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Page 2 of 8 Dolan et al. Mini-invasive Surg 2021;5:3 I http://dx.doi.org/10.20517/2574-1225.2020.101

Technical aspects of wedge resection and segmentectomy are discussed for high-risk patients, and future
directions of lung cancer treatment that could specifically benefit high-risk patients are noted.

DEFINITION OF HIGH-RISK
One of the most used definitions for high-risk patients come from the American College of Surgeons
Oncology Group (ACOSOG) Z4032 trial of stage I non-small cell lung cancer (NSCLC), with tumors ≤ 3
[1]
cm, that focused on clinical details to define high risk . Patients were considered high-risk for sublobar
resection, or sublobar resection with brachytherapy, if their pulmonary function tests (PFTs) showed
a Forced Expiratory Volume in 1 second (FEV1) ≤ 50% of predicted, or if their Diffusing Capacity for
Carbon Monoxide (DLCO) was ≤ 50% of predicted, or if they met two of the following criteria: age ≥ 75
years, FEV1 51%-60% predicted, DLCO 51%-60%, diagnosed with pulmonary hypertension (pulmonary
artery systolic greater > 40 mmHg) as estimated by echocardiography or right heart catheterization, left
ventricular ejection fraction ≤ 40%, resting or exercise arterial pO ≤ 55 mmHg or SpO ≤ 88%, pCO >
2
2
2
45 mmHg, or Modified Medical Research Council Dyspnea Scale score ≥ 3.
[2]
However, while ACOSOG Z4032 provides a precise definition, controversy still exists. Puri et al. reported
the non-propensity score matched findings of their review of 1066 patients from the Washington University
School of Medicine. They found that perioperative outcomes for the high-risk group by ACOSOG Z4032
were not different from normal-risk patients - respiratory failure, 4% (7/194) in high risk vs. 5% (41/872)
in normal risk (P = 0.70); prolonged air leak of > 5 days, 8% (16/194) in high risk vs. 6% (54/872) in normal
risk (P = 0.36); and 30 day/hospital mortality 1% (2/194) in high risk vs. 2% (14/872) in normal risk (P =
0.75). The most recent National Comprehensive Cancer Network NSCLC guidelines focus on a definition of
high-risk that is aimed at risk of recurrence and leaves the definition of ‘operative’ high-risk unresolved .
[3]

PERI-OPERATIVE OUTCOMES OF HIGH-RISK PATIENTS UNDERGOING SUBLOBAR
RESECTION
[4]
Fernando et al. reported perioperative outcomes for their high-risk patients in 2011. Three deaths (1.4%,
3/222), one in the sublobar resection group and two in the sublobar resection with brachytherapy group,
occurred within 30 days. Three more deaths occurred by 90 days (2.7% 6/222), and four of the deaths
[5]
within 90 days were attributed to the surgery performed. Kent et al. provided a further operative and
pathologic analysis of this patient group in 2013. When segmentectomy (n = 57 patients) was compared to
wedge resection (n = 153 patients), they found that segmentectomies had better margin size than wedge
resections, median 1.5 cm (range 0.1-6.5 cm) vs. 0.8 cm (0-3.6 cm), P = 0.0001; greater number of lymph
node stations sampled, median 3 (0-6) vs. 1 (0-6), P < 0.0001; and greater number of lymph nodes removed,
median 4 (0-20) vs. 1 (0-23), P < 0.0001.

[6]
Sancheti et al. reported on their institution’s experience with ‘high-risk’ patients defined by ACOSOG
z4032. The study focused on Stage I NSCLC and, in their sub-analysis of patients who underwent sublobar
resection, reported shorter operative time in the high-risk group vs. standard risk group, median 89.0 min
(range 64.0-110.0) vs. 112.5 min (74.0-145.5), P = 0.04; but longer length of stay, median 4 days (3-7) in
the high risk group vs. median 3 days (2-5) in the standard risk group, P = 0.003. They found no statistical
difference in total patient numbers with major morbidity, 12.3% (7/57) high risk group vs. 6.7% (4/40)
standard risk group, P = 0.39; but, noted more patients with minor morbidity in the high-risk group, 43.9%
(25/57) vs. 20% (12/60) in the standard risk group, P = 0.02. The 3-year survival from sublobar resection
was worse for high risk patients than standard risk patients, 57% vs. 71%, but not statistically significant, P
= 0.15.