Biomarker-driven therapy, minimally invasive diagnostics and surgery are expanding options—but accurate staging and treatment sequencing remain essential.

Lung cancer care increasingly requires decisions based on tumor biology as well as stage and resectability.

In a recent Baptist Health Doc-to-Doc podcast, Bruna Pellini, M.D., chief of thoracic medical oncology at Baptist Health Herbert Wertheim Cancer Institute, and Ian C. Bostock, M.D., a thoracic surgeon at the Institute, examined how earlier detection, molecular profiling and multidisciplinary planning are changing treatment pathways.

Earlier Detection Demands Thoughtful Nodule Evaluation

Low-dose CT screening and incidental imaging findings are bringing smaller pulmonary lesions to clinical attention.

Annual low-dose CT screening is recommended by the U.S. Preventive Services Task Force for adults ages 50 to 80 with a 20-pack-year smoking history who currently smoke or quit within 15 years. Yet these criteria do not include many patients who develop lung cancer, including never-smokers.

Dr. Bostock emphasized evaluating pulmonary nodules by size, morphology, patient-specific risk and change on serial imaging—not size alone. Solid versus subsolid composition, location and prior studies also matter.

PET/CT can help characterize suspicious lesions and assess disease extent, although inflammation can yield false positives and small or low-metabolic-activity tumors can yield false negatives.

When tissue is needed, options include CT-guided transthoracic biopsy and robotic-assisted navigational bronchoscopy.

The latter can be paired with endobronchial ultrasound-guided sampling of mediastinal and hilar nodes, potentially providing diagnosis and staging under one anesthetic. Lesion accessibility, procedural risk and the information required for treatment planning should guide selection.

Molecular Findings Can Shape Treatment Before Surgery

In non-small cell lung cancer (NSCLC), biomarker testing now informs some perioperative decisions as well as treatment of advanced disease.

“We want to individualize the approach,” Dr. Bostock said.

Relevant markers include EGFR mutations and ALK rearrangements, which can identify candidates for targeted treatment in defined settings, and PD-L1 expression, which can help inform immunotherapy selection in clinical context.

Dr. Pellini also addressed investigational strategies involving ROS1, HER2 and KRAS G12C alterations.

“Adequate tissue for histology and appropriate molecular profiling is important before committing to a treatment sequence,” Dr. Pellini said. “Oncogenic drivers may affect the suitability of perioperative systemic therapy and subsequent options.”

Treatment Sequencing Matters in Resectable Disease

For selected patients with resectable, locally advanced NSCLC, neoadjuvant chemotherapy plus immunotherapy, followed by surgery and sometimes postoperative treatment, has changed the traditional surgery-first approach.

Dr. Bostock emphasized multidisciplinary review of stage 2 and 3 disease, especially when tumor burden or nodal involvement raises recurrence risk.

Technical resectability alone does not determine the best initial treatment. Molecular status, potential response, functional status and the extent of disease must be considered.

“Not all stage 3 tumors are operable, and perioperative immunotherapy is not suitable for every molecular subtype,” said Dr. Bostock. “For unresectable disease, definitive chemoradiation and appropriate consolidation or maintenance therapy remain important.”

Local Therapy May Have a Role in Oligometastatic Disease

In carefully selected patients with a limited number of metastases—often described in studies as three to five or fewer—surgery or radiation to the primary tumor and metastatic sites may be considered alongside systemic therapy.

Drs. Pellini and Bostock stressed that disease distribution, systemic treatment response and the feasibility of comprehensive local therapy govern these decisions. Oligometastatic status alone is not an indication for surgery; evidence on selection and timing continues to evolve.

Robotic Surgery and Oncologic Quality

Robotic-assisted thoracic surgery offers enhanced visualization and instrument articulation for complex resections.

For selected small (2 cm or smaller), peripheral, node-negative tumors, segmentectomy may preserve lung parenchyma while achieving appropriate margins and nodal staging, Dr. Bostock noted.

Lobectomy remains appropriate for other tumors, depending on anatomy, histology, lung function and nodal status.

Dr. Bostock reported that approximately 90% of thoracic surgical cases in his Baptist Health program are performed robotically and that 80% to 90% of those patients are discharged the next day. Many return to usual activities within three to four weeks, although recovery varies. He noted that enhanced recovery protocols address pain control, mobilization, nutrition and rehabilitation.

The operative platform does not replace fundamental oncologic principles: adequate margins, anatomical resection when indicated and systematic lymph node assessment.

Occult nodal disease can be found on surgical pathology even after negative preoperative PET/CT and endobronchial ultrasound. Inadequate nodal evaluation risks understaging and can alter postoperative treatment decisions.

Clinical Trials and Early Referral

At Wertheim Cancer Institute, research is exploring biomarker-directed therapies, including approaches involving KRAS G12C, and new treatment strategies after surgery or chemoradiation.

Dr. Pellini emphasized the role of systemic treatment research, while Dr. Bostock underscored surgical participation in trials addressing resectability, local control and sequencing.

For referring physicians, the practical priority is early coordination among thoracic medical oncology, surgery, radiation oncology, pathology and imaging—ideally before definitive therapy begins.

“Where you go first matters and the sequencing of events is critical,” Dr. Bostock said. “Early multidisciplinary referral can help preserve options for accurate staging, molecular testing, treatment selection and clinical trial consideration.”

Click here to learn more about thoracic oncology and multidisciplinary lung cancer care services and specialists available at Baptist Health Herbert Wertheim Cancer Institute.