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Purpose: To model late fecal incontinence after high-dose prostate cancer radiotherapy (RT) in patients accrued in the AIROPROS (prostate working group of the Italian Association of Radiation Oncology) 0102 trial using different endpoint definitions., Methods and Materials: The self-reported questionnaires (before RT, 1 month after RT, and every 6 months for ≤3 years after RT) of 586 patients were available. The peak incontinence (P_INC) and two longitudinal definitions (chronic incontinence [C_INC], defined as the persistence of Grade 1 or greater incontinence after any Grade 2-3 event; and mean incontinence score [M_INC], defined as the average score during the 3-year period after RT) were considered. The correlation between the clinical/dosimetric parameters (including rectal dose-volume histograms) and P_INC (Grade 2 or greater), C_INC, and M_INC of ≥1 were investigated using multivariate logistic analyses. Receiver operating characteristic curves and the area under the curve were used to assess the predictive value of the different multivariate models., Results: Of the 586 patients, 36 with a Grade 1 or greater incontinence score before RT were not included in the present analysis. Of the 550 included patients, 197 (35.8%) had at least one control with a Grade 1 or greater incontinence score (M_INC >0). Of these 197 patients, 37 (6.7%), 22 (4.0%), and 17 (3.1%) were scored as having P_INC, M_INC ≥1, and C_INC, respectively. On multivariate analysis, Grade 2 or greater acute incontinence was the only predictor of P_INC (odds ratio [OR], 5.9; p = .0009). Grade 3 acute incontinence was predictive of C_INC (OR, 9.4; p = .02), and percentage of the rectal volume receiving >40 Gy of ≥80% was predictive of a M_INC of ≥1 (OR, 3.8; p = .008) and of C_INC (OR, 3.6; p = .03). Previous bowel disease, previous abdominal/pelvic surgery, and the use of antihypertensive (protective factor) correlated highly with both C_INC and M_INC ≥1. The predictive values of the models for C_INC (area under the curve, 0.83) and M_INC ≥1 (area under the curve, 0.73) were greater than the ones for P_INC (area under the curve, 0.62) and more reliable (p = .0001-.0003 against p = .02). Nomograms for the two longitudinal definitions were derived., Conclusions: The longitudinal definitions of fecal incontinence (C_INC and M_INC ≥1) were helpful in accounting for both the persistence and the severity of the incontinence. A significant fraction of peak events was consequential to acute incontinence, and a longer duration of symptoms mainly depended on the rectal dose bath (percentage of rectal volume receiving >40 Gy), and pretreatment clinical factors., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: Development of user-friendly tools for the prediction of single-patient probability of late rectal toxicity after conformal radiotherapy for prostate cancer., Methods and Materials: This multicenter protocol was characterized by the prospective evaluation of rectal toxicity through self-assessed questionnaires (minimum follow-up, 36 months) by 718 adult men in the AIROPROS 0102 trial. Doses were between 70 and 80 Gy. Nomograms were created based on multivariable logistic regression analysis. Three endpoints were considered: G2 to G3 late rectal bleeding (52/718 events), G3 late rectal bleeding (24/718 events), and G2 to G3 late fecal incontinence (LINC, 19/718 events)., Results: Inputs for the nomogram for G2 to G3 late rectal bleeding estimation were as follows: presence of abdominal surgery before RT, percentage volume of rectum receiving >75 Gy (V75Gy), and nomogram-based estimation of the probability of G2 to G3 acute gastrointestinal toxicity (continuous variable, which was estimated using a previously published nomogram). G3 late rectal bleeding estimation was based on abdominal surgery before RT, V75Gy, and NOMACU. Prediction of G2 to G3 late fecal incontinence was based on abdominal surgery before RT, presence of hemorrhoids, use of antihypertensive medications (protective factor), and percentage volume of rectum receiving >40 Gy., Conclusions: We developed and internally validated the first set of nomograms available in the literature for the prediction of radio-induced toxicity in prostate cancer patients. Calculations included dosimetric as well as clinical variables to help radiation oncologists predict late rectal morbidity, thus introducing the possibility of RT plan corrections to better tailor treatment to the patient's characteristics, to avoid unnecessary worsening of quality of life, and to provide support to the patient in selecting the best therapeutic approach., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To predict acute Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) and Subjective Objective Signs Management and Analysis/Late Effect of Normal Tissue (SOMA/LENT) toxicities of the lower gastrointestinal (LGI) syndrome in patients with prostate cancer undergoing three-dimensional conformal radiotherapy using a tool (nomogram) that takes into account clinical and dosimetric variables that proved to be significant in the Italian Association for Radiation Oncology (AIRO) Group on Prostate Cancer (AIROPROS) 0102 trial., Methods and Materials: Acute rectal toxicity was scored in 1,132 patients by using both the RTOG/EORTC scoring system and a 10-item self-assessed questionnaire. Correlation between clinical variables/dose-volume histogram constraints and rectal toxicity was investigated by means of multivariate logistic analyses. Multivariate logistic analyses results were used to create nomograms predicting the symptoms of acute LGI syndrome., Results: Mean rectal dose was a strong predictor of Grade 2-3 RTOG/EORTC acute LGI toxicity (p = 0.0004; odds ratio (OR) = 1.035), together with hemorrhoids (p = 0.02; OR = 1.51), use of anticoagulants/antiaggregants (p = 0.02; OR = 0.63), and androgen deprivation (AD) (p = 0.04; OR = 0.65). Diabetes (p = 0.34; OR = 1.28) and pelvic node irradiation (p = 0.11; OR = 1.56) were significant variables to adjust toxicity prediction. Bleeding was related to hemorrhoids (p = 0.02; OR = 173), AD (p = 0.17; OR = 0.67), and mean rectal dose (p = 0.009; OR = 1.024). Stool frequency was related to seminal vesicle irradiation (p = 0.07; OR = 6.46), AD administered for more than 3 months (p = 0.002; OR = 0.32), and the percent volume of rectum receiving more than 60 Gy (V60Gy) V60 (p = 0.02; OR = 1.02). Severe fecal incontinence depended on seminal vesicle irradiation (p = 0.14; OR = 4.5) and V70 (p = 0.033; OR = 1.029)., Conclusions: To the best of our knowledge, this work presents the first set of nomograms available in the literature specific to symptoms of LGI syndrome and provides clinicians with a tailored probability of the specific outcome. Validation of the tool is in progress.

Purpose: To find predictors for rectal and intestinal acute toxicity in patients with prostate cancer treated with > or =70 Gy conformal radiotherapy., Methods and Materials: Between July 2002 and March 2004, 1,132 patients were entered into a cooperative study (AIROPROS01-02). Toxicity was scored using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale and by considering the changes (before and after treatment) of the scores of a self-administered questionnaire on rectal/intestinal toxicity. The correlation with a number of parameters was assessed by univariate and multivariate analyses. Concerning the questionnaire, only moderate/severe complications were considered., Results: Of 1,132 patients, 1,123 were evaluable. Of these patients, 375, 265, and 28 had Grade 1, 2, and 3 Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer toxicity, respectively. The mean rectal dose was the most predictive parameter (p = 0.0004; odds ratio, 1.035) for Grade 2 or worse toxicity, and the use of anticoagulants/antiaggregants (p = 0.02; odds ratio, 0.63) and hormonal therapy (p = 0.04, odds ratio, 0.65) were protective. The questionnaire-based scoring revealed that a greater mean rectal dose was associated with a greater risk of bleeding; larger irradiated volumes were associated with frequency, tenesmus, incontinence, and bleeding; hormonal therapy was protective against frequency and tenesmus; hemorrhoids were associated with a greater risk of tenesmus and bleeding; and diabetes associated highly with diarrhea., Conclusion: The mean rectal dose correlated with acute rectal/intestinal toxicity in three-dimensional conformal radiotherapy for prostate cancer, and hormonal therapy and the use of anticoagulants/antiaggregants were protective. According to the moderate/severe injury scores on the self-assessed questionnaire, several clinical and dose-volume parameters were independently predictive for particular symptoms.

Purpose: Prostate cancer patients in Italy are offered the choice of the full spectrum of possible treatment options for their disease, but the diffusion of the more recent technological refinements among the Radiation Oncology centers is not homogeneous and there is a need to establish a reference "historical" data source. This retrospective study describes the changing patterns in prostate cancer patient practice and the therapeutic results obtained in nine Radiation Oncology centers of Northern and Central Italy (five in Northern Italy and four in Central Italy)., Methods and Materials: A total of 1759 prostate cancer patients, radically treated in the nine radiotherapy (RT) centers between 1980 and 1998, made up the study population. Data collected for each patient included clinical, pathologic, therapeutic features, and toxicity. The overall survival, disease-specific survival (DSS), and clinical relapse-free survival (RFS) were calculated for the whole series and for the subsets of patients defined by different clinical, pathologic, and therapeutic features, according to three accrual periods (A, 1980-1990; B, 1991-1994; and C, 1995-1998). Univariate and multivariate analyses were performed to identify prognostic factors related to survival and late adverse effects (cystitis and proctitis) probability., Results: Patient accrual increased markedly during the 2 decades considered, and the percentage of cases with Stage C or D disease dropped from 49% (period A) to 43% (period B) to 37% (period C) (p < 0.0001, chi-square). The baseline prostate-specific antigen value was available for 10%, 76%, and 95% of the cases treated in the three different periods. The major changes in the therapeutic options were an increase in dose to the prostate (>66 Gy in 44%, 84%, and 93% of the patients treated in period A, B, and C, respectively); a reduction in treated volumes, including pelvic lymphatic drainage (56-39% before 1995, 22% thereafter); and an increase in cases treated in association with hormonal therapy (50% before 1991, 80% thereafter). Lower energy (<10 MV) photon beams were progressively abandoned (12% before 1990 vs. 6-7% thereafter), along with an increase in the use of blocks (60% in the last 4 years of the study vs. about 30-40% before 1995) and "conformal" RT (applied in 41% of cases treated after 1994). The actuarial RFS, DSS, and overall survival rate at 5 years was, respectively, 60% +/- 2%, 75% +/- 2%, 66% +/- 2% for period A; 74% +/- 2%, 90% +/- 1%, 83% +/- 2%, for period B; and 67% +/- 5%, 90% +/- 2%, 79% +/- 5% for period C. The actuarial overall survival, DSS, and RFS rate for the whole series of 1759 patients was 77% +/- 1%, 86% +/- 1%, and 68% +/- 1% at 5 years, respectively. Multivariate analysis showed that only American Urologic Association stage, grade, dose to the prostate, accrual period, association with hormonal treatment after (or both after and before) RT (only in terms of DSS and RFS), and baseline prostate-specific antigen value (only for RFS) retained prognostic significance in the final Cox model., Conclusion: The increase in the accrual of prostate cancer patients radically treated with RT has been accompanied by considerable changes in the clinical features at presentation, as well as in the staging and treatment procedures. Patients treated more recently had better survival results. An earlier stage and more favorable grade were linked with better overall, DSS, and RFS at multivariate analysis. Lower prostate-specific antigen baseline values were also related to better RFS. Better results were obtained with higher radiation doses, and the dose to tumor seemed the most important treatment-related prognostic factor. The toxicity (cystitis and proctitis, every Radiation Therapy Oncology Group grade) was substantially the same in the different accrual periods, but larger treated volumes and higher doses appeared to increase the incidence of late effects.