Lack of guideline-concordant treatment for early-stage non-small cell lung cancer common

Disclosures: Kehl reports personal fees from Aetion, grants from IBM and honoraria from Roche outside the submitted work. Please see the study for all other authors’ relevant financial disclosures.

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A substantial proportion of patients with resected early non-small cell lung cancer who consented to an adjuvant therapy screening trial did not receive adequate lymph node dissection or adjuvant chemotherapy, according to study results.

The retrospective cohort study, published in JAMA Oncologyincluded participants in the Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST) screening study.

Outcomes from the ALCHEMIST trial.
Data derived from Kehl KL, et al. JAMA Oncol. 2022; doi: 10.1001 / jamaoncol.2022.0039.

“In this cohort, 53% of patients underwent lymph node dissection considered adequate by National Comprehensive Cancer Network guidelines at the time of surgery, and 57% received any adjuvant chemotherapy. We did not observe significant disparities by sociodemographic characteristics in our analysis, although patients with more advanced disease stage were more likely to receive chemotherapy, ” Kenneth L. Kehl, MD, MPH, researcher in the division of population sciences in the department of medical oncology at Dana-Farber Cancer Institute and Harvard Medical School, told Healio.

Background and methodology

Kehl and colleagues pursued the study because, despite its use as standard treatment for patients with resectable NSCLC, many patients historically have not received anatomic resection with adequate lymph node dissection and adjuvant chemotherapy.

Kenneth L. Kehl, MD, MPH

Kenneth L. Kehl

“At the same time, targeted therapies and immunotherapy are increasingly being studied in the adjuvant setting for NSCLC and are becoming standard options for patients,” Kehl said. “Interpretation of the results of these adjuvant trials of novel therapies could be impacted if trial participants do not always receive guideline-concordant standard treatment.”

Thus, researchers sought to determine the rates of guideline-concordant surgery and adjuvant chemotherapy among patients with early-stage NSCLC in the United States.

The analysis included 2,833 patients (mean age, 66.5; standard deviation, 9.2 years; 53% women) with stage IB to stage IIIA NSCLC with tumors of at least 4 cm and / or positive lymph nodes who enrolled in the ALCHEMIST study from Aug. 18, 2014, to April 1, 2019, and did not enroll in a therapeutic adjuvant clinical trial.

Researchers analyzed care patterns overall and according to demographics and clinical factors, such as age, race, ethnicity, education level and geography, among others. They reported five outcomes, including whether patients:

  • had anatomic surgical resection;
  • had adequate lymph node dissection (1 N1 nodal station plus 3 N2 nodal stations);
  • received any adjuvant chemotherapy;
  • received any cisplatin-based adjuvant chemotherapy; and
  • received at least four cycles of adjuvant chemotherapy.

Key findings

Results showed 2,697 patients (95% of the cohort) underwent anatomic surgical resection, 1,513 (53%) had adequate lymph node dissection, 1,617 (57%) received any adjuvant chemotherapy and 1,237 (44%) received at least four cycles of adjuvant platinum -based chemotherapy. Additionally, 965 (34%) received any cisplatin-based adjuvant chemotherapy.

Kehl and colleagues noted similar rates across race and ethnicity.

“The apparent low rates of guideline-concordant therapies were, to some degree, surprising, although the rates of adjuvant chemotherapy were similar to those observed in other recent therapeutic trials of novel agents,” Kehl told Healio. “The absence of disparities by sociodemographic characteristics was also somewhat surprising, although this may represent a dynamic in which such disparities may create barriers to enrollment in studies like ALCHEMIST, such that the disparities are less likely to be observed among patients who do enroll.”


Researchers concluded that efforts are essential to optimize use of proven therapies for early-stage NSCLC and that current adjuvant trial results in this space should be interpreted in light of the potentially suboptimal standard therapy participants receive.

“I think these results illustrate the importance of reporting metrics of guideline-concordant therapy delivery in adjuvant trials of novel agents to aid interpretation,” Kehl said. “At the moment, cytotoxic chemotherapy also remains the only adjuvant systemic therapy modality with a demonstrated overall survival benefit, [and] improved outcomes observed with adjuvant novel agents should not be interpreted as implying that chemotherapy can be omitted for appropriate patients unless clinical trials are specifically designed to investigate the question of that omission. ”

The results of the ALCHEMIST screening study also pave the way for future studies examining barriers to widespread adoption of evidence-based treatment guidelines in routine practices, Chee Khoon Lee, MBBS, MMedSci, MBiostat, PhD, and Monica TangMBBS, MMed, both of the Center for Big Data Research in Health at the University of New South Wales in Australia, wrote is an accompanying editorial.

“When real-world evidence does not support the use of existing treatments, such as extensive nodal dissection or cisplatin-based chemotherapy for older patients with poor performance status, additional prospective clinical trial evidence will be needed to investigate more appropriate treatment strategies for these patient populations, ”they wrote. “If variations in the rates of guideline-recommended practice are attributable to health system or sociodemographic factorsthen addressing these system-level barriers will be critical for promoting equitable cancer care and improving outcomes for all patients with early-stage NSCLC. ”


Kehl KL, et al. JAMA Oncol. 2022; doi: 10.1001 / jamaoncol.2022.0039.
Tang M, et al. JAMA Oncol. 2022; doi: 10.1001 / jamaoncol.2022.0038

For more information:

Kenneth L. Kehl, MD, MPH, can be reached at Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215; email: [email protected]

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