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Purpose: To compare GI symptoms, measures of generic and disease specific health related quality of life (HRQoL), anorectal and pudendal nerve function and anal sphincter morphology between (i) patients ≥2 years after 3D conformal radiotherapy (3D-CRT)±high dose rate (HDR) brachytherapy for carcinoma of the prostate and aged matched patients before radiotherapy and (ii) symptomatic and asymptomatic patients ≥2 years after 3D-CRT ± HDR brachytherapy., Material and Methods: Methodology included: (i) modified LENT-SOMA scales for GI symptoms, (ii) EORTC QLQ-C30 and EORTC QLQ-PR25 questionnaires for generic and disease specific HRQoL, (iii) anorectal manometry and terminal motor latency for anorectal and pudendal nerve function and (iv) endorectal ultrasound for anal sphincter morphology. GI symptoms, parameters of HRQoL, anorectal and pudendal nerve function and anal sphincter morphology were compared using Mann-Whitney's U, unpaired t and χ 2 tests., Results: Impairment of HRQoL bowel symptoms in the patients ≥2 years after 3D-CRT ± HDR brachytherapy was associated with worse anorectal motor and sensory function, internal and external anal sphincter morphology and 5× greater prevalence of pudendal nerve dysfunction compared with age matched patients before radiotherapy. Symptomatic patients had worse (i) HRQoL measures including global quality of life and bowel and urinary symptom scores, (ii) rectal bleeding, fecal urgency and incontinence scores and (iii) a 2× higher prevalence of pudendal nerve dysfunction compared with asymptomatic patients. Rectal and anal (i) V 40 Gy >65%, (ii) Dmax >60 Gy, (iii) pudendal nerve Dmax >60 Gy and (iv) Anal V 60 Gy >40% were associated with a greater prevalence of pudendal nerve dysfunction., Conclusions: 3D-CRT ± HDR brachytherapy for prostate carcinoma, impairs late functional measures including HRQoL, anorectal and pudendal nerve function. Rectal, anal and pudendal nerve radiation dose constraints are proposed for reducing the prevalence of pudendal nerve dysfunction.

Purpose: To evaluate the long-term efficacy and toxicity of a hypofractionated (55 Gy in 20 fractions within 4 weeks) vs. a conventionally fractionated (64 Gy in 32 fractions within 6.5 weeks) dose schedule for radiotherapy (RT) for localized carcinoma of the prostate., Methods and Materials: A total of 217 patients were randomized to either the hypofractionated (n=108) or the conventional (n=109) dose schedule. Most patients (n=156) underwent RT planning and RT using a two-dimensional computed tomography method. Efficacy using the clinical, radiologic, and prostate-specific antigen data in each patient was evaluated before RT and at predetermined intervals after RT until death. Gastrointestinal and genitourinary toxicity using the modified Late Effect in Normal Tissue-Subjective Objective Management Analytic (LENT-SOMA) scales was also evaluated before and at intervals after RT to 60 months., Results: The whole group has now been followed for a median of 90 months (range, 3-138). Of the 217 patients, 85 developed biochemical relapse (nadir prostate-specific antigen level+2 μg/L), 36 in the hypofractionated and 49 in the conventional group. The biochemical relapse-free, but not overall, survival at 90 months was significantly better with the hypofractionated (53%) than with the conventional (34%) schedule. Gastrointestinal and genitourinary toxicity persisted 60 months after RT and did not differ between the two dose schedules. Multivariate analyses revealed that the conventional schedule was of independent prognostic significance, not only for biochemical failure, but also for an increased risk of worse genitourinary symptoms at 4 years., Conclusions: A therapeutic advantage of the hypofractionated compared with the conventional dose schedule for RT of prostate cancer was evident at 90 months in the present study., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: Normal tissue complication probability (NTCP) of the rectum, bladder, urethra, and femoral heads following several techniques for radiation treatment of prostate cancer were evaluated applying the relative seriality and Lyman models., Methods: Model parameters from literature were used in this evaluation. The treatment techniques included external (standard fractionated, hypofractionated, and dose-escalated) three-dimensional conformal radiotherapy (3D-CRT), low-dose-rate (LDR) brachytherapy (I-125 seeds), and high-dose-rate (HDR) brachytherapy (Ir-192 source). Dose-volume histograms (DVHs) of the rectum, bladder, and urethra retrieved from corresponding treatment planning systems were converted to biological effective dose-based and equivalent dose-based DVHs, respectively, in order to account for differences in radiation treatment modality and fractionation schedule., Results: Results indicated that with hypofractionated 3D-CRT (20 fractions of 2.75 Gy/fraction delivered five times/week to total dose of 55 Gy), NTCP of the rectum, bladder, and urethra were less than those for standard fractionated 3D-CRT using a four-field technique (32 fractions of 2 Gy/fraction delivered five times/week to total dose of 64 Gy) and dose-escalated 3D-CRT. Rectal and bladder NTCPs (5.2% and 6.6%, respectively) following the dose-escalated four-field 3D-CRT (2 Gy/fraction to total dose of 74 Gy) were the highest among analyzed treatment techniques. The average NTCP for the rectum and urethra were 0.6% and 24.7% for LDR-BT and 0.5% and 11.2% for HDR-BT., Conclusions: Although brachytherapy techniques resulted in delivering larger equivalent doses to normal tissues, the corresponding NTCPs were lower than those of external beam techniques other than the urethra because of much smaller volumes irradiated to higher doses. Among analyzed normal tissues, the femoral heads were found to have the lowest probability of complications as most of their volume was irradiated to lower equivalent doses compared to other tissues.

Purpose: We performed a randomized trial to compare the GI and urogenital toxicity of radiotherapy (RT) for localized (confined to the organ), early-stage (T1-T2N0M0, TNM classification) carcinoma of the prostate, using a conventional (64 Gy in 32 fractions within 6.5 weeks) vs. a hypofractionated (55 Gy in 20 fractions within 4 weeks) schedule and to determine the efficacy of the respective treatment schedules., Methods and Materials: This report is based on an interim analysis of the first 120 consecutive patients in this Phase III trial after a median follow-up of 43.5 months (range 23-62). RT planning was based on two-dimensional CT data, and the treatment was delivered using a three- or four-field 6-23-MV photon technique. GI and urogenital toxicity (symptom questionnaires incorporating the subjective elements of the late effects of normal tissues-subjective, objective, management, analytic classification of late effects and the European Organization for Research and Treatment of Cancer sexual function questionnaire) were evaluated before RT and 1 month, 1 year, and 2 years after RT completion. The efficacy of RT was assessed clinically (digital rectal examination and radiologic imaging) and biochemically (prostate-specific antigen assay) at baseline, and every 3 months for 2 years after RT and every 6 months subsequently., Results: RT, whether conventional or hypofractionated, resulted in an increase in all six symptom categories used to characterize GI toxicity and in four of five symptom categories used to document urinary morbidity 1 month after therapy completion. Sexual dysfunction (based on limited data), which existed in more than one-third of patients before RT, also increased to just more than one-half of patients 1 month after RT. The increase in urinary toxicity after RT was not sustained (diurnal urinary frequency had decreased significantly at 2 years). In contrast, all six symptom categories of GI toxicity remained increased 1 year after RT. Four of the six GI symptom categories (rectal pain, mucous discharge, urgency of defecation, and rectal bleeding) were still increased at 2 years compared with baseline. Except for a slightly greater percentage of patients experiencing mild rectal bleeding at 2 years among those who received hypofractionated RT, no differences were noted in toxicity between the conventional and hypofractionated RT schedule. The mean prostate-specific antigen level was 14.0 +/- 1.0 ng/mL at baseline and declined to a nadir of 1.3 +/- 0.2 ng/mL at a median of 16.8 months (range 0.8-28.3) after RT completion. However, it then rose in 17 patients (8 in the hypofractionated and 9 in the conventional treatment group). Only 8 of these 17 patients were found to have signs of clinical relapse (5 local, 1 regional lymph node, and 2 systemic [bony metastases]) after histopathologic and radiologic reassessment). The remaining 9 patients had biochemical relapse only (defined as three consecutive rises in prostate-specific antigen after nadir). The 4-year biochemical relapse-free survival rate was 85.8% for all patients and did not differ significantly between the two radiation dose schedules (86.2% for the hypofractionated and 85.5% for the conventional fractionation group)., Conclusion: RT for prostate carcinoma, using a three- or four-field 6-23-MV photon technique without posterior shielding of the lateral fields, is an underestimated cause of persistent GI morbidity. The incidence of clinically significant GI and urogenital toxicity after conventional and hypofractionated RT appears to be similar. Hypofractionated RT for carcinoma of the prostate seems just as effective as conventional RT after a median follow-up approaching 4 years.