Surgery plus ablation (SPA): An emerging treatment modality for multiple ground glass nodule-like lung cancer
Year: 2025
Type: article
Abstract: Dear Editor, Lung cancer is the leading cause of cancer-related morbidity and mortality worldwide.[1] Thus, early detection, diagnosis, and treatment are crucial to reduce associated mortality. In 2011, the National Lung Screening Trial reported that screening using low-dose computed tomography (LDCT) instead of standard chest X-rays significantly improved early lung cancer detection, reducing mortality by 20%.[2] The popularization and application of LDCT have resulted in a significant year-on-year increase in the detection rate of pulmonary nodules, particularly ground-glass nodules (GGNs).[3,4] Although GGNs are frequently considered to be precancerous lesions (precursor glandular lesions) or predictors of early-stage lung cancer, only 0.5%–1.5% are GGN-like lung cancer.[5] GGN-like lung cancer is characterized by indolent development and very few lymph node or distant metastases. The prognosis is favorable, with a 10-year cancer-specific survival (CSS) rate of 95%–100% after surgery.[6,7] These features distinguish GGN-like lung cancer from traditional early-stage lung cancers, making this a unique subtype. Surgery is the gold standard treatment for patients with early-stage lung cancer. Compared with open thoracotomy, video-assisted thoracoscopic surgery (VATS) results in significantly better postoperative pulmonary function, less trauma, shorter chest tube duration, shorter hospital stay, and lower morbidity. Furthermore, oncological outcomes after VATS are equivalent to those of traditional open thoracotomy. Thus, over the past decade, VATS has supplanted open thoracotomy for treating most early-stage lung cancers. For GGN-like lung cancer, the 10-year CSS rate after VATS can reach 95%–100%.[6,7] However, VATS has several limitations, including anesthesia-related accidents, reduced pulmonary function, and postoperative pain. Image-guided thermal ablation (IGTA) is a super minimally invasive local therapy or local ablative treatment approach that includes radiofrequency ablation (RFA), microwave ablation (MWA), cryoablation, and laser ablation. The 5-year CSS rate after IGTA can reach 95-100% for GGN-like cancer.[5,8,9] However, IGTA has some limitations. For example, it was reported that lesions >3 cm may be associated with higher rates of local recurrence and complications.[10] Multiple GGN-like lung cancer, typically characterized by the synchronous or metachronous presence of two or more neoplastic lesions, comprises approximately 40% of GGN-like lung cancers and is classified as a special subtype of multiple primary lung cancer.[8] Surgery remains the primary and most effective approach. All lesions, or as many as possible, should be removed during a single surgery under one anesthetic, subject to oncological principles and a lung parenchyma-sparing strategy. However, due to the limitations of the patient’s cardiopulmonary function and the surgical complexity, this approach may not be fully realized, making the management of multiple GGN-like lung cancer challenging. Because the aim is to preserve as much lung function as possible, one should explore whether surgical removal of the dominant lesion, followed by thermal ablation of the secondary lesions, is feasible. Recently, several clinical studies have reported surgery plus ablation (SPA) as a novel hybrid treatment approach for multiple primary lung cancer.[11-15] There are three types of SPA: (1) sequential ablation after VATS, (2) simultaneous VATS and ablation, and (3) sequential VATS after ablation. In 2022, Qu et al.[11] investigated 11 patients with multiple ground-glass opacities (GGOs) who underwent electromagnetic navigation bronchoscopy (ENB)-guided MWA plus uniportal VATS. Of the 37 lesions observed, 21 underwent MWA, and the remainder were surgically resected. The technical success rate of MWA under ENB guidance was 100%. There were no serious complications or procedure-related deaths, except one patient, who developed postoperative pneumothorax and subcutaneous emphysema and was successfully discharged after symptomatic treatment. Thus, SPA was considered a safe and effective option for treating pulmonary multiple GGNs. In 2025, Chang et al.[12] reported that 11 patients of same-session ablation with lung resection were performed. The average procedural time was 226 min, which is significantly shorter than the 27 patients of separate surgery and ablation. The authors also concluded that SPA is feasible and safe, and the technique can also be incorporated into a one-stop treatment with concomitant lung resection. In 2025, Zhang et al.[13] investigated 105 patients (30 males and 75 females; mean age, 55.1 years) with multiple GGOs who underwent CT-guided RFA plus VATS. A total of 293 lesions were treated: 113 underwent ablation and 180 underwent surgical resection. The postoperative complication morbidity rate was 9.5%, with a major complication rate of 1.0%. There were no perioperative deaths, and the median hospital stay was 5 days. Furthermore, no recurrence was observed during the short-term follow-up period. This study also concluded that SPA (simultaneous VATS and ablation) was a safe and feasible therapeutic approach for patients with multiple pulmonary GGNs. In 2025, Huang et al.[14] studied 47 patients with multiple GGOs who underwent CT-guided MWA plus VATS (sequential ablation after VATS). In total, 173 GGOs were removed, of which 83 were surgically resected, and 90 secondary nodules were treated with CT-guided MWA during either a single hospitalization or multiple hospitalizations. The technical success rate was 100%, with no local tumor progression or recurrence observed during the follow-up. Event-free survival was 100% at 3 years and 66.82% at 5 years, and the 5-year overall survival (OS) rate was 97.5% (one patient died from an unrelated cause). The authors concluded that SPA marked the onset of an era in which surgeons could use a “needle” and a scalpel simultaneously. In 2025, Hu et al.[15] studied 216 patients with residual GGN-like lung cancer who underwent 235 CT-guided percutaneous MWA procedures after VATS (R0) of stage I-IIA lung adenocarcinoma. The technical success rate was 100%. The major complications after MWA included pneumothorax (12.3%), pleural effusion (5.5%), pulmonary infection (2.6%), hydropneumothorax (1.3%), intrathoracic hemorrhage (0.4%), and bronchopleural fistula (0.4%), with no MWA procedure-related deaths. Pulmonary function test results at 1–3 months after MWA did not differ significantly from baseline. These findings suggested that MWA in residual GGN-like lung cancer after VATS was a lung parenchyma-sparing local treatment that might not aggravate the damage to pulmonary function. The 1-, 3-, and 5-year OS rates were 100%, 99.1%, and 96.3%, respectively, and the 1-, 2-, and 3-year local progression-free survival rates were 100%, 97.7%, and 96.3%, respectively, suggesting that SPA (sequential ablation after VATS) effectively improved local control and survival. The findings of the above-mentioned studies evidently indicate that SPA is a safe and feasible treatment approach for patients with multiple GGNs or GGN-like lung cancer, with significant clinical application potential and expanding our understanding of SPA. However, these studies result also have certain limitations. First, the studies were all retrospective, single-arm, non-randomized and controlled. Second, failure to identify the pathology of all lesions before SPA may have led to the ablation or resection of some benign lesions, undoubtedly causing additional harm. Third, the follow-up periods were short, and the long-term prognosis, such as local recurrence and 10-year OS, has yet to be verified. Finally, multidisciplinary teams (MDTs) and shared decision-making (SDM) were not adopted to discuss and formulate personalized treatment plans before SPA. Thus, further multicenter, prospective, and randomized controlled clinical trials with a large sample size and long-term follow-up are warranted to better clarify the role of SPA as a possible first-choice treatment for multiple GGN-like lung cancer. Furthermore, the discussion and formulation of individualized treatment plans before SPA should involve MDTs and SDM. Soon, we firmly believe that SPA will become an emerging treatment modality for multiple GGN-like lung cancer.
Author: Xin Ye
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7117646484