What is the optimal management of patients with stage II lung cancer without nodal metastasis, but unresectable due to poor pulmonary reserve?
How do you approach patients with stage II lung cancer without nodal metastasis who are unresectable?
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This population of stage II patients without nodal involvement would include T2bN0 (stage IIA) or T3N0 (stage IIB) disease.
NCCN 2020 lists either CRT or hypofractionated RT/SBRT as acceptable options. In my experience, if these patients are nonsurgical, then they typically also have multiple co-morbidities that make chemo unattractive as well. There is often a push in our tumor boards for RT alone.
Such patients (the T3 ones especially), are at high risk for distant failure and I often insist on mediastinal staging (EBUS or Med) and usually MRI brain as well (especially if adeno) before committing to RT alone. I would try not to just use PET for mediastinal staging here. This has been more difficult recently given COVID.
These patients fall into a few common cases as outlined below.
Case 1:
T3 because of two small tumors in one lobe. This will usually turn into a tumor board philosophical debate of T3 vs synchronous primaries. The data is somewhat limited, but treating as synchronous primaries with SBRT can have reasonably good outcomes(Ayoub et al., IJROBP 2020).
It's unclear to me if patients like this who are labeled as "synchronous" primary will end up having worse distant failure than those who present with a solitary true stage I NSCLC. The vast majority of literature on this right now is retrospective and small institutional series.
I believe synchronous primaries are now allowed on Pacific 4 (SBRT + placebo vs durva) in the latest amendment, which will provide much needed prospective data on this situation.
Case 2:
In the case of T3 based on size, we know that while local control may be somewhat reduced when treating larger tumors, the outcomes are still quite good (Peterson et al., Clin Lung Cancer 2017).
One argument in favor of SBRT upfront would be that if you were to treat a large T3 tumor with CRT (fields not including any nodes) and they have a nodal failure soon after you finish, then salvage therapy after that is difficult—reirradiation with CRT again??, more systemic therapy alone??
In my mind, a better situation might be to treat with SBRT first, closely follow, and if an isolated mediastinal failure occurs, treat with CRT at that time.
Be mindful in planning SBRT in these cases that you might have to come back later, especially if you are unable to invasively stage the mediastinum. If you do have an isolated mediastinal failure on followup, then fractionated CRT or hypofractionated RT in the mediastinum can be challenging and sometimes dangerous, but outcomes are reasonable if EQD2 constraints can be met (Kilburn et al., J Thorac Oncol 2014).
There are no agreed upon great constraints in this setting though, admittedly.
Case 3:
T2 based on involvement of bronchus and size.
If the bronchus is involved, you probably need to think twice about doing SBRT due to concerns over bronchial toxicity
Roesch et al., Radiat Oncol 2016
A more fractionated out but still "hypofractionated" course of RT alone is sometimes appropriate.
In summary: CRT and RT alone are both reasonable options. Usually these folks can't get chemo either if they are nonsurgical, and in such cases I think RT alone is very reasonable. Ensure that they are truly node negative/no distant mets before committing to RT alone. Follow closely for mediastinal failure.
Would like more clarity on how nodal status was assessed, location of tumor and clinical TNM staging. If stage IIB, we can consider chemoradiation (ideally concurrent) followed by maintenance immunotherapy, extrapolating data from PACIFIC trial for stage unresectable stage III. If IIA, there is data for SBRT alone and ongoing trials are looking at maintenance immunotherapy following SBRT [example: PACIFIC-4 (NCT03833154), STILE (NCT03383302)]