title: Timing cystectomy and perioperative chemotherapy in the treatment of muscle invasive bladder cancer.
abstract: BACKGROUND
  The ability of cystectomy to cure patients with muscle-invasive transitional carcinoma of the bladder (TCC) is diminished by the presence of occult micrometatases. Chemotherapy contributes to cure to the extent that it may eradicate these micrometastases. In the absence of methods to preoperatively stage TCC precisely or assess tumor biology, we review the current literature regarding the timing of cystectomy and use of perioperative chemotherapy. Based on this data, we suggest optimal and feasible strategies for treating TCC in a resource-constrained environment.
  
  
  METHODS
  Systematic reviews of TCC were sought using electronic databases to obtain optimal information about: 1) the relationship between TNM stage and survival, 2) the effect of surgical waiting times on tumor stage and survival outcomes, 3) the benefits of neoadjuvant and adjuvant chemotherapy, and 4) the patients who benefit most from perioperative chemotherapy.
  
  
  RESULTS
  Prospective data from the largest contemporary series of patients treated with cystectomy confirmed long-term survival in patients with extravesical and/or lymph node disease of 25%-47% at 5 years and 17%-27% at 10 years. Lymph node involvement was more common in patients with extravesical tumors. Retrospective studies of the effect of delay to cystectomy on outcomes showed higher tumor stage and reduced survival with delay of cystectomy beyond 12 weeks. Two individual patient data meta-analyses, including all currently available randomized controlled trials (RCTs), comparing neoadjuvant and adjuvant chemotherapy to local therapy alone confirmed that overall survival is modestly improved by cisplatin-based combination neoadjuvant chemotherapy. None of these RCTs showed a detrimental effect of delaying cystectomy for this treatment. Tumor status at cystectomy appears to correlate with overall survival.
  
  
  CONCLUSIONS
  We propose immediate use of neoadjuvant chemotherapy in patients suspected of having extravesical TCC. As most have micrometatastases, immediate surgery is less critical. For patients suspected of having organ-confined TCC, immediate cystectomy is recommended with adjuvant chemotherapy recommendations based on pathological staging. If surgery within 12 weeks is not possible for these patients, neoadjuvant chemotherapy with monitoring of response can be used. Improved preoperative staging and understanding of tumor biology are required to optimize the multimodality treatment of TCC.
authors.affiliation: Department of Surgery, University of Western Ontario, London Health Sciences Centre, London, Ontario, Canada.
authors.forename: Jonathan I
authors.initials: JI
authors.lastname: Izawa
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Chin
authors.forename: Eric
authors.initials: E
authors.lastname: Winquist
mesh_terms: D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000401:mortality* / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D015653:Cystectomy; D006801:Humans; D008207:Lymphatic Metastasis; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000628:therapy*