In lung cancer of 2.0 cm or less, a safe surgical margin to avoid locoregional recurrence after sublobar resection is widely recognized as “the clinical tumor size or more”. However, no consensus has been reached in lung cancer larger than 2.0 cm. Since the size of the solid component is considered to be very important, we examined the optimal surgical margin to avoid locoregional recurrence after sublobar resection in NSCLC larger than 2.0 cm. We demonstrated that a sufficient surgical margin distance to avoid locoregional recurrence was “the size of the solid part or more” for GGO-dominant type, but was undefinable for solid-dominant type.
Based on the results shown in Table 2, most pathological characteristics indicated that patients with GGO-dominant tumor had a better outcome than those with solid-dominant tumor. Regarding pathological invasiveness, neither lymph node metastasis, lymphatic permeation nor vascular invasion was observed in GGO-dominant tumors. Because we included only cN0M0 NSCLC in this study, there were few lymph node metastases even in solid-dominant tumor. Moreover, the size of the invasive part of solid-dominant type was significantly larger than that of GGO-dominant type (p < 0.001). Tsutani et al. reported that the size of the invasive part was significantly associated with malignant behavior and recurrence in lung adenocarcinoma . Regarding the predominant subtype in adenocarcinoma, several studies have shown that micropapillary and solid adenocarcinoma were associated with poor survival [28–32]. In our study, while micropapillary and solid adenocarcinoma were not observed in GGO-dominant type, they were observed in 4.2% and 11.1% of solid-dominant type, respectively. We thought that these pathological characteristics of GGO-dominant type as mentioned above might support the notion that the minimum surgical margin distance required to avoid locoregional recurrence in GGO-dominant type was smaller than that in solid-dominant type.
In our study, there was no recurrence in GGO-dominant tumor (Table 4), suggesting that we may be able to avoid locoregional recurrence if we achieve complete resection. Moon et al. reported that there was no locoregional recurrence if they could achieve R0 resection in GGO-dominant NSCLC of 3.0 cm or less (HR 3.87, p = 0.027) . However, we previously reported that, while lymph node metastasis was not observed, lymphatic permeation (7.5%) and vascular invasion (11.3%) were observed in 53 GGO-dominant NSCLC larger than 3.0 cm that were resected by lobectomy . As such, the surgical margin should be considered, even if the target lesion for surgery is GGO-dominant type, to achieve R0 resection by sublobar resection.
Our suggestions for the optimal surgical margin for NSCLC are shown in Fig. 2, which was made by combining the results in this study for NSCLC larger than 2.0 cm with current standards for NSCLC of 2.0 cm or less based on previous studies [23, 24] From the results that all GGO-dominant tumors larger than 2.0 cm were resected with a margin distance of the size of the solid part or more and there was no recurrence, we thought that this could be regarded as a standard surgical margin to avoid locoregional recurrence for GGO-dominant tumor. In contrast, for a solid-dominant tumor, locoregional recurrence occurred even if the tumor was resected with a margin distance of the clinical tumor size or more, which is why we thought that a standard surgical margin to avoid locoregional recurrence for solid-dominant type was undefinable. It may be better to add postoperative radiation therapy or chemotherapy to sublobar resection to avoid locoregional recurrence in solid-dominant tumor larger than 2.0 cm.
This study was limited by its retrospective nature and the small number of cases because we focused on relatively rare cases that underwent sublobar resection for large tumor, which was contrary to the current gold standard for the surgical treatment of lung cancer. To our knowledge, previous studies to determine the optimal surgical margin in NSCLC included only about 30% tumors larger than 2.0 cm that underwent sublobar resection (Additional Table 1) [23–25, 35–37]. If possible, we will accumulate more cases and validate our results and theories in a larger population in the near future. As another limitation, 39 of the 85 (45.8%) patients did not undergo lymph node dissection. Three patients recurred in lymph node after surgery, however those patients had undergone lymph node dissection and were assessed as pathological N0. In other words, none of the patients without lymph node dissection showed lymph node recurrence after sublobar resection, suggesting that this limitation had little influence on our results. As for operative mode, lymph node dissection and adjuvant chemotherapy, we performed a univariate analysis to verify the influence of these factors on our results (Additional Table 2). As a result, none of these factors was significantly associated with locoregional recurrence. We could not perform a multivariate analysis because of the small number of events.
In conclusion, the optimal surgical margin to avoid locoregional recurrence after sublobar resection in NSCLC larger than 2.0 cm was “the size of the solid part or more” for GGO-dominant tumor, while it was undefinable for solid-dominant tumor. We believe that our results represent important findings for the daily treatment of large tumor showing GGO, particularly in patients with low lung function. Moreover, our results should help future multicenter prospective trials to determine indications for sublobar resection for large tumor showing GGO.