title: Intravesical seeding of upper urinary tract urothelial carcinoma cells during nephroureterectomy: an exploratory analysis from the THPMG trial.
abstract: OBJECTIVE
  The Pirarubicin Monotherapy Study Group trial was a randomized Phase II study that evaluated the efficacy of intravesical instillation of pirarubicin in the prevention of bladder recurrence after nephroureterectomy for upper urinary tract urothelial carcinoma. This study conducted further analysis of the Pirarubicin Monotherapy Study Group cohort, focusing on intravesical seeding of cancer cells.
  
  
  METHODS
  Using the data from the Pirarubicin Monotherapy Study Group trial, bladder recurrence-free survival rates and factors associated with bladder recurrence in the control group were analyzed.
  
  
  RESULTS
  Of 36 patients in the control group, 14 with positive urine cytology had more frequent recurrence when compared with the 22 patients with negative cytology (P = 0.004). Based on the multivariate analysis in the control group, voided urine cytology was an independent predictive factor of bladder recurrence (hazard ratio, 5.54; 95% confidence interval 1.12-27.5; P = 0.036). Of 72 patients in the Pirarubicin Monotherapy Study Group trial, 31 had positive urine cytology. Among the 31 patients, 17 patients who received pirarubicin instillation had fewer recurrences when compared with 14 patients who received control treatment (P = 0.0001). On multivariate analysis, pirarubicin instillation was an independent predictor of better recurrence-free survival rates in the patients with positive urine cytology (hazard ratio, 0.02; 95% confidence interval, 0.00-0.53; P = 0.018). Of 21 patients with bladder recurrence, 17 had recurrent tumor around cystotomy or in the bladder neck compromised by the urethral catheter, supporting the notion that tumor cells seeded in the injured urothelium.
  
  
  CONCLUSIONS
  Intravesical instillation of pirarubicin immediately after nephroureterectomy significantly reduced the bladder recurrence rate in patients with positive voided urine cytology. The results suggest that intravesical seeding of upper urinary tract urothelial carcinoma occurs during nephroureterectomy.
authors.affiliation: *1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan. itoaki@uro.med.tohoku.ac.jp.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ito
authors.forename: Ichiro
authors.initials: I
authors.lastname: Shintaku
authors.forename: Makoto
authors.initials: M
authors.lastname: Satoh
authors.forename: Naomasa
authors.initials: N
authors.lastname: Ioritani
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Tochigi
authors.forename: Isao
authors.initials: I
authors.lastname: Numata
authors.forename: Takashige
authors.initials: T
authors.lastname: Namima
authors.forename: Koichi
authors.initials: K
authors.lastname: Kambe
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kyan
authors.forename: Seiji
authors.initials: S
authors.lastname: Ueno
authors.forename: Shinnosuke
authors.initials: S
authors.lastname: Katoh
authors.forename: Hisanobu
authors.initials: H
authors.lastname: Adachi
authors.forename: Shinichi
authors.initials: S
authors.lastname: Yamashita
authors.forename: Takuhiro
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Arai
mesh_terms: D000283:Administration, Intravesical; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy*; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D009366:Neoplasm Seeding; D009392:Nephrectomy / Q000379:methods; D016017:Odds Ratio; D018570:Risk Assessment; D012307:Risk Factors; D055502:Secondary Prevention / Q000379:methods*; D014513:Ureter / Q000601:surgery; D001749:Urinary Bladder Neoplasms / Q000209:etiology* / Q000517:prevention & control*; D014556:Urine / Q000166:cytology; D014571:Urologic Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D004317:Doxorubicin; C027260:pirarubicin
keywords: intravesical seeding; upper urinary tract urothelial carcinoma; voided urine cytology