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Objectives: To analyse the risk of uretero-enteric anastomotic stricture in patients randomised to open (ORC) or robot-assisted radical cystectomy (RARC) with extracorporeal urinary diversion., Patients and Methods: We included 118 patients randomised to RARC (n = 60) or ORC (n = 58) at a single, high-volume institution from March 2010 to April 2013. Urinary diversion was performed by experienced open surgeons. Stricture was defined as non-malignant obstruction on imaging, corroborated by clinical status, and requiring procedural intervention. The risk of stricture within 1 year was compared between groups using Fisher's exact test., Results: In all, 58 and 60 patients were randomised to RARC and ORC, respectively. We identified five strictures, all in the ORC group. In patients with ≥1 year of follow-up, the increase in risk of stricture from open surgery was 9.3% (95% confidence interval 1.5%, 17%). Of the five strictures, three were managed endoscopically while two required open revision. There was no evidence that perioperative Grade 3-5 complications were associated with development of a stricture (P = 1) and no evidence of a difference in 24-month estimated glomerular filtration rate between arms (P = 0.15)., Conclusions: In this study at a high-volume centre, RARC with extracorporeal urinary diversion achieved excellent ureteric anastomotic outcomes. Purported increased risk of stricture is not a reason to avoid RARC. Future research should examine the impact of different surgical techniques and operator experience on the risk of stricture, especially as more intracorporeal diversions are performed., (© 2022 BJU International.)

Objective: To evaluate whether urothelial carcinoma (UC) with sarcomatoid differentiation is associated with a lower pathological response rate to neoadjuvant chemotherapy (NAC) and worse oncological outcomes compared to UC without variant histology among patients undergoing radical cystectomy., Patients and Methods: Patients with UC undergoing cystectomy from 1995 to 2018 at the Memorial Sloan Kettering Cancer Centre were identified. Patients with sarcomatoid differentiation at transurethral resection (TUR) or cystectomy, and patients without variant histology were selected. Downstaging from ≥cT2 to ≤pT1N0 defined partial response and pT0N0 defined complete response. Recurrence-free, cancer-specific and overall survival were modelled., Results: We identified 131 patients with sarcomatoid differentiation and 1722 patients without variant histology, of whom 25 with sarcomatoid histology on biopsy and 313 without variant histology received NAC. Those with sarcomatoid differentiation presented with higher consensus tumour stage (94% ≥T2 vs 62%; P < 0.001) and were, therefore, more likely to receive NAC (29% vs 18%; P = 0.003). We found no evidence to support a difference in partial (24% vs 31%) or complete (20% vs 24%) response between patients with sarcomatoid histology and those with pure UC at TUR (P = 0.6). Among patients with sarcomatoid differentiation, 5-year recurrence-free survival was 55% (95% confidence interval [CI] 41-74) among patients receiving NAC and 40% (95% CI 31-52) among patients undergoing cystectomy alone (P = 0.1). Adjusting for stage, nodal involvement, margin status and receipt of NAC, sarcomatoid differentiation was associated with worse recurrence-free (hazard ratio [HR] 1.82, 95% CI 1.39-2.39), disease-specific (HR 1.66, 95% CI 1.23-2.22), and overall survival (HR 1.37, 95% CI 1.06-1.78)., Conclusions: Sarcomatoid differentiation was associated with higher stage at presentation and independently associated with worse survival. Given similar pathological response rates if sarcomatoid differentiation is detected at initial resection, and greater survival among patients receiving NAC, treatment with NAC appears warranted. Other drivers of the poor outcomes of this histology must be investigated., (© 2021 The Authors BJU International © 2021 BJU International.)

Objectives: To evaluate treatment patterns and associated outcomes of patients with urethral cancer., Patients and Methods: After obtaining institutional review board approval we identified 165 patients treated for primary urethral cancer between 1956 and 2017. Treatment included monotherapy (surgery or radiation), dual therapy (surgery+radiation, surgery+chemotherapy, or chemotherapy+radiation) or triple therapy (surgery+radiation+chemotherapy). Rates of different treatments were described by treatment year. The association between treatment type and outcomes was evaluated with multivariable Cox regression models, adjusting for disease characteristics., Results: The study cohort included 74 men and 91 women, with a median age of 61 years. Common histologies were squamous cell (36%), urothelial (27%) and adenocarcinoma (25%). At presentation, 72% of patients had invasive disease, 24% had nodal involvement, and 5% had metastases. Treatment included monotherapy (57%), dual therapy (21%), and triple therapy (10%). The use of monotherapy decreased over time, while rates of dual therapy remained consistent, and rates of triple therapy increased. The median follow-up was 4.7 years. Estimated 5-year local recurrence-free, disease-specific and overall survival were 51%, 48% and 41%, respectively. Monotherapy was associated with decreased local recurrence-free survival after adjusting for stage, histology, sex and year of treatment (P = 0.017). There was no evidence that treatment type was associated with distant recurrence, cancer-specific or overall survival., Conclusions: We found preliminary evidence that multimodal therapy, more commonly used in recent years, was of benefit in patients with primary urethral cancer. This finding should be confirmed in further studies involving multiple centres because of the low incidence of the disease., (© 2020 The Authors BJU International © 2020 BJU International Published by John Wiley & Sons Ltd.)

Objectives: To characterise the outcomes of neoadjuvant chemotherapy (NAC) pre-treated patients found to be lymph node (LN)-positive at the time of radical cystectomy and pelvic lymph node dissection (RC/PLND) for urothelial carcinoma of the bladder (UCB)., Patients and Methods: Of 1484 patients treated with RC/PLND for UCB from 2000 to 2010, we analysed 198 patients with clinically non-metastatic (cN0M0) muscle-invasive UCB who were found to be LN-positive at RC/PLND. As patients not receiving perioperative chemotherapy were significantly older and comorbid, we compared LN-positive patients previously treated with NAC (32 patients) to LN-positive patients treated with adjuvant chemotherapy (AC, 49 patients) using Cox proportional hazards models. A sensitivity analysis was designed to account for the additional time to RC in NAC patients., Results: The 3-year recurrence-free survival estimate for LN-positive NAC patients was 26%, compared with 60% for LN-positive AC patients. LN-positive patients treated with NAC had significantly higher risks of disease recurrence and cancer-specific mortality in univariate analyses (hazard ratio [HR] 2.86, 95% confidence interval [CI] 1.58-5.19, P = 0.001 and HR 2.50, 95% CI 1.34-4.65, P = 0.004, respectively) and multivariable analyses adjusting for pathological stage and LN density (HR 3.11, 95% CI 1.59-6.07, P = 0.001 and HR 3.05, 95% CI 1.46-6.35, P = 0.003, respectively). Sensitivity analyses similarly demonstrated worse outcomes for NAC pre-treated LN-positive patients., Conclusion: LN-positive patients previously treated with NAC have a poor prognosis, significantly worse than LN-positive patients subsequently treated with AC, and should be considered for protocols using sandwich chemotherapy approaches or novel agents. These results should be considered in the interpretation of and stratification for clinical trials., (© 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.)

Objective: To describe the pathological outcomes of patients with muscle-invasive micropapillary bladder cancer who have undergone neoadjuvant chemotherapy., Patients and Methods: A total of 82 patients with muscle-invasive micropapillary bladder cancer were treated between 1997 and 2010. After excluding those with metastatic disease, micropapillary histology only at radical cystectomy (RC), and chemo-radiation as primary treatment, 44 patients remained. All patients had ≥cT2 disease before chemotherapy/surgery. The median follow-up after RC was 28 months. Neoadjuvant chemotherapy was initiated in 29 (66%) patients and all patients underwent RC (93%) or partial cystectomy (7%)., Results: Micropapillary histology was diagnosed at first transurethral resection in 37 (84%) patients. Final RC pathology revealed pT0 in 15 (34%) patients and positive lymph nodes in 13 (31%) patients. Down-staging to pT0 occurred in 13 (45%) of those who received neoadjuvant chemotherapy compared with two (13%) of those who did not (P = 0.049). Patients with pT0 disease with micropapillary histology had higher overall survival rates (25 vs. 92%) and lower rates of bladder cancer recurrence (21 vs. 79%) at the 24-month follow-up., Conclusions: Almost half of the patients responded completely to neoadjuvant chemotherapy with a pT0 rate of 45%; therefore, patients with the micropapillary variant of urothelial carcinoma should not be excluded from consideration for neoadjuvant chemotherapy., (© 2013 BJU International.)

Unlabelled: Cigarette smoking is the leading cause of urothelial carcinoma; however, the impact of smoking on outcomes after surgery for upper tract urothelial carcinoma is unknown. One study suggests that patients with a smoking history have an increased risk of recurrence in the bladder compared with never smokers but these patients did not differ with respect to time to pelvic recurrence or distant metastasis. We subdivided smokers into current and former smokers and performed multivariate analyses that showed that smoking status was not an independent predictor of recurrence when traditional prognostic factors were taken into account. In addition, competing risks analyses showed that although current smoking did not increase the risk of recurrence, it imparted a significant risk of dying compared with former and never smoking., Objective: To evaluate the impact of smoking exposure on oncological outcomes in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU)., Materials and Methods: Patient and disease characteristics from 288 patients with UTUC treated with RNU between 1995 and 2008 were collected from a prospectively maintained database at the Memorial Sloan-Kettering Cancer Center. Disease recurrence was defined as distant metastases, or local failure in the operative site or regional nodes. Factors associated with recurrence and death were determined., Results: The prevalence of current, former and never smoking at diagnosis was 19.1%, 55.2%, and 25.7%, respectively. 71.0% of patients reported a ≥20 pack-year smoking history. With a median follow-up of 4.02 years, disease recurrence occurred in 27% (n = 79) of patients and 41% (n = 117) died during follow-up. While age at diagnosis, American Society of Anesthesiologists score, advanced stage, nodal involvement and high grade adversely affected recurrence-free survival, smoking status was not associated with risk of recurrence or death in multivariate analysis (P = 0.60). Multivariate competing risks regression showed that current smokers faced a significantly higher risk of death than never smokers (hazard ratio 3.64, 95% confidence interval 1.59-8.34)., Conclusions: While smoking status at diagnosis and cumulative smoking exposure were not associated with UTUC recurrence, our findings highlight the substantial risk of death in patients with UTUC who are active smokers. Treatment plans to promote smoking cessation are recommended for these patients., (© 2012 BJU International.)

Objective: To create a preoperative multivariable model to identify patients at risk of muscle-invasive (pT2+) upper tract urothelial carcinoma (UTUC) and/or non-organ confined (pT3+ or N+) UTUC (NOC-UTUC) who potentially could benefit from radical nephroureterectomy (RNU), neoadjuvant chemotherapy and/or an extended lymph node dissection., Patients and Methods: We retrospectively analysed data from 324 consecutive patients treated with RNU between 1995 and 2008 at a tertiary cancer centre. Patients with muscle-invasive bladder cancer were excluded, resulting in 274 patients for analysis. Logistic regression models were used to predict pT2+ and NOC-UTUC. Pre-specified predictors included local invasion (i.e. parenchymal, renal sinus fat, or periureteric) on imaging, hydronephrosis on imaging, high-grade tumours on ureteroscopy, and tumour location on ureteroscopy. Predictive accuracy was measured by the area under the curve (AUC)., Results: The median follow-up for patients without disease recurrence or death was 4.2 years. Overall, 49% of the patients had pT2+, and 30% had NOC-UTUC at the time of RNU. In the multivariable analysis, only local invasion on imaging and ureteroscopy high grade were significantly associated with pathological stage. AUC to predict pT2+ and NOC-UTUC were 0.71 and 0.70, respectively., Conclusions: We designed a preoperative prediction model for pT2+ and NOC-UTUC, based on readily available imaging and ureteroscopic grade. Further research is needed to determine whether use of this prediction model to select patients for conservative management vs RNU, neoadjuvant chemotherapy, and/or extended lymphadenectomy will improve patient outcomes., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Objective: •To evaluate the effect of preoperative cisplatin-based chemotherapy on the regional lymph nodes of patients with bladder cancer who attain pathological T0 status in the bladder after chemotherapy followed by radical cystectomy., Patients and Methods: •Patients who underwent radical cystectomy at MSKCC for urothelial carcinoma of the bladder were retrospectively reviewed. •Those patients achieving pT0 status after preoperative chemotherapy were identified and classified into two groups, those rendered pT0: (i) after receiving neoadjuvant chemotherapy and (ii) after receiving definitive chemotherapy (defined in this case as chemotherapy given for unresectable or regionally metastatic disease). •These two groups were analyzed separately for lymph node status at cystectomy and regional lymph node recurrence., Results: •Of 169 pT0 patients, 24 patients (14%) had received neoadjuvant chemotherapy, whereas 17 patients (10%) had received definitive chemotherapy for unresectable or regionally metastatic disease. •No patient rendered pT0 after neoadjuvant chemotherapy had lymph node involvement at radical cystectomy or recurrence within the regional lymph node template. •Among patients with advanced disease rendered pT0 by definitive chemotherapy, 35% had lymph node involvement at radical cystectomy or subsequent recurrence within the dissection template., Conclusions: •Patients achieving pT0 status after receiving neoadjuvant chemotherapy had no evidence of lymph node involvement at cystectomy. •Patients undergoing definitive chemotherapy for advanced disease followed by cystectomy experienced reduced rates of nodal involvement compared to the lymph node-positive rates predicted by preoperative clinical staging. However, there remains a risk of regional lymph node involvement in this group., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

While patient age and gender are important factors in the clinical decision-making for treating urothelial carcinoma of the bladder (UCB), there are no evidence-based recommendations to guide healthcare professionals. We review previous reports on the influence of age and gender on the incidence, biology, mortality and treatment of UCB. Using MEDLINE, we searched for previous reports published between January 1966 and July 2009. While men are three to four times more likely to develop UCB than women, women present with more advanced disease and have worse survival rates. The disparity among genders is proposed to be the result of a differential exposure to carcinogens (i.e. tobacco and chemicals) as well as reflecting genetic, anatomical, hormonal, societal and environmental factors. Inpatient length of stay, referral patterns for haematuria and surgical outcomes suggest that inferior quality of care for women might be an additional cause of gender inequalities. Age is the greatest single risk factor for developing UCB and dying from it once diagnosed. Elderly patients face both clinical and institutional barriers to appropriate treatment; they receive less aggressive treatment and sub-therapeutic dosing. Much evidence suggests that chronological age alone is an inadequate indicator in determining the clinical and behavioural response of older patients to UCB and its treatment. Epidemiological and mechanistic molecular studies should be encouraged to design, analyse and report gender- and age-specific associations. Improved bladder cancer awareness in the lay and medical communities, careful patient selection, treatment tailored to the needs and the physiological and physical reserve of the individual patient, and proactive postoperative care are particularly important. We must strive to develop transdisciplinary collaborative efforts to provide tailored gender- and age-specific care for patients with UCB.

Unlabelled: The importance of markers in urological cancer is well recognised and many attempts are being made to find one which will be of prognostic significance. Authors from New York found that low expression of p27Kip1 in patients with bladder cancer was a significant predictor of pelvic recurrence, progression to metastasis and death. Authors from Switzerland examined patients with a primary solitary distal ureteric TCC; they found that distal ureteric resection in such patients is feasible, and that the long-term oncological outcome appears to be comparable to more radical treatment of this condition., Objective: To define the prognostic significance of p27(Kip1) expression in bladder cancer for overall, disease-specific, metastasis-free and pelvic recurrence-free survival, and to identify clinical and pathological correlates of p27(Kip1) immunophenotypes., Patients and Methods: Tumour samples from 128 evaluable patients with bladder cancer were assessed by immunohistochemistry for p27(Kip1) and E2F-1 expression. Immunoreactivity of p27(Kip1) was correlated with clinicopathological variables, E2F-1 immunoreactivity, and outcome. Multivariate analysis was used to assess predictors of outcome. The median follow-up was 30.9 months overall and 105.7 months in the 32 patients alive at the last follow-up., Results: The fraction of tumour cells with p27(Kip1) nuclear immunoreactivity was <5% in 15, 5-25% in 30, 25-50% in 19, 50-75% in 51, and > or = 75% in 13 patients. High-grade tumours and those with lower E2F-1 nuclear reactivity had a lower mean percentage p27(Kip1) reactivity (P = 0.047 and 0.011, respectively). On multivariate analysis, the percentage p27(Kip1) reactivity was a significant independent predictor of pelvic recurrence (P = 0.017), progression to metastases (P = 0.046), death from disease (P = 0.008), and death from any cause (P = 0.017), with a low expression portending a worse prognosis. Suspicion of vascular invasion was a significant independent predictor of progression to metastases (P = 0.002), death from disease, and death from any cause (both P < 0.001). Lymph node involvement was a significant independent predictor of progression to metastases (P = 0.006)., Conclusions: Low expression of p27(Kip1) was a significant independent predictor of pelvic recurrence, progression to metastasis, death from disease and death from any cause, in patients with bladder cancer.