Can dose–response models predict reliable normal tissue complication probabilities in radical radiotherapy of urinary bladder cancer? The impact of alternative radiation tolerance models and parameters

Purpose: To analyze the consequences of selecting alternative normal tissue complication probability (NTCP) models and parameters for evaluation of radiotherapy of urinary bladder cancer. Methods and Materials: Treatment plans of 24 bladder cancer patients referred to radical 4-field conformal radiotherapy were analyzed. Small intestinal and rectal NTCPs were determined using both the probit and relative seriality models with several sets of published radiation tolerance parameters. Various combinations of NTCP models and parameters were applied to find the prescription dose in individual patients as well as to estimate the benefit of the conformal radiotherapy setup. Results: Different risk estimates were predicted from the two NTCP models, even when the same clinical radiation tolerance doses were fitted into the two models. The demonstrated variability translated into significant deviations (7–10 Gy) in the recommended prescription doses. Even if it was possible to discriminate between a 2-field plan and the 4-field conformal setup using a given complication model and set of tolerance parameters, the estimated benefit of the conformal treatment in terms of permitted dose escalation varied with as much as 10–12 Gy between the different NTCP models/parameters used. Conclusion: Different NTCP models and tolerance parameters might propose different answers to important clinical questions in radiotherapy treatment of bladder cancer, such as dose prescription and scoring of rival treatment plans. We therefore recommend that the variability caused by tolerance parameter uncertainty and model selection should be taken into account in dose–response modeling of radiotherapy treatment.