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

Abstract

AimTo 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 materialsPopulation included 1336 patients, 3-year minimum follow-up, treated with 66–80Gy. 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. Results4% 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 (30–50Gy) 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. ConclusionBest 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.