Adjuvant radiotherapy for rectal cancer: a systematic overview of 8,507 patients from 22 randomised trials
Gray R., Hills RK., Stowe R., Clarke M., Peto R., Buyse M., Piedbois P.
BACKGROUND: At least 28 randomised, controlled trials have compared outcomes of surgery for rectal cancer combined with preoperative or postoperative radiotherapy with those of surgery alone. We have done a collaborative meta-analysis of these results to give a more balanced view of the total evidence and to increase statistical precision. METHODS: We centrally checked and analysed individual patient data from 22 randomised comparisons between preoperative (6,350 patients in 14 trials) or postoperative (2157 in eight trials) radiotherapy and no radiotherapy for rectal cancer. FINDINGS: Overall survival was only marginally better in patients who were allocated to radiotherapy than in those allocated to surgery alone (62% vs 63% died; p=0.06). Rates of apparently curative resection were not improved by preoperative radiotherapy (85% radiotherapy vs 86% control). Yearly risk of local recurrence was 46% (SE 6) lower in those who had preoperative radiotherapy than in those who had surgery alone (p=0.00001), and 37% (10) lower in those who had postoperative treatment than those who had surgery alone (p=0.002). Fewer patients who had preoperative radiotherapy died from rectal cancer than did those who had surgery alone (45% vs 50%, respectively, p=0.0003), but early (\ensuremath</=1 year after treatment) deaths from other causes increased (8% vs 4% died, p\ensuremath<0.0001). INTERPRETATION: Preoperative radiotherapy (at biologically effective doses \ensuremath>/=30 Gy) reduces risk of local recurrence and death from rectal cancer. If safety can be improved without compromising effectiveness, then overall survival would be moderately improved by use of preoperative radiotherapy, especially for young, high risk patients. Postoperative radiotherapy also reduces local recurrence, but short preoperative radiation schedules seem to be at least as effective as longer schedules.