Gen Li

Systematic Review and Meta-Analysis on the Efficacy of Chemotherapy with Transurethral Resection of Bladder Tumors as Definitive Therapy for Muscle Invasive Bladder Cancer

Background: Bladder-sparing treatment of muscle invasive bladder cancer (MIBC) with systemic chemotherapy plus transurethral resection of bladder tumors (TURBT) is increasingly seen in the literature –both in case series and subanalyses of patients who opt out of or are unfit for radical cystectomy (RC). Survival outcomes among these patients are often impressive, but these are typically small retrospective studies from single institutions and therefore of limited clinical value. Objectives: Our aim is to summarize the literature regarding definitive treatment of MIBC with systemic chemotherapy plus TURBT and provide a meta-analysis of survival outcomes for patients who received this treatment. Methods: A systematic literature search was performed consistent with the Prisma statement to identify publications reporting the outcomes of patients treated with TURBT and systemic chemotherapy as definitive treatment for locally confined MIBC. Identified studies were screened in a two-stage process: first by title and abstract; then by full-text reading. 18 publications (518 patients) were included in the qualitative systematic review and 10 publications (266 patients) were included in the meta-analysis. The primary objective was overall survival (OS). Results: Overall survival ranged from 20% to 87.5% across studies at median follow-up ranging 4 to 120 months. 5-year survival rate for all patients included in the meta-analysis was estimated to be 72% [95% CI: 64%, 82%]. Conclusions: Definitive treatment with systemic chemotherapy plus TURBT can lead to favorable survival outcomes in select patients. Further study to improve patient selection for this method of treatment is needed.

Discordance between Ureteroscopic Biopsy and Final Pathology for Upper Tract Urothelial Carcinoma

Purpose: We evaluated the discordance between ureteroscopic biopsy and surgical pathology findings for grading and staging upper tract urothelial carcinoma. We also sought to establish preoperative predictors of aggressive tumors. Materials and Methods: We retrospectively reviewed the records of 314 patients who underwent ureteroscopic biopsy followed by surgical management of upper tract urothelial carcinoma from 2000 to 2016 at a total of 3 institutions. Our primary outcomes were muscle invasive (pT2 or greater) disease at surgical pathology and upgrading of clinical low grade tumors to pathological high grade. Results: At biopsy 61% of the patients had clinical high grade tumors and 21% had subepithelial connective tissue invasion (cT1+). On final pathology 79% of the patients had pathological high grade tumors and 45% had stage pT2 or greater. On multivariate analysis advanced patient age, clinical high grade and cT1+ were independently associated with pT2 or greater. The combined presence of clinical high grade and cT1+ had 86% positive predictive value for muscle invasion while the combined absence of clinical high grade and cT1+ had 80% negative predictive value. The likelihood of missing invasion on biopsy in patients with muscle invasive disease was increased when biopsy fragments were limited to 1 mm or less. Of clinical low grade cases on biopsy 51% were upgraded at surgery. The presence of positive urine cytology was associated with an increased risk of upgrading but this was not statistically significant. Conclusions: Clinical high grade, cT1+ on biopsy and advanced patient age are independent risk factors for muscle invasive upper tract urothelial carcinoma. There is a significant risk of upgrading in patients with clinical low grade tumors on biopsy, especially when urine cytology is positive. The predictive value of biopsy can likely be improved by more extensive ureteroscopic sampling.

Conservative Management Following Complete Clinical Response to Neoadjuvant Chemotherapy of Muscle Invasive Bladder Cancer: Contemporary Outcomes of a Multi-Institutional Cohort Study

Purpose We report the outcomes in patients with muscle invasive bladder cancer from 2 institutions who experienced a clinically complete response to neoadjuvant platinum based chemotherapy and elected active surveillance. It was unknown whether conservative treatment could be safely implemented in these patients. Materials and Methods We retrospectively reviewed the records of patients with muscle invasive bladder cancer at our institutions who elected surveillance following a clinically complete response to transurethral resection of bladder tumors and neoadjuvant chemotherapy from 2001 to 2017. A clinically complete response was defined as absent tumor on post‐chemotherapy transurethral resection of bladder tumor, negative cytology and normal cross‐sectional imaging. Results In the 148 patients followed a median of 55 months (range 5 to 145) the 5‐year disease specific, overall, cystectomy‐free and recurrence‐free survival rates were 90%, 86%, 76% and 64%, respectively. Of the patients 71 (48%) experienced recurrence in the bladder, including 16 (11%) with muscle invasive disease and 55 (37%) with noninvasive disease. Salvage radical cystectomy prevented cancer specific death in 9 of 12 patients (75%) who underwent cystectomy after muscle invasive relapse and in 13 of 14 (93%) after noninvasive relapse. Conclusions We observed high rates of overall and disease specific survival with bladder preservation in patients who achieved a clinically complete response to neoadjuvant chemotherapy. These outcomes support the safety of active surveillance in carefully selected, closely monitored patients with muscle invasive bladder cancer. Future studies should aim to improve patient selection by identifying biomarkers predicting invasive relapse and developing novel imaging methods of early detection.