The recent NCCN Guideline update represents an important advancement in the treatment of early-stage NSCLC.
Following the positive Phase III LIBRETTO-432 results, RET fusion testing is now recommended as part of biomarker evaluation for patients with resectable or early-stage NSCLC, and selpercatinib is recommended as a treatment option for eligible patients with RET fusion–positive disease.
As precision medicine continues to move earlier in the treatment pathway, comprehensive biomarker testing remains essential to ensuring that every patient has access to the most personalized and effective treatment options available.
What This Means For RET Lung Cancer Patients
What Are the NCCN Guidelines?
The National Comprehensive Cancer Network (NCCN) is a nonprofit alliance of leading cancer centers dedicated to improving cancer care through evidence-based recommendations. The NCCN Guidelines are widely recognized as the standard for clinical decision-making and are regularly updated to reflect the latest scientific evidence and advances in cancer treatment.
For patients with non–small cell lung cancer (NSCLC), the NCCN Guidelines provide recommendations across the entire continuum of care, including:
- Diagnosis and staging
- Biomarker testing
- Surgical management
- Radiation therapy
- Systemic treatments, including targeted therapies and immunotherapy
- Follow-up and survivorship care
These guidelines help ensure that patients receive the most appropriate and personalized treatment based on the unique characteristics of their cancer.
Who Reviews the NCCN Guidelines?
The NCCN Guidelines are developed and reviewed by disease-specific expert panels composed of multidisciplinary specialists from NCCN member institutions. The NSCLC Panel typically includes:
- Medical oncologists
- Thoracic surgeons
- Radiation oncologists
- Pulmonologists
- Pathologists
- Molecular diagnostics experts
- Oncology pharmacists
- Oncology nurses
- Patient advocates and other specialists as needed
Panel members are nominated by NCCN member institutions and are led by a Panel Chair and Vice Chair. Recommendations are carefully reviewed, discussed, and voted upon by the panel.
How Often Do They Meet?
Although NCCN Guidelines undergo a comprehensive review at least annually, updates may occur much more frequently when important new clinical evidence becomes available.
How Are New Recommendations Added?
When evaluating potential guideline updates, the panel reviews:
- Published clinical trial data
- FDA approvals and regulatory actions
- Safety and efficacy outcomes
- Clinical relevance and impact on patient care
- Expert consensus
Based on the strength of the evidence and level of agreement among panel members, recommendations are assigned a category reflecting both evidence quality and consensus.
From Biomarker to Standard of Care:
How the LIBRETTO-432 Results Elevated RET Testing and Selpercatinib in Early-Stage NSCLC
For many years, comprehensive biomarker testing was considered standard practice primarily for patients with advanced or metastatic NSCLC. However, the treatment landscape is rapidly evolving, and molecular testing is now playing an increasingly important role in earlier stages of disease.
Based on the positive results of the phase III LIBRETTO-432 trial, presented at the 2026 ASCO Annual Meeting and simultaneously published in the The New England Journal of Medicine, the NCCN Guidelines for NSCLC (Version 6.2026) were updated on June 15, 2026.
The Updated Guidelines Now:
This marks a significant milestone for the RET-positive lung cancer community and reflects the growing role of precision oncology in early-stage disease.
Following a Familiar Path
The inclusion of RET testing and selpercatinib in the NCCN Guidelines follows a pattern established by other targeted therapies that successfully moved from advanced disease into earlier-stage treatment settings:
- Osimertinib following the results of the ADAURA Trial trial for EGFR-mutated NSCLC
- Alectinib following the results of the ALINA Trial trial for ALK-positive NSCLC
- Selpercatinib following the results of the LIBRETTO-432 trial for RET fusion-positive NSCLC
The inclusion of RET testing in the NCCN Guidelines underscores the importance of understanding the molecular profile of every patient’s tumor—regardless of stage.
Reference
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer, Version 6.2026, updated June 15, 2026.
