Stereotactic Ablative Radiotherapy Versus Surgery in Early Lung Cancer: A Meta-Analysis of Propensity Score-Adjusted Comparative Effectiveness Studies

Abstract

Stereotactic ablative radiotherapy (SABR) represents an alternate modality to surgery in early-stage non-small cell lung cancer (ES-NSCLC). However, no completed randomized controlled trial (RCT) comparing these treatments in operable patients is available. A number of retrospective studies have compared SABR vs. surgery in patients with similar assigned scores based on their likelihood to receive a certain treatment. These propensity score (PS)-adjusted studies attempt to minimize inherent biases of confounding by indication. We performed a meta-analysis of PS-adjusted studies comparing surgery vs. SABR in patients with ES-NSCLC, and hypothesize that the two modalities achieve similar survival outcomes after compensation for covariates. In accordance with the PRISMA guidelines, a systematic review was carried out by querying the MEDLINE and Embase databases from inception until December 2016. Two reviewers independently reviewed titles, abstracts and full texts, with discrepancies settled by a third. Hazard ratios (HR) with confidence intervals (CI) for overall survival (OS) and disease-specific survival (DSS) were extracted directly, where available, or estimated from Kaplan-Meier survival curves. Meta-analysis of HRs was carried out with inverse variance-weighted random-effects models. After reviewing a total of 1,038 records, 16 PS-adjusted studies comprising 19,999 patients were included in the final analysis. HRs for OS were available from all studies, and for DSS from 8 studies. Eight studies reported data specifically for SABR vs. lobectomy, and 6 for SABR vs. sublobar resection. Seven studies used data from national population-level databases. Overall HR for OS favored surgery (HR = 0.67 [95% CI: 0.58-0.77], p < 0.001), while DSS did not significantly differ (HR = 0.86 [0.63-1.16], p = 0.32). Between-study heterogeneity was high for the OS meta-analysis (I2 = 71.2%) but low for the DSS meta-analysis (I2= 35.5%). On subgroup analyses, OS was superior for both lobectomy (HR = 0.64 [0.50-0.83], p < 0.001) and sublobar resection (HR = 0.75 [0.65-0.87], p < 0.001) vs. SABR while the differences in DSS again did not show statistical significance (HR = 0.64 [0.25-1.61] and HR = 0.84 [0.60-1.19], respectively). On sensitivity analysis, censoring results from national population-level databases (to reduce multiple counting of patients) and including other balanced studies not using a PS-adjusted technique resulted in no changes to the study conclusions. Patients undergoing surgery for ES-NSCLC demonstrated superior OS to SABR in this meta-analysis of PS-adjusted comparative effectiveness studies. However, the effectiveness of SABR is reflected in a similar DSS to surgery, which was further observed over a range of sensitivity analyses. Whether this observed benefit in OS is real or due to residual confounders requires confirmation in currently-recruiting RCTs.