UROLOGICAL ONCOLOGY

An interval longer than 12 weeks between the diagnosis of muscle invasion and cystectomy is associated with worse outcome in bladder carcinoma
Sanchez-Ortiz RF, Huang WC, Mick R, Van Arsdalen KN, Wein AJ, Malkowicz SB
Division of Urology, Department of Surgery, University of Pennsylvania Medical Center, Philadelphia, PA, USA
J Urol. 2003; 169:110-5

• Purpose: The standard of care for muscle invasive transitional cell carcinoma of the bladder is radical cystectomy. Definitive therapy may often be delayed for various reasons. We assessed whether pathological stage and survival correlated with the length of time between diagnosis of muscle invasion and cystectomy.
• Materials and Methods: The records of 290 consecutive patients who underwent radical cystectomy between February 1987 and July 2000 were reviewed. Of 265 (91.4%) cystectomies performed for transitional cell carcinoma data were available for 247 (85.2%) and 189 (65.2%) patients were identified who underwent surgery for muscle invasive disease (T2 or greater). The interval between diagnosis of muscle invasion and cystectomy was calculated for each patient. Patients were divided into groups based on time to surgery as group 1 - less than 4 weeks, 2 - 4 to 6 weeks, 3 - 7 to 9 weeks, 4 - 10 to 12 weeks, 5 - 13 to 16 weeks, and 6 - greater than 16 weeks. Exploratory univariate and multivariate analyses were performed to test the association of time lag with clinical features and postoperative survival.
• Results: Mean patient age was 66 years (range 37 to 84) and overall 3-year Kaplan-Meier estimated survival was 59.1% +/- 4% (median follow-up 36 months). For all patients mean interval from diagnosis to cystectomy was 7.9 weeks (range 1 to 40). Extravesical disease (P3a or greater) or positive nodes were identified in 84% (16 of 19) of patients when the delay was longer than 12 weeks, compared with 48.2% (82 of 170) in those with a time lag of 12 weeks or less (p < 0.01). Similarly 3-year estimated survival was lower (34.9% +/- 13.5%) for patients with a surgery delay longer than 12 weeks compared to those with a shorter interval 62.1% +/- 4.5% (hazards ratio 2.51, 95% CI 1.30-4.83, p = 0.006). When adjusted for nodal status, and clinical and pathological stages the interval was still statistically significant (adjusted hazards ratio 1.93, 95% CI 0.99-3.76, p = 0.05).
• Conclusions: In patients, undergoing radical cystectomy a delay in surgery of greater than 12 weeks was associated with advanced pathological stage and decreased survival. Although this relationship persisted after adjusting for nodal status, and clinical and pathological stages, the presence of lymph node metastasis remained the strongest predictor of patient outcome.
  
  
• Editorial Comment
  The authors analyze their cystectomy cases in terms of the interval between diagnosis of muscle invasion for bladder cancer and cystectomy. A total of 189 patients were identified to fulfilled the criterion. The mean interval from diagnosis to cystectomy was 7.9 weeks. The overall 3-years estimated survival was 59.1%. However, extravesical disease was identified in 84% when the delay was longer than 12 weeks, in contrast to 48,2% in those with a time lag of 12 weeks or less (p < 0,01). Consequently, Kaplan-Meier survival curves show clearly distinct differences between these 2 groups, reflecting the biology of extravesical disease.
  This data supports the notion that too long a delay between diagnosis and therapy of invasive bladder cancer will result in impaired outcome for the patient. However, the 12 weeks limit is artificial, and does not reflect clinical reality. It remains to state that patients should be advocated not to wait too long to seek definitive curative treatment.

Dr. Andreas Böhle
Professor and Vice-Director of Urology
Medical University of Luebeck
Luebeck, Germany