1. A Propensity-matched Study of Lobectomy Versus Segmentectomy for Radiologically Pure Solid Small-sized Non-small Cell Lung Cancer Terumoto Koike 1, Seijiro Sato 1, Takehisa Hashimoto 1, Tadashi Aoki 2, Teruaki Koike 2, Katsuo Yoshiya 2, Shin-ichi Toyabe 3, Masanori Tsuchida 1 1 Division of Thoracic and Cardiovascular Surgery, Niigata University, Niigata, Japan 2 Division of Chest Surgery, Niigata Cancer Center Hospital, Niigata, Japan 3 Niigata University Crisis Management Office, Niigata University Hospital, Niigata, Japan

2. Relevant Financial Relationship Disclosure Statement The authors have no conflicts of interest to declare.

3. BACKGROUND 1.Lobectomy has been performed as a standard surgical procedure for non-small cell lung cancer (NSCLC) patients. 2.In NSCLC patients with a large proportion of ground-glass opacity (GGO) component on CT, excellent surgical outcomes after limited resection were demonstrated. 3.Indications for limited resection for NSCLC patients with radiologically pure solid tumors remain controversial.

4. OBJECTIVE To compare postoperative outcomes after lobectomy and segmentectomy in patients with small radiologically pure solid NSCLC.

5. METHODS (1) Patients Inclusion Criteria: 1.cT1a N0 M0 NSCLC (≤2 cm) 2.Radiologically “pure solid” appearance 3.Peripheral location 4.Underwent lobectomy or segmentectomy in 1998— 2009 5.Complete resection

6. 1. Preoperative characteristics were matched using propensity score methods. 2. Overall survival (OS) and disease- free survival (DFS) were evaluated by the log-rank test and McNemar test. 3. The preoperative factors and surgical procedure were analyzed with a multivariate analysis for OS and DFS. METHODS (2) Analysis Radiologically Pure Solid cT1a N0 M0 NSCLC Patients (n = 251) Lobectomy (n = 151) Segmentectomy (n = 100) Lobectomy (n = 87) Segmentectomy Propensity Score—Matching

7. RESULTS

8. Post-adjustment Preoperative Characteristics of the Patients with Radiologically Pure Solid cT1a N0 M0 NSCLC CharacteristicLobectomySegmentectomy P value All cases, n 8787 Age [y], median (range) 68 (37–81) 68 (42–83).399 Sex, n (%) Male 48 (55) 51 (59).760 Female 39 (45) 36 (41) Smoking index, median (range) 500 (0–2200) 500 (0–2400).809 Percent predicted VC [%], median (range) 114 (67–156) 114 (57–152).897 FEV 1 /FVC ratio [%], median (range) 73 (43–96) 75 (40–89).620 Preoperative CEA [ng/ml], median (range) 2.8 (0.1–25) 2.8 (0.5–18).441 Radiological tumor size [cm], median (range) 1.6 (0.8–2.0) 1.6 (0.6–2.0).919 Tumor histology, n (%) AdSqOthers 68 (78) 70 (80).915 14 (16) 13 (15) 5 (6) 4 (5)

9. Overall Survival Curves for Patients in Propensity Score– Matched Lobectomy and Segmentectomy Groups Years from resection O v e r a l l s u r v i v a l [ % ] Patients at risk Lobectomy Segmentectomy 87 87 83 81 58 48 41 34 29 7 13 0 1 0 85.2% 75.4% 65.5% 84.2% 80.4% 63.1% p = 0.767 = 0.767

10. Disease-free Survival Curves for Patients in Propensity Score–Matched Lobectomy and Segmentectomy Groups D i s e a s e - f r e e s u r v i v a l [ % ] Patients at risk Lobectomy Segmentectomy 87 87 76 74 55 44 40 31 29 7 13 0 1 0 80.0% 71.7% 63.8% 76.9% 73.1% 58.0% p = 0.635 = 0.635

11. Outcomes of Segmentectomy Compared to Lobectomy for Propensity Score–Matched Pairs of the Patients Overall Survival, n (%) Survival Interval LobectomySegmentectomy OR (95% CI) P Value 3-year 74 (91.4) 73 (90.1) 1.143 (0.362–3.702) 1.000 5-year 44 (88.0) 40 (80.0) 1.800 (0.542–6.837).424 7-year 28 (77.8) 1.000 (0.299–3.341) 1.000 Disease-free Survival, n (%) Survival Interval LobectomySegmentectomy OR (95% CI) P Value 3-year 68 (84.0) 69 (85.2) 0.923 (0.385–2.194) 1.000 5-year 43 (82.7) 39 (75.0) 1.500 (0.564–4.230).503 7-year 28 (71.8) 27 (69.2) 1.111 (0.406–3.090) 1.000

12. Multivariate Cox Proportional Hazard Analysis of OS and DFS for the 174 Propensity Score–Matched Patients Overall Survival Disease-free Survival VariableHR 95% CI P Value HR 95% CI P Value Age [years] 1.0631.025–1.103.0011.0401.008–1.074.015 Smoking status (Brinkman Index) 1.0011.000–1.001.0011.0011.000–1.001<.001 FEV 1 /FVC ratio [%] 1.0651.027–1.104.0011.0581.024–1.093.001 Preoperative serum CEA [ng/ml] 1.1001.015–1.193.0211.0841.010–1.164.024 Segmentectomy was not a significant independent predictor of poor OS or DFS

13. CONCLUSIONS  Postoperative outcomes of radiologically pure solid small NSCLC patients were compared in propensity score– matched lobectomy and segmentectomy groups.  Oncological outcomes were similar after lobectomy and segmentectomy.  Even for patients with radiologically pure solid NSCLC, outcomes of segmentectomy may be non-inferior.