Changing guidelines in oncology: What to watch for in 2026—and beyond
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[In 2026] you will see guidelines will become easier to read and understand.
—Jaffer A. Ajani, MD, chair of the NCCN guideline panel for gastric cancers and Professor of Gastrointestinal Medical Oncology at MD Anderson Cancer Center
Oncology practice is adapting as disease biology understanding deepens and new evidence emerges. The National Comprehensive Cancer Network (NCCN) continues to update the Clinical Practice Guidelines in Oncology across tumor types, with changes targeting treatment selection, sequencing, supportive care, and guideline accessibility.[]
These updates have practical implications for clinical workflows and decision making in 2026. Here's what oncologists can watch for in 2026 and beyond.
NCCN’s evolving role in cancer care
“NCCN has become one of the most important guideline platforms in the world,” said Jaffer A. Ajani, MD, chair of the NCCN guideline panel for gastric cancers and Professor of Gastrointestinal Medical Oncology at MD Anderson Cancer Center.[]
“Currently, 33 comprehensive cancer centers participate. [The NCCN] not only generates guidelines for cancer treatment but also supportive care,” he continued. In addition, the NCCN “also produces patient-directed documentation” and “modifies guidelines almost instantly.” In 2026, he said, “you will see guidelines will become easier to read and understand.”
What's new in non–small cell lung cancer (NSCLC)
In NSCLC version 1.2026, the role of novel therapies expanded.[] Datopotamab deruxtecan-dlnk (Dato-DXd; Datroway) is designated as a preferred second-line option after progression on frontline osimertinib plus chemotherapy, and as a preferred third-line option following all other first-line regimens.
Osimertinib with carboplatin, and cisplatin/pemetrexed, as well as amivantamab plus lazertinib, moved to category 1 as preferred frontline regimens for patients with EGFR mutations identified before first systemic therapy.
“The emergence of novel targeted therapies for NSCLC reiterates the importance of biomarker testing, particularly in patients with advanced/metastatic NSCLC, to help clinicians identify the most appropriate treatment options for patients,” said Tejas Patil, MD, member of the NCCN NSCLC panel and Assistant Professor of Medicine at the University of Colorado Anschutz Medical Campus.[]
Precision and molecular guidance across tumor types
Across guidelines, there is a clear trend toward genomic-driven therapy selection and personalized approaches. Consider the following:
Chronic myeloid leukemia (CML)
Updated NCCN guideline version 1.2026[] emphasizes a more patient-specific approach: Do distress screening at baseline, consider myeloid mutational analysis in chronic phase in select cases, and choose first-line TKIs. For TKI selection, use not only risk scores but also BCR::ABL1 transcript type, and consider dosing practicality, treatment goals, and cost. Confirm transcript details before using asciminib because fusions lacking ABL1 exon 2 (for example, b2a3, b3a3) are flagged for lack of activity.
Prostate cancer
NCCN guideline version 3.2026 continues to refine criteria for risk stratification and treatment sequencing, focusing on tailored management for castration-resistant disease.[]
Colon cancer
NCCN guideline version 5.2025 provides recommendations for colon cancer.[] Al B. Benson, III, MD, chair of the colon cancer panel, noted that incorporating data from trials such as ATOMIC supports checkpoint inhibitors earlier in colon cancer treatment, indicating a shift toward immunotherapy integration where molecular features suggest benefit.[]
Ovarian cancer
Ovarian cancer updates from NCCN, Version 3.2025, reflect an increased specificity in therapeutic options based on molecular subtypes, highlighting precision oncology’s role.[][]
Implementation and clinical considerations
These guideline changes affect frontline and subsequent therapy choices, along with diagnostic workflows and patient counseling.
Biomarker testing should be comprehensive and front-loaded in high-risk solid tumors such as NSCLC to align with guideline-preferred regimens.
Genomic and pharmacogenomic data should inform treatment selection and toxicity mitigation. Updates in CML demonstrate emphasis on detailed molecular guidance for TKI use.
Supportive care and survivorship recommendations continue to evolve, with NCCN outlining structured follow-up and symptom management approaches specific to prior therapy exposures.
Guideline access and usability is expanding; updated tools like the NCCN Guidelines Navigator™ aim to reduce cognitive load and improve rapid decision support.[]
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