Morbidity and Mortality of Major Pulmonary Resections in Patients With Early-Stage Lung Cancer: Initial Results of the Randomized, Prospective ACOSOG Z0030 Trial

doi:10.1016/j.athoracsur.2005.06.066

The Annals of Thoracic Surgery

Volume 81, Issue 3, March 2006, Pages 1013-1020

Presented at the Forty-first Annual Meeting of The Society of Thoracic Surgeons, Tampa, FL, Jan 24–26, 2005. Winner of the J. Maxwell Chamberlain Memorial Award for General Thoracic Surgery.

https://doi.org/10.1016/j.athoracsur.2005.06.066 Get rights and content

Background

Little prospective, multiinstitutional data exist regarding the morbidity and mortality after major pulmonary resections for lung cancer or whether a mediastinal lymph node dissection increases morbidity and mortality.

Methods

Prospectively collected 30-day postoperative data was analyzed from 1,111 patients undergoing pulmonary resection who were enrolled from July 1999 to February 2004 in a randomized trial comparing lymph node sampling versus mediastinal lymph node dissection for early stage lung cancer.

Results

Of the 1,111 patients randomized, 1,023 were included in the analysis. Median age was 68 years (range, 23 to 89 years); 52% were men. Lobectomy was performed in 766 (75%) and pneumonectomy in 42 (4%). Pathologic stage was IA in 424 (42%), IB in 418 (41%), IIA in 37 (4%), IIB in 97 (9%), and III in 45 (5%). Lymph node sampling was performed in 498 patients and lymph node dissection in 525. Operative mortality was 2.0% (10 of 498) for lymph node sampling and 0.76% (4 of 525) for lymph node dissection. Complications occurred in 38% of patients in each group. Lymph node dissection had a longer median operative time and greater total chest tube drainage (15 minutes, 121 mL, respectively). There was no difference in the median hospitalization, which was 6 days in each group (p = 0.404).

Conclusions

Complete mediastinal lymphadenectomy adds little morbidity to a pulmonary resection for lung cancer. These data from a current, multiinstitutional cohort of patients who underwent a major pulmonary resection constitute a new baseline with which to compare results in the future.

Section snippets

Material and Methods

From June 1999 to February 2004, 1,111 patients were randomized into the Z0030 trial. Eligibility requirements included patients older than 18 years of age, an Eastern Cooperative Oncology Group (ECOG) performance score lower than 3, and a tissue diagnosis of a clinically resectable T1 or T2, N0 or nonhilar N1, M0 non–small-cell lung cancer (squamous cell carcinoma, large cell carcinoma, or adenocarcinoma, including bronchoalveolar carcinoma) established before randomization. Patients underwent

Results

There were 529 (52%) men and 494 (48%) women randomized to either LNS only (498 patients) or LND (525 patients; Table 1). The median age was 68 years with a range of 23 to 89 years. The race was white in 955 patients (93%), black in 46 (4%), and other in 22 (2%). An ECOG performance score of zero was recorded in 687 patients (67%), one in 308 (30%), and two in 28 (3%). Tumor location is shown in Figure 1; the most common tumor location was the right upper lobe (38%). Mediastinoscopy was

Comment

Performing a complete mediastinal lymphadenectomy at the time of pulmonary resection for primary lung cancer is controversial. Complete dissection is purported to be associated with a lower risk of local recurrence and better long-term survival because of improved staging. Passlick and associates [5] demonstrated that patients with immunohistochemically detected lymph node metastasis have increased long-term survival if a mediastinal LND is performed. The arguments against complete

References (11)

C.F. Mountain et al.
Regional lymph node classification for lung cancer staging [see comment]
Chest
(1997)
R.J. Ginsberg et al.
Modern thirty-day operative mortality for surgical resections in lung cancer
J Thorac Cardiovasc Surg
(1983)
H. Wada et al.
Thirty-day operative mortality for thoracotomy in lung cancer
J Thorac Cardiovasc Surg
(1998)
J. Deslauriers et al.
Prospective assessment of 30-day operative morbidity for surgical resections in lung cancer
Chest
(1994)
D.H. Harpole et al.
Prognostic models of thirty-day mortality and morbidity after major pulmonary resection
J Thorac Cardiovasc Surg
(1999)

There are more references available in the full text version of this article.

Cited by (580)

Importance of Lymph Node Evaluation in ≤2-cm Pure-Solid Non-Small Cell Lung Cancer
2024, Annals of Thoracic Surgery
The prevalence of lymph node (LN) metastasis in small-sized lung cancer varies depending on the tumor size and proportion of ground-glass opacity. We investigated occult LN metastasis and prognosis in patients with small-sized non-small cell lung cancer (NSCLC), mainly focusing on the pure-solid tumor.
We retrospectively reviewed patients with ≤2-cm clinical N0 NSCLC who underwent lung resection with curative intent from 2003 to 2017. Among them we analyzed patients who also underwent adequate complete systematic LN dissection. Pathologic results and disease-free survival of the radiologically mixed ground-glass nodule (mGGN) and pure-solid nodule (PSN) groups were analyzed.
Of 1329 patients analyzed, 591 had mGGNs and PSNs. As tumor size increased, patients in the mGGN group showed no difference in LN metastasis: ≤1 cm, 2.27%; 1.0 to 1.5 cm, 2.19%; and 1.5 to 2.0 cm, 2.18% (P = .999). However the PSN group showed a significant difference in LN metastasis as the tumor size increased: ≤1 cm, 2.67%; 1.0 to 1.5 cm, 12.46%; and 1.5 to 2.0 cm, 21.31% (P < .001). In the multivariate analysis tumor size was a significant predictor of nodal metastasis in the PSN group but not in the mGGN group. In terms of 5-year disease-free survival, the mGGN group showed a better prognosis than the PSN group (94.4% vs 71.2%, P < .001).
We need to conduct a thorough LN dissection during surgery for small-sized NSCLC, especially for pure-solid tumors ≥ 1 cm.
A Shift in Paradigm: Selective Lymph Node Dissection for Minimizing Oversurgery in Early Stage Lung Cancer
2024, Journal of Thoracic Oncology
Systematic lymph node dissection has been widely accepted and turned into a standard procedure for lung cancer surgery. In recent years, the concept of “minimal invasive surgery (MIS)” has greatly changed the surgical paradigm of lung cancer. Previous studies revealed that excessive dissection of lymph nodes without metastases had uncertain clinical benefit. Meanwhile, it leads to the elevated risk of postoperative complications including chylothorax and laryngeal nerve injury. In addition, dissection of nonmetastatic lymph nodes may disturb systematic immunity, resulting in the secondary effect on primary tumor or latent metastases. The past decades have witnessed the innovative strategies such as lobe-specific lymph node dissection and selective lymph node dissection. On the basis of evolution of lymph node dissection strategy, we discuss the negative effects of excessive nonmetastatic lymph node dissection and summarize the recent advances in the optimized dissection strategies, hoping to provide unique perspectives on the future directions.
Selective Mediastinal Lymph Node Dissection Strategy for Clinical T1N0 Invasive Lung Cancer: A Prospective, Multicenter, Clinical Trial
2023, Journal of Thoracic Oncology
We aimed to prospectively evaluate our previously proposed selective mediastinal lymph node (LN) dissection strategy for peripheral clinical T1N0 invasive NSCLC.
This is a multicenter, prospective clinical trial in China. We set six criteria for predicting negative LN stations and finally guiding selective LN dissection. Consolidation tumor ratio less than or equal to 0.5, segment location, lepidic-predominant adenocarcinoma (LPA), negative hilar nodes (stations 10–12), and negative visceral pleural invasion (VPI) were used separately or in combination as predictors of negative LN status in the whole, superior, or inferior mediastinal zone. LPA, hilar node involvement, and VPI were diagnosed intraoperatively. All patients actually underwent systematic mediastinal LN dissection. The primary end point was the accuracy of the strategy in predicting LN involvement. If LN metastasis occurred in certain mediastinal zone that was predicted to be negative, it was considered as an “inaccurate” case.
A total of 720 patients were enrolled. The median number of LN dissected was 15 (interquartile range: 11–20). All negative node status in certain mediastinal zone was correctly predicted by the strategy. Compared with final pathologic findings, the accuracy of frozen section to diagnose LPA, VPI, and hilar node metastasis was 94.0%, 98.9%, and 99.6%, respectively. Inaccurate intraoperative diagnosis of LPA, VPI, or hilar node metastasis did not lead to inaccurate prediction of node-negative status.
This is the first prospective trial validating the specific mediastinal LN metastasis pattern in cT1N0 invasive NSCLC, which provides important evidence for clinical applications of selective LN dissection strategy.
Assessment of Updated Commission on Cancer Guidelines for Intraoperative Lymph Node Sampling in Early Stage NSCLC
2022, Journal of Thoracic Oncology
The American College of Surgeons Commission on Cancer recently updated its sampling recommendations for early stage NSCLC from at least 10 lymph nodes to at least one N1 (hilar) and three N2 (mediastinal) lymph node stations. Nevertheless, intraoperative lymph node sampling minimums remain subject to debate. We sought to evaluate these guidelines in patients with early stage NSCLC.
We performed a cohort study using a uniquely compiled data set from the Veterans Health Administration. We manually abstracted data from operative notes and pathology reports of patients with clinical stage I NSCLC receiving surgery (2006–2016). Adequacy of lymph node sampling was defined using count-based (≥10 lymph nodes) and station-based (≥three N2 and one N1 nodal stations) minimums. Our primary outcome was recurrence-free survival. Secondary outcomes were overall survival and pathologic upstaging.
The study included 9749 patients. Count-based and station-based sampling guidelines were achieved in 3302 (33.9%) and 2559 patients (26.3%), respectively, with adherence to either sampling guideline increasing over time from 35.6% (2006) to 49.1% (2016). Adherence to station-based sampling was associated with improved recurrence-free survival (multivariable-adjusted hazard ratio = 0.815, 95% confidence interval: 0.667–0.994, p = 0.04), whereas adherence to count-based sampling was not (adjusted hazard ratio = 0.904, 95% confidence interval: 0.757–1.078, p = 0.26). Adherence to either station-based or count-based guidelines was associated with improved overall survival and higher likelihood of pathologic upstaging.
Our study supports station-based sampling minimums (≥three N2 and one N1 nodal stations) for early stage NSCLC; however, the marginal benefit compared with count-based guidelines is minimal. Further efforts to promote widespread adherence to intraoperative lymph node sampling minimums are critical for improving patient outcomes after curative-intent lung cancer resection.
Efficacy of an Autologous Blood Patch for Prolonged Air Leak: A Systematic Review
2022, Annals of Thoracic Surgery
Prolonged air leak after pulmonary surgery remains a clinical challenge and sometimes needs surgical reintervention. An autologous blood patch (ABP) may provide a noninvasive method to stop air leak. Its value, however, is debatable. The aim of this systematic review is to synthesize evidence regarding the efficacy of ABP in patients with prolonged air leak.
A comprehensive search for published studies was performed in the Medline database, Embase, and the Cochrane library. Randomized controlled trials, case-control studies, and case series in which a postoperative ABP was performed were included. Findings from these studies were tabulated and data were synthesized graphically (PROSPERO registration number CRD42020157591).
A total of eight studies was included in the analysis, comprising 151 patients. Studies demonstrated heterogeneity in ABP timing and practice, and an intermediate to high risk of bias was scored. The majority of studies demonstrated a beneficial effect of the ABP, with a high rate of success of more than 89%. One randomized trial did not find a difference in time to cessation of air leak after ABP compared with conservative tube thoracostomy. The overall complication rate was 10%.
Quality of included studies is limited owing to lack of comparison groups. Synthesized data in this review demonstrate a high rate of successful procedures and acceptable complication rates, and seems encouraging enough to justify a large randomized clinical trial on the use of ABP for patients who have prolonged air leak after thoracic surgery.
Commentary: Thoracoscopic right middle lobectomy—small but tricky
2022, JTCVS Techniques

View all citing articles on Scopus

^⁎: Members of the American College of Surgeons Oncology (ACOSOG) Z0030 study group and their affiliations are listed in the Appendix.

View full text

J. Maxwell Chamberlain memorial paperMorbidity and Mortality of Major Pulmonary Resections in Patients With Early-Stage Lung Cancer: Initial Results of the Randomized, Prospective ACOSOG Z0030 Trial

Background

Methods

Results

Conclusions

Section snippets

Material and Methods

Results

Comment

Chest

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

Chest

J Thorac Cardiovasc Surg

J. Maxwell Chamberlain memorial paper
Morbidity and Mortality of Major Pulmonary Resections in Patients With Early-Stage Lung Cancer: Initial Results of the Randomized, Prospective ACOSOG Z0030 Trial