title: The utility of neoadjuvant gemcitabine plus carboplatin followed by immediate radical cystectomy in patients with muscle-invasive bladder cancer who are ineligible for cisplatin-based chemotherapy.
abstract: BACKGROUND
  There are currently no data supporting carboplatin-based regimens in muscle-invasive bladder cancer patients who are unsuitable for neoadjuvant cisplatin treatment. The aim of this study was to investigate the potential benefit of carboplatin-based regimens in patients with muscle-invasive bladder cancer who were unsuitable for cisplatin.
  
  
  METHODS
  We focused on 171 patients ineligible for cisplatin, including 98 patients who received neoadjuvant gemcitabine and carboplatin (GCarbo) followed by immediate radical cystectomy (GCarbo cohort) and 73 patients who underwent radical cystectomy (RC alone cohort) at Hiroaki University or Aomori Prefectural Hospital. In the neoadjuvant GCarbo cohort, patients underwent two 21-day cycles of GCarbo the two courses of neoadjuvant chemotherapy were followed by radical cystectomy at an interval of 1 month.
  
  
  RESULTS
  Of the enrolled patients, 165 (95.3 %) had renal impairment. The median age of the enrolled patients was 71 years, and the median follow-up period was 63 months. The 5-year overall survival rates for the GCarbo and the RC-alone cohorts were 79.5 and 53.8 %, respectively (P < 0.001), while the 5-year disease-free survival rates were 75.5 and 55.4 %, respectively (P = 0.013). Surgical specimens of 16 (16.3 %) patients in the GCarbo cohort indicated stage pT0 disease. The rate of positive surgical margins in the RC-alone cohort was significantly higher than that in the GCarbo cohort (P < 0.001).
  
  
  CONCLUSIONS
  In this study, the oncological outcomes were significantly improved in cisplatin-unfit patients with muscle-invasive bladder cancer who received neoadjuvant GCarbo chemotherapy, compared with those in patients who underwent RC alone. The standard of care for muscle-invasive bladder cancer, especially for patients who are unfit for cisplatin, may include neoadjuvant carboplatin chemotherapy followed by radical cystectomy.
authors.affiliation: Department of Urology, Hirosaki University, Graduate School of Medicine, 5 Zaifucho, Hirosaki, 036-8562, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Murasawa
authors.affiliation: Department of Urology, Hirosaki University, Graduate School of Medicine, 5 Zaifucho, Hirosaki, 036-8562, Japan. goodwin@hirosaki-u.ac.jp.
authors.forename: Takuya
authors.initials: T
authors.lastname: Koie
authors.affiliation: Department of Urology, Hirosaki University, Graduate School of Medicine, 5 Zaifucho, Hirosaki, 036-8562, Japan.
authors.forename: Chikara
authors.initials: C
authors.lastname: Ohyama
authors.affiliation: Department of Urology, Hirosaki University, Graduate School of Medicine, 5 Zaifucho, Hirosaki, 036-8562, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Department of Urology, Hirosaki University, Graduate School of Medicine, 5 Zaifucho, Hirosaki, 036-8562, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Imai
authors.affiliation: Department of Urology, Hirosaki University, Graduate School of Medicine, 5 Zaifucho, Hirosaki, 036-8562, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Hatakeyama
authors.affiliation: Department of Urology, Hirosaki University, Graduate School of Medicine, 5 Zaifucho, Hirosaki, 036-8562, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yoneyama
authors.affiliation: Department of Urology, Hirosaki University, Graduate School of Medicine, 5 Zaifucho, Hirosaki, 036-8562, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hashimoto
authors.affiliation: Department of Urology, Aomori Prefectural Central Hospital, Higashitsukurimichi 2-1-1, Aomori, Japan.
authors.forename: Ikuya
authors.initials: I
authors.lastname: Iwabuchi
authors.affiliation: Department of Urology, Aomori Prefectural Central Hospital, Higashitsukurimichi 2-1-1, Aomori, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Ogasawara
authors.affiliation: Department of Urology, Aomori Prefectural Central Hospital, Higashitsukurimichi 2-1-1, Aomori, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kawaguchi
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D015653:Cystectomy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000473:pathology; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D018365:Neoplasm, Residual; D015996:Survival Rate; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000473:pathology* / Q000628:therapy*; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D016190:Carboplatin; D000093542:Gemcitabine
keywords: Carboplatin; Cisplatin-unfit; Muscle-invasive bladder cancer; Neoadjuvant chemotherapy