Original StudyPatterns of Distant Metastases After Surgical Management of Non–Small-cell Lung Cancer
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.
References (25)
- et al.
The IASLC Lung Cancer Staging Project: validation of the proposals for revision of the T, N, and M descriptors and consequent stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumours
J Thorac Oncol
(2007) - et al.
Treatment of operable carcinoma of the bronchus—clinical trial to compare surgery and supervoltage radiotherapy
Lancet
(1963) - et al.
Hypofractionated image-guided radiation therapy for patients with limited volume metastatic non-small cell lung cancer
J Thorac Oncol
(2012) - et al.
Multiple primary lung cancers
J Thorac Cardiovasc Surg
(1975) - et al.
New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)
Eur J Cancer
(2009) - et al.
Local treatment of oligometastatic recurrence in patients with resected non-small cell lung cancer
Lung Cancer
(2013) - et al.
Definitive primary therapy in patients presenting with oligometastatic non-small cell lung cancer
Int J Radiat Oncol Biol Phys
(2014) - et al.
Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial
Lancet Oncol
(2006) - et al.
Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial
Lancet
(2004) - et al.
Radical treatment of non-small-cell lung cancer patients with synchronous oligometastases: long-term results of a prospective phase II trial (Nct01282450)
J Thorac Oncol
(2012)
An individual patient data metaanalysis of outcomes and prognostic factors after treatment of oligometastatic non-small-cell lung cancer
Clin Lung Cancer
Cancer statistics, 2015
CA Cancer J Clin
Cited by (42)
Characterization of Metastatic Non-Small Cell Lung Cancer and Oligometastatic Incidence in an Era of Changing Treatment Paradigms
2022, International Journal of Radiation Oncology Biology PhysicsCitation Excerpt :Pending phase III trial data, there could be a large portion of patients with metastatic NSCLC who could benefit from SABR that are currently only treated with systemic therapy or palliative intent radiation therapy. Prior estimates of the incidence of oligometastatic NSCLC, based on counting the number of metastases (maximum of 3 or 5), have ranged from 20% to 50%.6-8 Prior studies have established a correlation between the number of metastatic tumors and survival outcomes.9,10
Local Ablative Therapy in Oligometastatic NSCLC
2021, Seminars in Radiation OncologyCitation Excerpt :Oligometastatic disease (OMD) has been widely recognized as a unique disease state that has historically been defined by a small number (usually 1-5) of metastases that are controllable or even curable with aggressive metastasis directed treatment. The prevalence of OMD in stage IV non-small cell lung cancer (NSCLC) has been estimated to range between 25% and 50%.1-3 Definitive stereotactic ablative radiotherapy (SABR) has been increasingly used in the treatment of OMD among radiation oncologist and most commonly treated organs included lung, liver and spine.4
Practical Considerations for the Implementation of a Stereotactic Body Radiation Therapy Program for Oligo-Metastases
2021, Advances in Radiation OncologyCitation Excerpt :The oligo-metastatic state hypothesizes that surgical or ablative treatment of a limited metastatic burden may lead to prolonged survival or even cure.1 With multiple studies showing that patients with oligo-metastatic disease frequently exist, it is an emerging paradigm that has entered clinical practice.2,3 In fact, recent studies have shown benefit with this approach in delaying potentially toxic systemic therapy, increasing progression-free survival, and possibly even overall survival.4-8
Thoracic Radiation Oncology Clinical Trial Accrual and Reasons for Nonenrollment: Results of a Large, Prospective, Multiyear Analysis
2020, International Journal of Radiation Oncology Biology PhysicsCitation Excerpt :For example, Table 4 shows that the majority of excluded NE patients had metastatic disease. Although our data did not stratify patients with metastatic disease into subgroups, estimates for oligometastatic disease range from 26% to 50% for stage IV NSCLC, highlighting the number of potential patients who might be eligible for such trials.24,25 In addition to optimizing studies in the oligometastatic space, other trials might address the polymetastatic cohort, such as comparing palliative approaches using alternative endpoints (eg, toxicity or quality of life).26