Neoadjuvant radiotherapy vs. surgery alone for stage II/III mid-low rectal cancer with or without high risk factors: A multicenter randomized trial.

Abstract

3537 Background: Neoadjuvant (chemo)radiotherapy (NRT) is the standard treatment for locally advanced rectal cancer (RC),which reducing local recurrence (LR) without survival benefit. There are also reports claiming similar local control achieved by surgery alone in selected patients, that raising the issue of omitting NRT in low risk patients. The aim of this study was to clarify the benefit of NRT in stage II/III RC with or without high risk factors. Methods: Eligible participants with mid-low cT3-4aN± RC were included and classified as high risk patients and low risk patients according to the clinical staging. High risk was defined as T3 tumor with extramural spread > 5mm, T4a or lymph node > 8mm. High and low risk patients were both randomized into two groups: high risk radiotherapy (HRR) or high risk surgery (HRS), low risk radiotherapy (LRR) or low risk surgery (LRS) separately. Patients in HRR and LRR received short term NRT (5*5Gy) + TME, while patients in HRS and LRS underwent surgery alone. The primary endpoint was 3-y LR. The secondary endpoints were OS, DFS, quality of surgery and safety. Results: From Jun. 2011 to Dec. 2015,401 consecutive patients were analyzed (LRS 99, LRR 97, HRS 102, HRR 103). As for primary endpoint, 3-y LR was obviously lower in low risk patients (3% vs. 9%, p = 0.026), but comparable in LRR vs. LRS (3% vs. 2%, p = 0.32) and HRR vs. HRS (11% vs. 7%, p = 0.42). Concerning secondary endpoints, low risk patients were favorable in 3-y OS (p < 0.001), DFS (p < 0.001), and distant metastasis (p = 0.001), compared to the high risk. And 3-y OS in HRR was higher than that in HRS (82% vs. 70%, p = 0.032). NRT caused 1.5% grade 3/4°radiation-related complications with a higher rate of late leakage (4.5% vs 0.0%, p = 0.004). Besides, positive CRM was higher in HRS (HRS 14.7% vs. HRR 4.9%, p = 0.017). Conclusions: Depth of extramural spread and lymph node status are favorable predictors for LR and survival. NRT may improve OS for high-risk RC. Low-risk RC has very low LR, suggesting against routine use of NRT. Relatively high LR and better OS in high risk patients justify use of NRT or NCR. Short-term radiation is safe for Asian patients, given caution be paid to more late leakage. Clinical trial information: NCT01437514.