PREDICTIVE FACTORS FOR OUTCOME IN INVASIVE BLADDER-CANCER TREATED WITH ALTERNATING CHEMORADIOTHERAPY

PURPOSE In order to select patients properly for a bladder preservatio n program, this retrospective study aimed to evaluate the predictive r ole of pretreatment- and treatment-related factors in a group of patie nts with invasive bladder cancer treated with alternating chemoradioth erapy at a single institution. METHODS AND MATERIALS From 1986 to 1994 , 72 patients with invasive bladder cancer, stages T1 poorly different iated or T2-4M0 refusing surgery or not eligible for surgery, were tre ated with alternating chemoradiotherapy. Each patient had a pretreatme nt cystoscopy with an attempted complete transurethral resection of th e bladder tumor (TURB). The treatment schedule consisted of chemothera py (cisplatin, 5-fluorouracil, or methotrexate) alternated with radiot herapy. Over the years, the treatment schedule was modified with respe ct to the total number of chemotherapy cycles, the type of chemotherap y drugs, the dose per fraction and total dose of radiation therapy, an d the presence of a planned treatment gap at midtreatment. Treatments were aligned in order of their received average relative dose intensit ies of both chemotherapy (ARDICT) and radiotherapy (RDIRT). RESULTS Tw enty-two patients (76%) developed infiltrative bladder recurrences for an estimated 5-year pelvic control rate of 68% +/- 6%; 5-year actuari al survival with intact bladder is 40% +/- 6%. Obstructive uropathy at diagnosis, residual disease after TURB, and ARDICT value equal or bel ow the median were independent predictive factors for pelvic failure, with hazard ratios of 2.87 (95% confidence interval [CI], 1.16-7.04), 8.13 (95% CI, 2.74-24.1), and 3.36 (95% CI, 1.23-8.74), respectively. A more detailed model including interactions among these factors showe d that the negative prognostic effect of obstructive uropathy at digno sis was not modified by ARDICT or TURF resection; on the contrary, the risk of local failure for patients with incomplete TURB was markedly affected by different levels of ARDICT. Also, a trend toward a better local outcome was observed for patients with RDIRT above the median. H ydronephrosis and incomplete TURB were also independent predictors of distant metastases and overall survival, but no effect was found for A RDICT on these endpoints. DISCUSSION As a result of this analysis we b elieve that (1) patients with obstructive uropathy should not be offer ed a bladder-sparing approach, (2) gross total TURB of the primary tum or should be maximized, (3) prompt surgery should be considered for pa tients with incomplete TURB who are not compliant with the combined-mo dality treatment, and (4) the intrinsic value of dose intensity of bot h chemotherapy and radiotherapy should be confirmed in a prospective, controlled study.