Radiochemotherapy After Transurethral Resection for High-Risk T1 Bladder Cancer: An Alternative to Intravesical Therapy or Early Cystectomy?

Christian Weiss, From the Department of Radiation Therapy, Department of Urology, University of Erlangen,

Journal of Clinical Oncology, Vol 24, No 15 (May 20), 2006: pp. 2318-2324

Management of high-grade transitional cell carcinoma involving the lamina propria (stage T1) but not penetrating into the muscularis propria represents a challenge for the treating physician. With transurethral resection of the bladder tumor (TURBT) alone, the risk of recurrence for this group of patients approaches 80% and the risk of progression to muscle-invasive disease is 50% to 65%. Adjuvant intravesical therapy with Bacille Calmette-Guérin (BCG) or chemotherapeutic agents, such as mitomycin, may decrease the overall recurrence rate by approximately 30% compared with TURBT alone. However, tumor progression still occurs in 15% to 40% within the first 5 years, and these patients are at risk of dying from urothelial cancer.  
Thus, several groups have recommended immediate cystectomy without a trial of intravesical treatment to prevent any risk of progression.  Five-year disease-specific survival (DSS) rates in the range of 70% to 90% have been achieved with this radical approach; however, the morbidity and mortality associated with cystectomy are still in the range of 20% and 1% to 4%, respectively, and quality of life is altered despite techniques of orthotopic bladder reconstruction. It is evident that undertreatment and overtreatment are critical and controversial issues for this group of patients.

It is our hypothesis that radiotherapy (RT) with or without chemotherapy may be more effective in preventing tumor progression than standard intravesical treatment, and that this approach may also help to select nonresponding patients at high risk for tumor progression for salvage cystectomy at an early time point. It has been the ongoing policy at the University of Erlangen (Erlangen, Germany) to use RT or radiochemotherapy (RT/RCT) after TURBT with selective bladder preservation for high-risk T1 bladder cancer since 1982. We now present the long-term result of this approach in a group of 141 patients with a median follow-up of 62 months.PURPOSE: For high-risk T1 bladder cancer, the most important issue is how to restrict radical cystectomy to selective patients with a high likelihood of tumor progression and to choose an initial bladder-sparing approach in others without affecting survival. Radiotherapy or radiochemotherapy (RT/RCT) may help to strike a balance between intravesical treatment and early cystectomy.

PATIENTS AND METHODS: Between 1982 and 2004, 141 patients with high-risk T1 bladder cancer (84 patients with T1 grade 3 [T1G3]; others with T1G1/2 and associated carcinoma-in-situ, multifocality, tumor diameter > 5 cm, or multiple recurrences) were treated with RT (n = 28) or platinum-based RCT (n = 113) after transurethral resection of bladder tumor (TURBT). Six weeks after RT/RCT, response was evaluated by restaging TURBT. Salvage cystectomy was recommended for patients with persistent disease and for tumor progression after initial complete response (CR). Median follow-up was 62 months; 65 patients have been observed for 5 years or more.

Treatment was commenced by TURBT aimed at maximal, complete resection (if feasible) of the tumor mass. Residual tumor was assessed histologically by biopsies from all resection margins: R0 indicated a visibly and microscopically complete TURBT, R1 indicated microscopic residual tumor, and R2 indicated macroscopic residual tumor. Additional evaluation included chest radiography and computed tomography of the abdomen and pelvis. RT was initiated 4 to 6 weeks after initial TURBT using 6- to 10-MV photons and a four-field box technique with individually shaped portals and daily fractions of 1.8 to 2 Gy on 5 consecutive days. A median dose of 55.8 Gy (range, 45.0 to 61.4 Gy) was applied to the bladder. Pelvic nodes were irradiated with a median dose of 50.4 Gy (range, 36.0 to 54.1 Gy). Since October 1985, chemotherapy has been given simultaneously for 5 consecutive days during the first and fifth week of RT. Forty-three patients received cisplatin 25 mg/m2/d; in 16 patients with decreased creatinine clearance (< 50 mL/min), carboplatin 65 mg/m2/d was administered. Since 1993, 54 patients were treated with a combination of cisplatin or carboplatin and fluorouracil 600 mg/m2/d. A total of eight patients also received deep regional hyperthermia within an ongoing phase II study.

RESULTS: CR was achieved in 121 of 137 patients (88%; four patients without restaging TURBT). Tumor progression for the entire group of 141 patients was 19% and 30% at 5 and 10 years, respectively (for 121 patients with CR, 15% and 29%; for 84 patients with T1G3, 13% and 29%, respectively). Disease-specific survival rates were 82% and 73% at 5 and 10 years (CR, 89% and 79%; T1G3, 80% and 71%, respectively). More than 80% of survivors preserved their bladder; 70.4% were "delighted" or "pleased" with their urinary function.

CONCLUSION: RT/RCT after TURBT with selective bladder preservation is a reasonable alternative to intravesical treatment or early cystectomy for high-risk T1 bladder cancer.