Despite curative-intent surgical resection, cancer recurrence is common among patients with early-stage lung cancer, occurring in up to 50% of patients, according to Brendan T. Heiden, MD, MPHS. “Our research demonstrates that certain high-risk features are associated with a dramatically increased risk for cancer recurrence,” he says. “Therefore, considering these factors in a multivariable risk score may aid oncologists in determining eligibility for additional treatments, such as chemotherapy or immunotherapy following complete surgical resection.”

Dr. Heiden and colleagues presented their research at the 2023 American Association for Cancer Research (AACR) annal meeting recently held in Orlando, Florida.

For patients with completely resected non-small cell lung cancer (NSCLC) with high-risk features, the current guidelines recommend adjuvant therapy, Dr. Heiden explains, adding that the “association between these features and cancer recurrence is poorly interpreted.”

Six High-Risk Clinicopathologic Features Examined

The study team examined the link between six high-risk clinicopathologic features and the risk for cancer recurrence in patients with early-stage lung cancer following complete surgical resection. They conducted a retrospective cohort study using a dataset from the Veterans Health Administration (VHA) that included all veterans with pathologic early-stage NSCLC (N=3,799) receiving definitive surgical treatment. A cohort of 63,232 patients from the National Cancer Database (NCBD) was used to further test the scores; higher scores remained linked with worse OS (median OS, low-risk: 9.4 years; moderate-risk: 8.0 years; high-risk: 6.3 years) (Figure).

The high-risk features evaluated were:

  • adequacy of nodal sampling
  • tumor grade
  • tumor size
  • visceral-pleural invasion,
  • lymphovascular invasion, and
  • non-anatomic wedge resection.

“Using these variables, we created a multivariable risk score, the VA Lung Cancer Recurrence (VALCAN-R) score,” Dr. Heiden says. “We observed that higher scores were associated with dramatically higher risk for recurrence and worse overall survival.”

In 21.1% of patients, cancer recurrence was detected. The link between high-risk features and cancer recurrence were adequacy of nodal sampling (adjusted HR [aHR] 1.392; 95% CI, 1.149-1.687, P<0.001), tumor grade (aHR 1.884; 95% CI, 1.448-2.449, P<0.001), tumor size (aHR, 1.676; 95% CI, 1.229-2.285, P=0.001), visceral-pleural invasion (aHR 1.096; 95% CI, 0.905-1.329, P=0.35), lymphovascular invasion (aHR 1.747; 95% CI, 1.441-2.117, P<0.001), and non-anatomic wedge resection (aHR 1.335; 95% CI, 1.101-1.619, P=0.003).

VALCAN-R Score Will Be ‘Highly Useful for Oncologists’

The score was divided into low- (0-11, N=1,263, 33.3%; 5-year recurrence risk 13.0%), moderate- (12-15, N=1,134, 29.9%; 5-year recurrence risk 19.0%), and high-risk (16-36, N=1,402, 36.9%; 5-year recurrence risk 27.1%) categories. Higher scores were linked with reduced overall survival (median OS, low-risk: 9.0 years; moderate-risk: 7.3 years; high-risk: 5.4 years).

The VALCAN-R score will prove “highly useful for oncologists as they consider the benefits of chemotherapy and other novel treatment options in patients with early-stage lung cancer following surgical resection,” Dr. Heiden explains. “We also hope that this score better informs patient-centered treatment decisions during the cancer survivorship period.”

In the future, Dr. Heiden and colleagues would like to see that this comprehensive, yet easy-to-use, score inform oncologists, surgeons, and other healthcare professionals in assessing the risk for recurrence in patients with early-stage lung cancer.

“While this score is associated with risk for recurrence, it is unclear if patients with higher scores will benefit from specific therapies or other interventions,” he says. “This is something we hope to examine further in the future.”