Initial results of retrospective study: preoperative transurethral excision plus chemotherapy and radiation therapy and trial of bladder preservation.

BACKGROUND: For patients with invasive bladder cancer the usual recommended treatment is radical cystectomy, although transurethral resection of the tumor, systemic chemotherapy, and radiotherapy are each effective in some patients. This retrospective study evaluated the experience of the Clinical Oncology Department, Tanta University Hospital with combined modality treatment and selective bladder preservation in patients with muscle-invading bladder cancer with assessment of its safety, tolerance, and efficacy to determine whether these treatments in combination might be as effective as radical cystectomy and thus might allow the bladder to be preserved and the cancer cured and to identify factors that may predict treatment response, risk of relapse and survival.

PATIENTS AND METHODS: Between January 2000 and January 2006, 55 consecutive patients with muscleinvading bladder cancer (stages T2 through T4, NX M0) were treated with as complete transurethral surgery as possible, followed by induction combination chemotherapy, and irradiation with 4500 cGy with concurrent cisplatin administration. Urologic evaluation by cystoscopy, cytology, and rebiopsy 2-3 weeks later of the tumor response directed further therapy: either radical cystectomy in the patients who had incomplete responses, or additional chemotherapy with the same drugs and doses and radiotherapy up to 6480 cGy in the patients who had complete responses. The median follow-up was 48 months.

RESULTS: In 37 patients (67.3%) the bladder was free of invasive tumor and functioning well, even though in 13(23.6%) a superficial tumor recurred and required further transurethral surgery and intravesical drug therapy. Of the 18 (32.7%) patients who still had detectable tumor after initial treatment, all of them underwent radical cystectomy. None of the patients had required a cystectomy for radiation toxicity. Of the 37 (67.3%) patients who had complete responses with no tumor detectable on urine cytology or rebiopsy after initial treatment, 89.2% had functioning tumor-free bladders. The overall survival (OAS) at 5 years is 43.12%. The three year bladder intact survival rate is 60%. A total of 10 patients (18.2%) developed grade 3 hematologic toxicity in conjunction with this treatment. Complete response (CR) was achieved in 67.3% of patients. Local control after CR without muscle-invasive relapse was maintained in 60% of patients at 3 years. Distant metastases were diagnosed in 24 patients (43.6%) with an actuarial rate of distant metastasis-free survival of 43.68% at 5 years. Early tumor stage, absence of hydronephrosis and a complete response were the most important factors predicting bladder preservation rate and survival (all p=< or 01).

CONCLUSIONS: Conservative combination treatment may be an acceptable alternative to immediate cystectomy in selected patients with bladder cancer. Both the 67.3% complete response rate to induction therapy and the 60% three-year survival with an intact bladder are encouraging, although a randomized clinical trial that included a group for simultaneous comparison would be required to produce definitive results. Longer follow-up will be necessary to assess efficacy.