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

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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