Combination transurethral resection, systemic chemotherapy, and pelvic radiotherapy for invasive (T2-T4) bladder cancer unsuitable for cystectomy: A Phase I/II Southwestern Oncology Group study

Objectives. Primarily to evaluate the toxicity and, secondarily, the tumor response and patient survival associated with a three-phase combined modality treatment plan for patients with invasive transitional cell carcinoma (TCC) of the bladder [T2-T4,NX-N2,M0] who are medically unsuitable far or who refuse cystectomy. Methods. Eligible patients initially underwent extensive transurethral resection (TUR) of the primary tumor with the attempt to resect disease totally. Subsequently, they received systemic combination chemotherapy consisting of two cycles of methotrexate, cisplatin, and vinblastine (MCV), followed by cystoscopic re-evaluation of the bladder tumor. Patients then received 6480 cGy radiotherapy to the bladder with concurrent systemic cisplatin. Toxicity, primary tumor response, and overall survival were evaluated. Results. Of 34 eligible patients, 27 patients completed the treatment series, Twenty-two received 80% to 100% of the prescribed doses of MCV and only 2 patients experienced grade 4 hematologic toxicities, The most common toxicities were gastrointestinal (23), hematologic (21), and renal (8). The complete response (CR) rate after all treatment phases was 56% (19 of 34), 10 patients achieving a complete tumor resection of visible tumor at the initial TUR of the bladder (TURB); 3, a CR after MCV; and 6, after radiotherapy and concomitant cisplatin. The median overall survival was 21 months with 6 of 34 (18%) alive at 57 months (range, 36 to 75). Complete resection of tumor by TURB was associated with prolonged overall survival. The bladder was the initial site of recurrence in 85% of patients who had achieved a CR status. Conclusions. This older age patient group tolerated this combined modality therapy with acceptable toxicities, but the overall survival rate was not improved compared with those reported with radiotherapy alone.