Patients With Distant Recurrent NSCLC Had Better OS vs Those With De Novo Disease

Patients with distant recurrent non-small cell lung cancer (NSCLC) possessed significantly better overall survival (OS) than those who had de novo disease, and were associated with characteristics that may impact OS, according to a cohort study in JAMA Network Open.

“This finding can help inform future clinical trial designs to ensure a balance for baseline patient characteristics.,” emphasized the researchers.

Even though there have been recent breakthroughs in advanced lung cancer therapy, it is still a therapeutic challenge. The survival profile of patients with metastatic lung cancer continues to not be well understood.

The researchers aimed to analyze the association of metastatic disease type on OS among patients with NSCLC and to pinpoint possible mechanisms underlying any survival difference.

Almost 50% of patients with lung cancer receive a diagnosis at an advanced stage, and one-third of patients with early stage (stage I-III) disease will relapse and experience advanced disease recurrence. Most major clinical trials for advanced lung cancer have not differentiated between these 2 types of metastatic disease, although prior literature does suggest a significantly higher OS for those with recurrence.

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A cohort study was conducted 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. Patient data from Stanford Healthcare (SHC) were used for diagnoses between 2009 and 2019 and followed up for 13 years as the validation cohort. Participants from the NLST with de novo metastatic or distant recurrent NSCLC diagnoses also were included.

Data were evaluated from January 2021 to March 2023. Exposures consisted of de novo stage IV vs distant recurrent metastatic disease, and the main outcome was OS following diagnosis of metastatic disease.

The NLST and SHC cohorts comprised 660 and 180 participants, respectively (411 [62.3%] vs 109 men [60.6%], 602 [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 had significantly better OS than patients with de novo metastasis (adjusted HR [aHR], 0.72; 95% CI, 0.60-0.87; P < .001) in NLST, which was reproduced in the SHC data (aHR, 0.64; 95% CI, 0.43-0.96; P = .03).

Among the patients from SHC, those with de novo metastasis progressed more frequently to have bone metastasis (63 patients with de novo metastasis [52.5%] vs 19 patients with distant recurrence [31.7%]) or pleura (40 [33.3%] vs 8 patients [13.3%], respectively) than patients with distant recurrence and were primarily identified through symptoms (102 [85.0%]) compared with posttreatment surveillance (47 [78.3%]) in the latter. The main finding stayed consistent.

A first implication of these findings is that most major clinical trials have not differentiated between the types of metastatic disease from lung cancer, but the results of this study suggest that the metastatic disease type is a key—and possibly an independent­—factor linked with outcomes.

Also, although higher tumor burden and metastasis to the pleura and bone might be linked with delayed detection among patients with de novo metastasis, they have all been determined as independent negative prognostic factors in various treatment settings. Finally, the disease factor linked with outcomes should also be accounted for in cost-effectiveness analyses, including microsimulation models where it may possess a substantial influence.

It might be worthwhile for future studies to consider using observational data to examine the effectiveness of first-line treatments by metastatic disease type, the authors emphasized.

There are some limitations to these findings. In the NLST cohort, 238 patients were excluded because of unavailable progression data for unknown reasons, which could end in selection bias. Also, the findings might not be generalizable beyond tertiary centers.

“This factor [metastasis to the pleura and bone] associated with outcomes may have important implications in future clinical trials and cost effectiveness analyses, and the treatment effectiveness for patients with metastatic NSCLC warrants further evaluation,” concluded the researchers.

Reference

Su CC, Wu JT, Choi E, et al. Overall survival among patients with de novo stage IV metastatic and distant metastatic recurrent non–small cell lung cancer. JAMA Netw Open. Published online September 26, 2023. doi:10.1001/jamanetworkopen.2023.35813