Lung cancer remains the leading cause of cancer-related death worldwide, but advances in molecular biology have transformed treatment from a one-size-fits-all approach to one guided by precision medicine.
At the 2025 ONS Bridge Conference, Julie Martin, DNP, APRN, Director of Cancer Research at Prisma Health, reflected on how far the field has come. “Historically, lung cancer was classified into 2 broad categories—small cell or non–small cell—based primarily on what it looked like under the microscope,” she said. “Treatment decisions were largely empirical; we relied on chemotherapy and radiation therapy.”
But that approach has shifted dramatically. “Molecular profiling has revolutionized lung cancer care,” Dr Martin explained. “It identifies actionable variants and immune signatures, allowing us to treat patients with targeted therapies and immunotherapies. It’s been a game changer.”
She added that the future of treatment holds promise with CAR T-cell and other engineered cell therapies, which may one day provide durable or even curative outcomes for patients with lung cancer.
Understanding and Staging Lung Cancer
Because non–small cell lung cancer (NSCLC) accounts for the vast majority of lung cancer cases (approximately 87%), treatment decisions typically focus on this subtype. For patients with NSCLC, accurate histologic classification and staging help determine the most appropriate therapy.
Common symptoms, such as a persistent cough, shortness of breath, or chest pain, often lead to diagnostic imaging. CT scans help define tumor size and location, PET-CT scans reveal metabolic activity and possible metastases, and brain MRI is used to detect spread to the central nervous system, particularly in advanced disease.
“Adenocarcinoma is the most common subtype of NSCLC,” Dr Martin noted. “It’s often seen in nonsmokers and younger patients and is frequently associated with specific gene variants such as EGFR, ALK, and KRAS.” Squamous cell carcinoma is more commonly linked to smoking and tends to appear centrally in the lungs, while large-cell and large-cell neuroendocrine carcinomas are less common and more aggressive.
Case Study: Kathy’s Diagnosis and Treatment Journey
To illustrate how these concepts play out in practice, Dr Martin presented the case of “Kathy,” a 54-year-old woman with no smoking history who sought care for a persistent cough and shortness of breath. Imaging revealed a large mass in the left lung and mediastinal lymph node involvement. Biopsy confirmed metastatic NSCLC with bone metastases.
After outlining Kathy’s case, Dr Martin reviewed how treatment decisions are generally made for patients with NSCLC. For early-stage disease, “complete surgical resection remains standard,” she said. Patients who are not surgical candidates may receive radiation, radiofrequency ablation, or cryoablation. Stage III disease is usually treated with concurrent chemoradiotherapy, while stage IV disease typically requires systemic therapy—immunotherapy, targeted therapy, or chemotherapy—tailored to disease biology and symptom burden.
The Importance of Biomarker Testing
Kathy’s oncologist ordered comprehensive biomarker testing, a decision Dr Martin called essential. “Biomarker testing should be performed at diagnosis for all patients with non–small cell lung cancer, regardless of stage,” she said. “Matching a targeted drug to an identified driver variant often results in significantly improved efficacy and decreased toxicity.”
The 2025 NCCN Clinical Practice Guidelines in Oncology recommend testing for EGFR, ALK, KRAS, ROS1, BRAF, NTRK, MET, RET, ERBB2, NRG1, and PD-L1. “If you don’t have enough tissue, consider rebiopsy or a liquid biopsy,” Dr Martin advised. “Biomarker testing is that important.” Broad molecular profiling, she added, helps identify rare variants for which effective drugs or clinical trials may already exist.
When Kathy’s tumor showed a ROS1 rearrangement, she began an oral targeted therapy, crizotinib, and achieved stable disease for nearly a year—a strong response for metastatic lung cancer. In an alternate scenario where insurance denied comprehensive testing, Kathy underwent multiple rounds of chemotherapy before the ROS1 variant was eventually detected. By then, the disease had progressed, and her response to targeted therapy was shorter. “The difference in outcomes really underscores the importance of testing up front,” she emphasized.
Managing Oncologic Emergencies
Dr Martin turned to the topic of oncologic emergencies, highlighting complications that oncology nurses and navigators may encounter in patients with lung cancer. Superior vena cava syndrome can present with facial swelling, dyspnea, or distended neck veins; management focuses on reducing tumor burden through chemotherapy, radiation, or targeted therapy. Hypercalcemia of malignancy, more common in squamous histology, is treated with IV fluids and bisphosphonates. SIADH and Cushing’s syndrome, often associated with small cell carcinoma, require fluid restriction and correction of electrolyte abnormalities while treating the underlying cancer.
Finally, she stressed vigilance for spinal cord compression, a true oncologic emergency. “Early detection is key,” she said. “Patients who go 48 hours or longer without being able to walk before diagnosis are less likely to regain function.” Radiation, surgery, or kyphoplasty may be used to relieve pressure and prevent further damage.
“Staging and histology matter; they’re key to treatment planning,” Dr Martin concluded. “Biomarker testing is integral to identifying patients who may benefit from targeted therapy, and oncologic emergencies must be identified and treated early to achieve the best possible outcomes.”
For oncology nurses and navigators, understanding the evolving biomarker landscape and recognizing potential complications are essential to helping patients navigate today’s increasingly complex lung cancer treatment pathways.
Copyright © 2025 Oncology Practice Management. Reprinted with permission.