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Page 4 of 8 Dolan et al. Mini-invasive Surg 2021;5:3 I http://dx.doi.org/10.20517/2574-1225.2020.101

Cryoablation is the other common ablative technique and works by creating a freezing zone that first
freezes the extracellular fluid and then the intracellular fluid, causing cellular and tissue destruction during
multiple cycles with temperature ranges typically in the -20C to -40C range [15,16] . For Stage I NSCLC,
[17]
Yamauchi et al. reported a 3-year overall survival of 88% and a disease-free 3-year survival of 67%,
[18]
while Moore et al. reported a 5-year overall survival of 67.8% ± 15.3, cancer-specific survival of 56.6%
± 16.5, and 5-year progression-free survival rate of 87.9% ± 9. Yamauchi reported pneumothorax in 28%
cases (7/25) vs. Moore’s report of 51.0% (24/45); and each reported 1 case requiring chest tube insertion.
[19]
Zemlyak et al. performed a small retrospective, non-propensity matched comparison between sublobar
resection (n = 25), radiofrequency ablation (n = 12) and percutaneous cryoablation (n = 27) and found
that the 3-year overall survival was 87.1%, 87.5%, and 77%, respectively, P > 0.05. Additionally, the 3-year
cancer-specific and cancer-free survival for sublobar resection, radiofrequency ablation, and percutaneous
cryoablation groups was 90.6% and 60.8%, 87.5% and 50%, and 90.2% and 45.6%, respectively with P > 0.05
for intergroup comparisons of 3-year cancer specific survival and 3-year cancer free survival. They noted
that the lack of significance was likely due to a small sample size.

The American Society of Radiation Oncology defines SBRT as ablation radiation doses in 1-5 fractions with
[20]
high conformal techniques . They note in these consensus guidelines that stage I NSCLC patients with
“high operative risk” should be offered SBRT as an alternative to sublobar resection, but the longer-term
outcomes over 3 years are not well-established. Some of the longest survival data for SBRT comes from a
follow-up of the North Central Cancer Trials Group N0927 randomized phase II study, comparing 34 Gy
vs. 48 Gy SBRT for medically inoperable stage I peripheral NSCLC [21-22] . They found that the 5-year overall
survival in the 34 Gy and 48 Gy groups were 29.6% (95%CI: 16.2%-44.4%) and 41.1% (95%CI: 26.6%-
55.1%) respectively. Progression-free survival at 5 years was 19.1% (95%CI: 8.5%-33.0%) and 33.3% (95%CI:
20.2%-47.0%) for the 34 Gy and 48 Gy groups respectively. A recent systematic review and pooled analysis
compared RFA to SBRT, and found that SBRT has better 5 year local tumor control rate, 42% (95%CI: 30%-
54%) RFA vs. 86% (95%CI: 85%-88%) SBRT P < 0.001; but similar OS, 32% (95%CI: 22% -43%) for RFA vs.
[24]
[23]
40% (95%CI: 36%-45%) for SBRT P = 0.41 . In 2019, Ager et al. reviewed the National Cancer Database
and compared 14,651 SBRT patients to 1141 patients who underwent some form of percutaneous local
tumor ablation therapy (LTA). After propensity score matching, their Cox modeling found a hazard ratio
of 0.83, 95%CI: 0.73-0.94, P = 0.002, showing improved survival for SBRT patients. Adjusted rates of OS at
[25]
5 years were 31.0% and 26.2% for SBRT and LTA, respectively. Chi et al. also reviewed the National
Cancer Database and compared SBRT to multiple different forms of surgery for early stage lung cancer.
They found that the 5-year overall survival for the resection groups ranged from 48.1% (wedge resection)
to 64.6% (lobectomy), compared to 30.4% in the SBRT cohort, P < 0.01 for each resection type vs. SBRT.
Their Cox model hazard ratios for wedge resection, segmentectomy, and lobectomy compared to SBRT
demonstrated improved overall survival with surgery with values from 0.55 (wedge resection) to 0.40
(lobectomy), each P value < 0.01.

[26]
In terms of surgical treatment, Jensik et al. were the first to propose segmentectomy as an appropriate
alternative to lobectomy for small-sized lung cancers. Since then, the debate has continued with findings
for and against this in randomized trials, large database studies, and meta-analysis reviews, with lobectomy
continuing as the standard of care with allowances for sublobar resection of high-risk cases [3,7,27,28] . Relatively
[28]
few studies have focused on direct comparisons of surgical options in high-risk patients. Ijsseldijk et al.
recently published a comprehensive systematic review and meta-analysis of 100 studies comparing SBRT,
sublobar resection, and lobectomy. In this work, they found that lobar resection had a 5-year OS of 74%
[0.69, 0.78], sublobar resection had a 70% OS [0.64, 0.77], and SBRT had a 46% OS [0.35, 0.57], with both
surgical survivals statistically better compared to SBRT, both P < 0.01. Disease-free survival at 5 years in
patients who had lobar resection was 76% [0.71, 0.82], sublobar resection was 71% [0.67, 0.76], and SBRT
was 46% [0.35, 0.57], with both surgical survivals statistically better compared to SBRT, P < 0.01. However,