title: Risk factors in carcinoma in situ of the urinary bladder. Dutch South East Cooperative Urological Group.
abstract: OBJECTIVE
  In this article we describe the long-term follow-up of patients with carcinoma in situ (CIS) of the urinary bladder and examine whether the extent of CIS, the presence of associated papillary tumors, or the response to treatment influence the course of the disease.
  
  
  METHODS
  Fifty-two patients with CIS of the bladder, treated in a randomized prospective study, are described. In 23 patients with concomitant papillary tumors all macroscopically visible lesions were completely resected transurethrally (TUR). CIS was histologically confirmed in all patients by biopsy, 29 of whom had primary CIS. The patients were treated with intravesical mitomycin, bacille Calmette-Guérin (BCG)-RIVM or BCG-Tice and followed regularly by urine cytology, cystoscopy, and biopsy.
  
  
  RESULTS
  Complete response was achieved in 65% of the patients. Of these responders, 24% later had a recurrence of CIS or a superficial tumor and 18% had progressive disease (PD). In the nonresponding patients, progression occurred in 67%. In the whole group, PD was seen in 35% of the patients, and radical cystectomy was performed in 21%. The disease-related death rate was 13%. The risk for recurrence or PD was not higher in patients with more extensive CIS, defined as three or more positive biopsy results or when CIS was associated with papillary tumors compared to patients with one or two biopsy specimens positive for CIS or CIS alone. Nonresponding patients showed a significantly higher progression rate and cystectomy rate than responding patients (P = 0.0012 and 0.008, respectively).
  
  
  CONCLUSIONS
  CIS of the bladder is a malignancy with a poor prognosis, especially in patients not responding after intravesical treatment. Early detection and adjuvant intravesical treatment after TUR of concomitant papillary tumors are required. In patients not responding after intravesical treatment, radical surgery is necessary before progression occurs. The number of biopsies positive for CIS, not the presence of concomitant superficial tumors, was an indicator for progression or recurrence.
authors.affiliation: Department of Urology, University Hospital Nijmegen, The Netherlands.
authors.forename: R J
authors.initials: RJ
authors.lastname: van Gils-Gielen
authors.forename: W P
authors.initials: WP
authors.lastname: Witjes
authors.forename: C T
authors.initials: CT
authors.lastname: Caris
authors.forename: F M
authors.initials: FM
authors.lastname: Debruyne
authors.forename: J A
authors.initials: JA
authors.lastname: Witjes
authors.forename: G O
authors.initials: GO
authors.lastname: Oosterhof
mesh_terms: D002278:Carcinoma in Situ / Q000556:secondary / Q000628:therapy; D005500:Follow-Up Studies; D006801:Humans; D009378:Neoplasms, Multiple Primary / Q000628:therapy; D012307:Risk Factors; D001749:Urinary Bladder Neoplasms / Q000473:pathology / Q000628:therapy