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Reverberi et al. Mini-invasive Surg 2020;4:43 I http://dx.doi.org/10.20517/2574-1225.2020.33 Page 7 of 10

significantly improved 3-year OS (OR = 2.11, 95%CI: 1.55-2.86) and 5-year OS (OR = 2.40, 95%CI: 1.71-
[33]
3.36), 3-year CSS (OR = 1.94, 95%CI: 1.05-3.57) and 3 year PFS (OR = 1.63, 95%CI: 1.12-2.36) .

Many observational studies suggest that the survival advantages reported from lobectomy could have
been a consequence of treatment selection criteria. Data on patients deemed fit for surgery but treated
with SBRT have suggested that OS (HR = 1.68, 95%CI: 0.72-3.90) and PFS (HR = 0.61, P = 0.09) were
[34]
comparable to that from surgery. Performance status was also found to impact significantly on OS . The
pattern of failure studied in a t-matched comparison study was similar between patients who underwent
an optimal surgical operation and those who received SBRT. There was a trend of a distant-recurrence free
interval in favor of lobectomy because of reported occult nodal involvement. Nodal metastases have been
detected in 20% of patients treated with surgery and almost 15% received adjuvant systemic therapy (pN2).
Surgical patients had higher OS rate (63.5% vs. 29.6%, P < 0.0001) with no difference in CSS. The rate of
complete response was similar, whereas the 4-year LC rate was significantly higher in resected patients
[35]
(98.7% vs. 93.6% P = 0.015) . Surgery had a 1 in 6 chance of discovering occult nodal metastasis, while
only 1 in 9 would benefit from adjuvant chemotherapy. Adjuvant chemotherapy improved OS in patients
with nodal involvement, but surgery (either lobectomy or sub-lobar resection) was related with severe
adverse events and mortality rate. A meta-analysis confirmed that patients who underwent surgery had
2
better OS over SBRT [HR = 1.48, (95%CI: 1.26-1-72), P < 0.001, I = 80.5%] but there was no difference in
[36]
lung cancer-specific survival . Lobectomy demonstrated survival advantages over SBRT even when data
analysis had been restricted by exclusion of older patients, poor performance status and clinical stage IB. A
meta-analysis noted that SBRT treatment was delayed compared to surgery. A possible explanation is that
patients who are not candidates for surgery may require repeat CT scans in order to demonstrate increase
[37]
of the unbiopsied nodule’s size . Surgery (lobectomy and sub-lobar-resection) showed statistically
superior outcomes for OS, CSS, PFS and loco-regional control compared to SBRT in both matched and
un-matched cohorts for mid- and long-term outcomes. Distant control was not statistically improved by
surgery but there was a trend suggesting lobectomy could show an advantage in the long term. The extent
of favorable long-term outcomes in surgery may be influenced however, by imbalances in baseline patient
[38]
characteristics, preoperative comorbidities or tumor characteristics .

SBRT vs. limited resection
Detection of early stage lung cancer is increasing due to the development of diagnostic imaging, and
clinicians have to face difficult treatment decisions, particularly in older patients with comorbidities
and poor lung function. Less invasive procedures such as SBRT and limited lung resection (wedge,
segmentectomy) provide a good alternative because they are better tolerated and have fewer adverse events.
Segmentectomy is an anatomic lung resection in which interlobar and parenchymal nodes are identified
and removed for pathology; wedge resection is a non-anatomic resection without nodal sampling. SBRT
and wedge resections have similar survival outcomes, while the OS and CSS rates supported segmentectomy
over SBRT, probably due to patient characteristics. Lung adverse events were reported more frequently
[39]
after surgery (28% vs. 14%, P < 0.001) . Patients ineligible for lobectomy could be candidates for wedge
resection or SBRT, unless SBRT patients have more comorbidities and are older; no statistical difference
in loco-regional recurrence, distant metastasis, and PFS were observed between groups. In an unmatched
cohort analysis, there was a trend towards decreased local recurrence in SBRT over wedge resection: 4%
vs. 20% (P = 0.07). OS was also higher in the wedge resection arm (87% with surgery vs. 72% in SBRT,
P = 0.01) but the CSS was equivalent (93% in SBRT vs. 94% with wedge). The authors suggested that the
reduced OS in the SBRT arm could be related to both a higher rate of comorbidities before treatment,
[40]
and complications and mortality rate post-treatment . Sub-lobar resection for Stage I NSCLC showed
survival advantages over SBRT in a propensity-score matched analysis with 1-and 2-year OS rates of 92%
and 82%. Moreover, even though segmental resection showed better OS vs. wedge resection, both of them
have survival advantages over SBRT of a median dose of 30-66 Gy in 2-8 fractions. The 1-, 2-, 3- and 5-year