Abstract
The role of radiotherapy for the treatment of clinical stage T3b transitional cell carcinoma of the bladder is controversial. The options range from definitive radiotherapy alone, to preoperative radiotherapy and cystectomy, to chemotherapy and radiation for bladder preservation. Our data show that long-term local control after definitive radiotherapy is only 27% and that death attributable to local-regional failure in this setting is 43%. Thus, definitive radiotherapy is only used in patients who are considered poor candidates for surgical and chemotherapy procedures. Preoperative radiotherapy (PREOP) has been studied in a number of randomized series, all of which failed to establish an improvement in patient outcome over those treated with radical cystectomy alone (CYST). However, these studies are subject to criticism, mostly because of poor patient accrual and low numbers of patients available for the analyses. A retrospective review of patients treated at MD Anderson Cancer Center indicates that local control is superior with PREOP as compared with CYST. An analysis of the impact of local control on distant metastasis rates in patients treated with CYST showed that local control was an independent correlate of distant metastasis and survival. Thus, preoperative radiotherapy may be beneficial to patients with late-stage muscle-invasive bladder cancer by securing local control and reducing distant metastasis rates as a result. The success of bladder preservation for stage T3b patients rests with the ability to select patients with radiosensitive tumors. To this end, the immunohistochemical staining status of tumor p53 and pRB was investigated in patients treated with PREOP. Abnormal pRB expression was very strongly related to radiation response, whereas altered p53 expression was associated with high distant metastasis-free and overall survival rates. These two molecular markers were complementary and show promise in facilitating the selection of late-stage patients for bladder preservation.