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. 2023 Sep 5;6(9):e2335813.
doi: 10.1001/jamanetworkopen.2023.35813.

Overall Survival Among Patients With De Novo Stage IV Metastatic and Distant Metastatic Recurrent Non-Small Cell Lung Cancer

Chloe C Su  1   2 , Julie T Wu  3   4 , Eunji Choi  2 , Nathaniel J Myall  3 , Joel W Neal  3   5 , Allison W Kurian  1   3   5 , Henning Stehr  5 , Douglas Wood  6 , Solomon M Henry  6 , Leah M Backhus  4   5   7 , Ann N Leung  8 , Heather A Wakelee  3   5 , Summer S Han  1   2   5   9
Affiliations

Overall Survival Among Patients With De Novo Stage IV Metastatic and Distant Metastatic Recurrent Non-Small Cell Lung Cancer

Chloe C Su et al. JAMA Netw Open. .

Abstract

Importance: Despite recent breakthroughs in therapy, advanced lung cancer still poses a therapeutic challenge. The survival profile of patients with metastatic lung cancer remains poorly understood by metastatic disease type (ie, de novo stage IV vs distant recurrence).

Objective: To evaluate the association of metastatic disease type on overall survival (OS) among patients with non-small cell lung cancer (NSCLC) and to identify potential mechanisms underlying any survival difference.

Design, setting, and participants: Cohort study of a national US population based at a tertiary referral center in the San Francisco Bay Area using participant data from the National Lung Screening Trial (NLST) who were enrolled between 2002 and 2004 and followed up for up to 7 years as the primary cohort and patient data from Stanford Healthcare (SHC) for diagnoses between 2009 and 2019 and followed up for up to 13 years as the validation cohort. Participants from NLST with de novo metastatic or distant recurrent NSCLC diagnoses were included. Data were analyzed from January 2021 to March 2023.

Exposures: De novo stage IV vs distant recurrent metastatic disease.

Main outcomes and measures: OS after diagnosis of metastatic disease.

Results: The NLST and SHC cohort consisted of 660 and 180 participants, respectively (411 men [62.3%] vs 109 men [60.6%], 602 White participants [91.2%] vs 111 White participants [61.7%], and mean [SD] age of 66.8 [5.5] vs 71.4 [7.9] years at metastasis, respectively). Patients with distant recurrence showed significantly better OS than patients with de novo metastasis (adjusted hazard ratio [aHR], 0.72; 95% CI, 0.60-0.87; P < .001) in NLST, which was replicated in SHC (aHR, 0.64; 95% CI, 0.43-0.96; P = .03). In SHC, patients with de novo metastasis more frequently progressed to the bone (63 patients with de novo metastasis [52.5%] vs 19 patients with distant recurrence [31.7%]) or pleura (40 patients with de novo metastasis [33.3%] vs 8 patients with distant recurrence [13.3%]) than patients with distant recurrence and were primarily detected through symptoms (102 patients [85.0%]) as compared with posttreatment surveillance (47 patients [78.3%]) in the latter. The main finding remained consistent after further adjusting for metastasis sites and detection methods.

Conclusions and relevance: In this cohort study, patients with distant recurrent NSCLC had significantly better OS than those with de novo disease, and the latter group was associated with characteristics that may affect overall survival. This finding can help inform future clinical trial designs to ensure a balance for baseline patient characteristics.

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Conflict of interest statement

Conflict of Interest Disclosures: Ms Su reported receiving grants from the National Institutes of Health (NIH) National Cancer Institute (NCI) during the conduct of the study and serving as a summer intern at ZS Associates, Inc, outside the submitted work. Dr Wu reported receiving grants from the Veterans Affairs (VA) Office of Research and Development and financial support from the VA National Oncology Program during the conduct of the study. Dr Neal reported receiving honoraria from CME Matters, Clinical Care Options CME, Research to Practice CME, Medscape CME, Biomedical Learning Institute CME, MLI Peerview CME, Prime Oncology CME, Projects in Knowledge CME, Rockpointe CME, MJH Life Sciences CME, Medical Educator Consortium, HMP Education; serving as a consultant or in an advisory role for Astra Zeneca, Genentech/Roche, Exelixis, Takeda Pharmaceuticals, Eli Lilly and Company, Amgen, Iovance Biotherapeutics, Blueprint Pharmaceuticals, Regeneron Pharmaceuticals, Natera, Sanofi/Regeneron, D2G Oncology, Surface Oncology, Turning Point Therapeutics, Mirati Therapeutics, Gilead Sciences, Abbvie, Summit Therapeutics, Novartis, Novocure, Janssen Oncology, Anheart Therapeutics; receiving research funding from Genentech/Roche, Merck, Novartis, Boehringer Ingelheim, Exelixis, Nektar Therapeutics, Takeda Pharmaceuticals, Adaptimmune, GSK, Janssen, AbbVie, Novocure; and royalities from UpToDate, all outside of the summited work. Dr Backhus reported serving as an advisor and speaker for Genentech, AstraZeneca, and Johnson and Johnson outside the submitted work; and serving as a member of the National Lung Cancer Roundtable of the American Cancer Society. Dr Leung reported receiving grants from the NIH during the conduct of the study. Dr Wakelee reported receiving grants from AstraZeneca, Bayer, BMS, Genentech/Roche, Helsinn, Merck, SeaGen, and Xcovery; and receiving personal fees from Mirati Service outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Overview of Study Cohort
The National Lung Screening Trial enrolled 52 342 participants, of whom 2058 developed primary lung cancer between 2002 and 2009. Among 2058 cases, 51 cases with unknown lung cancer stage and 3 cases of occult carcinoma were excluded. Of the remaining 2004 stage I to IV lung cancers, a total of 1503 non–small cell lung cancers were identified after excluding 501 other lung cancers. After excluding an additional 843 cases due to no progression, unknown progression, or missing progression data, the main study cohort is made up of 660 cases. NOS indicates not otherwise specified. aClassification of other histologic findings based on International Classification of Diseases for Oncology, Third Revision codes including 8000, 8001, 8022, 8032, 8033, 8083, 8084, 8260, 8310, 8323, 8480, 8481, 8490, 8550, 8560, 8570, 8980.
Figure 2.
Figure 2.. Survival Difference Between Patients With Distant Recurrence and Patients With De Novo Metastatic Disease
P values are calculated according to hazard ratio and CI adjusted for age, sex, race, and histologic findings of primary lung cancer, with the addition of screening modality and smoking status for the National Lung Screeing Trial (NLST) cohort. SHC indicates Stanford Healthcare. aSample size in panel A excludes patients with regional recurrence (39 patients) from the entire cohort (660 patients).
See this image and copyright information in PMC

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