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Galvez et al. Mini-invasive Surg 2020;4:86 I http://dx.doi.org/10.20517/2574-1225.2020.86 Page 7 of 12

pulmonary function, chronic lung disease, old age, and poor performance status). The 5-year RFS was
higher in the SLR group (69.7% vs. 50.2%; P = 0.036), but there were no statistically differences in OS (75.2%
vs. 70.2%; P = 0.40) or in disease-specific survival (89.5% vs. 76.0%; P = 0.78). In tumors larger than 2 cm in
diameter, RFS and disease-specific survival were higher in the SLR group, while in tumors less than 2 cm
in diameter there were no differences in OS, RFS, or disease-specific survival. Local recurrence rate was
higher in the SABR group (P = 0.0082) in tumors located in the outer third of lung parenchyma, while no
significant difference could be seen in the internal group. Regional recurrence and distant metastasis rate
showed no differences between both groups.

None of these studies was randomized, so the evidence is limited, but it seems that in these compromised
patients, both treatments show similar overall survival, with a trend to better local control in surgical
patients, especially with tumors larger than 2 cm or in the outer third of the lung.

The SABRTooth trial was a UK multi-center, randomized controlled feasibility study targeting patients
with peripheral stage I NSCLC considered to be at higher risk of surgical complications. They planned
to randomize 54 patients 1:1 to SABR or surgery. Between July 2015 and January 2017, 318 patients were
considered for the study but only 106 assessed as eligible (33.3%), from whom 24 patients (22.6%) were
randomized to SABR (n = 14) or surgery (n = 10). The main reason for nonparticipation was treatment
preference with 43 (41%) preferring non-surgical treatment and 19 (18%) preferring surgery. The average
monthly recruitment rate was 1.7 patients against an initial target of 3. Only 15 patients underwent their
allocated treatment, 12 SABR and 3 surgery, proving the difficulty of setting a randomized trial in this high-
[44]
risk population .
Sublobar resection and SABR in operable stage I NSCLC
Despite lobectomy still being the standard treatment for early stage lung cancer [28,45] , sublobar resections,
mainly anatomical segmentectomy, have progressively increased for treating stage I NSCLC less than 2 cm
without nodal involvement due to similar oncological outcomes in terms of local control and overall
[4-8]
survival . Sometimes, patients refuse surgical treatment due to personal concerns or frightens when
facing the postoperative risks, so SABR is the most common alternative offered in these situations. It
has shown optimal local control (92% 5-year local progression-free rate in stage IA, and 73% in stage IB)
[46]
and acceptable 5-year overall survival rates (72% in stage IA, and 63.2% in stage IB ). But which are the
comparative results of these treatments in those stage I patients where SLR can be offered?

A meta-analysis was published in 2017 comparing surgery (i.e., lobectomy and SLR) with SABR in stage I
[47]
NSCLC . No randomized trial was included, but 12 cohort studies, with more than 13,000 patients. SABR
showed worse outcomes in terms of 3-year survival (RR = 0.78; P = 0.001) and OS (HR = 1.60; P < 0.001),
but when a subgroup analysis was performed comparing SLR with SABR (4 of 12 studies), there were no
significant differences in terms of 3-year survival, OS, and 3-year locoregional control. This meta-analysis
did not distinguish between wedge or anatomical segmentectomy, and also included studies dealing with
the elderly or high-risk patients, so this heterogeneity highlights the need for careful conclusions.

Chen et al. published another meta-analysis of 16 propensity score studies including more than 19,000
[48]
patients. Results favored SLR compared to SABR (HR = 1.28; 95% CI: 1.06-1.56) in terms of OS, but there
were no statistical differences in terms of lung cancer specific survival (HR = 1.22; 95% CI: 0.95-1.57).
There was also no distinction between wedge and anatomical segmentectomy, and the meta-analysis also
included comparative studies in the elderly or high-risk surgical patients.

[49]
Iguchi et al. published a single-center retrospective evaluation of the results of 3 modalities in stage
I NSCLC (i.e., radiofrequency ablation, SABR, and SLR). SLR has achieved longer survival, but after
adjustment, only reduce HR of disease progression and death of any cause were observed (P = 0.038).