Redefining long-term oncologic outcomes of minimally invasive surgery for non-small cell lung cancer: a narrative review

Introduction

Background

Lung cancer is the leading cause of cancer-related mortality worldwide, accounting for nearly 1.8 million deaths annually (1). Non-small cell lung cancer (NSCLC) accounts for 80–85% of all lung cancer cases, for which surgical resection remains the first-line curative treatment for early stage disease (2). Open thoracotomy (OT) is the standard surgical approach for NSCLC, providing direct visualization of the tumor as well as access for anatomical resection and systematic lymphadenectomy (3). However, OT is associated with substantial postoperative pain, prolonged recovery, and increased perioperative morbidity, particularly in older adults or patients with comorbidities (4,5). These limitations have driven the development of less-invasive alternatives that reduce surgical trauma without compromising oncological efficacy.

Minimally invasive surgery (MIS) for lung cancer began with the development of video-assisted thoracoscopic surgery (VATS) lobectomy in the early 1990s (6). Multiportal VATS (M-VATS) avoids rib spreading and results in less postoperative pain and a shorter hospital stay than OT (4,5). In the early 2010s, uniportal VATS (U-VATS) was introduced, further minimizing trauma due to surgical access, requiring only a single incision and ensuring the feasibility of complex resections (7,8). Robotic-assisted thoracic surgery (RATS) was later introduced, enabling three-dimensional visualization of the tumor, tremor filtration, and enhanced dexterity compared with prior methods (9,10). These technological advances have expanded the indications for MIS from early stage NSCLC to include complex and advanced cases (11-13). Figure 1 illustrates the chronological evolution of MIS.

Figure 1 Timeline of the development and evolution of minimally invasive thoracic surgery. Major milestones in the evolution of MIS in the thoracic cavity include the development of M-VATS and RATS as well as the subsequent global adoption of these techniques during the 2010s. MIS, minimally invasive surgery; M-VATS, multi-portal video-assisted thoracoscopic surgery; RATS, robotic-assisted thoracic surgery; U-VATS, uniportal video-assisted thoracoscopic surgery.

Rationale and knowledge gap

Despite the widespread adoption of MIS, questions remain regarding the differences in the short- and long-term outcomes between MIS and OT. M-VATS, U-VATS, and RATS provide short-term benefits such as reduced pain, shorter hospital stay, and faster recovery over OT (4,5,14-16). However, concerns persist in the use of MIS regarding the adequacy of R0 resection and lymph node dissection as well as the risk of missed microscopic disease (17). Although retrospective studies and meta-analyses generally demonstrate that the long-term survival rates are comparable between MIS and OT, evidence from randomized controlled trials (RCTs) remains limited, particularly for RATS (18-23). Moreover, interprocedural differences, such as the enhanced precision of RATS or reduced invasiveness of U-VATS, have not yet been linked to improved long-term prognosis (24,25). Finally, whether MIS meaningfully improves prognosis remains unclear. Reviews have mainly focused on perioperative and short-term outcomes of MIS: the long-term survival, recurrence, and durable cancer control achieved with MIS have been insufficiently characterized. Systematic reviews have emphasized postoperative pain, feasibility, or short-term recovery, but few reviews have synthesized long-term oncologic outcomes among M-VATS, U-VATS, and RATS. We aimed to fill this gap in knowledge through focusing on the long-term survival, recurrence, and oncological quality of MIS for NSCLC in this review.

Objective

Lung cancer imposes a major global health burden, and the long-term oncological outcomes of MIS must be understood for clinical decision-making. We synthesized the current evidence on the outcomes of M-VATS, U-VATS, and RATS, with a focus on their impact on long-term prognosis. We aimed to provide an evidence-based framework for optimizing MIS to achieve durable outcomes in lung cancer via outlining the evolution, advantages, limitations, and controversies associated with these approaches. We present this article in accordance with the Narrative Review reporting checklist (available at https://vats.amegroups.com/article/view/10.21037/vats-2025-1-52/rc).

Methods

The literature in the PubMed and Web of Science databases published was comprehensively searched between August 8, 2025 and August 10, 2025, to identify studies that reported the long-term postoperative outcomes of M-VATS, U-VATS, and RATS in patients with lung cancer. Comparative studies that evaluated the surgical or oncological outcomes using these approaches were also included.

The search terms comprised “video-assisted thoracoscopic surgery”, “VATS”, “multiportal VATS”, “uni-portal video-assisted thoracoscopic surgery”, “uni-portal VATS”, “robot-assisted thoracic surgery”, “RATS”, “lung cancer”, “prognosis”, “outcomes”, “survival”, and “recurrence”. Only English publications published after 1990 were considered, reflecting the contemporary adoption of MIS. To ensure comprehensive coverage, no restrictions were imposed on the study design.

The study titles and abstracts were screened to exclude studies not directly addressing MIS outcomes as well as those limited to technical descriptions, cost analyses, cosmetic results, or non-lung-cancer malignancies. All authors independently assessed the eligible articles. Data on the study design, cohort characteristics, surgical outcomes, and long-term results were extracted using a standardized form. Discrepancies were resolved via consensus, with no disagreements in the final review.

The extracted data were qualitatively synthesized, emphasizing comparative analyses of perioperative (short-term) and long-term outcomes between MIS and OT as well as among different MIS approaches. The detailed search strategies are presented in Table 1.

M-VATS

M-VATS is a safe and effective alternative to OT for patients with NSCLC (4,5). M-VATS shows perioperative advantages over OT, including reduced postoperative pain, shorter chest drainage duration, fewer complications, and shorter hospital stay (4,5). Importantly, the long-term oncological outcomes of M-VATS appear comparable to those of OT (13-16,20,21,24-26). However, evidence regarding the long-term prognosis and quality of life (QOL) of patients after M-VATS remains sparse, as most QOL studies have focused on the first postoperative year (4,5).

Short-term outcomes

Bendixen et al. compared VATS with anterolateral OT for early stage lung cancer in a RCT (4). The clinically relevant postoperative pain within 24 hours was significantly lower (38% vs. 63%, P=0.0012) and the EuroQoL 5 dimensions (EQ-5D) QOL scores were higher over 52 weeks for VATS than OT, and the major complications and mortality were similar between the methods. These findings support the perioperative and first-year benefits of VATS. Large-database analyses reinforced these results. Paul et al. reported shorter hospital stays and lower in-hospital mortality with VATS than with OT, whereas Yang et al. found hospitalizations were shorter without higher 30-day mortality in those with stage I–II NSCLC who underwent VATS compared with those who underwent OT (21,24,25). Chen et al. and Pan et al. further demonstrated that VATS remains feasible in locally advanced disease or after neoadjuvant immunochemotherapy, with perioperative outcomes comparable to those of OT (11,17).

Long-term outcomes

Dai et al. found no significant differences in 3-year overall survival (OS), cancer-specific survival (CSS), or disease-free survival (DFS) between VATS and OT (18). Yang et al. and Chen et al. reported equivalent 5-year OS and DFS rates in early and locally advanced-stage disease (11,24,25). Collectively, these studies indicated that VATS provides perioperative benefits without compromising long-term survival. Xu et al. suggested that OT yields a more thorough nodal assessment in small cell lung cancer than VATS, but the survival outcomes remain similar (26).

Lymph node dissection for oncological quality

Several studies have addressed concerns expressed about the adequacy of the results of lymphadenectomy using VATS. Lim et al. demonstrated that the nodal harvest and R0 resection rates were equivalent between VATS and OT in a multicenter RCT (5). Medbery et al. found slightly higher nodal upstaging with OT, particularly at N1 stations, compared with VATS; however, the differences were smaller in academic centers (20). Reichert et al. and Matsuura et al. confirmed comparable staging accuracy between VATS and OT when systematic dissection was performed (27,28).

Special procedures

The application of VATS has been extended to include complex resections. Yang et al. reported comparable perioperative mortality and morbidity rates in pneumonectomies with similar long-term survival after adjustment between VATS and OT (29). Xie et al. and Mayne et al. confirmed that VATS sleeve lobectomy achieves oncologic outcomes equivalent to those of OT, with perioperative advantages such as reduced blood loss and shorter hospital stays (12,13).

Segmentectomy is a parenchyma-sparing option in sublobar resection. A large Japanese phase III RCT demonstrated the noninferiority of segmentectomy to lobectomy for small peripheral tumors (30). Approximately 90% of these surgeries were performed using VATS, supporting VATS segmentectomy as a viable alternative; however, definitive long-term data are lacking.

Summary

In diverse clinical settings, M-VATS consistently confers perioperative and short-term benefits while maintaining oncological outcomes comparable to those of OT (Table 2). These advantages extend to complex resections and segmentectomies, establishing M-VATS as a standard MIS approach. Further refinements, including U-VATS and RATS, are currently being examined; however, their long-term oncological impacts require further validation.

U-VATS

U-VATS is a refinement of MIS that evolved from M-VATS to earlier single-incision techniques. First applied for lobectomy in 2011 (31), U-VATS advanced with specialized instrumentation and approaches, such as the use of the subxiphoid route (32,33). The postoperative pain is reduced, chest tube use duration is shorter, and recovery is faster with M-VATS than with M-VATS (34-37). However, evidence of the long-term oncological outcomes of M-VATS remains limited because of the relatively recent adoption of M-VATS (38,39).

Short-term outcomes

Meta-analyses and multicenter studies have consistently shown that U-VATS produces perioperative results equivalent to those of M-VATS and has some advantages over M-VATS. A systematic review of 20 studies reported fewer complications (odds ratio, 0.76; P=0.008), shorter chest tube duration (−0.63 days, P=0.002), shorter hospital stays (−0.54 days, P=0.009), and reduced postoperative pain (P=0.004) with U-VATS compared with M-VATS (40). Dai et al. found a lower patient-reported symptom burden, including pain, fatigue, cough, and dyspnea, with U-VATS than with M-VATS (18). A large multi-institutional analysis confirmed reduced intraoperative blood loss, shorter operative time, and decreased pneumonia rates with U-VATS compared with M-VATS (35). Collectively, these findings establish U-VATS as a safe and effective perioperative alternative to OT.

Long-term outcomes

The data on NSCLC survival after U-VATS show improved survival compared with OT; however, these data are limited. Most available studies were retrospective, involved small sample sizes, and had relatively short follow-ups. High-quality prospective studies with standardized lymphadenectomy protocols are needed to clarify long-term oncologic equivalence. Nachira et al. found that the 3-year OS (78% vs. 74%), DSS (97% vs. 89%), and DFS (62% vs. 66%) rates were similar between U-VATS and OT, with less postoperative and chronic pain in the U-VATS group (37). Ruan et al. compared U-VATS and M-VATS lobectomies with mediastinal lymphadenectomy and reported equivalent 5-year OS (89.2% vs. 86.5%) and DFS (89.5% vs. 89.6%). Multivariate analysis identified the tumor-node-metastasis (TNM) stage but not the surgical approach as an independent predictor of survival (40). Shahoud et al. reported comparable recurrence rates for U-VATS and RATS (41). These data suggest that U-VATS preserves long-term oncological outcomes, while offering perioperative benefits.

Lymph node dissection for oncological treatment quality

Concerns regarding the adequacy of lymphadenectomy using U-VATS have been addressed in prospective and retrospective studies. Yao et al. demonstrated no significant difference in lymph node yield between U-VATS and M-VATS (42). Zhou et al. reported similar nodal harvests in segmentectomy, although slightly fewer stations were dissected using U-VATS without affecting survival (43). Similarly, Ruan et al. found no significant differences in the nodal numbers or stations between U-VATS and M-VATS (40). However, Shahoud et al. observed a lower nodal yield with U-VATS than with RATS, suggesting limitations of robotic platforms (41). Overall, U-VATS appears to be oncologically adequate for systematic dissection.

Special procedures

The application of U-VATS has been extended beyond lobectomies. Zhou et al. reported equivalent 1-, 3-, and 5-year OS and DFS rates for U-VATS and M-VATS segmentectomies, with low recurrence rates (43). Gao et al. demonstrated that the survival outcomes of U-VATS pneumonectomy were comparable to those of OT after propensity score matching (38). These findings support the feasibility of using U-VATS for complex resections; however, further validation is required.

Summary

U-VATS is a refinement of the MIS approach, reducing access trauma while maintaining oncological integrity. The current evidence demonstrates the perioperative advantages of U-VATS, which results in long-term survival rates comparable to those of M-VATS, OT, and RATS (Table 3). However, the adoption of U-VATS requires substantial technical expertise, and the learning curve of U-VATS is steeper than that M-VATS. As such, institutional and surgeon experience are important determinants of U-VATS outcomes.

RATS

RATS is the most recent advancement in MIS for NSCLC treatment (10,23). Despite the potential advantages of RATS, RATS has been more slowly adopted than that of VATS or U-VATS, mainly because of the high cost and limited access to robotic platforms (44). Nevertheless, the accumulating evidence confirms that RATS is safe and oncologically effective, with increasing attention being directed toward the long-term outcomes of RATS (45).

Short-term outcomes

Multiple large cohort studies have demonstrated the perioperative advantages of RATS, such as shorter hospital stays, lower tumor conversion rates, and more extensive lymph node retrieval, compared with those of VATS and OT. Yang et al. reported significantly shorter hospitalization and higher lymph node harvest amounts with RATS, reinforcing the perioperative advantages of RATS over VATS and OT (22). A meta-analysis of 7,438 patients showed that RATS was superior in terms of 30-day mortality (0.7% vs. 1.1%) and conversion (10.3% vs. 11.9%) rates compared with OT (46). A multicenter analysis of 5,721 lobectomies confirmed shorter operative times, reduced conversions, and lower transfusion rates with RATS than with OT or VATS (47).

The results of RCTs further support these findings. The RVlob trial demonstrated comparable perioperative outcomes between RATS and VATS but significantly increased lymph node harvest with RATS, highlighting its technical advantages over VATS and OT (19,48). The RAVAL trial also confirmed noninferior patient-reported outcomes and provided important evidence regarding cost-effectiveness, underscoring the clinical and economic feasibility of RATS (44). Collectively, these data establish RATS as a feasible alternative to MIS and the perioperative advantages of RATS; however, the economic barriers remain to be overcome.

Long-term outcomes of RATS

The evidence of survival after RATS has become increasingly robust. Park et al. reported a 5-year OS rate of 80% in 325 patients who underwent RATS, with stage-specific survival rates of 91% (IA), 88% (IB), and 49% (II) (10). A multicenter cohort of 1,339 patients confirmed higher survival across cancer stages, with 5-year OS rates of 83% (IA), 77% (IB), 68–70% (II), and 62% (IIIA) (23). Kent et al. found higher unadjusted 5-year OS for OT (84%) and RATS (81%) compared to VATS (74%), with multivariate analysis favoring RATS (49). Yang et al. also showed higher 5-year DFS for RATS than for VATS (72.7% vs. 65.5%) (22). However, a single-center RCT with >5 years of follow-up found no significant difference in the OS or DFS between RATS and VATS, confirming the noninferiority of RATS (48).

Lymph node dissection for oncological treatment quality

RATS appears to enhance the results of lymphadenectomy because of the increased visualization and instrument dexterity. Zhou et al. reported 100% 5-year OS and RFS in RATS segmentectomy for ≤2 cm tumors and slightly lower rates for VATS (45). Multiple meta-analyses have demonstrated that the lymph node yield is higher with RATS than with VATS, and RATS may confer a modest DFS advantage, particularly in early-stage disease (50,51). Fabbri et al. prospectively reported a higher 5-year DFS (90.3% vs. 77.6%) and lower recurrence with RATS, particularly in stages I and III disease, than with VATS (52). However, OS remained equivalent across approaches, suggesting that the oncological benefit of RATS is primarily driven by increased staging accuracy rather than intrinsic survival superiority between the approaches.

Special procedures

RATS has been used for complex resections. Liu et al. reported high 5-year OS rates (82.2%, 69.7%, and 63.7% for stages I–III, respectively) with robotic sleeve lobectomy, with outcomes strongly affected by N2 disease (53). Zirafa et al. reported comparable 5-year OS rates between patients who underwent RATS and OT with locally advanced disease. These results support the feasibility of using RATS for advanced or technically demanding procedures; however, further validation of this hypothesis is required (54).

Summary

RATS offers perioperative benefits and higher-accuracy lymph node assessment than VATS; RATS produces long-term oncologic outcomes that are at least equivalent to those of VATS (Table 4). However, questions remain regarding the cost-effectiveness of RATS, optimal patient selection, and generalizability of RATS across healthcare systems. As economic barriers gradually decrease, RATS adoption may broaden.

Discussion

Summary of evidence

Surgical resection remains the cornerstone of curative treatment for NSCLC (2). Since the late 1990s, MIS techniques such as M-VATS, U-VATS, and RATS have been widely adopted, consistently demonstrating perioperative advantages over OT (4,5,21,24,25). Large database analyses and meta-analyses have confirmed that long-term survival after VATS is at least equivalent to that after OT, and VATS is superior to OT in some cohorts (21,23-25). Evidence from high-volume centers further supports favorable outcomes when patient selection and surgical techniques are optimized with VATS (11,13,28). Similarly, U-VATS and RATS demonstrate perioperative safety and feasibility, with emerging data suggesting the long-term survival is comparable between these methods (37,40,49,52). Because essential oncologic maneuvers are similar among the MIS platforms, substantial differences among the methods in long-term survival are unlikely. The observed variations likely reflect selection bias and surgeon- or center-related factors.

Interpretation

The oncological adequacy of MIS appears to depend less on the number of ports or robotic assistance than on adherence to surgical principles. Surgeon experience and technical precision are major determinants of oncological outcomes and may more strongly influence outcomes than the choice of MIS platform. Complete (R0) resection and systemic lymphadenectomy remain the strongest determinants of survival (5,20,28). Although OT has historically yielded higher nodal upstaging rates (20,28), experienced MIS teams can achieve equivalent staging accuracy (27,29,40). Although RATS may offer technical advantages in nodal dissection, the survival benefits of RATS over OT remain heterogeneous (22,45,49,50).

Overall, MIS provides perioperative benefits without compromising oncological integrity, and, in selected contexts, MIS may indirectly improve long-term outcomes by increasing recovery and tolerance to adjuvant therapy (24,25,44).

Limitations of current evidence

The available evidence is limited by several interrelated biases that may confound the comparisons between MIS and OT. First, most comparative data were derived from retrospective cohorts and registry analyses, which are prone to selection bias in which healthier patients with smaller tumors are preferentially selected for MIS (11,17,21,25,37,40). Second, surgeon and center experience, such as learning curve effects and institutional lymphadenectomy standards, substantially affect nodal yield and upstaging rates, which have been widely variable among studies (20,28,29). Third, the staging workup, use and timing of neoadjuvant or adjuvant systemic therapies, and definitions of outcomes (e.g., variable definitions of DFS or nodal stations assessed) are heterogenous, reducing the comparability of results. Fourth, the follow-up duration differed among surgical approaches in several studies, potentially underestimating late recurrence after newer MIS techniques (19,44,48). Fifth, cost and access barriers, particularly to RATS, limit the generalizability of RATS across health systems (44,47). MIS is associated with attenuated inflammatory and stress responses, such as lower cytokine release and increased preservation of cellular immunity, compared with OT. These physiological advantages may influence the long-term oncological outcomes of MIS and warrant further comparative investigations of MIS platforms. These limitations underscore the need for multicenter RCTs with standardized surgical and lymphadenectomy protocols, pre-specified outcome definitions, and adequate long-term follow-up.

Future directions

To clarify the true prognostic role of MIS, well-designed multicenter RCTs with standardized lymphadenectomy protocols and long-term follow-up are essential (19,48,52). Future studies should stratify outcomes according to stage, histology, and patient profile and incorporate patient-reported endpoints such as QOL and functional recovery (4,5,37). Studies that directly compare U-VATS and RATS are required to determine whether the distinct technical refinements of each platform, such as reduced access trauma in U-VATS and enhanced articulation in RATS, translate into meaningful differences in long-term survival or recurrence patterns in patients (40,41,49). Finally, the integration of MIS into multimodal strategies, including neoadjuvant immunochemotherapy, warrants prospective evaluation (17,54).

Overall, the current evidence supports the oncological safety and feasibility of MIS when performed in accordance with oncological principles. Furthermore, U-RATS represents the convergence of uniportal access and robotic articulation. Early clinical experience demonstrates the feasibility and promising perioperative outcomes of U-RATS; however, the long-term oncological role of U-RATS remains to be defined.

Conclusions

MIS provides superior perioperative recovery without compromising the long-term oncological outcomes when complete resection and systematic lymphadenectomy are performed. The differences among MIS platforms are generally small and likely reflect surgeon- and center-related factors rather than intrinsic superiority. High-quality multicenter RCTs with standardized lymphadenectomy protocols and long-term follow-up are needed to clarify the prognostic contributions of U-VATS and RATS.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://vats.amegroups.com/article/view/10.21037/vats-2025-1-52/rc

Peer Review File: Available at https://vats.amegroups.com/article/view/10.21037/vats-2025-1-52/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://vats.amegroups.com/article/view/10.21037/vats-2025-1-52/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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