PROGNOSTIC FACTORS AND RISK GROUPS IN T1G3 PATIENTS INITIALLY TREATED WITH BCG: RESULTS OF A MULTICENTER RETROSPECTIVE SERIES IN 1743 PATIENTS

Introduction and Objectives: The impact of prognostic factors in T1G3 patients (pts) is critical for proper treatment decision making, however most available data are from small series of pts. The aim of the current study is to assess prognostic factors in a large group of pts who received BCG as initial treatment of T1G3 tumours and identify a subgroup of high risk pts who should be considered for early cystectomy. Patients and Methods: Individual pt data were collected for 1743 ptsfrom 20 centers who received induction or maintenance BCG between 1990 and 2008. Using Cox regression analysis, the prognostic importance of the following variables were assessed for time to recurrence, progression to muscle invasive disease and overall survival:age (<70 vs. >70yrs), gender, primary T1G3 vs. recurrent T1G3 after previous non T1G3 tumour, tumour size (<3 vs. >3 cm), multiplicity (single vs. multiple), concomitant CIS (no/yes), and maintenance BCG (no/yes). Results: Median age was 68yrs, 84% were male, 89% were primary T1G3, 50% had multifocal disease, 67% had tumours less than 3 cm, 24% had concomitant CIS, 30% had a restaging TUR, 52% received some sort of maintenance BCG. With a follow up out to 15 years, 801 pts (46%) recurred, 326 (19%) progressed, 291 underwent cystectomy (17%) and 409 (23%) died, 151 (9%) due to bladder cancer. In multivariate analyses, the most important prognostic factors (p<0.05) for recurrence were: tumour size and multiplicity; for progression: age, size and concomitant CIS; for overall survival: age and size. Maintenance BCG had a positive impact on recurrence (p<0.001), progression (p=0.059) and survival (p=0.01). Patients were divided into 4 risk groups according to the number of bad factors for progression among age >70, size >3 cm and presence of CIS. Progression free rates at 10 yrs were 84%, 75%, 66% and 28% for patients with 0, 1, 2 and 3 bad factors while the corresponding overall survival rates were 78%, 56%, 45% and 6%, respectively. Conclusion: T1G3 patients treated with BCG have a heterogeneous prognosis, with overall survival at 10 yrs ranging from 78% to 6%. Although maintenance BCG improves outcome as compared to induction alone, fit pts over 70 yrs of age with tumours greater than 3 cm and concomitant CIS should be considered for an early cystectomy.