乌鸦传媒視頻

In a cohort study of patients with non-small cell lung cancer (NSCLC), improved overall survival (OS) was observed among those with distant recurrent disease versus those with de novo disease, according to a recent study published in JAMA Network Open.¹

Among patients with lung cancer, approximately half are diagnosed at an advanced stage, and one-third who have early-stage diagnoses relapse and develop advanced disease.^2-4 Prior studies have suggested different survival rates based on the type of metastasis in patients with lung cancer.^5,6

鈥淧ast literature suggested that patients with de novo stage IV metastasis may have a different survival profile compared to those with distant recurrence,鈥� lead author Chloe C. Su, BS, and corresponding author Summer S. Han, PhD, both from Stanford University School of Medicine, Stanford, Calif., told 乌鸦传媒視頻 in a joint statement. 鈥淗owever, it鈥檚 not well established and major clinical trials have not explicitly accounted for this factor. Thus, we were inspired to properly characterize this factor so that it will be accounted for in future clinical trial designs, if it is indeed an independent prognostic factor.鈥�

Study design and patient population

The primary study cohort included 660 participants from the National Lung Screening Trial (NLST) who had a diagnosis of de novo stage IV metastatic NSCLC (n=392) or documented metastatic disease recurrence following an initial diagnosis of stage I to III disease (n=268).¹ Among the 660 patients included, 62.3% were male, 52.1% had adenocarcinoma histology, and 59.4% were current smokers at the time of enrollment. The mean age at metastatic disease diagnosis was 66.8 years.

The validation cohort included 180 patients with metastatic NSCLC who had molecular testing performed between 2009 and 2019 and were followed up through August 2022 at Stanford Healthcare. Of these patients, 60.6% were male and 81.1% had adenocarcinoma histology; the mean age of the cohort at diagnosis was 71.4 years. There were 120 patients (66.7%) with de novo stage IV NSCLC and 60 (33.3%) with distant recurrence.

Metastatic disease type and overall survival

In the primary study cohort, patients with distant recurrence had significantly longer OS than patients with de novo disease (3-year OS 21.7% versus 10.5%, respectively; adjusted hazard ratio [aHR] 0.72, 95% confidence interval [CI] 0.60 to 0.87; P<.001). This association was also seen in the validation cohort, where patients with distant recurrence also had significantly higher OS compared with those who had de novo metastasis (aHR 0.64, 95% CI 0.43 to 0.96; P=.03).

Also in the validation cohort, a higher proportion of patients with de novo metastasis than distant recurrence (34.2% versus 6.7%) had a high tumor burden. Most patients with de novo metastasis had metastatic disease detected based on symptoms (85.0%) or incidental image findings (11.7%), whereas most patients with distant recurrence (78.3%) had metastatic disease detected through posttreatment surveillance.

Patients in the validation cohort with de novo metastasis, versus those with distant recurrence, had more frequent metastasis to the bone (52.5% and 31.7%, respectively) and to the pleura (33.3% and 13.3%, respectively).

鈥淲e were surprised to find that the difference in survival profile by metastatic disease type may primarily be driven by tumor burden at the time of diagnosis for distant metastasis, with distant recurrent patients having lower tumor burden than de novo patients,鈥� Ms. Su and Dr. Han explained. 鈥淭his was also reflected in the mode of disease detection, where patients with distant recurrence were detected through CT [computed tomography] surveillance following their initial diagnosis, versus patients with de novo disease who were detected symptomatically for the first time, likely at a later time and thus with higher tumor burden.鈥�

Limitations and conclusions

In this study, Ms. Su, Dr. Han, and their colleagues demonstrated that patients with distant recurrent NSCLC had significantly better survival following a metastatic disease diagnosis compared with patients with de novo stage IV NSCLC.

According to Ms. Su and Dr. Han, 鈥淚t would be interesting to further investigate whether there are intrinsic differences in tumor biology or tumor microenvironment by metastatic disease type鈥攊n addition to tumor burden differences鈥攖hat may have contributed to their differential survival, which will be insightful to developing therapies specifically aimed at patients with de novo metastasis.鈥�

The study was limited by the exclusion of 238 patients from the NLST cohort due to lack of progression data, which could have contributed to selection bias. There was also the potential that the findings may not be generalizable beyond tertiary centers. Moreover, the research team wasn鈥檛 able to adjust for method of primary lung cancer detection and smoking status in the validation cohort.

鈥淩esearchers should start recognizing patients with de novo metastasis as a distinct population from patients with distant recurrence and investigate their intrinsic differences,鈥� Ms. Su and Dr. Han concluded. 鈥淒rug developers and clinicians involved in clinical trials should consider this as a stratification factor to ensure a balance of these 2 types of patients in the treatment and control arms.鈥�

Published: January 19, 2024