Secondary Primary Lung Cancer Rates Similar in Early NSCLC Regardless of Resection Type


Secondary primary lung cancer rates and cumulative incidence rates were similar in multiple subgroups of patients with stage T1aN0 non–small cell lung cancer.

Secondary primary lung cancer rates and cumulative incidence rates were similar in multiple subgroups of patients with stage T1aN0 non–small cell lung cancer.

Secondary primary lung cancer rates and cumulative incidence rates were similar in multiple subgroups of patients with stage T1aN0 non–small cell lung cancer.

Secondary primary lung cancer (SPLC) rates and 5-year cumulative incidence were found to be similar across patients with stage T1aN0 non–small cell lung cancer (NSCLC), and regardless of whether they underwent sublobar resection (SLR) or lobar resection (LR), according to a secondary analysis of the Cancer and Leukemia Group B 140503 (Alliance) trial (NCT00499330) that was published in the Journal of Clinical Oncology.

At a median follow-up of 7 years, results showed that the rate per patient per year in the overall study population was 3.4% (95% CI, 2.9%-4.1%), the SLR arm was 3.8% (95% CI, 2.9%-4.9%), and the LR arm was 3.1% (95% CI, 2.4%-4.1%). The respective estimated 5-year cumulative SPLC rates were 15.9% (95% CI, 12.9%-18.9%), 17.2% (95% CI, 12.7%-21.5%), and 14.7% (95% CI, 10.6%-18.7%).

“The rate of SPLC observed is clinically significant and raises questions about the optimal frequency, duration, and type of surveillance imaging,” lead study author Thomas E. Stinchcombe, MD, of Duke Cancer Institute, and coinvestigators wrote in the study. “Our study did not identify an association between known risk factors and the development of SPLC. These findings are limited by the small number of SPLC events.”

Patients who have early-stage NSCLC and undergo curative surgery for their cancer are at risk for developing SPLC, defined as a tumor with a different histology, one that is diagnosed 2 years after the index lung cancer, or a tumor of a similar histology located in different lobes or segments that don’t intervene with nodal metastases. Current estimated incidence rates of SPLC are mainly retrospective cases or database studies of a heterogeneous patient population. However, the frequency and length of follow-up imaging are not standardized.

In the international, multicenter, phase 3 Cancer and Leukemia Group B 140503 (Alliance) trial, investigators evaluated whether SLR was noninferior to LR in terms of disease-free survival (DFS) in 697 patients with stage T1aN0 NSCLC. Between June 15, 2007, and March 13, 2017, patients were randomly assigned 1:1 to either SLR, specifically a wedge resection or segmentectomy (n = 340), or LR (n = 357). Following surgery, patients underwent CT surveillance every 6 months for 2 years, then once yearly for 5 additional years, for a total of 7 years after surgery. SPLC determinations were conducted by patients’ treating physician(s) and then recorded in the trial database.

To be eligible for enrollment, patients had to have tumors that were 2 cm or smaller in maximum diameter or their preoperative CT on the outer third of the lung.

Stratification factors included radiographic tumor size (1.5 cm-2.0 cm), histology (squamous cell carcinoma, adenocarcinoma, or other), and smoking status (never, former, or current). The primary end point was DFS but excluding SPLC, while the secondary end point was overall survival (OS).

The median age was 67.9 years (range, 37.8-89.7) and more than half of patients were female (57.4%). Twenty-five percent of patients had an ECOG performance score of 1, and half of patients were former smokers (50.1%). Most patients had adenocarcinoma (63.7%).

Previous results showed that SLR resection was found to have noninferior DFS to LR (HR,1.01; 90% CI, 0.83-1.24]). Additionally, SLR was noninferior to LR with OS (HR, 0.95; 95% CI, 0.72-1.26).

For the secondary analysis, investigators then analyzed the SPLC rate (per patient/year) as well as the 5-year cumulative incidence in both the overall study population and in the SLR and LR arms specifically.

Additional data showed that the univariable and multivariable analyses of risk factors potentially linked with a SPLC did not identify a statistically significant association. The 5-year OS rate was 52.0% in the study population with disease recurrence and 63.9% in those with SPLC. These rates were 50.9% and 52.8% in the 2-year postrandomization cohort.

The exploratory analysis for OS for patients in the study population with SPLC and disease recurrence revealed a restricted mean survival time (RMST) difference of 0.31 over 5 years (95% CI, –0.60 to 0.69; P = .104). A RMST difference of 0.20 (95% CI, 0.10-0.50; P = .18) over a 5-year horizon was noted 2 years after randomization.

“Future studies in patients who are surgically resected should prospectively determine the SPLC pathology, staging evaluation, specific criteria used to distinguish SPLC from disease recurrence, and the treatment of the SPLC,” the authors concluded. “Circulating tumor DNA surveillance is being investigated in patients with resected NSCLC, which may improve the early detection of recurrence or SPLC.”


Stinchcombe TE, Wang X, Damman B, et al. Secondary analysis of the rate of second primary lung cancer from cancer and Leukemia Group B 140503 (Alliance) trial of lobar versus sublobar resection for T1aN0 non–small-cell lung cancer. J Clin Oncol. Published January 12, 2024. doi:10.1200/JCO.23.01306

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