title: Role of marker lesion when applying intravesical instillations of IL-2 for non-muscle-invasive bladder cancer comparison of the therapeutic effects in two pilot studies.
abstract: OBJECTIVE
  Comparison of the therapeutic effect of treatment of non-muscle invasive bladder carcinoma (NMIBC) after intravesical Interleukin-2 (IL-2) instillations in the presence and absence of a marker tumour.
  
  
  METHODS
  Two pilot studies were performed in patients with NMIBC. The first study (10 patients) was performed in Krakow (Poland), the second (26 patients) in Vilnius (Lithuania). In Krakow the tumours were treated with incomplete transurethral resection (TUR) leaving a marker tumour of 0.5-1.0-cm followed by IL-2 instillations (3 × 10(6) IU IL-2) on five consecutive days. In Vilnius the tumours were treated with complete TUR, followed by IL-2 instillations (9 × 10(6) IU IL-2) on five consecutive days.
  
  
  RESULTS
  During 30 months follow-up, the recurrence-free survival was 5/10 (50%) and 6/26 (23%) after incomplete and complete TUR, respectively. So, the ratio of the recurrence-free survival after incomplete/complete TUR of 50/23=2.2. The median of the recurrence-free survival is >20.5 months and 7 months after incomplete and complete TUR, respectively. So, this ratio was >20.5/7= >2.9. The hazard ratio which combines both the chance of the disease recurrence and its timing for both censored and uncensored cases was 0.53, again confirming the better outcome after incomplete TUR.
  
  
  CONCLUSIONS
  A possible explanation for the better therapeutic effects after incomplete TUR compared with complete TUR is that the marker tumour has tumour-associated antigens (TAA) that could lead to an immune reaction that is stimulated by local application of IL-2. After complete TUR, no TAA are available to initiate and to stimulate an immune reaction; consequently, local IL-2 therapy is less effective after complete TUR. The results of these two pilot studies have led to the recent start of a randomised prospective clinical trial in which therapeutic effects of local IL-2 therapy after complete and incomplete TUR are compared.
authors: Department of Urology, Free University Medical Centre, Amsterdam, The Netherlands. W.denotter@vumc.nl
authors: Willem
authors: W
authors: Den Otter
authors: R Jeroen
authors: RJ
authors: Van Moorselaar
authors: John J L
authors: JJ
authors: Jacobs
authors: Ronald Ter
authors: RT
authors: Haar
authors: Jan W
authors: JW
authors: Koten
authors: Zygmunt
authors: Z
authors: Dobrowolski
authors: Waclaw
authors: W
authors: Lipczynski
authors: Vita
authors: V
authors: Pašukonienė
authors: Dainius
authors: D
authors: Characiejus
authors: Feliksas
authors: F
authors: Jankevičius
authors: Rimantas
authors: R
authors: Eidukevičius
authors: Theo M
authors: TM
authors: De Reijke
mesh_terms: D000283:Administration, Intravesical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use*; D008097:Lithuania; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000401:mortality* / Q000601:surgery; D009367:Neoplasm Staging; D010865:Pilot Projects; D011044:Poland; D011379:Prognosis; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000601:surgery
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007376:Interleukin-2
keywords: IL-2; NMIBC; Non-muscle invasive bladder carcinoma; interleukin-2; marker tumour