Long-term Quality of Life in Patients Treated in TROG 01.04: A Randomized Trial Comparing Short Course and Long Course Preoperative Radiation Therapy for Rectal Cancer

To compare long-term quality of life (QOL) between short course (SC) and long course (LC) preoperative radiation therapy for rectal cancer. This trial was performed under the auspices of TROG/AGITG/CSSANZ/RANZCR. Three hundred twenty-six patients with T3 rectal cancer were randomized to short course (SC) and long course (LC) preoperative radiation therapy. Two hundred ninety-five patients were eligible for QOL analysis. SC consisted of radiation therapy 5 x 5 Gy in 1 week, early surgery and 6 courses of adjuvant chemotherapy. LC was 50.4 Gy, 1.8 Gy/fraction, in 5.5 weeks, with continuous infusion 5-FU 225 mg/m2/day, surgery in 4 to 6 weeks, and 4 courses of chemotherapy. QOL was measured using the EORTC QLQ-C30 and QLQ-CR38. Assessments were performed at baseline and 1, 2, 3, 6, 9, 12, 18, 24, 36, 48, and 60 months in patients who had not relapsed. Changes from baseline of nine QOL scales, pertaining to global QOL and pelvic functioning and symptoms, were nominated as major endpoints (the Hochberg procedure was used to adjust for multiple comparisons) and an area-under-curve (AUC) statistic (from 1 to 5 years) was used as the main criterion and analyzed using linear mixed models. Pointwise differences, especially at 5-years, were compared using an exact 2-sample permutation test at the 1% level of significance. The overall completion rate of QOL questionnaires at 5 years was 80%. There appeared little difference in long-term QOL between SC and LC. AUC analyses indicated there was little difference in global health status/QOL between arms (p = 0.50) though there was a tendency for symptoms in the area of the gastrointestinal tract to be less prominent in SC patients (nominal p = 0.044; adjusted p = 0.31). There were no significant AUC differences for the other major endpoints (constipation, diarrhea, sexual functioning, sexual enjoyment, micturition, male sexual problems, and defecation). At five years (n = 156), global health status/QOL between arms was not significant (p = 0.64). Symptoms in the area of the gastrointestinal tract tended to favor SC (p = 0.040). There were no differences at 5 years between arms in symptom scales for constipation, diarrhea, micturition, sexual functioning, sexual enjoyment, male sexual problems or defecation. Female sexual problems was not analyzed due to lack in response to this question (n = 11). There were no significant differences between arms among physical functioning, role functioning, emotional functioning, cognitive functioning, or social functioning. We found no clear difference in long-term QOL between SC and LC for global health status/QOL and pelvic functioning and symptoms.