ⅠA期NSCLC：亚肺叶与肺叶切除生存率相当

明尼阿波利斯——一项纳入348例在筛查中发现ⅠA期非小细胞肺癌(NSCLC)的患者的队列研究显示，亚肺叶切除术与肺叶切除术具有相似的肺癌生存率和总复发率。

主要研究者、纽约长老会Weill Cornell医疗中心胸外科主任Nasser Altorki医生在美国胸外科学会(AATS)2013年会上报告，经过中位时间73个月的随访，亚肺叶切除组(n=54)和肺叶切除组(n=294)的肺癌死亡率分别为7%和10%(P=0.64)。两组的全因死亡率也相似，分别为17%和22%。

Nasser K. Altorki医生
 
尽管肺叶切除术自1994年起便已成为切除早期NSCLC的标准术式，但有多项研究支持对周围肿瘤较小和肺功能储备较差的老年患者实施亚肺叶切除术。对于心肺功能良好的较年轻患者的最佳手术治疗仍存在争议，目前美国和日本各有一项在此类患者中对比评估肺叶与亚肺叶切除的大规模试验正在进行中。近期证据级别最高的一项研究(Interact. CardioVasc. Thorac. Surg. 2012;14:816-20)显示，肺叶切除术仍是此类患者的最佳手术选择，并且与解剖性肺段切除术相比，楔形切除术的生存率较低、复发率较高。这两种亚肺叶切除术常被合起来与肺叶切除术比较，但实际上从技术或肿瘤学角度来看，这两种术式是有区别的。

在本项研究中，楔形切除术的复发率似乎高于肺段切除术。肺叶切除组和亚肺叶切除组分别有32例和8例患者复发(11% vs. 15%；P=0.40)，其中亚肺叶切除术后复发病例接受的都是楔形切除术(8/38或21%)。

本项研究纳入的348例患者均来自1993~2011年国际早期肺癌行动计划，均在CT筛查中发现实性结节而被诊断为ⅠA期NSCLC并接受了手术治疗。肺叶切除组与亚肺叶切除组在合并疾病方面没有明显差异，包括心脏病(6% vs. 11%)、慢性阻塞性肺病(15% vs. 26%)和糖尿病(9% vs. 7%)，中位年龄分别为63岁和65岁，中位吸烟量分别为48和49包/年。肺叶切除组患者的肿瘤明显更大(13 vs. 11 mm)，更多接受纵隔淋巴结活检(78% vs. 56%)，人均切除的淋巴结也更多(8 vs. 5枚)。

结果显示，所有患者的总体院内死亡率较低，为0.9%(3/348)，Altorki医生表示这是优秀筛查中心可以达到的水平。肺叶切除组和亚肺叶切除组的10年生存率分别为88%和90%(log rank P=0.64)。肿瘤＜2 cm的患者比例无明显差异(88% vs. 89%)。

Cox回归分析显示，在校正上述潜在混淆因素后，仅有年龄[危险比(HR)，2.9；P＜0.0001]和严重气肿(HR，4.2；P=0.005)可预测生存率，而亚肺叶切除不是生存率的预测因素(HR，0.8；P=0.60)。

特邀评论员、宾夕法尼亚大学医疗系统胸外科主任Joseph S. Friedberg医生评论称，“尽管参加本项研究的胸外科医生都有良好资质，但亚肺叶切除术却有70%为楔形切除术而非肺段切除术，而且亚肺叶切除组患者超过40%、肺叶切除组近25%的患者未曾接受纵隔淋巴结活检”令他感到惊讶。“根据肺癌研究组的分析和常识，我们有理由怀疑部分患者(尤其是亚肺叶切除患者)分期偏低和/或治疗不足，然而该研究的结果却与文献中报道的一样好，您如何解释这一点？”

Altorki医生答复称，对纵隔区域的评估情况并不理想，有必要加强有关纵隔评估的预后和治疗价值的患者教育，不过该研究中的纵隔淋巴结活检率仍然远高于文献数据。他还推测，多数患者接受的是电视辅助胸腔镜手术(VATS)，而在VATS中评估纵隔淋巴结的难度大于开放手术。

他还表示，很多外科医生可能认为楔形切除术与解剖性肺段切除术对1~1.2 cm肿瘤的治疗效果相当，“这是目前正在进行中的随机试验要解决的一个问题”。

Altorki医生报告称无相关利益冲突。

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By: PATRICE WENDLING, Oncology Practice

MINNEAPOLIS – Sublobar resection and lobectomy resulted in equivalent lung cancer survival and overall recurrence rates in a screen-detected cohort of 348 stage IA non–small-cell lung cancer patients.

In all, 7% of patients (4/54) who underwent sublobar resection and 10% of those (29/294) who underwent lobectomy died of lung cancer after a median follow-up of 73 months (P = .64).
 
All-cause mortality was also statistically similar at 17% and 22%, said Dr. Nasser Altorki, professor of cardiothoracic surgery and director of thoracic surgery at New York Presbyterian–Weill Cornell Medical Center in New York.

Although lobectomy has been the standard of care for resection of early-stage non–small-cell lung cancer since 1994, several studies support sublobar resection in patients with small peripheral tumors and the elderly with compromised pulmonary reserve.

The best surgical treatment for younger patients with adequate cardiopulmonary function remains controversial, with two large, ongoing trials in the U.S. and Japan evaluating lobar vs. sublobar resection in this setting. A recent best evidence paper (Interact. CardioVasc. Thorac. Surg. 2012;14:816-20) concluded that lobectomy is still the best surgical option for these patients, citing evidence of lower survival and higher recurrence rates with wedge resections than with anatomic segmentectomies. The two sublobar techniques are often lumped together in comparisons with lobectomy, but are not technically or oncologically the same.

Wedge resection in the current study seemed to be associated with a higher rate of recurrence than segmentectomy, Dr. Altorki said at the annual meeting of the American Association for Thoracic Surgery.

Recurrence occurred in 32 patients after lobectomy and 8 after sublobar resection (11% vs. 15%; P = .40), with all of the sublobar resection recurrences occurring after wedge resection (8/38 or 21% vs. 0%).

"I don’t want to say this is a practice-changing study; however, it is a study that calls for more technical equipoise in our approach to the [surgical] treatment of lung cancer," he said during a discussion of the results. "Clearly, we can apply this operation to patients who would be candidates for both lobectomy and sublobar resection, but it does not extend to those patients, for example, that would have been poor candidates for any surgical resection."

The 348 patients had c1A non–small-cell lung cancer that presented as a solid nodule on computed tomography screening and underwent surgery as part of the International Early Lung Cancer Action Program from 1993 to 2011. Comorbidities were similar among the lobectomy and sublobar patients including cardiac disease (6% vs. 11%), chronic obstructive pulmonary disease (15% vs. 26%) and diabetes (9% vs. 7%). Their median age was 63 vs. 65 years, and the median number of pack-years of smoking was 48 vs. 49, respectively.

The lobectomy group had significantly larger tumors (13 mm vs. 11 mm), more frequent sampling of mediastinal nodes (78% vs. 56%) and more resected lymph nodes (mean 8 vs. 5).

The overall rate of hospital mortality in the multicenter study was low at 0.9% (3/348) and "represents what is achievable in screening centers of excellence," Dr. Altorki said.

Ten-year survival was 88% with lobectomy and 90% with sublobar resection (log rank P = .64). There was no difference in patients with tumors less than 2 cm (88% vs. 89%), who represented the majority or 86% of the cohort.

Cox regression analysis, adjusted for the above potential confounders, showed that only age (hazard ratio, 2.9; P less than .0001) and severe emphysema (HR, 4.2; P = .005) significantly predicted survival, whereas sublobar resection did not (HR, 0.8; P = .60), he said.

Invited discussant Dr. Joseph S. Friedberg, chief of thoracic surgery at the University of Pennsylvania Health System-Presbyterian in Philadelphia, expressed surprise that despite undergoing surgery by highly qualified general thoracic surgeons, 70% of sublobar resections were performed as wedge and not segmentectomies, and that more than 40% of sublobar resection patients and nearly a quarter of lobectomy patients did not have one mediastinal node biopsied.

"One would expect, based on the Lung Cancer Study Group analysis and common sense, that some of these patients, especially sublobar resection patients, were understaged and/or undertreated and yet the results are as good as anything in the literature," he said. "How do you reconcile that?"

Dr. Altorki said assessment of the mediastinal field was disappointing and that further education is needed on the prognostic and therapeutic benefits of such assessment, but that the rate far exceeds what is in the published literature. He also speculated that most of the patients were done by video-assisted thoracic surgery and that mediastinal node assessment may not be as straightforward with VATS as it is with open surgery.

Dr. Altorki said that, going in, many of the surgeons may have thought that a 1- to 1.2-cm tumor may be equally resected with wedge resection and anatomic segmentectomy, and that this "is a job we have to address in ongoing randomized trials."

Dr. Altorki reported no relevant financial disclosures.