What is the optimal treatment for a 72‑year‑old patient with a 3.6 × 3 × 3.2 cm peripheral squamous cell carcinoma of the lung, hilar and mediastinal lymph‑node involvement (clinical stage IIIA T2b N2 M0) and ECOG performance status 0‑2?

Management of Stage IIIA (T2b N2 M0) Squamous Cell Lung Carcinoma in a 72-Year-Old Patient

This patient should receive concurrent platinum-based chemoradiotherapy (60-66 Gy) followed by consolidation immunotherapy, NOT surgery, as the presence of mediastinal N2 lymph node involvement makes this unresectable disease requiring definitive non-surgical multimodality treatment. 1, 2

Critical First Step: Multidisciplinary Assessment and Invasive Staging

Before any treatment decision, this patient requires:

• Pathological confirmation of N2 disease through invasive mediastinal staging (EBUS or EUS preferred as first-line procedures), as PET-positive mediastinal findings must be histologically confirmed before determining treatment strategy 1, 3
• Complete staging with brain MRI (or contrast-enhanced CT if MRI unavailable) to rule out occult brain metastases, which is mandatory for all patients being considered for curative-intent stage III treatment 1
• Multidisciplinary team discussion including thoracic surgeons, medical oncologists, and radiation oncologists at a high-volume center, as management should be carried out in specialized centers where high procedure volume is strongly associated with improved survival 1

Why Surgery is NOT Appropriate

The presence of enlarged discrete mediastinal N2 lymph nodes fundamentally changes the treatment approach:

• Mediastinal nodal involvement represents a contraindication to primary surgical resection, as this constitutes unresectable N2 disease requiring non-surgical multimodality treatment 1, 3
• The ESMO algorithm specifically categorizes "enlarged discrete N2 LNs" as requiring "Non-surgical multimodality treatment" rather than surgical approaches 1
• Even in potentially resectable N2 disease, surgery is questionable in patients with persistent N2 disease, and primary surgical resection for preoperatively identified discrete N2 disease should not be performed outside clinical trials 1, 3

Standard Treatment: Concurrent Chemoradiotherapy

Concurrent chemoradiotherapy is the treatment of choice for this patient with stage IIIA unresectable disease and good performance status (ECOG 0-2):

Chemotherapy Regimen

• Platinum-based doublet chemotherapy is mandatory, with options including 1:
  • Cisplatin + etoposide (most commonly used in concurrent regimens)
  • Carboplatin + paclitaxel
  • Cisplatin + vinorelbine
  • Note: Cisplatin + pemetrexed is NOT appropriate for squamous histology 1
• 2-4 cycles of concomitant chemotherapy should be delivered during radiotherapy 1
• For patients >70 years (this patient is 72), carboplatin monotherapy may be considered in combination with radiation if tolerability is a concern 1

Radiotherapy Specifications

• Total dose: 60-66 Gy in 30-33 daily fractions delivered concurrently with chemotherapy 1
• Maximum overall treatment time should not exceed 7 weeks to optimize outcomes 1
• Treatment should be delivered at a center with quality assurance of radiotherapy, as protocol deviations are associated with increased treatment failure and mortality 1

Sequential vs. Concurrent Approach

• If concurrent chemoradiotherapy is not possible due to patient factors (comorbidities, performance status concerns), sequential chemotherapy followed by definitive radiotherapy represents a valid alternative, though concurrent is superior 1

Consolidation Immunotherapy: Critical for Survival Benefit

After completing chemoradiotherapy without progression:

• Consolidation durvalumab for up to 12 months is recommended and has demonstrated significant survival benefit (median OS 47.5 months vs 29.1 months) 2, 4
• Durvalumab must be started 1-42 days after completing chemoradiotherapy, necessitating prompt post-treatment imaging assessment within 4-6 weeks 4
• Imaging must confirm no disease progression before initiating durvalumab 4

Age Considerations for This 72-Year-Old Patient

This patient's age requires specific attention:

• Age 72 is NOT a contraindication for definitive concurrent chemoradiotherapy, as age alone should not exclude patients from curative treatment in strictly selected cases 1
• However, most clinical trials included only 16% of patients >70 years, while the median age for lung cancer diagnosis is 72 years, highlighting that real-world patients are often older than trial populations 1
• Carboplatin-based regimens may be preferred over cisplatin in this age group to reduce toxicity while maintaining efficacy 1
• Careful cardiopulmonary function assessment is essential, including spirometry, diffusion capacity, ECG, and potentially echocardiography 1

Surveillance After Treatment

Following completion of chemoradiotherapy and durvalumab:

• Tumor assessment every 8 weeks during the 12-month durvalumab period using contrast-enhanced chest CT 4
• Surveillance visits every 6 months for the first 2 years, including history, physical examination, and contrast-enhanced chest CT at minimum at 12 and 24 months 4
• Transition to annual visits with chest CT after 2 years to detect second primary tumors or late relapse 4
• Brain MRI if neurological symptoms develop to detect potential brain metastases 4

Critical Pitfalls to Avoid

• Never proceed with surgical resection based solely on imaging without invasive pathological confirmation of N2 status 1, 3
• Do not delay initial post-treatment imaging beyond 6-8 weeks, as this may miss the window for durvalumab consolidation therapy 4
• Avoid using PET-CT alone for pre-durvalumab assessment due to high false-positive rates from post-radiation inflammation; obtain biopsy confirmation if salvage therapy is being considered 4
• Do not use pemetrexed-based regimens for squamous cell histology, as this is only appropriate for non-squamous NSCLC 1

Prognosis

• Stage IIIA disease has a 5-year survival of 24-36% with optimal multimodality treatment 2
• This is significantly better than stage IIIB (9-13% 5-year survival), reflecting the importance of accurate staging and appropriate treatment selection 2