LATE RECTAL BLEEDING FOLLOWING COMBINED X-RAY AND PROTON HIGH-DOSE IRRADIATION FOR PATIENTS WITH STAGES T3-T4 PROSTATE CARCINOMA

Purpose: Dose escalation for prostate cancer by external beam irradiat ion is feasible by a 160 MeV perineal proton beam that reduces the vol ume of rectum irradiated. We correlated the total doses received to po rtions of the anterior rectum to study the possible relationship of th e volume irradiated to the incidence of late rectal toxicity. Methods: We have randomized 191 patients with stages T3 and T4 prostatic carci noma to one of two treatment dose arms. These were: 1) 75.6 Cobalt-Gy- equivalent (CGE), 50.4 Gy delivered by 107-25 MV photons followed by 2 5.2 CGE delivered perineally by protons (Arm 1) or 2) 67.2 CGE deliver ed by 10-25 MV photons (Arm 2). Results: With a median follow-up of 3. 7 years, post-irradiation rectal bleeding (grades 1 and 2 only, none r equiring surgery or hospitalization) from telangietatic rectal mucosal vessels has occurred in 34% of 99 Arm-1 patients and 16% of 92 Arm-2 patients (p = 0.013). Dose-volume histograms (DVHs) for the anterior r ectal wall, the posterior rectal wall and the total rectum in 41 patie nts treated on Arm 1 were calculated from the three dimensional dose d istributions. Rectal bleeding has occurred in 14 or 34% of the 41 DVH- analyzed subset of Arm-1 patients. Both the fractional volume of the a nterior rectum and the total dose received by fractional volumes of th e anterior rectum significantly correlate with the actuarial probabili ty of bleeding. Conclusions: Clinicians planning dose escalation to me n with localized prostate cancer should approve with caution treatment plans raising more than 40% of the anterior rectum to more than 75 CG E without additional effort to protect the rectal mucosa because this late sequela data indicate that more than half of these men will other wise have rectal bleeding.