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

Please visit our website (TheFellowOnCall.com) for more information

Twitter: @TheFellowOnCall

Instagram: @TheFellowOnCall

Listen in on: Apple Podcast, Spotify, and Google Podcast