Treatment of T3 Bladder Cancer: Controlled Trial of Pre‐operative Radiotherapy and Radical Cystectomy Versus Radical Radiotherapy: Second Report and Review (for the Clinical Trials Group, Institute of Urology)

Summary— The relative values of pre‐operative pelvic radiotherapy (4000 rads) and elective radical cystectomy versus radical radiotherapy (4000 rads plus 2000 rads boost) for deeply invasive bladder cancer (category or stage T3 or B2C) have been explored in a multicentre prospective randomised trial involving 189 patients. All patients were eligible for analysis of 5‐year results, 1 74 had been followed for 7 years and 81 patients for 10 years. The overall 3‐year survival rates with no exclusions were 45% for pre‐operative radiotherapy and cystectomy and 33% for radical radiotherapy; the corresponding 5‐year figures were 38 and 29% respectively. Statistical analysis has shown no significant difference between these overall survival rates, but further analysis has revealed significant differences in certain subgroups of patients. The combined treatment produced better results in younger patients, especially those aged less than 60 (5‐year survival rates of 49 and 25% respectively) and in males (5‐year survival rates of 45 and 29% respectively); in contrast, there was no difference in survival rates for patients aged more than 65 and in females. Within each of the treatment groups, significantly better survival rates were obtained in patients showing a good response to radiotherapy, based on reduction of tumour stage in the surgical specimen or on reduction of tumour size at review cystoscopy. Following pre‐operative radiotherapy, reduction in tumour stage in the cystectomy specimen occurred in 49% of patients: no tumour or only in situ changes were present in 31%. Significantly better results were obtained after elective cystectomy when the lymph nodes were not involved (5‐year survival rate of 53% as against 1 6% when the nodes were positive). Metastases were found in the pelvic nodes in only 20% of all cases and were a rare finding in down‐staged cases (5.5%). Extremely good results (60% 5‐year survival rate) were obtained in 18 highly selected patients who had salvage cystectomy for local tumour recurrence following radical radiotherapy. The results of this trial indicate that the prognosis for patients with deeply invasive (T3 or B2C) carcinoma of bladder is influenced by such factors as age, sex, response to irradiation, tumour size and the presence or absence of pelvic metastases. These factors are analysed with a review of the relevant literature. We conclude that, at the present state of knowledge, it appears that cystectomy as an elective procedure after pre‐operative radiotherapy is the treatment of choice for patients aged less than 65, especially males. In patients over 65, and perhaps in females generally, the most suitable primary treatment is radical radiotherapy with salvage cystectomy reserved for highly selected patients with local tumour recurrence. Future research should be directed towards achieving a more frequent and greater response to irradiation, whether it be given pre‐operatively or as radical treatment.