Less Invasive NSCLC Surgery Does Not Compromise Survival

Liam Davenport

February 08, 2023

For patients with early stage non-small cell lung cancer (NSCLC), the survival outcomes  can be just as good with sublobar resection as with the more invasive lobar resection, suggests results from the CALGB 140503 trial, although strict patient selection remains key.

These new results contrast with those from a previous study from 1995, which found that local recurrence was three times higher and cancer mortality was twice as high with the less invasive procedure.

Those results from nearly 30 years ago established lobectomy as the standard of surgical care in this patient population, but since then advances in imaging and staging have allowed the detection of smaller and earlier tumors, which has "rekindled interest in sublobar resection," the authors comment.

Hence, they conducted the new trial, which involved almost 700 US patients with clinical T1aN0 NSCLC and a tumor size ≤ 2 cm, who were randomly assigned to lobar or sublobar tumor resection, and followed for 7 years.

The rates of both disease-free and overall survival were similar between the two groups, with no significant differences observed. There were also no substantial differences in rates of distant and locoregional recurrence.

In addition, there was a suggestion of less reduction in pulmonary function following the less invasive procedure.  

"These findings affirm that sublobar resection…is an effective management approach for this subgroup of patients with NSCLC," says lead author Nasser Altorki, MD, Weill Cornell Medicine, NewYork-Presbyterian Hospital, New York City.

"It is important that these results are interpreted strictly within the constraints of the eligibility criteria mandated by the trial, he emphasizes. "Specifically, the results are applicable only to a highly selected group of patients…in whom the absence of metastases to hilar and mediastinal lymph nodes is pathologically confirmed."

Nevertheless, Altorki said that "these results will become increasingly relevant as the proportion of patients with early-stage lung cancer increases with expanded implementation of lung cancer screening, and as the number of older persons with early-stage disease in whom sublobar resection may be the preferred surgical option increases."

The study was published online today in the New England Journal of Medicine.

In an accompanying editorial, Valerie W. Rusch, MD, Thoracic Service, Memorial Sloan Kettering Cancer Center, New York City, agrees. "As CT screening becomes more widespread, this patient population will increase in clinical practice," she explains.

However, Rusch also urges caution around patient selection, underlining that the results do not "provide a license for suboptimal surgical care."

She says that "safeguards" such as the meticulous and strict patient criteria used in the trial "must be preserved in routine practice."

"Thoracic surgeons will need to expand their expertise in sublobar resections, especially complex segmentectomies, and will need to collaborate closely with pathologists in assessing margins of resection, adequacy of lymph-node staging, and tumor characteristics that may predict recurrence."

While emphasizing that lobectomy should still be performed when appropriate, Rusch nevertheless says: "The era of 'precision' surgery for NSCLC has arrived."

Consistent With Japanese Results

The investigators also point out that their findings are "consistent" with those of a recent Japanese study that compared lobectomy with anatomical segmentectomy, which found that the 5-year overall survival was 91.1% for lobectomy and 94.3% for segmentectomy.

The authors suggest that the difference in overall survival rates between the two trials might be due to anatomical segmentectomy being "considered by most surgeons to be more oncologically sound than wedge resection."

In the current trial, wedge resection was allowed, however, "because it is the most frequently practiced method of sublobar resection in North America and Europe; thus, its inclusion would make the trial more representative of a 'real world' setting."

Another important difference could be that more than 90% of the patients in the Japanese trial had adenocarcinoma, 45% with an associated ground-glass component, which is associated with better survival than a completely solid adenocarcinoma.

Rusch agrees that there are likely to be various factors related to the survival differences between the two trials, including patient selection, intraoperative management, and tumor characteristics.

"However, these two landmark trials are practice-changing because they establish sublobar resection as the standard of care for a select group of patients with NSCLC," Rusch concluded.

Study Details

Altorki and colleagues conducted the multicenter, international, randomized, noninferiority, phase 3 trial in patients with clinically staged T1aN0 NSCLC from 83 academic and community-based institutions in the United States, Canada, and Australia.

Patients were required to have a peripheral lung nodule with a solid component of ≤ 2 cm on preoperative CT, a tumor center in the outer third of the lung, and a tumor location amenable to sublobar resection, whether wedge or segment, or lobar resection, among other criteria.

In all, 697 patients were randomly assigned to undergo either lobar resection or sublobar resection, of whom 59.1% had wedge resection and 37.9% anatomical segmental resection. The median age was 67.9 years, and 57.4% were female. The vast majority (90%) were White.

After a median follow-up of 7 years, the 5-year disease-free survival was 63.6% with sublobar resection and 64.1% following lobar resection.

The team found that sublobar resection was not inferior to lobectomy for disease-free survival, at a hazard ratio for disease recurrence or death of 1.01 (90% CI, 0.83 - 1.24). which adjusted to 0.99 after taking into the site where the patient was treated.

The 5-year overall survival rate was 80.3% after sublobar resection, and 78.9% following lobar resection, at a hazard ratio for death of 0.95 (95% CI, 0.72 - 1.26).

The results were "generally consistent" when accounting for factors such as age group, sex, tumor location, histologic type, smoking history, tumor size, and ECOG performance status, the team says.

Turning to recurrence, they showed that, among 687 patients eligible for assessment, 30.4% of those in the sublobar resection group and 29.3% of those assigned to lobar resection experienced disease recurrence, with 13.4% and 10%, respectively, having locoregional recurrence.

An exploratory analysis indicated that 5-year recurrence-free survival was similar in the two groups, at 70.2% vs 71.2% or a hazard ratio for recurrence of 1.05 (95% CI, 0.80 - 1.39). The cumulative incidence of death was also similar.

It was also notable that reduction in predictive forced expiratory volume in 1 second from baseline was lower with sublobar than lobar resection, at -4.0 vs -6.0, as was the reduction in predicted forced vital capacity, at -3.0 vs -5.0.

"Although this difference is arguably not clinically meaningful in this patient population with normal baseline pulmonary functions," the team writes, "it may be more clinically relevant in patients with compromised pulmonary functions, or in those with lower-lobe disease in whom lobar resection may be associated with greater impairment of pulmonary function."

Rusch suggests that "more sensitive or functional assessments" of pulmonary function might include "diffusion capacity and 6-minute walk tests," although she noted that even short-term differences in pulmonary function "may affect perioperative and functional outcomes, especially for tumors in the lower lobe."

The study was supported by the National Cancer Institute of the National Institutes of Health, including via grants to the Alliance for Clinical Trials in Oncology and the Canadian Cancer Trials Group, and supported in part by Covidien and Ethicon.

Altorki reports relationships with AstraZeneca, Genentech, Johnson & Johnson and Regeneron. Rusch reports relationships with Cancer Research UK, Genentech, and the National Cancer Institute.

N Engl J Med. Published online February 8, 2023. Abstract, Editorial

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