Sebag-Montefiore David, Stephens Richard J, Steele Robert, Monson John, Grieve Robert, Khanna Subhash, Quirke Phil, Couture Jean, de Metz Catherine, Myint Arthur Sun, Bessell Eric, Griffiths Gareth, Thompson Lindsay C, Parmar Mahesh
St James's University Hospital, Leeds, UK.
Lancet. 2009 Mar 7;373(9666):811-20. doi: 10.1016/S0140-6736(09)60484-0.
Preoperative or postoperative radiotherapy reduces the risk of local recurrence in patients with operable rectal cancer. However, improvements in surgery and histopathological assessment mean that the role of radiotherapy needs to be reassessed. We compared short-course preoperative radiotherapy versus initial surgery with selective postoperative chemoradiotherapy.
We undertook a randomised trial in 80 centres in four countries. 1350 patients with operable adenocarcinoma of the rectum were randomly assigned, by a minimisation procedure, to short-course preoperative radiotherapy (25 Gy in five fractions; n=674) or to initial surgery with selective postoperative chemoradiotherapy (45 Gy in 25 fractions with concurrent 5-fluorouracil) restricted to patients with involvement of the circumferential resection margin (n=676). The primary outcome measure was local recurrence. Analysis was by intention to treat. This study is registered, number ISRCTN 28785842.
At the time of analysis, which included all participants, 330 patients had died (157 preoperative radiotherapy group vs 173 selective postoperative chemoradiotherapy), and median follow-up of surviving patients was 4 years. 99 patients had developed local recurrence (27 preoperative radiotherapy vs 72 selective postoperative chemoradiotherapy). We noted a reduction of 61% in the relative risk of local recurrence for patients receiving preoperative radiotherapy (hazard ratio [HR] 0.39, 95% CI 0.27-0.58, p<0.0001), and an absolute difference at 3 years of 6.2% (95% CI 5.3-7.1) (4.4% preoperative radiotherapy vs 10.6% selective postoperative chemoradiotherapy). We recorded a relative improvement in disease-free survival of 24% for patients receiving preoperative radiotherapy (HR 0.76, 95% CI 0.62-0.94, p=0.013), and an absolute difference at 3 years of 6.0% (95% CI 5.3-6.8) (77.5%vs 71.5%). Overall survival did not differ between the groups (HR 0.91, 95% CI 0.73-1.13, p=0.40).
Taken with results from other randomised trials, our findings provide convincing and consistent evidence that short-course preoperative radiotherapy is an effective treatment for patients with operable rectal cancer.
术前或术后放疗可降低可手术直肠癌患者局部复发的风险。然而，手术和组织病理学评估的改进意味着放疗的作用需要重新评估。我们比较了短程术前放疗与初始手术加选择性术后放化疗。
我们在四个国家的80个中心进行了一项随机试验。1350例可手术的直肠腺癌患者通过最小化程序随机分配，接受短程术前放疗（25 Gy，分5次；n = 674）或初始手术加选择性术后放化疗（45 Gy，分25次，同时使用5-氟尿嘧啶），后者仅限于环周切缘受累的患者（n = 676）。主要结局指标是局部复发。分析采用意向性分析。本研究已注册，注册号为ISRCTN 28785842。
在包括所有参与者的分析时，330例患者已死亡（术前放疗组157例，选择性术后放化疗组173例），存活患者的中位随访时间为4年。99例患者发生了局部复发（术前放疗组27例，选择性术后放化疗组72例）。我们注意到接受术前放疗的患者局部复发的相对风险降低了61%（风险比[HR]0.39，95%CI 0.27 - 0.58，p < 0.0001），3年时的绝对差异为6.2%（95%CI 5.3 - 7.1）（术前放疗组4.4%，选择性术后放化疗组10.6%）。我们记录到接受术前放疗的患者无病生存率相对提高了24%（HR 0.76，95%CI 0.62 - 0.94，p = 0.013），3年时的绝对差异为6.0%（95%CI 5.3 - 6.8）（77.5%对71.5%）。两组的总生存率无差异（HR 0.91，95%CI 0.73 - 1.13，p = 0.40）。
结合其他随机试验的结果，我们的发现提供了令人信服且一致的证据，表明短程术前放疗是可手术直肠癌患者的一种有效治疗方法。
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