title: Efficacy of post-nephroureterectomy cisplatin-based adjuvant chemotherapy for locally advanced upper tract urothelial carcinoma: a multi-institutional retrospective study.
abstract: OBJECTIVE
  To evaluate the efficacy of adjuvant systemic chemotherapy for locally advanced (pT3-4pN0/xM0) upper tract urothelial carcinoma (UTUC).
  
  
  METHODS
  We retrospectively reviewed the medical records of 109 patients with pT3-4pN0/xM0 UTUC who had undergone radical nephroureterectomy between 1996 and 2013 at our four institutions. The patients were divided into two groups: those who received adjuvant chemotherapy (AC group) and those who did not (surgery-alone: SA group). All chemotherapy regimens were cisplatin-based. Cox proportional hazards regression models addressed the associations between clinicopathological factors and recurrence-free survival (RFS) and cancer-specific survival (CSS).
  
  
  RESULTS
  Forty-three (39.5%) out of the 109 patients underwent one to four cycles of adjuvant chemotherapy after nephroureterectomy. Median follow-up was 46.5 months. There were no significant differences in the background characteristics of the two groups, except for age. Recurrence developed in 11 (25.6%) and 29 (43.9%) patients in the AC and SA groups, respectively. Ultimately, six (14.0%) and 18 (27.3%) patients in the AC and SA groups, respectively, died of disease progression. On univariate analysis, hydronephrosis, nuclear grade, lymphovascular invasion, and adjuvant chemotherapy were significantly associated with both RFS and CSS. Charlson comorbidity index was associated only with CSS. On multivariate analysis, adjuvant chemotherapy was the only independent factor associated with improved RFS (p = 0.0178, HR = 0.41). Moreover, adjuvant chemotherapy (p = 0.0375, HR = 0.33), lower nuclear grade (p = 0.0070), and the absence of hydronephrosis (p = 0.0493) were independently associated with better CSS.
  
  
  CONCLUSIONS
  Locally advanced (pT3-4pN0/xM0) UTUC patients who underwent cisplatin-based adjuvant chemotherapy demonstrated better RFS and CSS than those without adjuvant chemotherapy.
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. tohru-tky@umin.ac.jp.
authors.forename: Tohru
authors.identifier: http://orcid.org/0000-0003-4041-7241
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.|Department of Urology, The Fraternity Memorial Hospital, 2-1-11 Yokoami, Sumida-ku, Tokyo, 130-8587, Japan.
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Komemushi
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.|Department of Urology, Musashino Red Cross Hospital, 1-26-1 Kyonan-cho, Musashino-shi, Tokyo, 180-8610, Japan.
authors.forename: Taketo
authors.initials: T
authors.lastname: Kawai
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.|Department of Urology, Musashino Red Cross Hospital, 1-26-1 Kyonan-cho, Musashino-shi, Tokyo, 180-8610, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Otsuka
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.|Department of Urology, Tokyo Teishin Hospital, 2-14-23 Fujimi, Chiyoda-ku, Tokyo, 102-8798, Japan.
authors.forename: Jimpei
authors.initials: J
authors.lastname: Miyakawa
authors.affiliation: Biostatistics Division, Central Coordinating Unit, Clinical Research Support Center, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Uemura
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kanatani
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.|Department of Urology, Tokyo Teishin Hospital, 2-14-23 Fujimi, Chiyoda-ku, Tokyo, 102-8798, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Taguchi
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Naito
authors.affiliation: Department of Urology, Tokyo Teishin Hospital, 2-14-23 Fujimi, Chiyoda-ku, Tokyo, 102-8798, Japan.
authors.forename: Motofumi
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Department of Urology, The Fraternity Memorial Hospital, 2-1-11 Yokoami, Sumida-ku, Tokyo, 130-8587, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nishimatsu
authors.affiliation: Department of Urology, The Fraternity Memorial Hospital, 2-1-11 Yokoami, Sumida-ku, Tokyo, 130-8587, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Hirano
authors.affiliation: Department of Urology, Musashino Red Cross Hospital, 1-26-1 Kyonan-cho, Musashino-shi, Tokyo, 180-8610, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Matsumoto
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Hideyo
authors.initials: H
authors.lastname: Miyazaki
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Fujimura
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fukuhara
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Haruki
authors.initials: H
authors.lastname: Kume
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Igawa
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Homma
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant / Q000379:methods; D002945:Cisplatin / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007564:Japan / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D008297:Male; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D000074682:Nephroureterectomy / Q000379:methods*; D010043:Outcome and Process Assessment, Health Care; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D019459:Urothelium / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin
keywords: Adjuvant chemotherapy; Cisplatin; Lymphovascular invasion; Nephroureterectomy; Upper tract urothelial carcinoma