What are the next steps in treatment and expected survival rates for a 67-year-old man with locally advanced non-small cell lung cancer (NSCLC), T4 N1 or N2 M0 staging, who underwent a bilobectomy with clear margins, and has a history of post-operative pneumonia and weight loss?

Treatment Approach for Resected T4N1-2 NSCLC

This patient requires adjuvant platinum-based chemotherapy as the next critical step, given the locally advanced stage IIIA/IIIB disease with clear surgical margins. 1

Immediate Next Steps

Oncology referral for adjuvant chemotherapy is mandatory for this patient with resected T4N1-2 disease, as chemotherapy improves survival in all subgroups of patients with locally advanced NSCLC, whether treated with surgery or radiotherapy. 1

Specific Treatment Recommendations

Adjuvant cisplatin-based doublet chemotherapy (2-4 cycles) is the standard of care for completely resected stage II-IIIA NSCLC. 1 The most commonly used regimens include:

• Cisplatin (80 mg/m² per cycle) plus etoposide (100-120 mg/m²) 1
• Cisplatin plus vinorelbine (at 60% of systemic dose, 15 mg/m²) 1

Carboplatin-based regimens are explicitly not recommended for this patient, as only 1 of 6 randomized studies in meta-analyses used carboplatin (involving only 91 of 1,205 patients), and elderly patients receiving carboplatin-paclitaxel had the highest risk of symptomatic radiation pneumonitis. 1

Role of Radiation Therapy

Postoperative radiotherapy (PORT) is NOT recommended for this patient with completely resected disease and clear margins (R0 resection), even with N1 or unexpected N2 disease, as meta-analyses demonstrate a detrimental effect on survival in completely resected cases. 1

PORT should only be considered if the resection was incomplete (positive margins), which is not the case here. 1

Survival Expectations

With Adjuvant Chemotherapy

For T4N0-1 disease with complete (R0) resection:

• 5-year survival: 20-54% depending on nodal status 1, 2
• Patients with T4N0-1 M0 achieving complete resection: median survival significantly better than chemoradiotherapy alone 1
• Complete resection (R0) with absence of N2 nodes: long-term survival is possible 1

For persistent single-station N2 disease after surgery:

• 5-year survival: 30-47% for single N2 station (skip or additionally N1) 3
• 5-year survival drops to <5% if multiple mediastinal stations involved 3

Without Adjuvant Treatment

Stage IIIA patients have a low chance of cure by surgery alone 1, with expected 5-year survival of approximately:

• Stage IIIA without adjuvant therapy: ~15-20% (extrapolated from guideline statements) 1
• Unresectable stage III with chemoradiotherapy alone: 9-14% 5-year survival 1

The survival benefit from adjuvant chemotherapy in completely resected stage II-III NSCLC is well-established in meta-analyses based on individual patient data. 1

Critical Management Considerations

Addressing Post-operative Complications

The patient's post-operative pneumonia and weight loss require optimization before chemotherapy:

• Nutritional assessment with BMI and serum albumin is necessary to evaluate risk of postoperative complications 4
• Performance status must be WHO 0-1 for standard chemotherapy 4
• If performance status is WHO 2 or worse, chemotherapy may need dose modification or delay 4

Molecular Testing

Targeted agents (EGFR-TKIs, ALK inhibitors) should NOT be used in the adjuvant setting, even if mutations are present, as randomized data showed worse survival with adjuvant gefitinib compared to placebo, even in EGFR-mutated tumors. 1

Multidisciplinary Discussion

Management of this patient with locally advanced disease must be discussed at multidisciplinary meetings involving physicians, surgeons, and oncologists. 1, 4

Common Pitfalls to Avoid

Do not delay oncology referral - adjuvant chemotherapy should ideally begin within 6-8 weeks of surgery when the patient has recovered sufficiently. 1

Do not add postoperative radiotherapy based solely on N1 or N2 involvement if margins are clear, as this worsens survival. 1

Do not use carboplatin-based regimens as first-line adjuvant therapy in this elderly patient, given increased pneumonitis risk. 1

Do not assume the patient is too frail for chemotherapy based on age alone (67 years) - base the decision on performance status, pulmonary function, and recovery from surgery. 4