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Patients with single-site synchronous oligometastatic non-small cell lung cancer (NSCLC) had better overall survival (OS) when they received surgery for their primary tumor, a retrospective review of nationwide data showed.
Surgery to the primary tumor was associated with a 33% reduction in the survival hazard, whereas surgery to the synchronous metastasis reduced the survival hazard by 20%. A propensity-score matched analysis showed primary surgery to be associated with a 16-month improvement in OS compared with systemic therapy without surgery.
The findings added to evidence that advances in systemic therapy are changing the historical clinical paradigm of excluding patients with metastatic disease from surgery, reported Brendon M. Stiles, MD, of Montefiore Medical Center in New York City, and co-authors in the Journal of the American College of Surgeons.
“Novel therapies, including immunotherapy and targeted therapy, have an enhanced synergistic effect with surgery, as compared with traditional cytotoxic chemotherapy,” co-author Jorge Humberto Rodriguez-Quintero, MD, also of Montefiore Medical Center, told MedPage Today. “This study was designed to unravel the benefits of surgery in the setting of a multimodal approach [to treatment].”
The findings also have implications for clinical guidelines that have traditionally emphasized systemic therapy as the mainstay of treatment for metastatic disease.
“More recently, [the guidelines] have included local therapies, such as surgery and radiation in selected cases,” said Rodriguez-Quintero. “However, the main problem is that guidelines still lack standardization and are based on lower or limited levels of evidence, so there’s much heterogeneity in the recommendations for resectability in the metastatic space. That’s leading to a lot of differences in practices across the United States.”
Recent investigations into the role of surgery for oligometastatic NSCLC have their genesis in the belief that local therapy may remove resistant cancer cells and immunosuppressive cells in the tumor microenvironment, potentially improving response to systemic therapy. Local therapy to the primary tumor, typically radiation therapy or surgery, has been investigated in several retrospective studies, the authors noted. Additionally, some prospective studies have produced evidence in support of local therapy for patients with oligometastatic disease.
In one small multicenter randomized trial, 49 patients with oligometastatic NSCLC received systemic therapy alone or systemic therapy with local consolidative treatment (radiation therapy or surgery) to the primary tumor and metastasis. The results showed that patients who underwent surgery had significantly better progression-free survival and OS.
Stiles and colleagues sought to determine whether primary tumor resection improves OS in a large cohort of patients with single-site synchronous oligometastatic NSCLC. Investigators queried the National Cancer Database for the years 2018 to 2020 to identify patients with clinical stage IVA/B disease treated with systemic therapy. They stratified the cohort according to whether a patient had surgery to the primary tumor.
The analysis included 12,215 patients, 349 (2.9%) of whom had surgery and 11,886 (97.1%) treated with systemic therapy without surgery. Within the surgery subgroup, 80 (22.9%) also had surgery for the single distant metastatic site.
Patients who underwent surgery were slightly younger (66 vs 68), had fewer comorbidities, were more likely to be white (82.5% vs 78.0%), were more often treated at an academic center (62.2% vs 52.2%), were more likely to have private insurance (36.4% vs 27.5%), were better educated, and had a higher income. Surgery was more common in New England (5.2%) and occurred less often in the West South-Central region (1.7%). Older age, Black race, and more advanced clinical T- and N-stages were independently associated with omission of surgery.
By multivariable analysis, resection of the primary tumor was associated with a significant reduction in the survival hazard (95% CI 0.56-0.80) as was surgery to the metastatic site (95% CI 0.72-0.88). Radiation therapy did not significantly affect survival (HR 0.99).
The investigators performed a propensity-matched analysis involving 698 patients, who had a median follow-up of 20.8 months. The analysis showed that patients who underwent surgery had a median OS of 36.8 months as compared with 20.8 months for patients who had systemic therapy alone (P
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