability of a modified Club Urológico Español de Tratamiento Oncológico (CUETO) scoring model and preoperative neutrophil-to-lymphocyte ratio (NLR) in patients with non-muscle invasive bladder cancer (NMIBC). From August 2005 to May 2016, a total of 281 patients received intravesical bacillus Calmette-Guérin therapy after transurethral resection of a bladder tumor. The pathologic stage of all patients was Ta or T1. Of 281 patients, 84 (29.9%) experienced recurrence and 14 (5.0%) developed progression. The mean follow-up period was 46 months. The cut-off value for NLRs was 2.29. One hundred-eight patients (38.4%) displayed a high NLR (> 2.29). In Kaplan-Meier curve analysis, a high NLR was associated with lower recurrence-free survival (RFS) (P < .001) and progression-free survival (PFS) (P = .002). CUETO scores were associated with RFS (P < .001), but not with PFS (P = .423). A combination of NLRs and the CUETO risk model correlated with RFS (P < .001) and PFS (P = .002). In multivariate analysis, female gender, concomitant carcinoma in situ (CIS), tumor number >3, recurrent tumors, and a high NLR were independent factors predicting recurrence (all P < .05). Concomitant CIS, recurrent tumors, and a high NLR were independent factors for predicting progression (all P < .05). In patients with NMIBC, an NLR >2.29 was identified as a significant factor for predicting tumor recurrence and progression. Inclusion of preoperative NLR enhanced the accuracy of the CUETO model to predict disease progression.

Concomitant carcinoma in situ is an independent prognostic predictor for patients with localized lymph node–negative upper-tract urothelial carcinoma undergoing nephroureterectomy

Purpose: This study aimed to determine the predictive value of concomitant carcinoma in situ (CIS) for cancer-specific survival (CSS) in patients with upper-tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy. Methods: This was a retrospective analysis of the clinicopathological features in a cohort of 126 patients with localized lymph node–negative UTUC who underwent radical nephroureterectomy with bladder-cuff excision in a tertiary medical center between January 1, 2007, and June 30, 2018. Cox proportional hazards models were used to identify risk factors for CSS in UTUC. Additionally, Kaplan–Meier analyses were performed in subgroups according to pathological tumor stage. Results: The median age and follow-up duration were 70 years and 3.5 years, respectively. Concomitant CIS, which was present in 21% of the patient specimens, was not associated with most clinical or pathological features, except for lymphovascular invasion and multifocality. Concomitant CIS (adjusted hazard ratio (HR)=4.64, 95% confidence interval (CI) 1.78–12.06, p=0.002) and pathological tumor stage (adjusted HR=4.07, 95% CI 1.99–8.31, p&lt;0.001) were significantly associated with CSS in the multivariate Cox regression model. In the subgroup analysis, concomitant CIS in patients with locally advanced (pT3/pT4) UTUC was associated with significantly worse CSS compared to those without CIS (HR=3.83, 95% CI 1.20–12.21). Conclusion: The pathological presence of concomitant CIS was independently associated with poor CSS in patients with localized lymph node–negative UTUC undergoing radical nephroureterectomy. These findings provide crucial information relevant for postoperative patient counseling, use of adjuvant therapy, follow-up intensity, and clinical trial enrollment. Level of evidence Level II.

Risk factors associated with positive surgical margins' location at radical cystectomy and their impact on bladder cancer survival.

To evaluate the risk factors associated with positive surgical margins' (PSMs) location and their impact on disease-specific survival (DSS) in patients with bladder cancer (BCa) undergoing radical cystectomy (RC). We analyzed a large multi-institutional cohort of patients treated with upfront RC for non-metastatic (cT1-4aN0M0) BCa. Multivariable binomial logistic regression analyses were used to assess the risk of PSMs at RC for each location after adjusting for clinicopathological covariates. The Kaplan-Meier method was used to estimate DSS stratified by margins' status and location. Log-rank statistics and Cox' regression models were used to determine significance. A total of 1058 patients were included and 108 (10.2%) patients had PSMs. PSMs were located at soft-tissue, ureter(s), and urethra in 57 (5.4%), 30 (2.8%) and 21 (2.0%) patients, respectively. At multivariable analysis, soft-tissue PSMs were independently associated with pathological stage T4 (pT4) (Odds ratio (OR) 6.20, p < 0.001) and lymph-node metastases (OR 1.86, p = 0.04). Concomitant carcinoma-in-situ (CIS) was an independent risk factor for ureteric PSMs (OR 6.31, p = 0.003). Finally, urethral PSMs were independently correlated with pT4-stage (OR 5.10, p = 0.01). The estimated 3-years DSS rates were 58.2%, 32.4%, 50.1%, and 40.3% for negative SMs, soft-tissue-, ureteric- and urethral PSMs, respectively (log-rank; p < 0.001). PSMs' location represents distinct risk factors' patterns. Concomitant CIS was associated with ureteric PSMs. Urethral and soft-tissue PSM showed worse DSS rates. Our results suggest that clinical decision-making paradigms on adjuvant treatment and surveillance might be adapted based on PSM and their location.

Abstract B06: Pathologic T1 substaging improves the identification of high-risk non-muscle invasive bladder cancer patients at risk of BCG failure

Abstract Introduction: High-risk non-muscle invasive bladder cancer (HR-NMIBC) patients represent a challenging group as they have the highest risk of treatment failure despite transurethral tumor resection (TUR) and adjuvant intravesical Bacillus Calmette-Guérin (BCG) instillations. Treatment failure is associated with an increased risk of progression and unnecessary exposure to toxicity of BCG, while continuing BCG shortage demands selective use of limited resources. The current risk stratification is insufficient at predicting BCG failure in HR-NMIBC patients. Therefore, we aim to investigate whether pathologic depth of tumor invasion (i.e., T1 substaging) is able to improve patient stratification. Methods: HR-NMIBC patients who received a TUR and at least induction BCG (5 of 6 instillations) were included at four European centers between 2000−2016. Clinicopathologic data were collected and all diagnostic TURs, re-TURs, and subsequent TURs of tumor recurrences were reviewed, which included T1 substaging (micro vs. extensive [pT1e]). Primary endpoint was BCG failure according to EAU guidelines. Progression was defined as muscle-invasive and/or metastatic disease. Logistic regression analysis and Cox regression models were used to identify predictive markers of BCG failure on diagnostic TUR and first recurrence. Results: N=513 HR-NMIBC patients were included: median age 70 years, 78% men. Median follow-up was 52 months. In total, 316 (62%) patients had pT1 disease, 144 (28%) pTa, and 53 (10%) pTis. BCG failure occurred in 28% (18% progression, 6% metastasis). Median time to progression was 18 months. Strongest predictors of BCG failure on diagnostic TUR were pT1e substaging (HR: 2.1; 95% CI 1.1–4.0; p=0.023), concomitant carcinoma in situ (CIS) (HR: 3.0; 95% CI 1.5–5.7; p=0.003), and lymphovascular invasion (LVI) (HR: 3.3, 95% CI 1.0–11, p=0.05). pT1e substaging combined with either concomitant CIS or LVI increased the risk of BCG failure (HR: 3.6; 95% CI 1.8–6.9; p&amp;lt;0.001). Interestingly, 5/12 patients with micropapillary disease were in this high-risk subgroup. Predictors of progression on diagnostic TUR: concomitant CIS (HR 2.1: 95% CI 1.1–3.9; p=0.018), LVI (HR: 2.6, 95% CI 1.1–6.4, p=0.036) and T1e (HR: 3.6; 95% CI 1.5–9.4; p=0.006). Risk of progression at first recurrence increased in case of a pT1 recurrence (HR: 4.1; 95% CI 2.3–7.2; p&amp;lt;0.001) and adding pT1e substaging increased the risk even more (HR: 5.9, 95% CI 3.2–10.8, p&amp;lt;0.001). Conclusion: Substaging has the potential to improve the current risk stratification model by identification of HR-NMIBC patients at the highest risk of BCG failure and is specifically able to identify patients at high risk of progression. Substaging can be performed by every pathologist with minimal additional training required. Combined with other pathologic markers, substaging can be used as a stratification tool for early cystectomy or to include patients in clinical trials. Citation Format: Florus C. de Jong, Robert F. Hoedemaeker, Jolien T.M. Mensink, Vebjørn Kvikstad, Egbert R. Boevé, Deric K.E. van der Schoot, Ellen C. Zwarthoff, Tahlita C.M. Zuiverloon. Pathologic T1 substaging improves the identification of high-risk non-muscle invasive bladder cancer patients at risk of BCG failure [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr B06.

Commentary on “A novel treatment strategy for newly diagnosed high-grade T1 bladder cancer: Gemcitabine and cisplatin adjuvant chemotherapy—A single-institution experience.”

BackgroundManagement of high-grade T1 (formerly T1G3) bladder cancer continues to be controversial. Should patients with T1G3 bladder cancer have an immediate radical cystectomy or should they receive intravesical bacillus Calmette-Guérin preserving bladder? Gemcitabine and cisplatin (GC) adjuvant chemotherapy may help to strike a balance between intravesical and early cystectomy. For purposes of this study, we continue to refer high-grade T1 lesion as “T1G3.” ObjectiveTo evaluate the characteristics and the long-term outcome of GC adjuvant chemotherapy in T1G3 bladder cancer after transurethral resection of bladder tumor (TURBT). Materials and methodsWe, retrospectively, reviewed 48 patients who were newly diagnosed with T1G3 bladder cancer between January 2009 and December 2012. A total of 48 patients received 4 cycles of GC adjuvant chemotherapy after TURBT. One month after 4 cycles of GC adjuvant chemotherapy, response was evaluated by re-TURBT. Median follow-up was 59.5 (range: 18–70) months, all patients have been observed for more than 3 years. Salvage cystectomy was recommended for patients with persistent disease and for tumor progression after initial complete response. ResultComplete response was achieved in 44 (91.7%) patients. Of complete responders, 5 patients experienced recurrence and 5 patients showed progression. The progression rate and disease-specific survival rate were 10.4% and 91.7% at 3 years, respectively. More than 80% of survivors preserved their bladder. Kaplan-Meier curves showed that concomitant carcinoma in situ (CIS) was the only factor that had an influence on progression-free survival (P = 0.022) and disease-specific survival (P = 0.017). Concomitant CIS was the prognostic factor for progression rate and disease-specific survival rate at 3 years (P = 0.008 and P = 0.035). ConclusionGC adjuvant chemotherapy is a safe conservative treatment for T1G3 bladder cancer, but effective is really a phase II study. Patients with T1G3 bladder cancer with concomitant CIS should be treated more aggressively because of the high risk of progression.

MP83-05 ONCOLOGICAL OUTCOME IN A RETROSPECTIVE COHORT OF T1G3 PRIMARY PATIENTS. DOES THE LOCATION OF CIS REALLY MATTER?

You have accessJournal of UrologyBladder Cancer: Non-invasive II1 Apr 2018MP83-05 ONCOLOGICAL OUTCOME IN A RETROSPECTIVE COHORT OF T1G3 PRIMARY PATIENTS. DOES THE LOCATION OF CIS REALLY MATTER? Francesca Pisano, Oscar Rodriguez Faba, Ferran Algaba, Lucia Mosquera Seoane, Josè Maria Gaya, Ruben Parada, Helena Vila Reies, and Joan Palou Francesca PisanoFrancesca Pisano More articles by this author , Oscar Rodriguez FabaOscar Rodriguez Faba More articles by this author , Ferran AlgabaFerran Algaba More articles by this author , Lucia Mosquera SeoaneLucia Mosquera Seoane More articles by this author , Josè Maria GayaJosè Maria Gaya More articles by this author , Ruben ParadaRuben Parada More articles by this author , Helena Vila ReiesHelena Vila Reies More articles by this author , and Joan PalouJoan Palou More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.2753AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES CIS has been already identified as one of the most important prognostic risk factors in NMIBC in BCG treated patients. Interestingly, this information mostly derived from studies that did not analysed the prognostic relevance of the localization of CIS or that not all the patients underwent multiple bladder diopsies. The aim of this study is to evaluate the role of CIS in prostatic urethra to predict recurrence, progression and cancer specific mortality. METHODS A total of 300 consecutive patients with primary T1G3 that all underwent multiple bladder biopsies including prostatic urethra, were retrospectively analysed. The variables analysed for recurrence, progression, and death due to bladder cancer (BCa) were gender, age, tumour multiplicity, diameter, aspect, concomitant carcinoma in situ (CIS), and CIS in the prostatic urethra. A back stepwise multivariate cox model was performed including clinical variables at baseline with a p value <0.2 in the bivariate analysis as independent variables. RESULTS The median follow-up was 8.5 yr; 261 (87%) were males, with a mean age at diagnosis of 67 years (SD 10). Globally concomitant CIS was present in 151 patients (50.3%) and 30 (10%) presented CIS in prostatic urethra. Tumors were multiple 160 cases (53.3%), 118 (39.3%) were >3cm. One-hundred and sixty-five patients (55%) had recurrence, 70 patients (23%) had progression, and 46 patients (16.1%) died because of BCa. Among patients with CIS in prostatic urethra 46% progressed. Patients presenting CIS in prostatic urethra have 3 times more risk to progress (HR=3.059, p=0.014), and 2 times more risk of death due to BCa (HR=3.794,p=0.004). Moreover female gender and multifocal tumours were confirmed as significant prognostic risk factors for progression (HR 2.73, p=0.014; HR 1.83, p=0.043 respectively) and CSS (HR 2.73, p=0.029; HR 2.65, p=0.012). CONCLUSIONS Since the presence of CIS in prostatic urethra strongly affects the risk of progression and death due to BCa, a routine evaluation of prostatic urethra is mandatory in primary high grade NMIBC. It is confirmed as well that female gender and multifocal disease are strongly related with worse outcomes. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e1117 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Francesca Pisano More articles by this author Oscar Rodriguez Faba More articles by this author Ferran Algaba More articles by this author Lucia Mosquera Seoane More articles by this author Josè Maria Gaya More articles by this author Ruben Parada More articles by this author Helena Vila Reies More articles by this author Joan Palou More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Interleukin-17-positive mast cells influence outcomes from BCG for patients with CIS: Data from a comprehensive characterisation of the immune microenvironment of urothelial bladder cancer.

The tumour immune microenvironment is considered to influence cancer behaviour and outcome. Using a panel of markers for innate and adaptive immune cells we set out to characterise and understand the bladder tumour microenvironment of 114 patients from a prospective multicentre cohort of newly-diagnosed bladder cancer patients, followed-up for 4.33±1.71 years. We found IL-17-positive cells were significantly increased in primary and concomitant carcinoma in situ (CIS), p<0.0001, a highly malignant lesion which is the most significant single risk factor for disease progression. Further characterisation of the tumour immunophenotype identified IL-17+ cells as predominantly mast cells rather than T-cells, in contrast to most other tumour types. Expression of the IL-17-receptor in bladder tumours, and functional effects and gene expression changes induced by IL-17 in bladder tumour cells in vitro suggest a role in tumour behaviour. Finally, we assessed the effects of IL-17 in the context of patient outcome, following intravesical BCG immunotherapy which is the standard of care; higher numbers of IL-17+ cells were associated with improved event-free survival (p = 0.0449, HR 0.2918, 95% CI 0.08762–0.9721) in patients with primary and concomitant CIS (n = 41), we propose a model of IL-17+ Mast cells mechanism of action. Thus, in the context of bladder CIS, IL-17+ mast cells predict favourable outcome following BCG immunotherapy indicative of a novel mechanism of BCG immunotherapy in UBC and could form the basis of a stratified approach to treatment.

A novel treatment strategy for newly diagnosed high-grade T1 bladder cancer: Gemcitabine and cisplatin adjuvant chemotherapy—A single-institution experience

BackgroundManagement of high-grade T1 (formerly T1G3) bladder cancer continues to be controversial. Should patients with T1G3 bladder cancer have an immediate radical cystectomy or should they receive intravesical bacillus Calmette-Guérin–preserving bladder? Gemcitabine and cisplatin (GC) adjuvant chemotherapy may help to strike a balance between intravesical and early cystectomy. For purposes of this study, we continue to refer high-grade T1 lesion as “T1G3.” ObjectiveTo evaluate the characteristics and the long-term outcome of GC adjuvant chemotherapy in T1G3 bladder cancer after transurethral resection of bladder tumor (TURBT). Materials and methodsWe retrospectively reviewed 48 patients who were newly diagnosed with T1G3 bladder cancer between January 2009 and December 2012. A total of 48 patients received 4 cycles of GC adjuvant chemotherapy after TURBT. One month after 4 cycles of GC adjuvant chemotherapy, response was evaluated by re-TURBT. Median follow-up was 59.5 (range: 18–70) months, all patients have been observed for more than 3 years. Salvage cystectomy was recommended for patients with persistent disease and for tumor progression after initial complete response. ResultComplete response was achieved in 44 (91.7%) patients. Of complete responders, 5 patients experienced recurrence and 5 patients showed progression. The progression rate and disease-specific survival rate were 10.4% and 91.7% at 3 years, respectively. More than 80% of survivors preserved their bladder. Kaplan-Meier curves showed that concomitant carcinoma in situ (CIS) was the only factor that had an influence on progression-free survival (P = 0.022) and disease-specific survival (P = 0.017). Concomitant CIS was the prognostic factor for progression rate and disease-specific survival rate at 3 years (P = 0.008 and P = 0.035). ConclusionGC adjuvant chemotherapy is a safe conservative treatment for T1G3 bladder cancer, but effective is really a phase II study. Patients with T1G3 bladder cancer with concomitant CIS should be treated more aggressively because of the high risk of progression.

Clinical, demographic and histopathological prognostic factors for urothelial carcinoma of the bladder.

IntroductionOur aim is to evaluate the influence of clinical and histopathological parameters, including age, gender, tumor stage, grade, tumor differentiation, necrosis, lymphovascular/perineural invasion (LVI/PNI) and concomitant carcinoma in situ (CIS), on outcomes of patients with urothelial carcinoma of the bladder (UCB).Material and methodsA total of 84 patients who underwent radical cystectomy (RC) (n = 11) and radical cystoprostatectomy (n = 73) for muscle-invasive bladder cancer at our hospital between 2007-2013, were included in the study.ResultsThe mean age of patients at diagnosis was 66.1, of whom 75 were males and 9 were females. Of the 84 patients, 38 were ≤65 years and 46 were >65 years. Mean tumor diameter was 3.66 cm. There were 38 cases which showed divergent differentiations. Concomitant CIS was observed in 30 tumors, 41 cases showed tumor necrosis, 44 PNI and 61 LVI.The rate of overall survival (OS) in patients aged ≤65 years was statistically significantly higher than in those aged >65 years. A negative statistical relationship was found between OS with lymph node metastasis (LNM) and tumor differentiation. On the other hand, necrosis did not remain significant on multivariate analysis.No statistically significant relationship was found between smoking, tumor stage, PNI, LVI and concomitant CIS and OS.ConclusionsIn this study, advanced age, LNM, tumor differentiation were found to be independent prognostic risk factors associated with OS after RC. These additional factors, which may explain the different clinical course in patients with similar tumor stage and lymph node status, should be taken into consideration in treatment planning.

Prognostic Factors and Risk Groups in T1G3 Non–Muscle-invasive Bladder Cancer Patients Initially Treated with Bacillus Calmette-Guérin: Results of a Retrospective Multicenter Study of 2451 Patients

BackgroundThe impact of prognostic factors in T1G3 non–muscle-invasive bladder cancer (BCa) patients is critical for proper treatment decision making. ObjectiveTo assess prognostic factors in patients who received bacillus Calmette-Guérin (BCG) as initial intravesical treatment of T1G3 tumors and to identify a subgroup of high-risk patients who should be considered for more aggressive treatment. Design, setting, and participantsIndividual patient data were collected for 2451 T1G3 patients from 23 centers who received BCG between 1990 and 2011. Outcome measurements and statistical analysisUsing Cox multivariable regression, the prognostic importance of several clinical variables was assessed for time to recurrence, progression, BCa-specific survival, and overall survival (OS). Results and limitationsWith a median follow-up of 5.2 yr, 465 patients (19%) progressed, 509 (21%) underwent cystectomy, and 221 (9%) died because of BCa. In multivariable analyses, the most important prognostic factors for progression were age, tumor size, and concomitant carcinoma in situ (CIS); the most important prognostic factors for BCa-specific survival and OS were age and tumor size. Patients were divided into four risk groups for progression according to the number of adverse factors among age ≥70 yr, size ≥3cm, and presence of CIS. Progression rates at 10 yr ranged from 17% to 52%. BCa-specific death rates at 10 yr were 32% in patients ≥70 yr with tumor size ≥3cm and 13% otherwise. ConclusionsT1G3 patients ≥70 yr with tumors ≥3cm and concomitant CIS should be treated more aggressively because of the high risk of progression. Patient summaryAlthough the majority of T1G3 patients can be safely treated with intravesical bacillus Calmette-Guérin, there is a subgroup of T1G3 patients with age ≥70 yr, tumor size ≥3cm, and concomitant CIS who have a high risk of progression and thus require aggressive treatment.

MP56-03 EXPRESSION PROFILE OF EPITHELIAL-MESENCHYMAL TRANSITION MARKERS IN NON-MUSCLE INVASIVE UROTHELIAL CARCINOMA OF THE BLADDER: CORRELATION WITH INTRAVESICAL RECURRENCE FOLLOWING TRANSURETHRAL RESECTION

You have accessJournal of UrologyBladder Cancer: Superficial1 Apr 2014MP56-03 EXPRESSION PROFILE OF EPITHELIAL-MESENCHYMAL TRANSITION MARKERS IN NON-MUSCLE INVASIVE UROTHELIAL CARCINOMA OF THE BLADDER: CORRELATION WITH INTRAVESICAL RECURRENCE FOLLOWING TRANSURETHRAL RESECTION Akira Miyazaki, Hideaki Miyake, Liu Bing, and Masato Fujisawa Akira MiyazakiAkira Miyazaki More articles by this author , Hideaki MiyakeHideaki Miyake More articles by this author , Liu BingLiu Bing More articles by this author , and Masato FujisawaMasato Fujisawa More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1571AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Introduction and Objectives Despite generally favorable prognosis in patients with non-muscle invasive urothelial carcinoma of the bladder (NMIUCB), intravesical recurrence following transurethral resection (TUR) has been reported in approximately 50% of patients with this disease. The objective of this study was to evaluate the expression of multiple molecular markers involved in epithelial-mesenchymal transition (EMT), a key process mediating the progression of a wide variety of malignant tumors, in NMIUCB to clarify the significance of these markers as predictors of intravesical recurrence in patients treated with TUR. Methods This study included a total of 161 patients with NMIUCB undergoing TUR at our institution. Expression levels of 13 EMT markers, including E-cadherin, N-cadherin, β-catenin, γ-catenin, fibronectin, MMP-2, MMP-9, Slug, Snail, Twist, vimentin ZEB1 and ZEB2, in TUR specimens obtained from these 161 patients were measured by immunohistochemical staining. These findings were analyzed according to several clinicopathological outcomes. Results Of these 13 proteins, expression levels of E-cadherin, N-cadherin, MMP-2, MMP-9 and TWIST significantly associated with several conventional predictive factors of intravesical recurrence. Univariate analysis identified expression level of E-cadherin, N-cadherin, MMP-2, MMP-9 and TWIST as significant predictors of intravesical recurrence as well, while tumor size, pathological T stage and concomitant carcinoma in situ (CIS) were also significant. Of these significant factors, expression levels of E-cadherin, MMP-9 and TWIST, tumor size and concomitant CIS appeared to be independently related to intravesical recurrence by multivariate analysis. Furthermore, there were significant differences in recurrence-free survival according to positive numbers of these three independent risk factors (i.e., negative vs positive for 1 or 2 factor vs positive for 3 or more factors). Conclusions Consideration of expression levels of EMT-associated markers in TUR specimens, in addition to conventional prognostic parameters, would contribute to accurate prediction of intravesical recurrence following TUR for NMIUCB. Moreover, combined evaluation of expression levels of E-cadherin, MMP-9 and TWIST, tumor size and concomitant CIS would be particularly useful for further refinement of the system in predicting recurrence of NMIUCB following TUR. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e564 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Akira Miyazaki More articles by this author Hideaki Miyake More articles by this author Liu Bing More articles by this author Masato Fujisawa More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...

PD35-08 RISK FACTORS FOR INTRAVESICAL RECURRENCE AFTER RADICAL NEPHROURETERECTOMY FOR UPPER TRACT UROTHELIAL CARCINOMA: A META-ANALYSIS

You have accessJournal of UrologyBladder Cancer: Upper Tract Tumors I1 Apr 2014PD35-08 RISK FACTORS FOR INTRAVESICAL RECURRENCE AFTER RADICAL NEPHROURETERECTOMY FOR UPPER TRACT UROTHELIAL CARCINOMA: A META-ANALYSIS Haichao Yuan, Ping Han, and Qiang Wei Haichao YuanHaichao Yuan More articles by this author , Ping HanPing Han More articles by this author , and Qiang WeiQiang Wei More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.2421AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The standard management for upper tract urothelial carcinoma (UTUC) is radical nephroureterectomy (RNU) with bladder cuff excision, but after surgery, approximately 22% to 47% of patients with UTUC develop subsequent intravesical recurrence (IVR), and recurrence in the contralateral upper tract is observed in 26% of patients. Considering this high incidence of IVR after RNU, several risk factors were reported as predictive for IVR after RNU. Until recently, most of the risk factors were still under debate. The aim of our study is to conduct a meta-analysis based on the recent literature to explore the risk factors for IVR after RNU for UTUC. METHODS An electronic search of the Medline, Embase, Cochrane Library, CancerLit and ClinicalTrials.gov databases was performed to identify relevant studies published prior to May 2013. The studies were included if they reported risk factors related to bladder or intravesical recurrence after RNU for UTUC. Studies were excluded from the analysis if they were case reports, meeting abstracts or conference proceedings. The studies which included neoadjuvant or adjuvant chemotherapy or intravesical instillation chemotherapy after RNU were excluded. RESULTS Forty studies, with 12,010 patients, were included in our meta-analysis. Our study indicated that a statistically significant difference in IVR after RNU was found in the male vs. female (OR: 0.72; 95%CI: 0.59 to 0.85), ureteral vs. renal pelvis (OR: 1.18; 95%CI: 1.00 to 1.36), T2-4 vs. Tis and Ta,1 (OR: 0.53; 95%CI: 0.40 to 0.66), larger vs. smaller tumor size (OR: 1.02; 95%CI: 1.01 to 1.03) and previous/synchronous bladder cancer vs. the absence of bladder cancer (OR: 1.59; 95%CI: 1.26 to 1.9). No significant differences in IVR after RNU were found in the high vs. low age, multifocal tumors vs. single tumor, G3 vs. G1,2, high vs. low grade, N0 vs. N+, concomitant carcinoma in situ (CIS) vs. the absence of CIS, positive vs. negative lymphovascular invasion, open versus laparoscopic nephroureterectomy and endoscopic vs. transvesical technique. CONCLUSIONS our study showed that female patient, ureteral tumor, larger tumor, low T stage (Tis, a, 1) and the history of bladder cancer were significant risk factors related to IVR after nephroureterectomy. The age, tumor multifocality, G grade, lymph node status, lymphovascular invasion, Concomitant CIS, type of surgery and management of the bladder cuff were not significantly associated with the risk of IVR after nephroureterectomy. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e893-e894 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Haichao Yuan More articles by this author Ping Han More articles by this author Qiang Wei More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Socio-economic deprivation and outcomes following radical nephroureterectomy for clinically localized upper tract transitional cell carcinoma

Little is known about the effects of socio-economic deprivation on the oncological outcomes of surgically treated upper tract transitional cell carcinoma. From January 1998 to December 2012, 161 patients underwent nephroureterectomy for upper urinary tract cancer at our tertiary medical centre. We included 124 patients where complete data were available for further analysis. This study also analysed the impact of the reported risk factors such as grade, stage, multifocality in addition to socio-economic deprivation on the long-term oncological outcomes after nephroureterectomy. One hundred and twenty-four (77 %) patients with complete data for socio-economic status were analysed in this study. The median age of the cohort was 73 years (interquartile range 45-86). There were 20, 18, 17, 40 and 29 patients in different socio-economic categories ranging from 1 to 5, respectively. The median duration of follow-up was 68 months (9-174). A statistically higher grade (p value 0.005) and higher stage (p value 0.0005) disease was seen in patients from less deprived categories on both univariate and multivariate analyses. The cancer-specific mortality and follow-up recurrences, however, did not significantly differ between the different socio-economic categories on multivariate analysis (p value 0.13; 0.6) and on univariate and multivariate analyses. A higher number of patients with multifocal disease and concomitant carcinoma in situ (CIS) had disease recurrences which were statistically significant (p values 0.026 and 0.014, respectively) on multivariate analysis. A lower recurrence-free survival was observed in patients with multifocal disease and those with concomitant CIS following nephroureterectomy for clinically localized disease. Long-term follow-up did not show any significant differences in cancer-specific survival between different deprivation categories.

Pattern and risk factors of intravesical recurrence after nephroureterectomy for upper tract urothelial carcinoma: A large Chinese center experience

There is currently no consensus about the pattern and risk factors of bladder recurrence after nephroureterectomy, especially in the Chinese population. We evaluated the pattern and risk factors based on data from a large Chinese center. The clinical and pathological data of 438 patients with upper tract urothelial carcinoma (UTUC), who underwent nephroureterectomy at Peking University First Hospital, Beijing, China between 2000 and 2010, was retrospectively analyzed. Univariate analysis by log-rank test and multivariate analysis by Cox proportional hazards regression model were used to determine the independent risk factors. A total of 135 patients (30.8%) developed intravesical recurrence within a median follow-up of 45 months (range: 12-144 months). The median interval of bladder recurrence was 15 months (range: 2.0-98.0 months), and the two peaks for recurrence were 4-6 months and 17-19 months. Lower tumor grade, tumor multifocality, concomitant carcinoma in situ (CIS) and tumors located in the lower ureter were significant risk factors by univariate and multivariate analysis. A risk-scoring system was developed and a significant difference was found between different risk evaluations. Patients with concomitant CIS tended to develop a late bladder recurrence. One hundred and eighteen patients (87.4%) received transurethral resection after bladder tumor recurrence. Lower tumor grade, tumor multifocality, concomitant CIS and tumors located in the lower ureter tend to be predictive for bladder recurrence after nephroureterectomy, although the underlying mechanism is not fully elucidated, and the scoring system could help risk stratification. Most recurrent tumors could be treated by transurethral resection and there were two peaks for recurrence, which is probably related to the mechanisms and may be unique to the Chinese population.

Impact of concomitant carcinoma in situ on upstaging and outcome following radical cystectomy for bladder cancer

To evaluate the impact of concomitant carcinoma in situ (CIS) on upstaging and outcome of patients treated with radical cystectomy with pelvic lymph node dissection. We collected and pooled a database of 1,968 patients who have undergone radical cystectomy between 1998 and 2008 in eight academic centers across Canada. Collected variables included patient's age, gender, tumor grade, histology and the presence of concomitant CIS with either cTa-1 or cT2 disease, dates of recurrence and death. In the presence of concomitant CIS, upstaging following radical cystectomy occurred in 48 and 55 % of patients with cTa-1 and cT2 disease, respectively. On univariate analysis, the presence of concomitant CIS with cT2 disease was associated with upstaging (p < 0.0001), and the presence of concomitant CIS with cTa-1 disease was also associated with upstaging but did not reach statistical significance (p = 0.0526). On multivariate analyses, the presence of concomitant CIS with either cTa-1 or cT2 tumors was independently prognostic of disease upstaging (p = 0.0001 and 0.0186, respectively). However, on multivariate analysis that incorporates pathologic stage, concomitant CIS was not significantly associated with worse overall, recurrence-free or disease-specific survival. These results demonstrate that while the presence of concomitant CIS on cystectomy specimens does not independently affect outcomes, its presence is significantly predictive of a higher rate of upstaging at radical cystectomy.

Impact of Distal Ureter Management on Oncologic Outcomes Following Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma

BackgroundThere is a lack of consensus regarding the optimal approach to the bladder cuff during radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). ObjectivesTo compare the oncologic outcomes following RNU using three different methods of bladder cuff management. Design, setting, and participantsRetrospective analysis of 2681 patients treated with RNU for UTUC at 24 international institutions from 1987 to 2007. InterventionThree methods of bladder cuff excision were performed: transvesical, extravesical, and endoscopic. Outcome measurements and statistical analysisUnivariable and multivariable models tested the effect of distal ureter management on intravesical recurrence, recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Results and limitationsOf the 2681 patients, 1811 (67.5%) underwent the transvesical approach; 785 (29.3%), the extravesical approach; and 85 (3.2%), the endoscopic approach. There was no difference in terms of RFS, CSS, and OS among the three distal ureteral management approaches. Patients who underwent the endoscopic approach were at significantly higher risk of intravesical recurrence compared with those who underwent the transvesical (p=0.02) or extravesical approaches (p=0.02); the latter two groups did not differ from each other (p=0.40). Actuarial intravesical RFS estimates at 2 and 5 yr after RNU were 69% and 58%, 69% and 51%, and 61% and 42% for the transvesical, extravesical, and endoscopic approaches, respectively. In multivariate analyses, distal ureteral management (p=0.01), surgical technique (open vs laparoscopic; p=0.02), previous bladder cancer (p<0.001), higher tumor stage (trend; p=0.01), concomitant carcinoma in situ (CIS) (p<0.001), and lymph node involvement (trend; p<0.001) were all associated with intravesical recurrence. Excluding patients with history of previous bladder cancer, all variables remained independent predictors of intravesical recurrence. ConclusionsThe endoscopic approach was associated with higher intravesical recurrence rates. Interestingly, concomitant CIS in the upper tract is a strong predictor of intravesical recurrence after RNU. The association of laparoscopic RNU with intravesical recurrence needs to be further investigated.