Consequential Late Effects up to 10 years Following Primary and Postoperative Radiotherapy for Prostate Cancer

Abstract

To evaluate the impact of acute toxicity on chronic problems following primary (pRT) and postoperative radiotherapy (opRT) for prostate cancer. Patients treated in the years 2003-2008 were surveyed prospectively using a validated questionnaire (EPIC, Expanded Prostate Cancer Index Composite) before the beginning of RT, at the last day, two months, 1-3 years, 5-8 years and 9-13 years after the end of RT. A score difference of 5 points is regarded as clinically significant, >20 points as a clinically large quality of life (QoL) change. Only patients treated up to 70.2-72Gy (pRT) and 66.0-66.6Gy (opRT) in 1.8-2.0Gy fractions were included. Patients were required to respond to the questionnaire before and at the end of RT, additionally at least one questionnaire >1 year after RT, resulting in 287 patients (n = 185 pRT and n = 102 opRT). The response rate to the questionnaire after 1-3 years was 85% (n = 245), after 5-8 70% (n = 201) and after 9-13 years 55% (n = 157). Significant differences before the start of RT between pRT and opRT were lower urinary (mean bother score of 87 vs. 82; p = 0.02) and sexual (mean bother score of 61 vs. 39; p<0.01) scores for opRT. However, larger changes at the end of RT were found for pRT (urinary score: 21 vs. 13 points; p<0.01; sexual score: 11 vs. -2 Punkte; p<0.01; negative change = QoL improvement). After 10 years, urinary scores declined less (5 vs. 14 points; p = 0.04), sexual scores declined more (18 vs. -2 points; p = 0.01) following pRT vs. opRT. For patients with a bother score decline >20 points in the bowel domain (Bdiff>20) and urinary domain (Udiff>20) at the last day of RT, the respective bowel baseline scores were similar both for pRT and opRT, urinary baseline scores only for opRT. However, patients with pRT and Udiff>20 had significantly higher baseline scores (85 vs. 79; p<0.01). For patients with Bdiff >20, both the difference in relation to baseline levels and the absolute bother scores 10 years after RT remained significantly worse in comparison to patients with smaller acute changes (71 vs. 93 10 years after pRT; p<0.01; 82 vs. 91 after opRT; p = 0.07). The same effect was found for patients with Udiff>20 in the urinary domain, statistically significant up to 5 years after pRT, but only up to 2 months after opRT. In comparison to opRT, significantly larger acute, but smaller chronic urinary changes resulted. Acute toxicity during radiotherapy has a significant impact on chronic problems as consequential late effects, especially in the bowel domain. These acute bowel score changes cannot be predicted by baseline problems before the beginning of treatment.