Clinical Approach for Unresectable Locally Advanced NSCLC - Episode 1

A Case of Unresectable Locally Advanced NSCLC

Jyoti Patel, MD:I’d like to tell you about a patient I saw last week. He’s a 63-year-old man with a history of hypertension who has been in really good health and developed some shortness of breath over the preceding weeks and a little bit of nonproductive cough. He went to his primary physician for a workup and noted that he had no other constitutional symptoms. He maintained medications of simvastatin and a regimen of inhalers that he’d been on for several years.

The primary physician ordered a chest X-ray, which showed a right upper lobe nodule. A CT was then obtained, which showed a 3.1-cm nodule in the right upper lobe, as well as a 1.7-cm paratracheal node and a 1.8-cm subcarinal node. He was referred to his pulmonologist. The pulmonologist then obtained a PET scan, which showed uptake in the mediastinal nodes, as well as the right upper lobe lesion, and no other distant disease. He obtained pulmonary function tests, which showed an FEV1 of 1.7 and a DLCOof only 55%.

He performed EBUS—so, bronchoscopy with ultrasound guided biopsy. He was able to sample the subcarinal nodes and both paratracheal nodes, 4R and level 7, were positive for adenocarcinoma. The 4L node was a lymphocyte and was negative for cancer.

He was then referred to my clinic. By that time, we had more information about his pathology. His PD-L1 score was 40%. He had noEGFR,ALK,ROS1, orBRAFalterations in the tumor. And I presented him at a multidisciplinary tumor board.

After discussion with the surgeon, who felt he was too high risk for surgery given that he had multistation disease and his poor DLCOand the deficit he would have with surgery, we decided to treat him with a concurrent chemoradiation approach with consolidation durvalumab. Following chemoradiation, which he tolerated quite well, his first CT scan demonstrated a partial response, and now he’s getting durvalumab every 2 weeks.

So, locally advanced disease represents almost 30% of all lung cancer diagnoses. Patients will often present with some nonspecific pulmonary symptoms and are surprised to find that they have more advanced disease with mediastinal nodal involvement. Many of our patients will have multistationed involvement, and for those patients, multidisciplinary input in evaluation is absolutely paramount.

We know that many patients will have different degrees of mediastinal adenopathy, but you can’t really call a patient who’s having stage 3 disease unless you have pathologic confirmation of those mediastinal nodes. Certainly, in places like the Midwest, where we see endemic fungal infections or in patients who may present with pneumonia, the chance of having false-positive lymph nodes is quite high, and so we recommend that all patients who have mediastinal adenopathy undergo EBUS for biologic confirmation.

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