Episode 026: Lung Cancer Series, Pt. 4: Treatment of early stage NSCLC

Lung cancer is one of the most commonly diagnosed type of cancer and so it is fitting that we start the first of our disease-specific oncology series with this diagnosis. This week, we go through treatment of early stage non-small cell lung cancer (NSCLC)!

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• How do we think about treatment of lung cancer?

• Recap on staging (see Episode 025)

  • Pro-tip: Highly recommend that you “forget” about the actual staging and focus more on the individual T, N, and M status 

  • Tumor size:

    • T1a <1 cm 

    • T1b <2 cm 

    • T1c <3 cm 

    • T2a <4 cm 

    • T2b <5 cm 

    • T3 5-7 cm

    • T4 cm 

  • Nodal status:

    • Double digit nodes = hilar or intrapulmonary (peripheral) = N1

    • Single digit nodes = mediastinal (central ) = N2

    • Contralateral nodes or supraclavicular = N3

  • Sites of metastatic disease
    

• Approach to treatment in a stepwise approach: 

  • Goal: Whenever feasible, we want to consider getting the patient to surgery to remove the cancer. 

  • Surgery or no surgery?

    • How do we decide if someone is appropriate for surgery: 

    • Do they want surgery?

    • Do they have the pulmonary reserve if they were to get surgery ?

    • Do they have the cardiac reserve to withstand surgery?

    • Is the tumor size too big? (Usually >7cm)

    • Is the tumor invading other structures?

      • If invading other structures, surgery may not be possible; highly consider tumor board discussion

    • Mediastinal lymph node involvement?

      • Central lymph node involvement usually requires definitive chemotherapy + radiation (not surgery up-front)

    • Supraclavicular lymph node or contralateral lymph node?

      • This would be treated with chemotherapy and radiation

• Speaking of surgery, what are the options for types of surgeries for lung cancer?

  • Sub-lobar:

    • Wedge (smallest resection)

    • Segmentecomy - ideally we want to do at least a segmentectomy

  • Lobar resection:

    • Lobectomy

  • Pneumonectomy

• What if a patient’s tumor is amenable to surgery, but the patient’s underlying co-morbid conditions preclude him from getting a surgical intervention? 

  • This is where we consider using radiation for treatment, specifically Stereotactic body radiation therapy (SBRT)

• Characteristics of surgical report?

  • The “R” status is if there is residual tumor after the surgery. This is a combination of evaluation by a pathologist AND by gross inspection by the surgeon

    • R0: No evidence of disease

    • R1: Microscopic sites of disease

    • R2: Macroscopic sites of disease (visible tumor)

  • Why does this matter?

    • If there is residual disease, there may be a role for further resection and/or systemic therapy

• When a tumor is >4cm, patients are higher risk for recurrence, even without nodal disease or metastatic disease. We will give these patients chemotherapy in the adjuvant setting.  

• Approach to adjuvant chemotherapy:

  • In NSCLC, it is often a two-drug regimen, including a platinum-based therapy

    • Cisplatin is important

      • Based on LACE Pooled Analysis (https://ascopubs.org/doi/10.1200/jco.2007.13.9030)

      • Cisplatin-based adjuvant therapy vs. placebo showed >5% improvement in survival when using cisplatin-based therapy

      • For adenocarcinoma:

        • Give cisplatin with pemetrexed

        • ALWAYS start patient on B12 and folate at least 1 week before starting pemetrexed and continue this throughout treatment, up to and including 3 weeks after their treatment course

      • For squamous cell caricnoma:

        • Give cisplatin with gemcitabine OR docetaxol (taxotere)

  • Nodal involvement (N1): Give two-drug regimen, as noted above

  • Additions to two-drug regimen:

    • IMPOWER 010 Trial: In patients with PDL1 >50%, patients did better with 1 year of immunotherapy (atezolizumab) after adjuvant therapy (https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02098-5/fulltext; https://ascopost.com/issues/november-10-2021/impower010-adjuvant-atezolizumab-improves-disease-free-survival-and-nsclc-relapse-in-patients-whose-tumors-express-pd-l1/)

    • Mutations matter!

      • ADAURA Trial: EGFR with exon 19 deletion or L858R can get osimertinib, which had an improved outcomes (https://www.nejm.org/doi/full/10.1056/NEJMoa2027071)

• References:

  • https://ascopubs.org/doi/10.1200/jco.2007.13.9030 - LACE Pooled analysis

  • https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02098-5/fulltext - IMPOWER 010 Trial

  • https://www.nejm.org/doi/full/10.1056/NEJMoa2027071- ADAURA Trial

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