By: Hamid Mirshahidi, MD – Loma Linda University
The AACR 9th Edition has introduced significant changes to the TNM staging system for lung cancer. These updates, effective as of April 2025, reshape how we categorize and treat the disease. They reflect advancements in understanding lymph node involvement and disease progression. This impacts treatment decisions and patient outcomes.
Lung Cancer Key Staging Changes
- N2 Disease Reclassified: Single lymph node involvement (N2A) in the mediastinum is now distinguished from multiple lymph node involvement (N2B). For example, as Hamid Mirshahidi, MD from Loma Linda University explains, “T1 N2A used to be stage 3A, now is a stage 2B,” while T1 N2B remains Stage 3A. T3/T4 with N2B upstages to Stage 3B. With N3, it moves to Stage 3C.
- Downstaging Impact: Some higher-stage cancers (e.g., Stage 3A to 2B) may now qualify for surgery. Others with multiple lymph nodes (N2B) require more aggressive approaches.
- M1C Updates: Metastatic disease is split into M1C1 (multiple metastases in one organ) and M1C2 (multiple metastases across organs). This slightly alters prognosis but not treatment.
These shifts can change treatment plans. For instance, Stage 2B patients (e.g., T1 N2A) might be candidates for preoperative chemo-radiation or immunotherapy rather than surgery alone. Stage 3B or 3C cases may lean toward systemic therapies.
Lung Cancer Treatment Innovations
- Immunotherapy Advances: Drugs like arianab (assumed name from transcript) have gained FDA approval for Stage 4 lung cancer (combined with chemo or as a single agent). More recently, they gained approval for Stage 3 after chemoradiation with curative intent. Trials for its use in resectable lung cancer as neoadjuvant therapy are complete. Updates expected at ASCO 2025 hint at improved overall survival (OS).
- Targeted Therapies: New agents, such as repotrectinib, show promise over existing drugs like crizotinib. This is especially true in ROS1-resistant mutations (e.g., G2032R), with response rates nearing 60%.
- Antibody-Drug Conjugates (ADCs): ADCs face challenges after inconclusive Phase 3 trials. However, retrospective data suggest better responses in non-squamous histology and patients with actionable mutations (e.g., EGFR, ALK). ADCs also offer strong CNS penetration compared to standard chemo, and biomarkers like 122 NMR may predict higher efficacy.
2024: A Milestone Year for Lung Cancer
Last year saw 13 FDA approvals for lung cancer therapies, including small cell lung cancer, marking a transformative period for Stages 3 and 4. Looking ahead to 2025, the focus is on downstaging Stage 3A/3B patients to make them surgical candidates. Hamid Mirshahidi, MD from Loma Linda University, highlights this potential: “A combination of chemoemotherapy preoperatly can help us to make this non-respectable stage treeung cancer as this respectable lung cancer with the improvement of good prognosis in the future.” This approach could turn previously inoperable cases into curable ones. It improves long-term outcomes.
The Future of Lung Cancer Care
Success hinges on multidisciplinary collaboration—oncologists and surgeons working together to tailor treatments. For Stage 3 patients with lymph node involvement, preoperative strategies could shift non-resectable cases to resectable Stage 2 disease. This offers a curative path. Finding skilled surgeons for mediastinal lymphadenectomy is critical.
With optimism, experts believe most Stage 3A/3B patients could become eligible for surgery post-immunotherapy, revolutionizing outcomes. The lung cancer treatment landscape is evolving rapidly—2025 promises to be a pivotal year.
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