Long-term outcomes of bladder-sparing therapy vs radical cystectomy in BCG-unresponsive non-muscle-invasive bladder cancer.

OBJECTIVE: To quantify the oncological risks of bladder-sparing therapy (BST) in patients with Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) compared to upfront radical cystectomy (RC). PATIENTS AND METHODS: Pre-specified data elements were collected from retrospective cohorts of patients with BCG-unresponsive NMIBC from 10 international sites. After Institutional Review Board approval, patients were included if they had BCG-unresponsive NMIBC meeting United States Food and Drug Administration criteria. Oncological outcomes were collected following upfront RC or BST. BST regimens included re-resection or surveillance only, repeat BCG, intravesical chemotherapy, systemic immunotherapy, and clinical trials. RESULTS: Among 578 patients, 28% underwent upfront RC and 72% received BST. The median (interquartile range) follow-up was 50 (20-69) months. There were no statistically significant differences in metastasis-free survival, cancer-specific survival, or overall survival between treatment groups. In the BST group, high-grade recurrence rates were 37% and 52% at 12 and 24 months and progression to MIBC was observed in 7% and 13% at 12 and 24 months, respectively. RC was performed in 31.7% in the BST group and nodal disease was found in 13% compared with 4% in upfront RC (P = 0.030). CONCLUSION: In a selected cohort of patients, initial BST offers comparable survival outcomes to upfront RC in the intermediate term. Rates of recurrence and progression increase over time especially in patients treated with additional lines of BST.

Multicenter evaluation of neoadjuvant and induction gemcitabine-carboplatin versus gemcitabine-cisplatin followed by radical cystectomy for muscle-invasive bladder cancer.

PURPOSE: Cisplatin-based chemotherapy followed by radical cystectomy (RC) is recommended in patients with muscle-invasive bladder cancer (MIBC). However, up to 50% of patients are cisplatin ineligible. The aim of this study was to compare clinical outcomes after ≥ 3 cycles of preoperative gemcitabine-carboplatin (gem-carbo) versus gemcitabine-cisplatin (gem-cis). METHODS: We identified 1865 patients treated at 19 centers between 2000 and 2013. Patients were included if they had received ≥ 3 cycles of neoadjuvant (cT2-4aN0M0) or induction (cTanyN + M0) gem-carbo or gem-cis followed by RC. RESULTS: We included 747 patients treated with gem-carbo (n = 147) or gem-cis (n = 600). Patients treated with gem-carbo had a higher Charlson Comorbidity Index (p = 0.016) and more clinically node-positive disease (32% versus 20%; p = 0.013). The complete pathological response (pCR; ypT0N0) rate did not significantly differ between gem-carbo and gem-cis (20.7% versus 22.1%; p = 0.73). Chemotherapeutic regimen was not significantly associated with pCR (OR 0.99 [95%CI 0.61-1.59]; p = 0.96), overall survival (OS) (HR 1.20 [95%CI 0.85-1.67]; p = 0.31), or cancer-specific survival (CSS) (HR 1.35 [95%CI 0.93-1.96]; p = 0.11). Median OS of patients treated with gem-carbo and gem-cis was 28.6 months (95%CI 18.1-39.1) and 45.1 months (95%CI 32.7-57.6) (p = 0.18), respectively. Median CSS of patients treated with gem-carbo and gem-cis was 28.8 months (95%CI 9.8-47.8) and 71.0 months (95%CI median not reached) (p = 0.02), respectively. Subanalyses of the neoadjuvant and induction setting did not show significant survival differences. CONCLUSION: Our results show that a subset of cisplatin-ineligible patients with MIBC achieve pCR on gem-carbo and that survival outcomes seem comparable to gem-cis provided patients are able to receive ≥ 3 cycles and undergo RC.

The impact of laparoscopic technique on the rate of perineal hernia after abdominoperineal resection of the rectum.

AIM: To determine the impact of surgical technique on the incidence of perineal hernia after abdominoperineal resection (APR). METHODS: A retrospective analysis was performed on patients who underwent APR between May 2007 and March 2018 at our institution using our prospectively maintained Colorectal Cancer Database. Demographic and clinical parameters were compared between the open APR (OAPR) and laparoscopic APR (LAPR) groups using Student's t test, chi-squared, or Fisher's exact test. Putative risk factors were then analyzed using a Cox proportional hazard model with perineal hernia as the outcome. RESULTS: The study included 261 patients (191 OAPR and 70 LAPR). Intraoperative blood loss (596.0 ± 633.4 vs. 307.0 ± 307.2 mL, p < 0.001), duration of OR (249.6 ± 115.6 vs. 212.6 ± 75.1 min, p = 0.004), and length of stay (15.6 ± 18.0 vs. 10.4 ± 12.6 days, p = 0.031) were all greater for OAPR than LAPR patients, but wound complications other than hernia did not differ significantly. Perineal hernia was observed in 2.1% of OAPR and 12.9% of LAPR patients. In multivariable analysis, significant risk factors for perineal hernia were age, laparoscopic technique, and closure of the perineal wound with myocutaneous flap (HR 1.08, 11.13, and 31.51, respectively, all p < 0.05). CONCLUSIONS: LAPR, although associated with less blood loss and shorter length of hospital stay than OAPR, was a significant risk factor for perineal hernia.

The effect of cisplatin-based neoadjuvant chemotherapy on the renal function of patients undergoing radical cystectomy.

INTRODUCTION: Cisplatin-based neoadjuvant chemotherapy (NAC) is the standard of care for patients with muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy (RC). Cisplatin, however, can induce renal toxicity. Furthermore, RC is an independent risk factor for renal injury, with decreases in estimated glomerular filtration rate (eGFR) of up to 6 mL/min/1.73 m2 reported at one year postoperatively. Our objective was to evaluate the effect of cisplatin-based NAC and RC on the renal function of patients undergoing both. METHODS: We analyzed a multicenter database of patients with MIBC, all of whom received cisplatin-based NAC prior to RC. eGFR values were collected at time points T1 (before NAC), T2 (after NAC but before RC), and T3 (one year post-RC). eGFR and proportion of patients with eGFR <60 ml/min/1.73m2 (chronic kidney disease [CKD] stage ≥3) were compared between these time points. As all patients in this dataset had received NAC, we identified a retrospective cohort of patients from one institution who had undergone RC during the same time period without NAC for context. RESULTS: We identified 234 patients with available renal function data. From T1 to T3, there was a mean decline in eGFR of 17% (13 mL/min/1.73 m2) in the NAC cohort and an increase in proportion of patients with stage ≥3 CKD from 27% to 50%. The parallel cohort of patients who did not receive NAC was comprised of 236 patients. The mean baseline eGFR in this cohort was lower than in the NAC cohort (66 vs. 75 mL/min/1.73 m2). The mean eGFR decline in this non-NAC cohort from T1 to T3 was 6% (4 mL/min/1.73 m2), and the proportion of those with stage ≥3 CKD increased from 37% to 51%. CONCLUSIONS: Administration of NAC prior to RC was associated with a 17% decline in eGFR and a nearly doubled incidence of stage ≥3 CKD at one year after RC. Patients who underwent RC without NAC had a higher rate of stage ≥3 CKD at baseline but appeared to have less renal function loss at one year.

Contemporary risk factors for ureteral stricture following renal transplantation.

INTRODUCTION: Allograft ureteral strictures after renal transplantation impact graft function and increase patient morbidity. They can be challenging to treat and may require complex surgical repair. Therefore, the objective of this study was to identify contemporary risk factors for the development of post-renal transplant ureteral strictures. METHODS: A retrospective analysis was performed on all renal transplant patients at Vancouver General Hospital from 2008-2019. Demographics, clinical parameters, and outcomes were compared between patients who did and did not develop ureteral strictures. Putative risk factors for ureteral stricture were analyzed using logistic regression. RESULTS: A total of 1167 patients were included with a mean followup of 61.9±40.8 months. Ureteral strictures occurred in 25 patients (2.1%). Stricture patients had no demographic differences compared to non-stricture patients but had significantly higher rates of postoperative complications, longer hospital stays, and decreased renal function one year post-transplant (all p<0.05). On multivariable analysis, cold ischemia time >435 minutes (odds ratio [OR] 43.9, confidence interval [CI] 1.6-1238.8, p=0.027), acute rejection (OR 3.0, CI 1.1-7.4, p=0.027), and postoperative complications (OR 112.4, CI 2.4-5332.6, p=0.016) were risk factors for stricture. CONCLUSIONS: Renal transplant patients with ureteral stricture experience greater morbidity and reduced post-transplant renal function compared to non-stricture patients. Our findings support attempts to reduce cold ischemia time, acute rejection, and postoperative complications to mitigate this potential complication. Our study is limited by the low incidence of ureteral stricture resulting in a small sample of stricture patients. Future research in a larger, multicenter setting is warranted.

Variant histology in bladder cancer: diagnostic and clinical implications.

Urothelial carcinoma differentiates into variant histological subtypes in approximately 25% of cases. Since every histological variant has unique characteristics, including metastatic potential, expression of immunotherapy targets, and susceptibility to radiation or chemotherapy, every variant offers a unique diagnostic and therapeutic challenge. However, since any single variant is relatively rare, there is a risk of missed pathological diagnosis and sub-optimal clinical management. Ensuring awareness among pathologists and wide-spread familiarity with the nuances of variants among urologists is therefore essential. Additionally, variant histologies may act as an intermediate between classical clinicopathological staging of bladder cancer and evolving molecular classification. Therefore, this review aims to provide a brief overview of the diagnostic, prognostic, and therapeutic implications of each variant histologic subtype. Despite the development of standardized diagnostic criteria, the diagnosis of variant histologies continues to pose a challenge and results in significant interobserver variability. The prognosis of any single variant is poorly studied. However, squamous and glandular differentiation are thought to have little effect on prognosis while micropapillary, sarcomatoid, plasmacytoid, and small cell carcinomas are associated with a poor prognosis. Although evidence surrounding therapeutic strategies is sparse, management guidelines have been developed for variant histologies, which are often treated more aggressively than pure urothelial carcinoma. For example, the presence of variant histology warrants radical cystectomy in patients with T1 disease. Recommendations surrounding neo-adjuvant chemotherapy and radiation therapy also differ with each variant. As new treatments emerge for advanced bladder cancer, studying outcomes in each variant will become critical. Since prognosis and management hinge on the presence of variant histologies, accurate diagnosis and a thorough understanding of these variants are imperative for optimal management of urothelial carcinoma.

Sex differences in surgically correctable congenital anomalies: A systematic review.

PURPOSE: This study aims to compare the prevalence and outcomes of surgically correctable congenital anomalies between sexes. METHODS: Upon registration on PROSPERO (CRD42019120165), a librarian aided in conducting a systematic review using PRISMA guidelines. The five largest relevant studies were included for each anomaly. Cumulative prevalence differences and confidence intervals were calculated, and the Cochran-Mantel-Haenszel test was performed. RESULTS: Of 42,722 identified studies, 68 were included in our analysis. All included anomalies had greater than 1000 patients except duodenal atresia (n = 787) and intestinal duplication (n = 148). Males had a significantly higher prevalence than females in 10/14 anomalies (Hirschsprung's disease, omphalomesenteric duct, congenital diaphragmatic hernia, anorectal malformation, malrotation, esophageal atresia, congenital pulmonary airway malformation, intestinal atresia, omphalocele, and gastroschisis; p < 0.001). There was no difference in the prevalence of duodenal atresia or intestinal duplication between sexes (p = 0.88 and 0.65, respectively). Females had a significantly higher prevalence of biliary anomalies (atresia and choledochal cyst). CONCLUSION: Our study indicates that males have higher prevalence rates of most congenital anomalies. Further investigations are required to illuminate the embryology underlying this sex distribution and whether sex influences outcomes. TYPE OF STUDY: Systematic review and meta-analysis. LEVEL OF EVIDENCE: Prognostic study, level II.

The prognostic value of the neutrophil-to-lymphocyte ratio in patients with muscle-invasive bladder cancer treated with neoadjuvant chemotherapy and radical cystectomy.

INTRODUCTION: The neutrophil-to-lymphocyte ratio (NLR) is an attractive marker because it is derived from routine bloodwork. NLR has shown promise as a prognostic factor in muscle invasive bladder cancer (MIBC) but its value in patients receiving neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) is not yet established. Since NLR is related to an oncogenic environment and poor antitumor host response, we hypothesized that a high NLR would be associated with a poor response to NAC and would remain a poor prognostic indicator in patients receiving NAC. METHODS: A retrospective analysis was performed on patients with nonmetastatic MIBC (cT2-4aN0M0) who received NAC prior to RC between 2000 and 2013 at 1 of 19 centers across Europe and North America. The pre-NAC NLR was used to split patients into a low (NLR ≤ 3) and high (NLR > 3) group. Demographic and clinical parameters were compared between the groups using Student's t test, chi-squared, or Fisher's exact test. Putative risk factors for disease-specific and overall survival were analyzed using Cox regression, while predictors of response to NAC (defined as absence of MIBC in RC specimen) were investigated using logistic regression. RESULTS: Data were available for 340 patients (199 NLR ≤ 3, 141 NLR > 3). Other than age and rate of lymphovascular invasion, demographic and pretreatment characteristics did not differ significantly. More patients in the NLR > 3 group had residual MIBC after NAC than the NLR ≤ 3 group (70.8% vs. 58.3%, P = 0.049). NLR was the only significant predictor of response (odds ratio: 0.36, P = 0.003) in logistic regression. NLR was a significant risk factor for both disease-specific (hazard ratio (HR): 2.4, P = 0.006) and overall survival (HR:1.8, P = 0.02). CONCLUSION: NLR > 3 was associated with a decreased response to NAC and shorter disease-specific and overall survival. This suggests that NLR is a simple tool that can aid in MIBC risk stratification in clinical practice.