In 1898, a patient with multiple primary cancers was reported by Billroth [11]; however, the concept of multiple primary lung cancers (MPLCs) was first described by Beyreuther in 1924 [11]. Martini and Melamed [8] published the first diagnostic criteria in 1975, and Antakli et al [9] supplemented the diagnostic criteria for second primary lung cancer in 1995 and incorporated elements of the new international multidisciplinary lung adenocarcinoma classification [12]. According to these criteria, MPLCs include two subsets frequently referred to as SMPLCs and metachronous multiple primary lung cancers (MMPLCs).
Due to diagnostic radiographic techniques and the introduction of helical CT in the screening of lung cancers, an increasing number of SMBPNs with GGO components have been identified, and many have proven to be SMPLCs. The incidence of SMPLCs in the reported literature varies from 0.7–6.1% of all lung cancer cases [13, 1]. According to our data, postoperative histopathology revealed that 65.7% of the cases had SMPLCs (23/35), 22.9% had single primary lung cancer (8/35), 2.86% had bilateral AAH (1/35), and 8.6% had bilateral benign nodules (3/35). The high incidence of SMPLCs is due to the preoperative multidisciplinary meeting of the institutional oncology team and the careful selection of therapeutic strategies, especially for SMBPNs containing GGO components. Hence, 71.1% (69/97) of nodules were confirmed to be lung adenocarcinoma, with 56.7% of nodules (55/97) having GGO components, including 39.2% with pGGO nodules (38/97) and 17.5% with mGGO nodules (17/97); additionally, solid nodules (14/97) did not appear to be numerous.
The appropriate management of patients with SMBPNs has become of increasing concern to clinicians due to the increased incidence of SMPLCs. Several attempts have been made to distinguish between clinical entities of SMBPNs. CHEST guidelines [14] for PN management have classified these nodules into three risk grades. However, the pretest probability of malignancy calculations by Tanner et al. [14] showed that 9.5% (n = 36) were at a low risk, 79.6% (n = 300) were at moderate risk, and 10.8% (n = 41) were at a high risk for malignancy, and that the false-positive rate for PET scans was 39%.
Surgical resection with curative-intent for bilateral nodules had a better survival rate than ipsilateral operation and contralateral combination therapy as well as non-surgical therapy [15]; especially for the node-negative subgroup [16], this was an appropriate treatment option. In the past, lobectomy was considered a standard surgical treatment for patients with stage I NSCLC [17]. Staged bilateral lobectomy with intervals of 4 to 6 weeks was more feasible in patients with bilateral lung cancers than simultaneous bilateral lobectomy [18]. However, in clinical stage IA lung adenocarcinoma with GGO component (CTR < 0.5), sublobar resection has been shown to be equivalent to lobectomy with regards to survival [19, 20], even for solid nodules [20]. Compared with staged bilateral pulmonary resection, simultaneous bilateral pulmonary resection (L-SL/SL-SL) is considered an effective strategy with shorter postoperative in-hospital stay, similar postoperative complications and duration of chest drain usage [5], and similar 3-year and 5-year survival rates [5, 21]. Compared with traditional multi-portal VATS, uniportal VATS has become a safe and feasible technique at our center, with similar duration of postoperative hospital stay and decreased postoperative thorax drainage [22]. Yao et al. [4] reported that the SL-SL group required less hospitalization after surgery than the L-L/SL group. However, in the present study, there was no significant change in hospital stay between the L-SL group and the SL-SL group.
The optimal surgical methods and suitable timing for synchronous bilateral lung cancer are still debated. Tanvetyanon et al. [23] analyzed 467 patients with multi-lobe synchronous multiple lung cancers. The results revealed that the histology of adenocarcinoma could independently predict the survival rate in multivariate analysis combining histology, sex, age, maximum T-size, highest N-stage, and laterality. They also highlighted that several N0 and T sized ≤ 3 cm, patients under 70 years of age, and female sex were favorable survival predictors. This research analyzed survival predictors for surgeons to select appropriate patients; unfortunately, it did not mention the surgical methods—whether single-stage or two-stage. Mun and Kohno [5] suggested a performance status of 3 or higher, when the predicted postoperative FEV 1 was < 800 mL, and bilateral lobectomy recommended staged pulmonary resections. Our research with 35 patients was selected on the premise that patients had good performance status (0−1), an FEV 1/FVC greater than 75%, and were cN0. To the best our knowledge, this is the largest study of surgical outcomes in patients with SMPLCs who underwent simultaneous bilateral pulmonary resection. There was no postoperative 30-day mortality, and the postoperative course was uneventful in 71.4% of cases. In the current study, the rate of postoperative complications was 28.6% (10/35), including pneumonia (n = 6), air leak (n = 1), atrial fibrillation (n = 2), pneumonia combined with air leak (n = 1), and respiratory and cardiac morbidities after the operation had been reported [10]. Of those with postoperative complications, the incidence of pneumonia was higher in the L-SL group than in the SL-SL group with a similar operative time. In the past few years, the duration of surgical resection (> 2 h) has presented an increased risk of pulmonary complications [10]; however, in our study—with a similar operative time and higher pneumonia morbidity—simultaneous bilateral SL-SL resection was the preferred therapeutic option compared to simultaneous bilateral L-SL resection, even if both are feasible and safe.
The results of this study indicate that simultaneous bilateral pulmonary resection by uniportal VATS may be a safe and feasible technique for patients with performance status (0−1), FEV 1/FVC more than 75%, and who are cN0. Given these conditions, for SMBPNs with GGO-dominant (CTR < 0.5), it is preferable to opt for simultaneous SL-SL pulmonary resection. For SMBPNs with GGO component (CTR > 0.5) contralateral GGO component (CTR < 0.5), it is preferable to opt for simultaneous L-SL pulmonary resection for selected patients. Additionally, for those patients with poor performance status and pulmonary function testing, a staged resection along with a bilateral lobectomy is preferred.
Finally, our research had several limitations. First, the selection of patients was biased because this is a single-center retrospective study. Second, the sample size was small, as only 35 patients underwent the evaluation. Finally, the follow-up time was short, and the evaluation of long-term survival is lacking. Therefore, multi-center design research with a larger sample size and a longer follow-up time is required to verify our conclusions.