PALO ALTO, CA – Even with new and improved therapies, clinicians remain challenged by how to deal with advanced lung cancer.
“The survival profile of patients with metastatic lung cancer remains poorly understood by metastatic disease type (i.e., de novo stage IV vs. distant recurrence),” according to a study led by Stanford University School of Medicine and the VA Palo Alto, CA, Healthcare System.
That’s why a study team sought 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. Results were published in JAMA Network Open.1
The cohort study of a national US population-based at a tertiary referral center in the San Francisco Bay Area used participant data from the National Lung Screening Trial (NLST). Participants were enrolled between 2002 and 2004 and followed up for up to seven years as the primary cohort; patient data from Stanford Healthcare (SHC) for diagnoses between 2009 and 2019 was followed up for up to 13 years as the validation cohort.
The current study included patients from NLST with de novo metastatic or distant recurrent NSCLC diagnoses. Data were analyzed from January 2021 to March 2023.
Using a cohort with de novo stage IV vs distant recurrent metastatic disease, the study team sought to determine overall survival after diagnosis of metastatic disease.
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),” the researchers reported. “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.”
The authors suggested their findings could “help inform future clinical trial designs to ensure a balance for baseline patient characteristics.”
The study advised that prior studies have suggested differential survival by type of metastasis in lung cancer—patients with recurrence were observed to have better survival than those with de novo metastasis— but added that “this finding is not universal among all cancers” and that “thus, the survival differences in metastatic lung cancer are unique and intriguing. However, findings from prior studies in lung cancer have not been fully validated in the US.”
Furthermore, they wrote, the mechanisms underlying the survival difference between patients with de novo metastasis vs. patients with lung cancer recurrence had not been investigated.
The researchers noted that the main result of their study was consistent across the two cohorts even though some baseline characteristics differed between the SHC and NLST cohorts, where fewer patients underwent cancer screening, a higher proportion of stage IV disease existed and the racial makeup was substantially different. “The SHC cohort also represents a more modern patient population who may have benefited from recent therapies, which could explain the overall older age at diagnosis for metastatic disease and longer follow-up after metastatic disease,” they explained. “Moreover, our finding was robust across multiple sensitivity analyses, even after adjusting for clinical characteristics associated with metastatic disease type.”
The study team posited that potential reasons for differential survival outcome in patients with distant recurrence vs de novo stage IV NSCLC could be attributed to differences in metastasis sites, tumor burden or methods for detecting metastases. “We found that a larger proportion of patients with de novo metastasis had more frequent metastasis to the bone or pleura than patients with recurrence,” the authors wrote.
They added, “In the context of our main finding—that patients with distant recurrence exhibit better survival than those with de novo disease—pleural and bone metastases have been identified as independent negative prognostic factors, with prior studies citing the immunosuppressive nature of their tumor microenvironments and, for pleura metastasis, the permeable nature of the pleura cavity that may reduce the efficacy of immunotherapy. In addition, patients with de novo disease had their metastasis largely detected through symptoms—likely at higher tumor burden—as opposed to posttreatment surveillance, which is more common for patients with distant recurrence and likely resulting in a lower tumor burden at the time of metastasis.”
Implications of their findings could be extensive, according to the researchers, who said they believed the study to be the first on the topic. “As there is no difference in how patients of different metastatic disease types are currently managed, it may be interesting for future studies to consider using observational data to investigate the effectiveness of first-line treatments by metastatic disease type,” they noted.
- Su CC, Wu JT, Choi E, Myall NJ, Neal JW, Kurian AW, Stehr H, Wood D, Henry SM, Backhus LM, Leung AN, Wakelee HA, Han SS. Overall Survival Among Patients With De Novo Stage IV Metastatic and Distant Metastatic Recurrent Non-Small Cell Lung Cancer. JAMA Netw Open. 2023 Sep 5;6(9):e2335813. doi:
