UROLOGICAL ONCOLOGY

Perioperative single dose instillation of epirubicin or interferon-alpha after transurethral resection for the prophylaxis of primary superficial bladder cancer recurrence: a prospective randomized multicenter study — Finnbladder III long-term results
Rajala P, Kaasinen E, Raitanen M, Liukkonen T, Rintala E; The Finnbladder Group
Divisions of Urology, Turku University Hospital, Turku, Finland
J Urol. 2002;168:981-5

• Purpose: We evaluated the long-term efficacy of a single dose of interferon or epirubicin administered immediately after transurethral resection compared with transurethral resection alone for primary superficial bladder cancer recurrence.
• Material and Methods: A total of 200 patients with primary superficial stages Ta to T1, grades 1 to 3 bladder cancer were randomized into 3 treatment groups, including transurethral resection alone, transurethral resection plus 50 milliunits interferon-alpha2b and transurethral resection plus 100mg epirubicin. The primary end point was time to first recurrence.
• Results: At a median followup of 72 months, we observed a sustained effect of a single epirubicin instillation compared to other treatments. To date only 46% of the patients in group 3 have experienced recurrence, in contrast to 73% and 68% in groups 1 and 2, respectively (p=0.002). At 72 months, the Kaplan-Meier disease-free estimates were 24%, 31%, and 51%, in groups 1 to 3, respectively (p=0.002). The Cox multivariate model revealed a more than 2-fold relative risk of recurrence in group 1 versus group 3 (p<0.001). Other significant variables predicting recurrence were grade and the number of tumors.
• Conclusions: A single perioperative instillation of 100mg epirubicin causes a significant and sustained decrease in primary superficial bladder cancer recurrence, whereas a single dose of 50 milliunits interferon-alpha2b is ineffective for prophylaxis.
  
  
• Editorial Comment
  This study provides the long-term results of 3-armed study of TUR versus TUR + Interferon versus TUR + Epirubicin. After a median follow-up of 22 months, the results are rather clear, showing clinical effectiveness of a single short instillation of Epirubicin after TUR. Both the Kaplan-Meier estimates after 72 months, and the Cox multivariate hazard regression, support the use of a cytotoxic drug to prevent implantation of floating tumor cells. Two comments are to be made with this study:
  1. The authors used 100mL physiological together with 100mg Epirubicin, and refer to the dose and not to the concentration, which might be more relevant in this context.
  2. Furthermore, the instillate remained for 2 hours in the bladder, which might involve problems if given immediately after a transurethral resection. Thus, the results of a further sub-evaluation regarding the timing of the instillation would be very interesting.

Dr. Andreas Böhle
Professor and Deputy Chairman of Urology
Medical University of Luebeck
Luebeck, Germany