Objective: To assess the prevalence of frailty, a status of vulnerability to stressors leading to adverse health events, in bladder cancer patients undergoing radical cystectomy (RC), and test the impact of frailty measurements on postoperative adverse outcomes. Methods: A systematic review of English-language articles published up to April 2020 was performed. Electronic databases were searched to quantify the frailty prevalence in RC patients and assess the predictive ability of frailty indexes on RC-related outcomes as postoperative complications, early mortality, hospitalization length (LOS), costs, discharge dispositions, readmission rate. Results: Eleven studies were selected. Patients’ frailty was identified by Johns Hopkins indicator (JHI) in two studies, 11-item modified Frailty Index (mFI) in four, 5-item simplified FI (sFI) in three, 15-point mFI in one, Fried Frailty Criteria in one. Considering all the frailty measurements applied, 8% and 31% of patients were frail or pre-frail, respectively. Frail (43%) and pre-frail patients (35%) were more at risk of major complications compared to non-frail (27%) using sFI; with JHI the percentages of frail and non-frail were 53% versus 19%. According to JHI and mFI frailty was related to longer LOS and higher costs. JHI identified that 3% of frail patients experience in-hospital mortality versus 1.5% of non-frail. Finally, using sFI, frail (28%), and pre-frail (19%) were more likely to be discharged non-home compared to non-frail patients (8%) and had a higher risk of 30-day mortality (4% and 2% versus 1%). Conclusions: Almost half of RC patients were frail or pre-frail, conditions significantly related to an increased risk of postoperative adverse events with higher rates of major complications and early mortality. The most-used frailty index was mFI, while JHI and sFI resulted the most reliable to predict early postoperative RC-related adverse outcomes and should be routinely included in clinical practice after better standardization throughout prospective comparative studies. Abbreviations: ACG: Adjusted Clinical Groups; ACS: American College Surgeons; AUC: area under the curve; BCa: bladder cancer; CCI: Charlson Comorbidity Index; CSHA-FI: Canadian Study of Health and Aging Frailty Index; CCS: Clavien-Dindo Classification Score; ERAS: Enhanced Recovery After Surgery; FFC: Fried Frailty Criteria; (e)(m)(s)FI: (extended) (modified) (simplified) Frailty Index; ICU: intensive care unit; IQR: interquartile range; (p)LOS: (prolonged) length of hospital stay; NSQIP: National Surgical Quality Improvement Program; OR: odds ratio; (O)PN: (open) partial nephrectomy; PRISMA: Preferred Reporting Items for Systematic reviews and Meta-Analyses; (O)(RA)RC: (open)(robot-assisted) radical cystectomy; (O)RN: (open) radical nephrectomy; ROC: receiver operating characteristic; RNU: radical nephroureterectomy; (R)RP: (retropubic) radical prostatectomy; RR: relative risk; THCs: total hospital charges; nephrectomy; UD: urinary diversion

Background: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) with pelvic lymph-node dissection is the standard treatment for cT2-4a cN0 cM0 muscle-invasive bladder cancer (MIBC). Despite the significant improvement of primary-tumor downstaging with NAC, up to 50% of patients are eventually found to have advanced residual disease (pT3–T4 and/or histopathologically confirmed nodal metastases (pN+)) at RC. Currently, there is no established standard of care in such cases. The aim of this systematic review and meta-analysis was to assess differences in survival rates between patients with pT3–T4 and/or pN+ MIBC who received NAC and surgery followed by adjuvant chemotherapy (AC), and patients without AC. Materials and Methods: A systematic search was conducted in accordance with the PRISMA statement using the Medline, Embase, and Cochrane Library databases. The last search was performed on 12 November 2020. The primary end point was overall survival (OS) and the secondary end point was disease-specific survival (DSS). Results: We identified 2124 articles, of which 6 were selected for qualitative and quantitative analyses. Of a total of 3096 participants in the included articles, 2355 (76.1%) were in the surveillance group and 741 (23.9%) received AC. The use of AC was associated with significantly better OS (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.75–0.94; p = 0.002) and DSS (HR 0.56, 95% CI 0.32–0.99; p = 0.05). Contrary to the main analysis, in the subgroup analysis including only patients with pN+, AC was not significantly associated with better OS compared to the surveillance group (HR 0.89, 95% CI 0.58–1.35; p = 0.58). Conclusions: The administration of AC in patients with MIBC and pT3–T4 residual disease after NAC might have a positive impact on OS and DSS. However, this may not apply to N+ patients.