title: Gemcitabine and cisplatin neoadjuvant chemotherapy for muscle-invasive urothelial carcinoma: Predicting response and assessing outcomes.
abstract: OBJECTIVE
  To evaluate gemcitabine-cisplatin (GC) neoadjuvant cisplatin-based chemotherapy (NAC) for pathologic response (pR) and cancer-specific outcomes following radical cystectomy (RC) for muscle-invasive bladder cancer and identify clinical parameters associated with pR.
  
  
  METHODS
  We studied 150 consecutive cases of muscle-invasive bladder cancer that received GC NAC followed by open RC (2000-2013). A cohort of 121 patients treated by RC alone was used for comparison. Pathologic response and cancer-specific survival (CSS) were compared. We created the Johns Hopkins Hospital Dose Index to characterize chemotherapeutic dosing regimens and accurately assess sufficient neoadjuvant dosing regarding patient tolerance.
  
  
  RESULTS
  No significant difference was noted in 5-year CSS between GC NAC (58%) and non-NAC cohorts (61%). The median follow-up was 19.6 months (GC NAC) and 106.5 months (non-NAC). Patients with residual non-muscle-invasive disease after GC NAC exhibit similar 5-year CSS relative to patients with no residual carcinoma (P = 0.99). NAC pR (≤ pT1) demonstrated improved 5-year CSS rates (90.6% vs. 27.1%, P < 0.01) and decreased nodal positivity rates (0% vs. 41.3%, P<0.01) when compared with nonresponders (≥ pT2). Clinicopathologic outcomes were inferior in NAC pathologic nonresponders when compared with the entire RC-only-treated cohort. A lower pathologic nonresponder rate was seen in patients tolerating sufficient dosing of NAC as stratified by the Johns Hopkins Hospital Dose Index (P = 0.049), congruent with the National Comprehensive Cancer Network guidelines. A multivariate classification tree model demonstrated 60 years of age or younger and clinical stage cT2 as significant of NAC response (P< 0.05).
  
  
  CONCLUSIONS
  Pathologic nonresponders fare worse than patients proceeding directly to RC alone do. Multiple predictive models incorporating clinical, histopathologic, and molecular features are currently being developed to identify patients who are most likely to benefit from GC NAC.
authors: Johns Hopkins Medical Institution, Baltimore, MD. Electronic address: nilaymgandhi@gmail.com.
authors: Nilay M
authors: NM
authors: Gandhi
authors: Johns Hopkins Medical Institution, Baltimore, MD.
authors: Alexander
authors: A
authors: Baras
authors: Johns Hopkins Medical Institution, Baltimore, MD.
authors: Enrico
authors: E
authors: Munari
authors: Johns Hopkins Medical Institution, Baltimore, MD.
authors: Sheila
authors: S
authors: Faraj
authors: Johns Hopkins Medical Institution, Baltimore, MD.
authors: Leonardo O
authors: LO
authors: Reis
authors: Johns Hopkins Medical Institution, Baltimore, MD.
authors: Jen-Jane
authors: JJ
authors: Liu
authors: Johns Hopkins Medical Institution, Baltimore, MD.
authors: Max
authors: M
authors: Kates
authors: Johns Hopkins Medical Institution, Baltimore, MD.
authors: Mohammad Obaidul
authors: MO
authors: Hoque
authors: Department of Pathology and Molecular Medicine, Queens University, Kingston, Ontario, Canada.
authors: David
authors: D
authors: Berman
authors: Johns Hopkins Medical Institution, Baltimore, MD.
authors: Noah M
authors: NM
authors: Hahn
authors: Johns Hopkins Medical Institution, Baltimore, MD.
authors: Mario
authors: M
authors: Eisenberger
authors: Johns Hopkins Medical Institution, Baltimore, MD.
authors: George J
authors: GJ
authors: Netto
authors: Montefiore Medical Center, New York, NY.
authors: Mark P
authors: MP
authors: Schoenberg
authors: Johns Hopkins Medical Institution, Baltimore, MD.
authors: Trinity J
authors: TJ
authors: Bivalacqua
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use*; D015331:Cohort Studies; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D017063:Outcome Assessment, Health Care / Q000379:methods*; D015996:Survival Rate; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine
keywords: Bladder cancer; Gemcitabine-cisplatin; Neoadjuvant chemotherapy; Pathologic response; Urothelial carcinoma