What is the role of neoadjuvant immunotherapy, such as pembrolizumab (pembrolizumab) or atezolizumab (atezolizumab), in the treatment of an elderly female patient with stage T3N0 squamous cell carcinoma of the lung and a history of Chronic Obstructive Pulmonary Disease (COPD)?

Neoadjuvant Immunotherapy in Stage T3N0 Squamous Cell Lung Cancer

For an elderly patient with stage T3N0 squamous cell carcinoma of the lung and COPD, neoadjuvant immunotherapy should NOT be used—proceed directly to surgical resection if pulmonary function is adequate (VO2 max ≥15 ml/kg/min and FEV1 >35% predicted), with consideration of adjuvant therapy postoperatively based on pathologic findings. 1, 2

Evidence Against Neoadjuvant Therapy in This Population

The current evidence strongly argues against neoadjuvant approaches in elderly patients with resectable disease:

• Elderly patients (≥75 years) receiving neoadjuvant chemotherapy experience significantly higher incidence and severity of postoperative complications compared to younger patients, with no demonstrated mortality benefit. 3, 2 This is particularly concerning given the patient's baseline COPD, which already increases surgical risk.

• The risk-benefit ratio for neoadjuvant therapy has not been adequately studied in patients over 80 years, and extrapolation from highly selected trial populations to real-world elderly patients with comorbidities is inappropriate. 3, 2

• No guideline-level evidence supports neoadjuvant immunotherapy for T3N0 disease in elderly patients. The available literature on neoadjuvant immunotherapy consists primarily of investigational studies in younger, more fit populations. 4, 5

Recommended Treatment Algorithm

Step 1: Pulmonary Function Assessment

• Measure VO2 max and FEV1 to determine surgical candidacy 1
• If VO2 max ≥15 ml/kg/min AND FEV1 >35% predicted → proceed to surgery 1
• If pulmonary function inadequate → consider stereotactic ablative body radiotherapy (SABR) as alternative 6

Step 2: Surgical Approach

• Perform lobectomy (not pneumonectomy) as the standard resection for T3N0 disease 1
• Utilize video-assisted thoracoscopic surgery (VATS) when available to minimize postoperative morbidity 6
• Ensure surgery is performed at a high-volume center 3, 2

Step 3: Postoperative Management

• Adjuvant chemotherapy should be considered based on final pathologic staging and patient recovery status 3, 2
• Adjuvant chemotherapy demonstrates survival benefit in elderly patients with tolerability similar to younger patients (<70 years) 3, 2
• Postoperative radiotherapy is NOT indicated for pathologically confirmed N0 tumors with complete resection 1

Why Surgery-First Strategy is Superior

The surgery-first approach offers several critical advantages in elderly patients:

• Allows pathologic staging to guide treatment intensity rather than clinical staging, which may be less accurate 2
• Permits assessment of surgical recovery and functional status before initiating systemic therapy 2
• Avoids compounding surgical complications with chemotherapy-related toxicity 3, 2
• Adjuvant chemotherapy has established survival benefit in elderly NSCLC patients, whereas neoadjuvant data in this population is limited 3, 2

Critical Caveats

Age Should Not Be the Deciding Factor

• Treatment decisions must be based on functional status, comorbidities, and life expectancy—not chronological age alone 3, 1, 2
• Performance status 0-1 elderly patients should receive the same aggressive curative approach as younger patients 3, 6

COPD-Specific Considerations

• The presence of COPD necessitates careful pulmonary function testing but does not automatically preclude surgery 1
• Conservative resection (lobectomy rather than pneumonectomy) is particularly important in patients with baseline lung disease 1

Squamous Histology Implications

• Squamous cell carcinoma is more common in elderly patients 3
• PD-L1 expression may be relevant for future treatment decisions if recurrence occurs, but this does not justify neoadjuvant immunotherapy in resectable disease 7

When Immunotherapy Has a Role

Immunotherapy (pembrolizumab or atezolizumab) should be reserved for:

• Recurrent or metastatic disease after surgery 8, 7
• Patients who are medically inoperable despite adequate staging 6
• Adjuvant setting in select cases based on emerging trial data (not yet standard of care for T3N0) 4, 5