Skip to main content

Sublobar resection versus ablation for stage I non-small-cell lung cancer: a meta-analysis

Abstract

Background

Stage I non-small-cell lung cancer (NSCLC) can be treated by both ablation and sublobar resection (SR). This meta-analysis was therefore designed to better compare the relative safety and efficacy of these two approaches to treating stage I NSCLC.

Materials and methods

Relevant studies published through November 2020 in the Cochrane Library, Embase, and PubMed databases were identified for analyses which were conducted with RevMan v5.3.

Results

In total, 816 potentially relevant articles were identified, of which 8 were ultimately included in the final meta-analysis. Patients in the SR group exhibited a signficantly lower pooled local recurrence (LR) rate (5.0% vs. 25.4%, P < 0.0001), although pooled distant recurrence (DR) rates were similar in both groups (25.7% vs. 23.1%, P = 0.75). The pooled hazard ratio (HR) for overall survival (OS) (HR: 1.23; 95% CI: 1.13–1.33, P < 0.00001), progression-free survival (PFS) (HR: 1.34; 95% CI: 1.15–1.55, P = 0.0002), and cancer-specific survival (HR: 1.39; 95% CI: 1.15–1.70, P = 0.0009) all indicated better survival outcomes among patients that underwent HR treatment, while pooled complication rates were similar in both groups (27.7% vs. 43.8%, P = 0.27). Patients that underwent ablation exhibited significantly shorter pooled post-operative hospitalization relative to those in the SR group (MD: 5.93; 95% CI: 0.78–11.07, P = 0.02). No evidence of publication bias was detected through funnel plot analyses.

Conclusions

SR treatment of stage I NSCLC patients was associated with a lower LR rate and longer survival as compared to ablation.

Peer Review reports

Background

Non-small-cell lung cancer (NSCLC) is the deadliest form of cancer globally [1,2,3], and many patients with early-stage NSCLC can undergo curative surgical resection following tumor detection via chest computed tomography (CT) screening [4,5,6]. Lobectomy with systematic mediastinal lymphadenectomy is the standard approach to treating stage I NSCLC [7,8,9]. However, in many cases, patients are elderly or have a history of comorbidities such as pulmonary dysfunction or atherosclerosis that may preclude their ability to undergo invasive surgical treatment s [4,5,6].

While sublobar resection (SR) is generally less effective as a curative procedure relative to lobectomy [4], it can better preserve patient pulmonary function [7,8,9]. In stage I NSCLC patients with tumors ≤ 2 cm in size, SR yields similar survival outcomes to lobectomy [5, 6]. However, 20–30% of stage I NSCLC patients are unable to undergo SR owing to their poor performance status [10,11,12,13,14,15,16,17]. In these patients, percutaneous ablation represents the most minimally invasive treatment strategy [10,11,12,13,14,15,16,17]. While prior studies have compared the relative efficacy of SR and ablation in stage I NSCLC patients, the majority of these analyses have been retrospective in design [10,11,12,13,14,15,16,17]. Conducting a meta-analysis would thus represent an effective means of reducing potential bias and increasing statistical power associated in order to develop more reliable conclusions.

The present meta-analysis was therefore designed to compare the relative safety and efficacy of SR and ablation for the treatment of individuals with stage I NSCLC.

Methods

Study selection

This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. This work was registered in https://inplasy.com/ (No. INPLASY202110075).

Relevant studies published as of November 2020 in the Cochrane Library, Embase, and PubMed databases were identified via the following search strategy: (((((radiofrequency[Title/Abstract]) OR (microwave[Title/Abstract])) OR (cryoablation[Title/Abstract])) OR (ablation[Title/Abstract])) AND ((((surgery[Title/Abstract]) OR (resection[Title/Abstract])) OR (Video assisted thoracoscopic surgery[Title/Abstract])) OR (VATS[Title/Abstract]))) AND ((lung cancer[Title/Abstract]) OR (NSCLC[Title/Abstract])).

Studies eligible for inclusion in this meta-analysis included (a) randomized controlled trials (RCTs) or retrospective analyses, (b) studies of stage I NSCLC patients, (c) studies in which SR and ablation were compared to treat NSCLC. Studies published in any language were eligible for inclusion.

Studies were excluded if they were (a) non-comparative studies, (b) animal or preclinical studies, or (c) reviews.

Data extraction

Baseline patient data, baseline study data, and treatment-related data were independently extracted by two investigators. Discussion with a third author was used to resolve any inconsistencies.

Quality assessment

Study quality was assessed independently by two researchers. RCT quality was assessed with the Cochrane risk of bias tool based upon selection, performance, detection, attrition, reporting, and other biases. All other studies were evaluated using the 9-point Newcastle–Ottawa scale (NOS) [18], with high-quality studies being those scoring ≥ 6 points.

Endpoints and definitions

Meta-analysis endpoints included rates of complications, recurrence rates, duration of postoperative hospitalization, and patient survival, with survival as the primary study endpoint.

For this study, SR was defined as both segmental and wedge resection operations [10,11,12,13,14,15,16,17]. Both local recurrence (LR) and distant recurrence (DR) outcomes were evaluated, with the latter of these including intra- and extra-pulmonary DR [11, 12]. Analyzed survival outcomes included overall, progression-free, and cancer-specific survival (OS, PFS, and CSS, respectively).

Meta-analysis

RevMan v5.3 was used for all meta-analyses. Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated via the Mantel–Haenszel method for dichotomous variables, whereas continuous variables were analyzed based upon mean difference (MD) values and 95% CIs. Pooled survival duration was assessed based upon hazard ratios (HRs) and 95% CIs. Study heterogeneity was evaluated based upon X2 tests and the I2 statistic, with I2 > 50% being indicative of significant heterogeneity. When significant heterogeneity was detected, data were analyzed with a random-effects model, whereas fixed-effects models were otherwise utilized. Sources of heterogeneity were assessed with sensitivity and subgroup analyses, and funnel plots were used to test the risk of publication bias.

Results

Study characteristics

The initial search strategy identified 816 potentially relevant articles, of which eight were ultimately included in our final meta-analysis (Fig. 1). These were all retrospective studies with NOS scores between 6 and 8 points (Table 1), incorporating 679 patients treated by SR and 468 that underwent ablation (Tables 1, 2). In five studies, patients underwent radiofrequency ablation (RFA) [10, 11, 13, 15, 16], while in three studies, wedge resection and ablation treatments were compared [11, 12, 17]. Treatment-associated data for these studies are shown in Table 2.

Fig. 1
figure 1

Flowchart diagram of our meta-analysis

Table 1 Characteristics of the included studies
Table 2 Characteristics of the treatment outcomes

Recurrence

LR was reported in three studies [11, 12, 16], with pooled LR rates being significantly lower in the SR group (5.0% vs. 25.4%, P < 0.0001, Fig. 2a). No significant heterogeneity pertaining to this endpoint was detected (I2 = 0%).

Fig. 2
figure 2

The pooled results of A LR rates, B DR rates, C OS, D PFS, E CSS, F complication rates, and G post-operative hospital stay via forest plots

DR was reported in two studies [11, 12], and pooled DR rates were similar between groups (25.7% vs. 23.1%, P = 0.75, Fig. 2b). No significant heterogeneity pertaining to this endpoint was detected (I2 = 0%).

Survival

OS was reported in all studies, and the pooled OS HR was more favorable in the SR group (HR: 1.23; 95% CI: 1.13–1.33, P < 0.00001, Fig. 2c). This endpoint was associated with significant heterogeneity (I2 = 73%), but omitting individual studies in a sensitivity analysis had no significant impact on overall heterogeneity.

PFS was reported in six studies [10,11,12,13, 15, 16], with the pooled PFS HR being more favorable in the SR group (HR: 1.34; 95% CI: 1.15–1.55, P = 0.0002, Fig. 2d). This endpoint was associated with significant heterogeneity (I2 = 76%), but omitting individual studies in a sensitivity analysis had no significant impact on overall heterogeneity.

CSS was reported in five studies [10, 11, 14, 16, 17], with the pooled CSS HR being more favorable in the SR group (HR: 1.39; 95% CI: 1.15–1.70, P = 0.0009, Fig. 2e). This endpoint was associated with significant heterogeneity (I2 = 74%), but omitting individual studies in a sensitivity analysis had no significant impact on overall heterogeneity.

Complications

Complication rates were reported in three studies [10, 11, 16], and were similar in both groups (27.7% vs. 43.8%, P = 0.27, Fig. 2f). This endpoint was associated with significant heterogeneity (I2 = 91%), and the omission of the study conducted by Zemlyak et al.[16] eliminated this heterogeneity. When this study was omitted, pooled complication rates remained similar between groups (P = 0.98).

Duration of postoperative hospitalization

Two studies reported the duration of postoperative hospitalization for treated patients [11, 13]. The pooled duration of postoperative hospitalization was significantly lower in the ablation group relative to the SR group (MD: 5.93; 95% CI: 0.78–11.07, P = 0.02, Fig. 2h). This endpoint was associated with significant heterogeneity (I2 = 68%).

Subgroup analyses

Five articles specifically compared SR and RFA as approaches to treating stage I NSCLC [10, 11, 13, 15, 16], and in these studies, pooled HRs pertaining to OS, PFS, and CSS were all favorable in the SR group (Table 3).

Table 3 Meta-analytic pooled results of survival based on the RFA versus SR

Three articles specifically compared wedge resection and ablation as approaches to treating stage I NSCLC [11, 12, 17], and in these studies, pooled HRs pertaining to OS, PFS, and CSS were all favorable in the SR group (Table 4).

Table 4 Meta-analytic pooled results of survival based on the ablation versus wedge resection

Publication bias

No evidence of publication bias was detected through funnel plot analyses.

Discussion

Current American College of Chest Physicians clinical practice guidelines suggest that stage I NSCLC patients undergo lobectomy with systematic mediastinal lymph node dissection when possible. SR is the preferred treatment in patients considered at high risk for lobar resection, although some studies have suggested that lobectomy and SR are associated with similar outcomes in those with stage I NSCLC [19, 20]. When patients are unable to tolerate SR, it is typically recommended that patients undergo ablation [14].

The present meta-analysis compared the relative safety and efficacy of SR and ablation for the treatment of stage I NSCLC. When comparing recurrence rates between these two patient groups, our analysis revealed LR rates to be significantly lower in the SR group (5.0% vs. 25.4%, P < 0.0001). This suggests that ablation cannot fully eliminate tumors, consistent with the fact that this approach is less effective when treating tumors adjacent to large vessels > 3 mm in diameter or to a bronchus > 2 mm in diameter owing to heat-sink effects [13]. However, there are certain advantages to the ablation procedure, including the fact that it can be performed repeatedly and can be employed to treat both synchronous and metachronous lesions [21]. We observed similar pooled DR rates in both patient groups (25.7% vs. 23.1%, P = 0.75), indicating that both SR and ablation are limited in their ability to control systematic tumor growth. Postoperative chemotherapy may represent a viable means of lowering DR rates [22].

Stage I NSCLC patient treatment primarily focuses on improving patient survival rates. We therefore analyzed OS, PFS, and CSS outcomes, revealing substantial variability among studies. Kwan et al. [14] detected similar OS (P = 0.695) and CSS (P = 0.819) between the SR and ablation groups following a propensity score-matched analysis, while Safi et al. [15] similarly found OS (P = 0.28) and PFS (P = 0.09) to be comparable in these two treatment groups, and Zemlyak et al. [16] found these two groups to exhibit similar OS (P > 0.05), CSS (P > 0.05), and PFS (P > 0.05) outcomes. While 2-year OS rates in the studies conducted by Kwan et al. and Safi et al. ranged from 66–85% and 62–74% in SR and ablation groups, respectively [14, 15], in other studies the survival of patients in the SR group was significantly longer than that of patients in the ablation group [11,12,13, 17]. These differences may be attributable to differences in sample size, tumor size, or patient selection criteria among studies. In pooled OS, PFS, and CSS analyses, survival rates were better in the SR group, and subgroup analyses further confirmed that wedge resection was associated with superior OS, PFS, and CSS outcomes relative to ablation.

The significantly prolonged survival observed following SR was primarily attributable to the significantly lower LR rate in these patients. In addition, an analysis of 100 NSCLC patients with tumors < 1 cm in diameter indicated that 5% of these patients exhibited lymph node involvement, suggesting that such involvement should still be considered even in those with mall lesions [21]. SR thus offers the additional advantage of facilitating lymph node sampling at time of surgery, enabling clinicians to more precisely stage patients and to thereby guide treatment [21].

Pooled complication rates were similar in both groups, suggesting that both SR and ablation exhibit similar safety profiles when used to treat those with stage I NSCLC. However, patients who underwent ablation experienced significantly shorter postoperative hospitalization relative to patients treated via SR, owing to the fact that ablation is a less invasive procedure not requiring the use of general anesthesia.

There were multiple limitations to this analysis. For one, the articles included in this meta-analysis were retrospective in nature, rendering them susceptible to selection bias. Additional RCTs will therefore be required to validate and expand upon these data. Secondly, certain study endpoints were associated with significant heterogeneity, and while the sources of such heterogeneity were identified when possible, additional RCTs will be essential to establish definitive research results. Third, preoperative imaging analyses were used for the evaluation of mediastinal and hilar lymph nodes in the context of RFA without any pathologic verification, potentially leading to an underestimation of accurate patient staging, thus biasing survival outcome data.

Conclusion

In summary, SR was associated with lower LR rats and prolonged survival relative to ablation when used to treat stage I NSCLC patients.

Availability of data and materials

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Abbreviations

CT:

Computed tomography

CSS:

Cancer-specific survival

DR:

Distant recurrence

LR:

Local recurrence

NSCLC:

Non-small-cell lung cancer

PFS:

Progression-free survival

OS:

Overall survival

SR:

Sublobar resection

WR:

Wedge resection

References

  1. Herbst RS, Morgensztern D, Boshoff C. The biology and management of non-small cell lung cancer. Nature. 2018;553:446–54.

    CAS  Article  Google Scholar 

  2. Rafei H, El-Bahesh E, Finianos A, et al. Immune-based therapies for non-small cell lung cancer. Anticancer Res. 2017;37:377–87.

    CAS  Article  Google Scholar 

  3. Akhurst T. Staging of non-small-cell lung cancer. PET Clin. 2018;13:1–10.

    Article  Google Scholar 

  4. Zhang Y, Sun Y, Wang R, et al. Meta-analysis of lobectomy, segmentectomy, and wedge resection for stage I non-small cell lung cancer. J Surg Oncol. 2015;111:334–40.

    Article  Google Scholar 

  5. Fan J, Wang L, Jiang GN, et al. Sublobectomy versus lobectomy for stage I non-small-cell lung cancer, a meta-analysis of published studies. Ann Surg Oncol. 2012;19:661–8.

    Article  Google Scholar 

  6. Namkoong M, Moon Y, Park JK. Lobectomy versus sublobar resection in non-lepidic small-sized non-small cell lung cancer. Korean J Thorac Cardiovasc Surg. 2017;50:415–23.

    Article  Google Scholar 

  7. Fu YF, Zhang M, Wu WB, et al. Coil localization-guided video-assisted thoracoscopic surgery for lung nodules. J Laparoendosc Adv Surg Tech A. 2018;28:292–7.

    Article  Google Scholar 

  8. Teng F, Wang ZS, Wu AL, et al. Computed tomography-guided coil localization for video-assisted thoracoscopic surgery of sub-solid lung nodules: a retrospective study. ANZ J Surg. 2019;89:E514–8.

    PubMed  Google Scholar 

  9. Yang ZJ, Liang YH, Li M, et al. Preoperative computed tomography-guided coil localization of lung nodules. Minim Invasive Ther Allied Technol. 2020;29:28–34.

    Article  Google Scholar 

  10. Alexander ES, Machan JT, Ng T, Breen LD, DiPetrillo TA, Dupuy DE. Cost and effectiveness of radiofrequency ablation versus limited surgical resection for stage I non-small-cell lung cancer in elderly patients: is less more? J Vasc Interv Radiol. 2013;24:476–82.

    Article  Google Scholar 

  11. Ambrogi MC, Fanucchi O, Dini P, et al. Wedge resection and radiofrequency ablation for stage I nonsmall cell lung cancer. Eur Respir J. 2015;45:1089–97.

    Article  Google Scholar 

  12. Hu H, Zhai B, Liu R, et al. Microwave ablation versus wedge resection for stage I non-small cell lung cancer adjacent to the pericardium: propensity score analyses of long-term outcomes. Cardiovasc Intervent Radiol. 2020. https://doi.org/10.1007/s00270-020-02601-7.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Iguchi T, Hiraki T, Matsui Y, et al. Survival outcomes of treatment with radiofrequency ablation, stereotactic body radiotherapy, or sublobar resection for patients with clinical stage I non-small-cell lung cancer: a single-center evaluation. J Vasc Interv Radiol. 2020;31:1044–51.

    Article  Google Scholar 

  14. Kwan SW, Mortell KE, Talenfeld AD, et al. Thermal ablation matches sublobar resection outcomes in older patients with early-stage non-small cell lung cancer. J Vasc Interv Radiol. 2014;25:1-9.e1.

    Article  Google Scholar 

  15. Safi S, Rauch G, Op den Winkel J, et al. Sublobar resection, radiofrequency ablation or radiotherapy in stage I non-small cell lung cancer. Respiration. 2015;89:550–7.

    Article  Google Scholar 

  16. Zemlyak A, Moore WH, Bilfinger TV. Comparison of survival after sublobar resections and ablative therapies for stage I non-small cell lung cancer. J Am Coll Surg. 2010;211:68–72.

    Article  Google Scholar 

  17. Zeng C, Lu J, Tian Y, et al. Thermal ablation versus wedge resection for stage I non-small cell lung cancer based on the eighth edition of the TNM classification: a population study of the us seer database. Front Oncol. 2020;10:571684.

    Article  Google Scholar 

  18. Wells GA, Shea BJ, O’Connell D, et al. The Newcastle–Ottawa scale (NOS) for assessing the quality of non-randomized studies in meta-analysis. Appl Eng Agric. 2000;18:727–34.

    Google Scholar 

  19. Okada M, Koike T, Higashiyama M, et al. Radical sublobar resection for small-sized non-small cell lung cancer: a multicenter study. J Thorac Cardiovasc Surg. 2006;132:769–75.

    Article  Google Scholar 

  20. Koike T, Yamato Y, Yoshiya K, et al. Intentional limited pulmonary resection for peripheral T1N0M0 small-sized lung cancer. J Thorac Cardiovasc Surg. 2003;125:924–8.

    Article  Google Scholar 

  21. Chen S, Yang S, Xu S, et al. Comparison between radiofrequency ablation and sublobar resections for the therapy of stage I non-small cell lung cancer: a meta-analysis. PeerJ. 2020;8:e9228.

    Article  Google Scholar 

  22. Pei J, Han B, Zhang J, et al. Multivariate survival analysis of patients with stage I NSCLC. Zhongguo Fei Ai Za Zhi. 2011;14:926–32.

    PubMed  Google Scholar 

Download references

Acknowledgements

None.

Funding

None.

Author information

Authors and Affiliations

Authors

Contributions

YYH designed this work. YL and FY searched the articles. YL, FY, and TW performed the data extraction and statistical analyses. YL wrote this article. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Ya-Yong Huang.

Ethics declarations

Ethics approval and consent to participate

This is a meta-analysis and ethics approval and consent to participate are not required.

Consent for publication

This is a meta-analysis and consent for publication is not required.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Li, Y., Yang, F., Huang, YY. et al. Sublobar resection versus ablation for stage I non-small-cell lung cancer: a meta-analysis. J Cardiothorac Surg 17, 17 (2022). https://doi.org/10.1186/s13019-022-01766-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s13019-022-01766-1

Keywords

  • Sublobar resection
  • Ablation
  • Lung cancer
  • Meta-analysis