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Purpose: To investigate the association of patients' sex with recurrence and disease progression in patients treated with intravesical bacillus Calmette-Guérin (BCG) for T1G3/HG urinary bladder cancer (UBC)., Materials and Methods: We analyzed the data of 2635 patients treated with adjuvant intravesical BCG for T1 UBC between 1984 and 2019. We accounted for missing data using multiple imputations and adjusted for covariate imbalance between males and females using inverse probability weighting (IPW). Crude and IPW-adjusted Cox regression analyses were used to estimate the hazard ratios (HR) with their 95% confidence intervals (CI) for the association of patients' sex with HG-recurrence and disease progression., Results: A total of 2170 (82%) males and 465 (18%) females were available for analysis. Overall, 1090 (50%) males and 244 (52%) females experienced recurrence, and 391 (18%) males and 104 (22%) females experienced disease progression. On IPW-adjusted Cox regression analyses, female sex was associated with disease progression (HR 1.25, 95%CI 1.01-1.56, p = 0.04) but not with recurrence (HR 1.06, 95%CI 0.92-1.22, p = 0.41). A total of 1056 patients were treated with adequate BCG. In these patients, on IPW-adjusted Cox regression analyses, patients' sex was not associated with recurrence (HR 0.99, 95%CI 0.80-1.24, p = 0.96), HG-recurrence (HR 1.00, 95%CI 0.78-1.29, p = 0.99) or disease progression (HR 1.12, 95%CI 0.78-1.60, p = 0.55)., Conclusion: Our analysis generates the hypothesis of a differential response to BCG between males and females if not adequately treated. Further studies should focus on sex-based differences in innate and adaptive immune system and their association with BCG response., (© 2021. The Author(s).) more...

Purpose: The goals of transurethral resection of a bladder tumor (TUR) are to completely resect the lesions and to make a correct diagnosis to adequately stage and treat the patient. Persistent disease after TUR is not uncommon and is why re-TUR is recommended in T1G3 patients. When there is T1 tumor in the re-TUR specimen, very high risks of progression (82%) have been reported. We analyze the risks of recurrence, progression to muscle-invasive disease and cancer-specific mortality (CSM) according to tumor stage at re-TUR in T1G3 patients treated with BCG., Methods: In our retrospective cohort of 2451 T1G3 patients, 934 patients (38.1%) underwent re-TUR. 667 patients had residual disease (71.4%): Ta in 378 (40.5%), T1 in 289 (30.9%) patients. Times to recurrence, progression and CSM in the three groups were estimated using cumulative incidence functions and compared using the Cox regression model., Results: During a median follow-up of 5.2 years, 512 patients recurred. The recurrence rate was significantly higher in patients with a T1 at re-TUR (P < 0.001). Progression rates differed according to the pathology at re-TUR, 25.3% in T1, 14.6% in Ta and 14.2% in case of no residual tumor (P < 0.001). Similar trends were seen in both patients with and without muscle in the original TUR specimen., Conclusions: Patients with T1G3 tumors and no residual disease or Ta at re-TUR have better recurrence, progression and CSM rates than previously reported, with a CSM rate of 13.1 and a 25.3% progression rate in re-TUR T1 disease. more...

Purpose: To evaluate the impact of timing of blood transfusion in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU)., Methods: Outcomes of consecutive patients with UTUC treated with RNU were analyzed. Clinicopathologic factors were compared using Fisher's exact test or the Wilcoxon rank-sum test between patients who received any transfusion and no transfusion, and between patients receiving intraoperative transfusion only and patients receiving no transfusion. Cancer-specific and overall survival were estimated and multivariable analyses were performed to assess the impact of timing of transfusion on clinical outcomes., Results: Among 402 patients included in this study, 71 (17.6%) patients received a transfusion at any point and 27 (6.7%) patients received an intraoperative blood transfusion. Transfusion at any time, patient comorbidity, high grade, advanced stage, positive surgical margins, low preoperative hemoglobin, longer operative duration, and increased blood loss were significantly associated with cancer-specific survival (DSS) on univariable analysis (HR 1.85, 95% CI 1.20-2.85, p < 0.005). In the multivariable analysis, transfusion at any point was not a prognostic factor (HR 1.00, 95% CI 0.60-1.68, p = 0.99). When examining intraoperatively transfusion only, transfusion was significantly associated with DSS (HR 1.91, 95% CI 1.01-3.59, p = 0.045) but no longer significant in multivariable analysis (HR 0.72, 95% CI 0.32-1.65, p = 0.440)., Conclusions: Our study indicates that the administration of blood transfusion either intraoperatively or postoperatively is not associated with clinical or oncological outcomes in patients with upper tract urothelial carcinoma when adjusted for other factors in multivariable analysis. Further study is required. more...

Purpose: To examine the mode of relapse detection and subsequent treatment after partial or radical nephrectomy in patients with low-risk (pT1, N0, Nx) kidney cancer., Methods: Retrospective study on 1404 patients treated with partial or radical nephrectomy for low-risk kidney cancer from the years 2000-2012. Scans for chest imaging (X-ray or CT) and abdominal imaging (CT, MRI, or ultrasound) are tabulated. For those patients with relapse, the site, mode of detection, and symptoms were recorded., Results: Twenty-one patients relapsed with a median follow-up of 4.1 years for patients who did not relapse. In 17 (81 %) patients, relapse was detected by imaging alone, while 4 (19 %) patients presented with symptoms. Of the patients who relapsed by imaging, 13 (76 %) were treated immediately, while 4 (24 %) continued observation. During the first 3 years of follow-up, 5762 imaging studies were performed to detect 8 relapses, with 6 patients receiving immediate treatment. The median number of imaging studies per patient per year for the first 3 years was 1.7 (interquartile range 1.0, 2.3) including 30 % CT, 3 % MRI, 36 % X-ray, and 31 % ultrasounds., Conclusion: We found a low yield of surveillance imaging in the first 3 years for pT1 kidney cancer. Nearly 1000 imaging studies were performed to detect one relapse that required treatment. Further studies are needed to evaluate the clinical impact of imaging surveillance according to recent guidelines. more...

Purpose: We analyzed radiographic parameters describing anatomic features of renal tumors to identify preoperative characteristics that could help predict long-term decline in renal function following partial nephrectomy., Methods: We retrospectively reviewed the records of 194 consecutive patients who underwent partial nephrectomy from January 2006 to March 2009 and analyzed a cohort of 53 patients for whom complete clinical, radiographic, and operative information was available. Computed tomography images were reviewed by a single radiologist. Radiographic criteria for describing renal tumor size and location included diameter, volume, endophytic properties, proximity to collecting system, anterior/posterior location, location relative to polar lines, and R.E.N.A.L. nephrometry score. Postoperative estimated glomerular filtration rate was calculated using the MDRD study group equation with serum creatinine at last follow-up., Results: The median preoperative and postoperative GFR values were 75 (IQR 65-97) and 66 (IQR 55-84) mL/min/1.73 m(2), respectively. At a median follow-up of 38 months, the median percentage decrease in GFR was 12%. On univariate analyses, tumor diameter (P = 0.002), tumor volume (P < 0.0001), nearness of tumor to collecting system (P = 0.017), and location relative to polar lines (P = 0.017) were associated with percentage decrease in GFR. Furthermore, higher R.E.N.A.L. nephrometry score was also associated with poorer renal functional outcomes following partial nephrectomy (P = 0.019)., Conclusions: Anatomic features of renal tumors defined by preoperative radiographic characteristics correlate with the degree of renal functional decline after partial nephrectomy. Identification of these parameters may assist in patient counseling and clinical decision making following partial nephrectomy. Validation in larger prospective studies is necessary. more...

Objectives: The primary endpoint in trials of perioperative systemic therapy for urothelial carcinoma is 5-year overall survival (OS). A shorter-term endpoint could significantly speed the translation of advances into practice. We hypothesized that disease-free survival (DFS) could be a surrogate endpoint for OS in upper tract urothelial carcinoma (UTUC) patients treated with radical nephroureterectomy (RNU)., Patients and Methods: The study included 2,492 patients treated with RNU with curative intent for UTUC., Results: 2/3-year DFS estimates were 78/73 %, and the 5-year OS estimate was 64 %. The overall agreements between 2- and 3-year DFS with 5-year OS were 85 and 87 %, respectively. Agreements were similar when analyzed in subgroups stratified by pathological stages, lymph node status, and adjuvant chemotherapy. The kappa statistic was 0.59 (95 % CI 0.55-0.63) for 2-year DFS/5-year OS and 0.64 (95 % CI 0.61-0.68) for 3-year DFS/5-year OS, indicating moderate reliability. The hazard ratio for DFS as a time-dependent variable for predicting OS was 11.5 (95 % CI 9.1-14.4), indicating a strong relationship between DFS and OS., Conclusions: In patients treated with RNU for UTUC, DFS and OS are highly correlated, regardless of tumor stage and adjuvant chemotherapy. While significant differences in DFS, assessed at 2 and 3 years, are highly likely to persist in OS at 5 years, marginal DFS advantages may not translate into OS benefit. External validation is necessary before accepting DFS as an appropriate surrogate endpoint for clinical trials investigating advanced UTUC patients. more...

Purpose: Small studies have suggested that older patients have worse outcomes following radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB). We evaluated the association of patient age with clinical outcomes in a large multi-institutional RC series., Methods: Data were collected from 4,429 patients treated with RC and lymphadenectomy for UCB without neoadjuvant chemotherapy. Age at RC was analyzed both as a continuous and categorical variable., Results: Higher age at RC, analyzed as a continuous or categorical variable, was associated with advanced pathologic stage (P < 0.001), higher tumor grade (P = 0.045), presence of lymphovascular invasion (P = 0.018), and positive soft-tissue surgical margin status (P = 0.004). Elderly patients were less likely to receive postoperative chemotherapy (P < 0.001). In multivariable analyses, higher age was associated with disease recurrence, cancer-specific, and overall mortality (P < 0.001). Patients ≥ 80 years had a significantly greater risk of cancer-specific mortality than patients <50 years (HR 1.763, P < 0.001). Age minimally improved the accuracy of a base model that included standard pathologic features for prediction of disease recurrence (+0.2-0.3%) and cancer-specific survival (+0.3%). Conversely, age improved the predictive accuracy for overall survival by a sizeable margin (+4.2-4.5%)., Conclusions: This large external validation study confirms that advanced patient age is minimally but significantly associated with worse prognosis after RC. Nevertheless, a large proportion of elderly patients benefitted from RC with curative intent. We need to improve our understanding of the reasons for the worse UCB outcomes in this growing segment of the population and to develop strategies to improve cancer care in the elderly. more...

Purpose: Bladder cancer is frequently diagnosed during a workup for hematuria. However, most patients with microscopic hematuria and many with gross hematuria are not appropriately referred to urologists. We hypothesized that in patients presenting with asymptomatic hematuria the risk of having bladder cancer can be predicted with high accuracy. Toward this end, we analyzed risk factors in patients with asymptomatic hematuria and developed a nomogram for the prediction of bladder cancer presence., Methods: Data from 1,182 consecutive subjects without a history of bladder cancer undergoing initial evaluation for asymptomatic hematuria were collected at three centers. Clinical risk factors including age, gender, smoking status, and degree of hematuria were recorded. All subjects underwent standard workup including voided cytology, upper tract imaging, and cystourethroscopy. Factors associated with the presence of bladder cancer were evaluated by univariable and multivariable logistic regression analyses. The multivariable analysis was used to construct a nomogram. Internal validation was performed using 200 bootstrap samples., Results: Of the 1,182 subjects who presented with asymptomatic hematuria, 245 (20.7 %) had bladder cancer. Increasing age (OR = 1.03, p < 0.0001), smoking history (OR = 3.72, p < 0.0001), gross hematuria (OR = 1.71, p = 0.002), and positive cytology (OR = 14.71, p < 0.0001) were independent predictors of bladder cancer presence. The multivariable model achieved 83.1 % accuracy for predicting the presence of bladder cancer., Conclusions: Bladder cancer presence can be predicted with high accuracy in patients who present with asymptomatic hematuria. We developed a nomogram to help optimize referral patterns (i.e., timing and prioritization) of patients with asymptomatic hematuria. more...

Introduction: While patient gender is an important factor in the clinical decision-making for the management of bladder cancer, there are minimal evidence-based recommendations to guide health care professionals. Recent epidemiologic and translational research has shed some light on the complex relationship between gender and bladder cancer. Our aim was to review the literature on the effect of gender on bladder cancer incidence, biology, mortality, and treatment., Methods: Using MEDLINE, we performed a search of the literature between January 1975 and April 2011., Results: Although men are nearly 3-4 times more likely to develop bladder cancer than women, women present with more advanced disease and have worse survival. Recently, a number of population-based and multicenter collaborative studies have shown that female gender is associated with a significantly higher rate of cancer-specific recurrence and mortality after radical cystectomy. The disparity between genders is proposed to be the result of a differences exposure to carcinogens (i.e., tobacco and chemicals) as well as reflective of genetic, anatomic, hormonal, societal, and environmental factors. Explanations for the differential behavior of bladder cancer between genders include sex steroids and their receptors as well as inferior quality of care for women (inpatient length of stay, referral patterns, and surgical outcomes)., Conclusions: It is imperative that health care practitioners and researchers from disparate disciplines collectively focus efforts to appropriately develop gender-specific evidence-based guidelines for bladder cancer patients. We must strive to develop multidisciplinary collaborative efforts to provide tailored gender-specific care for bladder cancer patients. more...

Purpose: Higher chronological age has been suggested to confer worse prognosis in patients with upper tract urothelial carcinoma (UTUC). The aim of the current study was to test this hypothesis in a large multicenter external validation cohort of patients treated with radical nephroureterectomy (RNU) while controlling for patient performance status., Materials and Methods: We retrospectively reviewed the data from 1,169 patients treated with RNU for UTUC. Age at RNU was analyzed both as a continuous and categorical variable (<50 years, n = 66; 50-59.9 years, n = 185; 60-69.9 years, n = 367; 70-79.9 years, n = 419; ≥80 years, n = 132). Median follow-up was 37 months., Results: Actuarial recurrence-free, cancer-specific, and all-cause survival estimates at 5 years after RNU were 69, 73, and 61%, respectively. Advanced age was associated with female gender, higher ECOG status, higher ASA score, and a lower probability of receiving adjuvant chemotherapy (all P values ≤ 0.02). In multivariable analyses, advanced age was associated with decreased recurrence-free (P = 0.021), cancer-specific (P = 0.002), and all-cause survival (P < 0.001) after controlling for the effects of gender, tumor location, number of lymph nodes removed, tumor grade, stage, architecture, necrosis, and lymphovascular invasion. After addition of ECOG status, age remained an independent predictor of only all-cause mortality (P > 0.001)., Conclusions: We confirmed that advanced patient age at the time of RNU is associated with worse clinical outcomes after surgery. However, ECOG performance status abrogated the association. Furthermore, a large proportion of elderly patients were cured with RNU. This suggests that chronological age alone is an inadequate indicator criterion to predict response of older UTUC patients to RNU. more...