Clinical Approach for Unresectable Locally Advanced NSCLC - Episode 2

Assessing Unresectable Locally Advanced NSCLC

Jyoti Patel, MD:Patients with stage 3 disease should have a number of diagnostic tests at workup. Certainly, they should undergo CT of the chest with contrast to include the adrenal glands. Patients undergo a PET scan to look for distant disease. Unfortunately, a significant minority of these patients will also present with brain metastases. So, anyone with suspected stage 3 disease should undergo brain MRI. And then, importantly, patients should undergo pulmonary function tests. So, we should absolutely understand where patients’ pulmonary function is prior to initiation of therapy, even if we believe that they will not be surgical candidates. We get information from serum chemistry such as creatinine, which may help us adjudicate therapy, and then certainly any high ALK phosphatase or liver enzymes may make us look a little bit further for evidence in metastatic disease.

Although patients with stage 3 disease have potentially curative therapy, only the minority of these patients are disease free at 5 years, and current estimates are about 15% or 20% of these patients are disease free. So, not only are they at risk of recurrence of their primary disease within the first 2 years, which is quite substantial and up to 70% of patients will recur in that time frame, they’re also at risk of developing new primaries over time. And so, even after patients have been treated curatively, we continue to follow them with CT scans every year, even after 5 years.

All patients with lung cancer, I think, deserve multidisciplinary assessment. Certainly, we have made significant improvements in our understanding of the integration of chemotherapy in early-stage disease in patients who are resected as their primary therapy. In patients with stage 3 disease, this is probably the most controversial stage of disease. There are many reasonable algorithms with which to treat patients: chemotherapy followed by surgery followed by radiation, chemoradiation alone, or chemoradiation followed by surgery. So, certainly, this takes effort by radiologists, pathologists, pulmonologists, medical oncologists, radiation oncologists, and surgical oncologists.

We know that the best therapy is multilayered in these patients. And so, having adequate pathologic assessment, not only of all the mediastinal nodes but also markers that help, may guide therapy and predict response to therapy, as well as adjudicating the best treatment, whether that local therapy is radiation or surgery.

Transcript edited for clarity.


  • A 63-year-old man presented to his PCP with intermittent cough and difficulty breathing on exertion
  • PMH: hyperlipidemia well-managed on simvastatin; hypothyroidism, managed on levothyroxine, COPD on inhalers
  • Recently quit smoking; has a 40-pack-year history
  • PE; intermittent wheezing; ECOG 1
  • Creatinine clearance, WNL
  • Imaging Studies:
    • Chest X-ray showed opacity in the lung right upper lobe
    • Chest CT revealed a 3.1-cm spiculated mass in the right upper lobe and 2 enlarged right mediastinal lymph nodes measuring 1.5 cm and 1.7 cm; moderate emphysema noted
    • PET confirmed the lung lesion and mediastinal lymphadenopathy without evidence of distant metastasis
    • Brain MRI was negative
  • Bronchoscopy with transbronchial lung biopsy and lymph node sampling revealed adenocarcinoma with positive nodes in stations 4R and 7; level 4L was negative
  • Genetic testing was negative for known driver mutations
  • Staging: T2aN2M0, stage IIIA
  • Based on the extent of mediastinal disease and emphysema, the patient’s cancer was deemed inoperable, and he was referred for consideration of concurrent chemotherapy and radiation
  • He underwent therapy with cisplatin/etoposide and concurrent thoracic radiotherapy
  • Follow-up imaging showed a partial response with shrinkage of the primary and nodal lesions