Modelling late stool frequency and rectal pain after radical radiotherapy in prostate cancer patients: Results from a large pooled population

Aim: To investigate late gastrointestinal toxicity in a large pooled population of prostate cancer patients treated with radical radiotherapy. Normal tissue complication probability models were developed for late stool frequency and late rectal pain. Methods and materials: Population included 1336 patients, 3-year minimum follow-up, treated with 66-80. Gy. Toxicity was scored with LENT-SOMA-scale. Two toxicity endpoints were considered: grade ≥2 rectal pain and mean grade (average score during follow-up) in stool frequency>1.DVHs of anorectum were reduced to equivalent uniform dose (EUD). The best-value of the volume parameter n was determined through numerical optimization. Association between EUD/clinical factors and the endpoints was investigated by logistic analyses. Likelihood, Brier-score and calibration were used to evaluate models.External calibration was also carried out. Results: 4% of patients (45/1122) reported mean stool frequency grade>1; grade ≥2 rectal pain was present in the TROG 03.04 RADAR population only (21/677, 3.1%): for this endpoint, the analysis was limited to this population.Analysis of DVHs highlighted the importance of mid-range doses (30-50. Gy) for both endpoints.EUDs calculated with n. =1 (OR. =1.04) and n. =0.35 (OR. =1.06) were the most suitable dosimetric descriptors for stool frequency and rectal pain respectively.The final models included EUD and cardiovascular diseases (OR. =1.78) for stool frequency and EUD and presence of acute gastrointestinal toxicity (OR. =4.2) for rectal pain. Conclusion: Best predictors of stool frequency and rectal pain are consistent with findings previously reported for late faecal incontinence, indicating an important role in optimization of mid-range dose region to minimize these symptoms highly impacting the quality-of-life of long surviving patients.