Rectal Toxicity 7 Years After High-Dose Radiation For Prostate Cancer: Clinical And Dosimetric Predictors

To evaluate long term prevalence of late rectal bleeding (lrb) and late fecal incontinence (linc) after high-dose RT in prostate cancer patients (pts) (AIROPROS 0102 trial, doses: 70-80 Gy, 1.8-2 Gy/fr) and to model the relationship between lrb/linc and clinical/dosimetric factors. Self-reported questionnaires of 515 pts with min follow-up of 6 yrs (median follow-up 7 yrs) were analyzed with respect to lbr and linc. Correlation between pre-treatment morbidities, hormonal therapy, drug prescription, presence of diabetes or hypertension, abdominal surgery prior to RT (surg), presence of >G1 acute RTOG toxicity, presence of G2-G3 acute fecal incontinence (alinc), pelvic nodes and seminal vesicles irradiation, mean rectal dose, DVH constraints (from V20 Gy to V75 Gy) and lrb/linc was investigated by uni- and multivariate (MVA) logistic analyses. Three hundred forty-seven of 515 pts had at least 3 toxicity questionnaires in the first 36 mos after RT. Correlation between the mean score of linc in the first 36 mos and linc at 7 yrs was also investigated. Thirty-two G1, 2 G2, 3 G3 lrb, and 50 G1, 3 G2, 3 G3 linc were reported. Lrb was only correlate to V75 Gy (continuous variable): p = 0.02, OR = 1.07. The prevalence of lrb ≥1 at 7 yrs was significantly correlated with incidence of G2-G3 lrb in the first 3 yrs after RT: 42.3% in pts with G2-G3 lrb in the first 3 yrs versus 5.6% in non-lrb pts (p < 0.0001). Linc was correlated to multiple variables. In MVA (overall p < 0.0001, AUC = 0.77) V40 Gy (continuous variable, p = 0.09, OR = 1.015), antihypertensives (protective factors, p = 0.005, OR = 0.38), surg (p = 0.004, OR = 4.7), hemorrhoids (p = 0.008, OR = 2.6) and alinc (p = 0.007, OR = 4.4) were correlated to linc. A nomogram for long term linc prediction was developed. Linc at 7 yrs was also correlated to the mean linc in the first 36 mos (p < 0.0001): pts without linc at 7 yrs had a mean score of 0.1 during the first 36 mos, while pts with G1 and with G2-G3 linc at 7 yrs had a mean score of 0.5 and 0.78 during the first 36 mos, respectively. A fraction of pts is still experiencing rectal toxicity symptoms 7 yrs after RT: 7.2% lrb and 10.9% linc. Prevalence of toxicity at 7 yrs is significantly correlated to incidence in the first 3 yrs after RT; this is an indication of a chronicization of symptoms, with linc playing the major role. Mean linc during the first 36 mos after RT can be used as a surrogate for long term linc. Linc is correlated to clinical and dosimetric risk factors and individualized toxicity prediction can be performed through the proposed nomogram.