Modeling severe late rectal bleeding: Results on a large pooled population of prostate cancer patients.

Abstract

82 Background: To develop a model for grade 3 (G3) late rectal bleeding (LRB) after radical radiotherapy (RT) for prostate cancer, in a pooled population from 2 large prospective trials: Airopros0102 (Fellin RO2014) and TROG 03.04 RADAR (Ebert IJROBP2015). Methods: Both trials included patients (pts) treated with 3DCRT at 66-80Gy, conventional fractionation. Planning data were available for all pts, G3 LRB was prospectively scored using the SOMA/LENT, with a minimum follow-up of 3 years. Rectal dose-volume histograms were reduced to Equivalent Uniform Dose (EUD) calculated with volume parameter n derived by 3 studies: n=0.06 (Rancati RO2004), n=0.05 (Rancati RO2011) and n=0.018 (Defraene IJROBP2011). EUD was inserted into multivariable logistic regression (MVL) together with clinical and treatment features. Irradiation of seminal vesicles (SV), irradiation of pelvic nodes, hormonal therapy, hypertension, previous abdominal surgery (SURG), use of anticoagulants, diabetes, cardiovascular diseases and presence of acute toxicity were considered as potential dose-modifying factors. Goodness of fit was evaluated with Hosmer Lemeshow test (HL), calibration through calibration slope and AUC was used for discrimination power. Results: 1,337 pts were available: 708 RADAR and 669 Airopros. G3 LRB was scored in 95 pts (7.1%): 62 RADAR and 33 Airopros. EUD calculated with n=0.05 was the best dosimetric predictor for G3 LRB. A 4-variable MVL model was fitted including EUD (OR=1.07 p=0.16), SV (OR=4.75 p<0.001), SURG (OR=2.30 p=0.02) and cardiovascular disease (OR=1.42 p=0.18). AUC=0.63, calibration slope=0.99 (R^2=0.89), p for HL=0.43. Inclusion of acute toxicity (OR=2.34 p<0.001) slightly improved AUC (0.65), confirming a possible role of consequential injury. Conclusions: EUD with n=0.05 was predictive of G3 LRB in this pooled population, confirming the importance of sparing the rectum from high doses. Irradiation of seminal vesicles together with the presence of cardiovascular disease and previous abdominal surgery were relevant dose-modifying factors highly impacting the incidence of G3 LRB. The study was funded by: AIRC IG16087, Fondazione Monzino, NHMRC (300705, 455521, 1006447)