*4.1. Surgical Intervention for Patients with Oligometastatic NSCLC*

Considering the indications for surgical intervention in oligometastatic NSCLC cases, brain and adrenal metastases as oligometastatic organs have been reported to have a relatively good prognosis with 5-year OS rates of 20% and 20–30% [24]. The ACCP guidelines state that in cases of single brain metastasis and adrenal metastasis, cN0–1 is indicated for local treatment of metastatic lesions and resection of the primary lesion [3]. In addition, the NCCN guidelines recommend local treatment for metastatic lesions and multidisciplinary treatments, including systemic treatment, for primary lesions in cases of single brain metastases [1]. There are two strategies including surgery for treating oligometastasis: (1) resection of the primary tumor in advance and then control of distant tumors using surgery/RT and micrometastasis with drug therapy, and (2) addition of local treatment (surgery/RT) for patients with residual tumors that responded to drug therapy and became localized; i.e., a salvage approach.

The efficacy of upfront resection of a primary lesion of oligometastatic NSCLC was reported by Wang et al. in 2018. They conducted a retrospective study of patients with oligometastatic NSCLC, and 172 patients were divided into two groups: group A underwent primary surgical treatment and adjuvant chemotherapy, while group B was treated with systematic chemotherapy and local RT. The MSTs in groups A and B were 48 months and 18 months, respectively, and the 5-year survival rates were 21.1% and 7.6%, respectively (*p* < 0.05). They concluded that the local surgical treatment of primary lesions of NSCLC significantly increased OS and the 5-year survival rates of patients with oligometastatic NSCLC [25].

Gomez et al. reported the efficacy of a salvage approach (the addition of local treatment after definitive drug therapy) for oligometastatic NSCLC in their phase II RCT. First-line therapy was four or more cycles of platinum doublet therapy or 3 or more months of EGFR or anaplastic lymphoma kinase (ALK) inhibitors. The locations of oligometastases were as follows: 13 brain, 10 bone, 8 adrenal gland, 7 pleura, 6 lung, 4 cervical lymph node, 2 liver, 2 spleen, 1 retroperitoneal lymph node, 1 paraspinal mass, and 1 kidney. After receiving first-line therapy, patients were randomly assigned to either a local consolidative therapy group (RT and/or surgery) or a maintenance treatment group. This study was terminated early after randomization of 49 patients. Among patients administered local consolidative therapies, 96% underwent some form of RT. The median PFS in the local consolidative therapy group

was 11.9 months versus 3.9 months in the maintenance treatment group (hazard ratio 0.35, *p* = 0.0054). Furthermore, no grade 4 or 5 toxicities were reported. They suggested that the addition of local therapy after first-line therapy might improve PFS of patients with oligometastatic NSCLC [26].

With regard to the optimal modality of local treatment for oligometastatic NSCLC, to date, no RCTs have compared SBRT and surgery. Otake and Goto reviewed salvage SBRT for oligometastatic NSCLC and concluded that SBRT appeared to provide a high level of local control with minimal associated toxicity [27]. Although surgery is a powerful local treatment, pre-treatment and/or post-treatment as a combined-modality approach is often required for oligometastatic NSCLC. It is necessary to carefully select surgery or RT as local treatment, considering the patient's ability to tolerate total therapies.
