Early Detection of PH May Be Key to Improving NSCLC Survival Rates

Pulmonary hypertension (PH) can be diagnosed before or after microscopically confirmed primary malignant non–small cell lung cancer (NSCLC) and survival outcomes will still be suboptimal compared with patients who have NSCLC alone, concludes a study of patients who received care at military treatment facilities within the US and whose cancer was diagnosed between 1998 and 2014.

These findings appear in a recent issue of Journal of Clinical Medicine.¹

“The survival implications of PH on patients with NSCLC have only been evaluated in small cohorts, with limited long-term follow-up,” the study authors wrote. “In many diseases affecting the human lung, PH when present, portends a poor prognosis.”

Using MilCanEpi, a database system linking the Department of Defense’s Central Cancer Registry (CCR) and the Military Health System Data Repository, the investigators’ primary outcome of interest was all-cause death from the impact of comorbid PH in patients with NSCLC who were diagnosed or treated at military treatment facilities. PH diagnosis was identified through International Classification of Disease, Ninth Edition and Tenth Edition codes and tumor stages per the sixth edition of the American Joint Committee on Cancer’s TNM system criteria.

The study population comprised 7946 patients, of whom 54% were 65 years and older and 81.3% did not have PH (ie, it was never noted in their records). Of those who did have comorbid PH, 1036 had PH diagnosed after their NSCLC diagnosis and 451 had PH diagnosed before their NSCLC diagnosis. The patient groups contained mostly male patients (no PH, 64.6%; PH after NSCLC diagnosis, 60.7%; PH before NSCLC diagnosis, 62.8%), and White patients (75.9%, 79.3%, and 83.4%, respectively).

Few previous studies have investigated the relationship between PH and NSCLS in large groups of patients. | Image Credit: © Vitalii Vodolazskyi -stock.adobe.com

Women were more likely to have PH diagnosed after NSCLC, while younger patients were more likely to have PH diagnosed before NSCLC, the study authors highlighted.

Diagnosis year was divided into 4 groups: 1998 to 1999, 2000 to 2004, 2005 to 2009, and 2010 to 2014. Overall, 2000 to 2004 had the most diagnoses for the no PH (35%) and PH after NSCLC diagnosis (37.6%) cohorts, and 2010 to 2014 for the PH before NSCLC diagnosis (36.4%).

The most common diagnosis stage was stage IV for those with no PH (38.9%), stage I for those with PH after NSCLC diagnosis (33.7%), and stage IV for those with PH before NSCLC diagnosis (34.8%). Median (IQR) follow-up was 353 days (142-684).

As for treatment, surgery, chemotherapy, and radiation therapy were seen in less than half of each patient group:

• Surgery:
  • No PH: 33.4%
  • PH after NSCLC: 44.5%
  • PH before NSCLC: 25.7%
• Chemotherapy:
  • No PH: 42.3%
  • PH after NSCLC: 48.8%
  • PH before NSCLC: 31.9%
• Radiation therapy:
  • No PH: 42.6%
  • PH after NSCLC: 40.2%
  • PH before NSCLC: 35.9%

Additional findings show a 15% higher risk of death when PH diagnosis precedes NSCLC diagnosis (HR, 1.15; 95% CI, 1.02-1.29), regardless of age, sex, race, or tumor stage, and an even greater elevated risk of 174% when PH was diagnosed after NSCLC (HR, 2.74; 95% CI, 2.51-2.99).

The study authors emphasize that their data show a clear association between PH diagnosis and reduced survival from comorbid NSCLC, with this relationship being even more apparent considering PH diagnosed after NSCLC. They highlight that these findings echo previous research in the space.^2,3

At the same time, they note the relationship between the 2 conditions is complex, because they could share the same risk factors and PH is a potential complication of NSCLC treatment or may be a direct result of it. Also, current evaluation recommendations for patient candidates for surgical resection do not include PH screening.

“Further research is warranted to understand the mechanisms for the development of PH in NSCLC,” they conclude. “Furthermore, this may provide a potential beneficial role for PH screening in patients with NSCLC and during follow-up after therapy [and} provide a target for therapy.”

References

1. Nations JA, Lin J, Park AB, Shriver CD, Zhu K. Pulmonary hypertension and survival among non-small cell lung cancer patients: a retrospective cohort study in the U.S. military health system. J Clin Med. 2024;13(11):3217. doi:10.3390/jcm13113217

2. Eul B, Cekay M, Pullamsetti SS, et al. Noninvasive surrogate markers of pulmonary hypertension are associated with poor survival in patients with lung cancer. Am J Respir Crit Care Med. 202115;203(10):1316-1319. doi:10.1164/rccm.202005-2023LE

3. Yan X, Wang L, Lin L, Liu X. Elevated pulmonary artery systolic pressure is associated with poor survival of patients with non-small cell lung cancer. Cancer Manag Res. 2020:12:6363-6371. doi:10.2147/CMAR.S26085