SIGNIFICANCE OF DOWNSTAGING IN MUSCLE-INVASIVE BLADDER-CANCER TREATEDWITH PREOPERATIVE RADIOTHERAPY

Purpose: The relationship between clinical-to-pathologic downstaging a nd patient outcome following preoperative radiotherapy was examined, f ocusing on the mechanism (selection vs, treatment effect) responsible for the benefit seen from such downstaging. Methods and Materials: Thr ee hundred and one patients were treated with preoperative radiotherap y plus cystectomy (PREOP) to a median dose of 50 Gy in 25 fractions be tween 1960-1983. These patients were compared to 225 patients treated with radical cystectomy, with or without chemotherapy (CYST), between 1984-1990, Multiagent chemotherapy was given to 68% of those in the CY ST group and was not given to any in the PREOP group, Lymph node invol vement was not formally evaluated in the PREOP group, while 20% had pa thologic involvement in the CYST group. Results: Clinical-to-pathologi c downstaging (P < T stage) was found in 73% treated with PREOP and 29 % treated with CYST (p < 0.0001, chi-square), The only factors that co rrelated with P < T staging for the PREOP and CYST groups when each wa s considered separately were clinical stage, blood urea nitrogen level , and creatinine Level (p < 0.05, chi-square), Multivariate logistic r egression revealed that treatment (PREOP vs, CYST) correlated independ ently with P ( T staging (p < 0.0001), The relationship of actuarial l ocal control to distant metastasis at 5 years in patients that were do wnstaged, as stratified by clinical stage and treatment, was then exam ined, Local control rates for P < T staged T2/T3a patients were indepe ndent of treatment (PREOP vs, CYST), while distant metastasis rates we re significantly greater for those in the PREOP group, In contrast, P < T staged T3b patients in the PREOP group had significantly better lo cal control and distant metastasis rates. Conclusions: Significantly h igher P < T staging rates were observed with PREOP as compared to CYST , and this was a consequence of the radiotherapy given, The relationsh ip of downstaging from radiotherapy to local control and distant metas tasis was contingent on clinical stage, The results of Stage T2/T3a an d T3b patients were divergent and supported treatment effect, rather t han selection, as the mechanism consistent with the patient outcomes o bserved. Copyright (C) 1997 Elsevier Science Inc.