Muscle-invasive bladder cancer treated with external beam radiation: influence of total dose, overall treatment time, and treatment interruption on local control.

PURPOSE: To evaluate and eventually quantify a possible influence of tumor proliferation during the external radiation course on local control in muscle invasive bladder cancer. METHODS AND MATERIALS: The influence of total dose, overall treatment time, and treatment interruption has retrospectively been analyzed in a series of 379 patients with nonmetastasized, muscle-invasive transitional cell carcinoma of the urinary bladder. All patients received external beam radiotherapy at the Netherlands Cancer Institute between 1977 and 1990. Total dose varied between 50 and 75 Gy with a mean of 60.5 Gy and a median of 60.4 Gy. Overall treatment time varied between 20 and 270 days with a mean of 49 days and a median of 41 days. Number of fractions varied between 17 and 36 with a mean of 27 and a median of 26. Two hundred and fourty-four patients had a continuous radiation course, whereas 135 had an intended split course or an unintended treatment interruption. Median follow-up was 22 months for all patients and 82 months for the 30 patients still alive at last follow-up. A stepwise procedure using proportional hazard regression has been used to identify prognostic treatment factors with respect to local recurrence as sole first recurrence. RESULTS: One hundred and thirty-six patients experienced a local recurrence and 120 of these occurred before regional or distant metastases. The actuarial local control rate was 40.3% at 5 years and 32.3% at 10 years. In a multivariate analysis total dose showed a significant association with local control (p = 0.0039), however in a markedly nonlinear way. In fact only those patients treated with a dose below 57.5 Gy had a significant higher bladder relapse rate, whereas no difference in relapse rate was found among patients treated with doses above 57.5 Gy. This remained the case even after adjustment for overall treatment time and all significant tumor and patient characteristics. The Normalized Tumor Dose (NTD) (alpha/beta = 10) and NTD (alpha/beta = 15) were not significantly related to local control (p = 0.96 and p = 0.053, respectively). Only weak evidence was found for an association between local control and overall treatment time (p = 0.067). No difference in bladder relapse rate was found among patients treated with a continuous course and patients who had treatment interruptions (p = 0.099). Neither the length of the interruption, nor the actual number of treatment days has a significant influence on local control (p = 0.04 and p = 0.09, respectively). CONCLUSION: In contrast to two earlier, but smaller reports, in this study no significant effect of treatment prolongation on outcome after radiotherapy could be demonstrated and thus no support was found for an important role for tumor proliferation as the cause of treatment failure in muscle-invasive bladder cancer. Results of large-sized phase III trials will have to be awaited to show any benefit from reduction of the overall treatment time and to quantify the potential effect of tumor proliferation.

Muscle-invasive bladder cancer treated with external beam radiotherapy: pretreatment prognostic factors and the predictive value of cystoscopic re-evaluation during treatment.

PURPOSE: To determine the relationship between tumour and patient characteristics and local control and survival for patients with T2 and T3 bladder cancer treated with radical external beam radiotherapy and to evaluate the predictive value of cystoscopic response evaluation during radiation on final outcome. MATERIALS AND METHODS: Records from 379 patients with non-metastasized T2 or T3 transitional cell carcinoma of the bladder were reviewed. All patient received external beam radiotherapy at The Netherlands Cancer Institute during the period from 1977 to 1990. The total dose varied from 50 to 75 Gy with a mean of 60.5 Gy and a median of 60.4 Gy. The median follow-up was 22 months for all patients and 82 months for the 30 patients still alive at last follow-up. A stepwise procedure using proportional hazard regression was used to identify prognostic factors with respect to local recurrence and survival. RESULTS: One hundred thirty-six patients experienced a local recurrence and 120 of these occurred before regional or distance metastases. The actuarial results at 5 years were 40.3% local control (SE 4.0%), 24.9% disease-free rate (SE 3.0%) and 22.2% overall survival (SE 2.2%). In the univariate analysis age, performance status, result of intravenous pyelography (IVP) and T-stage were found to be related to overall survival and multifocality was related to local control. Multivariate analysis revealed that only age and T-stage were related to survival and only multifocality was related to local control. In patients with solitary tumours who were identified as having the most favourable outcome. local control was 50% at 5 years. Local control in 89 patients who had a cystoscopic evaluation during treatment was identical regardless of whether a complete, partial or no response was observed. Furthermore, local control was identical in patients selected on the basis of a favourable response and in unselected patients. CONCLUSIONS: Although we identified some significant prognostic factors, their predictive value is not strong enough to allow accurate estimation of treatment effect and disease outcome. Cystoscopic response evaluation during treatment was found not to provide reliable information to direct further treatment. Prospective studies to identify ways to select patients for bladder conservation using definitive radiotherapy are urgently needed.