SMARCA4-UT was initially classified as a subtype of sarcoma [1, 4]. It is considered primarily to be smoking-associated undifferentiated carcinomas rather than primary thoracic sarcomas [1]. SMARCA4-UT presents as a large comprehensive mass in the mediastinum, pulmonary hilum, pleura, and lung [5]. There have also been reported cases in which the primary tumor site was the chest wall [4]. Immunohistochemically, complete loss of SMARCA4 expression is typical, and stem cell markers, including SALL4, CD34, and SOX2 are expressed in many cases [4, 5].

The prognosis of SMARCA4-UT is poor, with a median overall survival of 4–7 months [1, 2, 4, 6]. Most patients were treated with chemotherapy alone or palliation. The regimens used to treat sarcomas were not highly effective [2]. Cytotoxic chemotherapy alone was not considered to be effective for SMARCA4-UT. Standard treatment has not yet been established, and the therapeutic approach is in accordance with that used for NSCLC. However, surgical outcomes have not been well-reported. In a previous surgical case series, the median overall survival was 15.6 months [3]. There are few reports on radiotherapy for patients with advanced-stage disease with a poor prognosis [2].

In our cases, CRT with regimens used for NSCLC was effective, resulting in significant tumor shrinkage and complete resection combined with the chest wall. Combined vertebrectomy with tumor margins were safely performed using a CT-based navigation system while viewing the cutting line. Additionally, a large posterolateral incision, the Paulson approach, allows surgery to be performed from a single field of view without the prone position. Surgical resection following CRT may be effective for SMARCA4-UT in terms of local control.

Based on the histopathological findings in both cases, the tumor bed was primarily located in the chest wall. Viable tumor cells were observed only in the chest wall but not in the lung parenchyma. Therefore, the primary site of the tumor was considered to be the chest wall.

These two surgical cases had different postoperative courses. The relapse-free patient showed a major pathological response. In general, complete resection and major pathological responses result in a favorable prognosis for resected lung cancer [7]. The other patient, with 30% residual tumor in the tumor bed, had an early relapse with distant metastases. The development of effective adjuvant therapy is warranted to prevent distant metastatic recurrence in operable cases of SMARCA4-UT with many residual viable cells.

The efficacy of immune checkpoint inhibitors (ICIs) for SMARCA4-UT has been reported [8]. SMARCA4-UT has a high tumor mutation burden [1], which supports the potential efficacy of ICIs. PD-L1 expression, a biomarker for ICI treatment in NSCLC, shows variation in SMARCA4-UT, and its assessment is controversial [5]. In the genomic profile, SMARCA4-UT has a relatively high prevalence of STK11 or KEAP1 co-mutations after the TP53 mutation [1]. Mutations in STK11 and KEAP1 are associated with resistance to ICI treatment in lung adenocarcinoma [9], but these mutations are difficult to sufficiently predict the efficacy of ICI treatment in SMARCA4-UT [5]. ICI plus platinum-based chemotherapy has been suggested to be effective in the advanced stages [10]. In the perioperative period, there has been a report of successful conversion surgery following chemotherapy combined with ICI [11]. Several clinical trials on ICI treatment for SMARCA4-deficient tumors are ongoing [5]. Perioperative ICIs may be key drugs for SMARCA4-UT to improve the prognosis.