Segmentectomy Versus Lobectomy for Non-Small Cell Lung Cancers: Clinical Evidence

Four decades ago, the very first patients were enrolled into the Lung Cancer Study Group. It was a randomized, controlled trial that compared lobectomy to limited resection for biopsy-proven T1N0 non-small cell lung cancer (NSCLC). The results of this study were published in 1995. They demonstrated a three-fold increase in loco-regional recurrence and a 30 percent increase in overall death for patients who underwent limited resections (1).

In Western nations, lobectomy became the undisputed standard of care for resectable NSCLC. In Japan, there remained an ongoing interest in anatomical segmentectomies for small peripheral lung cancers, especially those with a ground-glass opacity (GGO) component. A systematic review and meta-analysis published in 2016 identified fifty-four studies that compared lobectomy procedures to sublobar resections (2). When studies were limited to lobectomies versus segmentectomies in an intentionally selected patient cohort, all six identified studies originated from Japan (3–8). A comprehensive meta-analysis of these six studies concluded no significant differences in overall or disease-free survival between the segmentectomy and lobectomy arms (2).

More recently, an extraordinary effort between the Japanese Clinical Oncology Group and the West Japan Oncology Group led to the completion of the JCOG 0802 trial. The trial included 1,106 patients with peripheral NSCLC ≤ 2cm who were randomized to either lobectomy (n = 554) or segmentectomy (n = 552) (9,10). The primary endpoint of the study was overall survival. After a 7.3-year median follow-up, patients who underwent segmentectomy were found to have a superior five-year overall survival rate compared to lobectomy survival rates: 94.3% versus 91.1% (p = 0.0082).

Interestingly, locoregional recurrence appeared to increase after segmentectomy compared to lobectomy (6.9% versus 3.1%). The lower rate of overall survival in the lobectomy group could have been attributed to a higher number of patients who died from a second cancer. Another surprising finding from the trial included the relatively modest improvement in forced expiratory volume in one second (FEV1) after segmentectomy compared to lobectomy; a 3.5% difference when measured one year after surgery.

Regarding postoperative outcomes, the participating institutions should be congratulated on a mortality rate of 0% in both surgical arms. Patients who underwent segmentectomies were found to have a higher rate of Grade ≥2 air leak and reinsertion of chest tube. Yet, other perioperative outcomes were similar between the two groups.

Based on the results of the JCOG 0802 study, there is now robust clinical evidence to justify a paradigm shift toward anatomical segmentectomies rather than lobectomies for selected patients with early stage NSCLC. Clinical implications of this new evidence may be further strengthened by the CALGB/Alliance 140503 trial if oncological outcomes are found to be similar between the lobectomy group and the sublobar resection group (11). However, it should be noted that more than half of the patients in the sublobar arm underwent wedge resections rather than anatomical segmentectomies in the CALGB study.

References

1. Ginsberg RJ, Rubinstein LV. Randomized trial of lobectomy versus limited resection for T1 N0 non-small cell lung cancer. Lung Cancer Study Group. Ann Thorac Surg 1995;60:615-622; discussion 622-613.
2. Cao C, Chandrakumar D, Gupta S, et al. Could less be more?-A systematic review and meta-analysis of sublobar resections versus lobectomy for non-small cell lung cancer according to patient selection. Lung Cancer 2015;89:121-132.
3. Tsutani Y, Miyata Y, Nakayama H, et al. Oncologic outcomes of segmentectomy compared with lobectomy for clinical stage IA lung adenocarcinoma: propensity score-matched analysis in a multicenter study. J Thorac Cardiovasc Surg 2013;146:358-364.
4. Hamatake D, Yoshida Y, Miyahara S, et al. Surgical outcomes of lung cancer measuring less than 1 cm in diameter. Interact Cardiovasc Thorac Surg 2012;15:854-858.
5. Okada M, Koike T, Higashiyama M, et al. Radical sublobar resection for small-sized non-small cell lung cancer: a multicenter study. J Thorac Cardiovasc Surg 2006;132:769-775.
6. Watanabe T, Okada A, Imakiire T, et al. Intentional limited resection for small peripheral lung cancer based on intraoperative pathologic exploration. Jpn J Thorac Cardiovasc Surg 2005;53:29-35.
7. Kodama K, Doi O, Higashiyama M, et al. Intentional limited resection for selected patients with T1 N0 M0 non-small-cell lung cancer: a single-institution study. J Thorac Cardiovasc Surg 1997;114:347-353.
8. Sugi K, Kobayashi S, Sudou M, et al. Long-term prognosis of video-assisted limited surgery for early lung cancer. Eur J Cardiothorac Surg 2010;37:456-460.
9. Suzuki K, Saji H, Aokage K, et al. Comparison of pulmonary segmentectomy and lobectomy: Safety results of a randomized trial. J Thorac Cardiovasc Surg 2019;158:895-907.
10. Nakamura K, Saji H, Nakajima R, et al. A phase III randomized trial of lobectomy versus limited resection for small-sized peripheral non-small cell lung cancer (JCOG0802/WJOG4607L). Jpn J Clin Oncol 2010;40:271-274.
11. Altorki NK, Wang X, Wigle D, et al. Perioperative mortality and morbidity after sublobar versus lobar resection for early-stage non-small-cell lung cancer: post-hoc analysis of an international, randomised, phase 3 trial (CALGB/Alliance 140503). Lancet Respir Med 2018;6:915-924.

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