Elsevier

Clinical Lung Cancer

Volume 18, Issue 1, January 2017, Pages e57-e70
Clinical Lung Cancer

Original Study
Patterns of Distant Metastases After Surgical Management of Non–Small-cell Lung Cancer

https://doi.org/10.1016/j.cllc.2016.06.011Get rights and content

Abstract

Background

Patients with limited metastases, oligometastases (OMs), might have improved outcomes compared with patients with widespread distant metastases (DMs). The incidence and behavior of OMs from non–small-cell lung cancer (NSCLC) need further characterization.

Patients and Methods

The medical records of patients who had undergone surgery for stage I-III NSCLC from 1995 to 2009 were retrospectively reviewed. All information pertaining to development of the first metastatic progression was recorded and analyzed. Patients with DMs were categorized into OMs (1-3 lesions potentially amenable to local therapy) and DM subgroups.

Results

Of 1719 patients reviewed, 368 (21%) developed DMs with a median follow-up period of 39 months. A single lesion was diagnosed in 115 patients (31%) and 69 (19%) had 2 to 3 lesions (50% oligometastatic). The median survival from the DM diagnosis for oligometastatic and diffuse DM was 12.4 and 6.1 months, respectively (hazard ratio, 0.54; 95% confidence interval, 0.42-0.68; P < .001). Patients with a single metastasis had the longest median survival at 14.7 months. Younger age, OM, the use of chemotherapy for the primary tumor, and DM detection by surveillance imaging were independently associated with improved survival.

Conclusion

DMs and OMs are common in surgically managed NSCLC. Overall survival appears to be prolonged with OM.

Introduction

In the United States, an estimated 221,200 new cases of lung cancer and 158,040 lung cancer deaths will have occurred in 2015.1 Of these cases, approximately 30% will have been clinical stage I-II, for which the 5-year survival ranges from 50% for stage IA disease to 25% for stage IIB disease.2 Resection of the tumor-containing lobe is the preferred approach for medically operable early-stage non–small-cell lung cancer (NSCLC).3 Despite the improved clinical outcomes with anatomically based surgery4 and adjuvant or neoadjuvant chemotherapy,5 recurrence is common.

The incidence of distant progression in surgically resected NSCLC has been well described. For example, in 1 analysis, the 5-year actuarial risk of any recurrence was 36%,6 with 75% of recurrences being distant metastases (DMs) alone or combined with locoregional recurrence. However, the distribution of clinically apparent DMs after surgery has not been well described, including the state of limited metastases known as oligometastases (OMs). Although a small analysis of metastatic NSCLC patients reported that 50% of such patients had only 1 to 3 metastases limited to ≤ 3 organs,7, 8 it is not known whether this could be generalizable to definitively treated patients with subsequent distant progression.

An improved understanding of the number and distribution of metastases in NSCLC patients is important for the development of personalized cancer management strategies. Although the standard treatment of metastatic NSCLC is systemic therapy, the response rates for nontargeted therapies have been low. Furthermore, the most likely sites of progression after systemic therapy are at known metastatic sites.7 Given that surgical and radiation series targeting limited NSCLC metastases have demonstrated high rates of treated metastasis control9 and that a significant fraction of patients with aggressive treatment of metastatic disease will have long disease-free intervals,10, 11 a population of patients might exist for whom metastasis-directed therapy could be beneficial. Therefore, we sought to determine the pattern and number of metastases present at distant progression in a cohort of initially operable, primarily early-stage NSCLC patients. Additionally, we sought to determine whether the number of metastases and method of detection was prognostic.

Section snippets

Patients and Methods

The present institutional review board-approved study was performed by searching the Duke Comprehensive Cancer Center database for patients who had undergone surgery for NSCLC at Duke University from 1995 to 2009. REDCap electronic data capture tools were used for analysis. Patients who had presented with synchronous primary lung tumors or had a history of lung cancer were excluded. The patients' medical records and pertinent radiologic imaging were retrospectively reviewed to characterize the

Results

From the database records of 1719 consecutive patients, 368 (21%) developed DM and constituted our study cohort (Tables 1 and 2). DMs were detected by symptoms in 186 (51%), surveillance imaging in 151 (41%), and indeterminate in 31 (8%) patients. The median follow-up period from the initial lung cancer diagnosis for living patients in the entire and study cohorts was 39 months (range, 0-189 months) and 38 months (range, 2-189 months), respectively. Pretreatment positron emission tomography was

Discussion

In the present analysis of resected stage I-III NSCLC patients, we found that a significant portion will present with OM at the time of metastatic progression. We did not find any baseline patient or tumor characteristics that influenced the pattern of distant metastatic progression. Our results are similar to those from a smaller analysis, in which 55% of surgically resected NSCLC patients who subsequently developed DM in the absence of local recurrence were classified as having limited

Conclusion

DMs often develop in patients with NSCLC after surgery with curative intent. Many patients will have limited disease at the first metastatic progression, and chemotherapy appears to shift the pattern of metastases. Patients with OMs, in particular, those with a single metastasis, appear to have an improved prognosis. Whether this results from aggressive management of the metastasis or underlying biology is unclear. Further research is warranted into the biology of limited metastatic disease and

Disclosure

The authors declare that they have no competing interests.

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