title: The effect of concomitant carcinoma in situ on neoadjuvant chemotherapy for urothelial cell carcinoma of the bladder: inferior pathological outcomes but no effect on survival.
abstract: OBJECTIVE
  It is generally believed that carcinoma in situ is refractory to chemotherapy but specific data are lacking to validate this. We evaluated the effect of concomitant clinical carcinoma in situ on cancer specific outcomes after neoadjuvant chemotherapy for muscle invasive bladder cancer.
  
  
  METHODS
  We performed an institutional review board approved, multi-institutional, retrospective review of the records of patients treated with neoadjuvant chemotherapy followed by radical cystectomy for muscle invasive bladder cancer from 2008 to 2012. Pretreatment clinical variables were collected and patients were stratified by the presence of clinical carcinoma in situ on precystectomy transurethral bladder tumor resection specimens. Pathological outcomes, including the complete response rate (pT0N0Mx) after neoadjuvant chemotherapy, were compared between the 2 groups. Recurrence-free, cancer specific and overall survival was analyzed.
  
  
  RESULTS
  Of 189 patients who met study criteria 56 (29.6%) had concomitant carcinoma in situ. The condition was associated with a significant decrease in the pathological complete response rate (10.7% vs 26.3%, p = 0.02). This difference was significant on univariate and multivariable analysis (OR 0.34, 95% CI 0.13-0.85, p = 0.02 and OR 0.31, 95% CI 0.12-0.81, p = 0.02, respectively). Despite the decreased complete response rate clinical carcinoma in situ was not associated with a difference in recurrence-free, cancer specific or overall survival. Additionally, when down-staging to pathological carcinoma in situ only disease was considered a complete response, there was no significant change in recurrence-free, cancer specific or overall survival.
  
  
  CONCLUSIONS
  Concomitant carcinoma in situ is associated with a decrease in the complete response rate but this does not appear to impact the survival outcome.
authors.affiliation: University of Kansas Medical Center, Kansas City, Kansas.
authors.forename: William P
authors.initials: WP
authors.lastname: Parker
authors.affiliation: M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Phillip L
authors.initials: PL
authors.lastname: Ho
authors.affiliation: M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Melquist
authors.affiliation: University of Kansas Medical Center, Kansas City, Kansas.
authors.forename: Katie
authors.initials: K
authors.lastname: Scott
authors.affiliation: University of Kansas Medical Center, Kansas City, Kansas.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Holzbeierlein
authors.affiliation: Kansas City Veterans Affairs Medical Center, Kansas City, Kansas.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Lopez-Corona
authors.affiliation: M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Ashish M
authors.initials: AM
authors.lastname: Kamat
authors.affiliation: University of Kansas Medical Center, Kansas City, Kansas. Electronic address: elee@kumc.edu.
authors.forename: Eugene K
authors.initials: EK
authors.lastname: Lee
mesh_terms: D002278:Carcinoma in Situ / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D015653:Cystectomy; D006801:Humans; D020360:Neoadjuvant Therapy; D009378:Neoplasms, Multiple Primary / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D012074:Remission Induction; D012189:Retrospective Studies; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery
keywords: carcinoma in situ; drug therapy; neoadjuvant therapy; urinary bladder; urothelium