早期直肠癌两种手术治疗方法旗鼓相当

菲尼克斯——美国结直肠外科医师协会(ASCRS)2013年会上公布的一项系统综述和meta分析显示，根治性切除术和局部切除术这2种手术治疗方法对早期直肠癌患者的疗效基本相当。

上述结论的依据是涉及2,855例T1N0M0期直肠腺癌患者的13项研究。所有这些研究均发表于1997年之后，当时，全直肠系膜切除和现代局部切除技术已应用于临床。

主要研究者、加拿大西安大略大学外科医生Sami A. Chadi博士报告称，TEMS(经肛内镜显微手术)和TAMIS(经肛微创手术)等新技术的应用改善了患者结局，当校正直肠下三分之一病变患者多接受局部切除术治疗这一选择性偏倚因素后，接受这2种手术方法治疗者的结局相当。

研究者指出，局部切除患者生活质量数据更佳。相对于根治性切除术而言，局部切除术与术后并发症风险下降87%、围手术期死亡率风险下降69%以及永久性造瘘术风险下降83%相关。虽然局部切除术也与5年死亡风险增加46%相关，但校正直肠下三分之一病变患者多采用局部切除术因素后，上述差异不再存在。

研究者认为，上述结果的意义在于，既然已经确定了2组T1N0M0期直肠腺癌手术患者呈“临床均势”，那么就有必要针对这2种手术方法开展一项前瞻性随机对照试验。同时还需要进一步的数据以评估新辅助治疗或辅助性治疗对这些患者是否有作用。目前正在进行有关辅助性治疗疗效评估以及T2期病变患者接受局部切除术治疗的可能性研究。

研究者分析了来自有关T1N0M0期直肠癌患者的12项观察性研究和1项随机对照试验数据。结果显示，局部切除术患者5年总生存率较差(相对风险，1.46)，其差异相当于局部切除术组每1,000例患者死亡病例多72例。但上述差异主要来源于经肛局部切除术(TAE)，TEMS局部切除术与根治性切除术患者5年总生存率并无显著差异。

研究者校正了直肠下三分之一病变患者多采用局部切除术治疗可能导致的选择性偏倚后，两组患者5年总生存率不再存在显著差异。

与根治性切除术相比，局部切除术可使术后并发症风险降低(发生率比，0.13)，相当于每1,000例患者术后并发症病例减少129例。TAE和TEMS患者分别与根治性切除术患者比较未见显著差异。

局部切除术还与围手术期死亡风险下降相关(发生率比，0.31)，相当于每1,000例患者中死亡病例减少11 例；局部切除术与永久性造瘘术风险减少也存在关联(发生率比，0.17)，相当于每1,000例患者永久性造瘘术病例减少225例。

Chadi博士声称无相关利益冲突。

专家点评：下一步工作是开展随机试验

新罕布什尔州Dartmouth-Hitchcock医学中心的Allyson H. Stone博士评论指出，局部切除术是早期直肠癌患者，即T1和(或)T2期无淋巴结受累和无转移患者的理想治疗策略。我们应大力推广局部切除术作为主要治疗策略。但目前文献资料显示根治性切除术患者肿瘤学结局更佳。

要确定应采取何种策略，必须有来自随机对照试验的强有力数据支持。Chadi博士称，这样的试验应纳入2种手术方法均适合的患者，并且是经过核磁共振成像或直肠腔内超声等标准程序确诊的患者。在试验设计时，还应将共病和辅助治疗列入主要混杂因素。研究亚组还应包括病变位置位于直肠下三分之一或上三分之二的患者，并且样本量要大到足以校正直肠下三分之一病变患者采取局部切除术的选择偏倚。

鉴于自局部切除术应用之初，新技术已经应用于临床实践，该手术已具有更好的可视性，切除也更为精准。这也使局部切除术肿瘤学结局有望与根治性切除术相媲美。

Stone博士无利益冲突披露。

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By: SUSAN LONDON, Oncology Practice

PHOENIX – Two differing surgical approaches for early rectal cancer – radical resection and local resection—appear to be essentially equivalent treatment options, finds a systematic review and meta-analysis.

The conclusion is based on an analysis of morbidity and mortality data from 13 studies with a total of 2,855 patients with stage T1N0M0 rectal adenocarcinoma. All of the studies were published after 1979, when total mesorectal excision and modern local resection techniques were being used.

There are "improved results with the newer techniques of TEMS [transanal endoscopic microsurgery] and TAMIS [transanal minimally invasive surgery], as well as comparable outcomes when we adjust for the fact that there is a bit of a selection bias in the literature for lower-third lesions to be performed by local resection," lead investigator Dr. Sami A. Chadi reported at the annual meeting of the American Society of Colon and Rectal Surgeons.

"We know that quality of life data is better with local resection," he commented. Relative to radical resection, local resection was associated with an 87% lower risk of postoperative complications, a 69% lower risk of perioperative mortality, and an 83% lower risk of permanent ostomy.

On the other hand, local resection also was associated with a 46% higher likelihood of death at 5 years. Survival no longer differed significantly, however, when analyses took into account the greater use of local resection for cancers located in the lower third of the rectum.

"The implication is that we have established clinical equipoise between groups with T1N0M0 adenocarcinoma of the rectum, thus prompting the need for a prospective randomized, controlled trial on these two procedures," he maintained. "We do need further data to assess whether or not there is a role for neoadjuvant or adjuvant therapy in these groups." Ongoing studies are assessing the role of therapy, as well as the potential for local resection to be performed for T2 lesions.

Dr. Chadi, a surgeon with the University of Western Ontario in London, and his colleagues analyzed data from 12 observational studies and one randomized, controlled trial among patients with T1N0M0 cancer.

The 5-year rate of overall survival was poorer with local resection (relative risk, 1.46), with the difference between groups corresponding to 72 more deaths per 1,000 patients in the local resection group, according to Dr. Chadi, who disclosed no conflicts of interest related to the research.

However, this difference was largely driven by transanal excision (TAE) local procedures. There was no significant difference in this outcome for TEMS local procedures as compared with radical resection.

The researchers also repeated the survival analysis with an adjustment for cancers in the lower third of the rectum. In these patients, the surgical choice is more often local resection, potentially leading to selection bias.

When the ratio of lower-third cancers was equal in both the radical and local resection groups, there was no longer a significant difference in 5-year overall survival.

Compared with radical resection, local resection yielded a lower risk of postoperative complications (rate ratio, 0.13), with the difference corresponding to 129 fewer complications per 1,000 patients in the local resection group. The difference was significant for both TAE and TEMS individually as compared with radical resection.

Local resection also was associated with a lower risk of perioperative mortality (rate ratio, 0.31), with the difference corresponding to 11 fewer deaths per 1,000 patients in the local resection group, and a lower risk of permanent ostomy (risk ratio, 0.17), with the difference corresponding to 225 fewer permanent ostomies per 1,000 patients in the local resection group.

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Randomized trial is next step

Local excision is an ideal management strategy for early-stage rectal cancer patients, T1 and/or T2 with no nodal involvement and no metastases. It would be great if we could pursue local excision as a primary management strategy. At this point, however, the data in the literature suggest that radical resection is associated with superior oncological outcomes.

Robust data from a randomized controlled trial are needed to decide management. Dr. Chadi was said that such a trial would have to include patients who are candidates for either procedure and are diagnosed using a standard procedure such as magnetic resonance imaging or endorectal ultrasound. Comorbidities and receipt of adjuvant therapy would be among the main confounders to consider in trial design. Study subgroups would include patients with lesions in either the lower one-third or the upper two-thirds of the rectum, and the sample size would need to be powered to account for the selection bias for lower third lesions to have local resection.

Since the initiation of local resection, newer techniques have become available that allow for better visualization and more precise dissections. This has given rise to the hope that oncologic outcomes—historically superior with radical resection—might now be similar with local resection.

Dr. Allyson H. Stone, of the Dartmouth-Hitchcock Medical Center in Lebanon, N.H., was the invited discussant of the study. She had no relevant financial disclosures.