Oncologic outcomes of lobectomy vs. segmentectomy in non-small cell lung cancer with clinical T1N0M0 stage: a literature review and meta-analysis

Abstract

Background: Lobectomy has long been regarded as the standard treatment for operable non-small cell lung cancer (NSCLC). Recent studies suggested that segmentectomy could achieve a good prognosis for early-stage NSCLC and might be an alternative to lobectomy in this cohort. Until now, on the issue of comparison between lobectomy and segmentectomy, there remains no published randomized controlled trial (RCT), and all existing evidence is low. Recently, a categorization of lower-level evidence has been proposed, namely, the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system.The aim of this meta-analysis is to compare the oncologic outcome between lobectomy and segmentectomy in NSCLC with the clinical T1N0M0 stage according to the GRADE system.Methods: PubMed, the PMC database, EMBASE, Web of Science, and the Cochrane library were searched prior to May 2019 to identify studies that compared the prognosis between lobectomy and segmentectomy for clinical T1N0M0 NSCLC. The evidence level of the included studies was assessed according to the GRADE system, including level IIA, probably not confounded nonrandomized comparison; level IIB, possibly confounded nonrandomized comparison; and level IIC, probably confounded nonrandomized comparison. The predefined outcomes included overall survival (OS) and disease-free survival (DFS).Univariable and multivariable hazard ratios (HRs) with 95% confidence intervals (95% CI) were pooled using a random-effects model. Results: Twelve nonrandomized studies involving 8,072 participants were included. Of these studies, two were classified as IIA level (16.7%), six as IIB level (50.0%), and four as IIC level (33.3%). When crude HRs were included, compared with lobectomy, segmentectomy was associated with shorter OS but comparable DFS in the entire cohort (OS, pooled HR =1.45, 95% CI, 1.23 to 1.67; DFS, pooled HR =1.03, 95% CI, 0.65 to 1.82) and in patients with nodules ≤2 cm (OS, pooled HR =1.55, 95% CI, 1.33 to 1.80; DFS, pooled HR =0.98, 95% CI, 0.55 to 1.77). When adjusted HRs were included, the impact of segmentectomy on OS and DFS was comparable to that of lobectomy in the entire cohort (OS, pooled HR =1.39, 95% CI, 0.92 to 2.10; DFS, pooled HR =0.83, 95% CI, 0.66 to 1.03) and in patients with nodules ≤2 cm (OS, pooled HR =1.61, 95% CI, 0.87 to 3.00; DFS, pooled HR =0.90, 95% CI, 0.63 to 1.27).Conclusions: Based on our results, although shorter OS is observed in patients received segmentectomy, it is necessary to wait for more results from RCT to draw a valid conclusion.

Application of BRACE Method to Address Treatment Selection Bias in Observational Data

“…Similarly, the MACH-NC meta-analysis, which investigated the effect of chemotherapy in addition to RT for 16485 patients across 87 randomized trials, reported an effect of chemotherapy on survival (HR 0.88), close to our BRACE-adjusted estimate. 32 While evidence regarding the comparative effectiveness of treatments for early stage NSCLC are conflicting, [33][34][35][36][37][38][39][40][41] our results indicated a survival advantage to lobectomy after BRACE correction. Though large randomized trials are lacking, in the meta-analysis by Zheng et al, the effect was attenuated in trials with higher levels of evidence.…”

“…Though large randomized trials are lacking, in the meta-analysis by Zheng et al, the effect was attenuated in trials with higher levels of evidence. 33 Of note, in some studies, lobectomy has been associated with higher 90-day mortality compared to stereotactic ablative radiotherapy (SABR); 41 if true, BRACE would under-correct for treatment selection bias.…”

“…†Note that the BRACE method does not result in a p value. ⱡReference values were obtained from randomized trials and meta-analyses ( a surgery vs. active monitoring; b radiotherapy vs. active monitoring; c lobectomy vs. segmentectomy; d locoregional therapy with chemotherapy vs. locoregional therapy alone) [32][33][34]. International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint this version posted May 18, 2021. ; https://doi.org/10.1101/2021.05.17.21257332 doi:…”

Short‐term local control after VATS segmentectomy and lobectomy for solid NSCLC of less than 2 cm

“…There is conflicting data in the literature regarding early‐stage NSCLC. A recent systematic review with meta‐analysis 15 included 12 nonrandomized studies involving 8072 participants and compared oncological outcomes of lobectomy versus segmentectomy in NSCLC patients with clinical T1N0M0. It showed that segmentectomy was associated with shorter overall survival (OS), but identified comparable disease‐free survival (DFS) for these patients and patients with nodules ≤2 cm 15 .…”

“…A recent systematic review with meta‐analysis 15 included 12 nonrandomized studies involving 8072 participants and compared oncological outcomes of lobectomy versus segmentectomy in NSCLC patients with clinical T1N0M0. It showed that segmentectomy was associated with shorter overall survival (OS), but identified comparable disease‐free survival (DFS) for these patients and patients with nodules ≤2 cm 15 . However, when multivariate HRs were included, the impact of segmentectomy on OS and DFS was comparable to that of lobectomy in the entire cohort as well as in patients with nodules ≤2 cm.…”