Towards elimination of anal-sphincter and rectal dysfunction after radiation therapy for prostate cancer

Background: External radiation therapy is one of the best management options available for localized prostate cancer. The higher the radiation therapy dose administered, the more likely local control will be obtained, but the radiation dose that can be given is limited by the need to restrict the frequency and severity of unwanted effects. Late side effects can permanently decrease well-being and the quality of life. The technology of 3-dimenssional treatment planning has opened up a possibility of quantitatively analyze the relationship between radiation long-term effects, dose and the volume of irradiated tissue. Little attention has been paid to assess fecal leakage in relation to the dose given to the anal-sphincter region. Patients and Methods: A selfadministered questionnaire for assessing symptoms indicating anal sphincter, large-bowel, urinarytract and sexual dysfunction was sent to all patients with clinically localized prostate adenocarcinoma treated by external beam radiation in 199396 in Stockholm. Information on the external beam radiation therapy was retrieved from hospital records. The dose-planning treatment data were restored to the treatment planning system and dosevolume histograms of the analsphincter region and rectum were produced. Long-term effects on anal sphincter and large-bowel function were investigated. Results: Of all the 158 available patients, 145 (92%) answered and returned the questionnaire. Defecation-urgency was reported by 28% (8/29) of the patients irradiated using 4 fields with a multi-leaf collimator and 20 percent (8/40) of the patients treated using 3 fields (one AP, two lateral) without multi-leaf collimator. Seven out of 29 patients (24%) treated with 4-field reported diarrhea or loose stools. None of the patients treated with 3 fields (one AP, two oblique) with a multi-leaf collimator reported this symptom. A statistically significant correlation was obtained between DVHs of the anal-sphincter region and risk of fecal leakage at intermediate dose (45-55 Gy). None of patients who received a dose of 35 Gy or more or 40 Gy or more to, at the most, 60 or 40 percent, respectively, of the anal-sphincter region volume reported fecal leakage. There was a statistically significant correlation between DVHs of the rectum and the risk of defecation-urgency and diarrhea in the dose interval 25-42 Gy. Preserved erectile function at 9-18 months was found in 17 of the 31 men (55%) and at the 4 to 5-year follow-up in five of 22 (23%). Conclusions: Among patients irradiated with a multi-leaf collimator, defecation-urgency, diarrhea and loose stools were more common after four fields than after three, but fecal leakage necessitating the use of pads and distress from the gastrointestinal tract were less common. Three fields (one AP and two lateral) without a multi-leaf collimator entailed a higher risk of defecation-urgency than three fields (one AP and two oblique) with a multi-leaf collimator. Among bowel symptoms, the strongest association with gastrointestinal distress was found for fecal leakage. Careful monitoring of unwanted radiation to the analsphincter region as well as rectum may reduce the risk of fecal leakage, blood and phlegm in stools, defection-urgency, and diarrhea; it is probably possible to define a threshold for a by and large harmless dose (in terms of induced dysfunction) to the anal sphincter region (35 Gy or more to, at the most, 60% or 40 Gy or more to, at the most, 40% of the anal sphincter region?)