Validation of prediction models for radiation-induced late rectal bleeding: Evidence from a large pooled population of prostate cancer patients

Purpose: To validate published models for the risk estimate of grade >= 1 (G1+), grade >= 2 (G2+) and grade = 3 (G3) late rectal bleeding (LRB) after radical radiotherapy for prostate cancer in a large pooled population from three prospective trials.Materials and methods: The external validation population included patients from Europe, and Oceanian centres enrolled between 2003 and 2014. Patients received 3DCRT or IMRT at doses between 66-80 Gy. IMRT was administered with conventional or hypofractionated schemes (2.35-2.65 Gy/fr). LRB was prospectively scored using patient-reported questionnaires (LENT/SOMA scale) with a 3-year follow-up.All Normal Tissue Complication Probability (NTCP) models published until 2021 based on the Equivalent Uniform Dose (EUD) from the rectal Dose Volume Histogram (DVH) were considered for val-idation.Model performance in validation was evaluated through calibration and discrimination.Results: Sixteen NTCP models were tested on data from 1633 patients. G1+ LRB was scored in 465 patients (28.5%), G2+ in 255 patients (15.6%) and G3 in 112 patients (6.8%). The best performances for G2+ and G3 LRB highlighted the importance of the medium-high doses to the rectum (volume parame-ters n = 0.24 and n = 0.18, respectively). Good performance was seen for models of severe LRB. Moreover, a multivariate model with two clinical factors found the best calibration slope.Conclusion: Five published NTCP models developed on non-contemporary cohorts were able to predict a relative increase in the toxicity response in a more recent validation population. Compared to QUANTEC findings, dosimetric results pointed toward mid-high doses of rectal DVH. The external validation cohort confirmed abdominal surgery and cardiovascular diseases as risk factors.(c) 2023 Elsevier B.V. All rights reserved. Radiotherapy and Oncology 183 (2023) 1-9