Phase III Study of Mediastinal Lymph Node Dissection for Ground Glass Opacity–Dominant Lung Adenocarcinoma

Author(s): Yang Zhang, MD^1,2,3; Bin Qian, MD⁴; Qingping Song, MD⁵; Junjie Ma, MD⁶; Hang Cao, MD^1,2,3; Chaoqiang Deng, MD^1,2,3; Shengping Wang, MD^3,7; Ting Ye, MD^1,2,3; Jiaqing Xiang, MD^1,2,3; Yawei Zhang, MD^1,2,3; Yihua Sun, MD^1,2,3; Yueren Yan, MD^1,2,3; Shanbo Zheng, MD^1,2,3; Haoxuan Wu, MD^1,2,3; Qingyuan Huang, MD^1,2,3; Hong Hu, MD^1,2,3; Yuan Li, MD, PhD^3,8; Fangqiu Fu, MD^1,2,3; Haiquan Chen, MD, PhD^1,2,3;

Source: doi.org/10.1200/JCO-25-00610

Dr. Anjan Patel's Thoughts

This large, well-done study compared systematic mediastinal lymph node dissection (LND) versus no LND in patients with GGO-dominant invasive lung adenocarcinoma (CTR ≤0.5, ≤3 cm, cT1N0M0). Interim analysis of 302 patients showed no lymph node metastases in either arm, with both groups achieving 3-year disease-free survival (DFS) and overall survival (OS) of 100% at the time of analysis. The no LND arm had significantly shorter surgery duration (74 vs 109 min), less blood loss (44 vs 82 mL), shorter hospital stays (3.9 vs 4.5 days), and fewer grade ≥2 complications (3.3% vs 9.3%). Based on these findings, the trial was terminated early for nonmaleficence, and the authors recommend omitting systematic mediastinal LND in this population. In short, for carefully selected GGO-dominant lung adenocarcinoma, skipping mediastinal LND appears safe and spares patients’ unnecessary morbidity—this could be a real practice-changer for our early-stage, node-negative cases.

PURPOSE

Systematic mediastinal lymph node dissection (LND) or sampling is currently recommended for patients with early-stage non–small cell lung cancer. We aimed to investigate whether no mediastinal LND was noninferior to systematic LND in patients with ground glass opacity (GGO)–dominant invasive lung adenocarcinoma.

METHODS

We conducted a multicenter, open-label, phase III, noninferiority randomized controlled trial comparing systematic mediastinal LND versus no mediastinal LND in patients with GGO-dominant invasive lung adenocarcinoma, who were predicted to have no lymph node metastasis on the basis of criteria established in our previous trial. The primary end point was 3-year disease-free survival. An interim analysis was planned upon enrollment of 300 patients, with predefined termination criteria if no mediastinal lymph node metastasis is detected and life-threatening complications occur in the systematic LND arm. This trial is registered on ClinicalTrials.gov (ECTOP-1009, identifier: NCT04527419).

RESULTS

Interim analysis of 302 patients revealed no lymph node metastasis in either study arm. The no LND arm had significantly reduced surgery duration (mean, 74 minutes v 109 minutes; P < .001), blood loss (mean, 44 mL v 82 mL; P = .033), and postoperative hospital stay (mean, 3.9 days v 4.5 days; P = .002). Complications observed in the systematic LND arm included chylothorax in one patient (0.7%) and intraoperative massive bleeding because of superior vena cava injury in one patient (0.7%). No lymphadenectomy-related complications occurred in the no LND arm.

CONCLUSION

On the basis of interim findings and the principle of nonmaleficence, the trial should be terminated. Systematic mediastinal LND should no longer be recommended for patients with GGO-dominant lung adenocarcinoma.

Author Affiliations

¹Department of Thoracic Surgery and State Key Laboratory of Genetics and Development of Complex Phenotypes, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; ²Institute of Thoracic Oncology, Fudan University, Shanghai, People's Republic of China; ³Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China; ⁴Department of Thoracic Surgery, Jiangdu People's Hospital Affiliated to Medical College of Yangzhou University, Jiangsu, People's Republic of China; ⁵Department of Thoracic Surgery, Liaocheng Cancer Hospital, Shandong, People's Republic of China; ⁶Department of Thoracic Surgery, Liaocheng Second People's Hospital, Shandong, People's Republic of China; ⁷Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; ⁸Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China

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