Non-Surgical Interventions for Patients With Stage 3 Non-Small Cell Lung Cancer

At the Great Debates and Updates in Lung Cancer Meeting in New York, New York, Charles Simone, MD, Memorial Sloan Kettering Cancer Center, New York, New York, argued that surgical approaches have a limited role in the treatment of patients with stage 3 non-small cell lung cancer (NSCLC). 

Dr Simone states, “For right now, in the large majority of our patients, there is not a routine role for surgery, and the standard care should be chemoradiation in combination with consolidation immunotherapy.” 

Transcript 

Hi, I'm Dr Charles Simone, I'm the research professor and Chief Medical Officer of the New York Proton Center and full member of Memorial Sloan Kettering Department of Radiation Oncology. I'm here at Great Debates and Updates in Lung Cancer in New York and I'm here to talk about the role of radiation in combination with systemic therapy versus surgical approaches in stage 3 non-small cell lung cancer. I’m taking the side of limited role of surgery in these patients.

Historically, there's been quite a limited role for surgery, in fact there have been several Cooperative Group trials both here in North America, as well as in Europe, showing there's no survival benefit to adding surgery in patients who are candidates for chemoradiation in locally advanced non-small cell lung cancer. Trial after trial has been negative, so why now is there a debate or more excitement for surgery in the stage 3 population? The answer is chemoimmunotherapy. The role of immunotherapy has really changed the dynamic and consideration for surgery in these patients in the past few years and that's really been driven by significant data showing that the addition of chemoimmunotherapy before surgery increases the pathologic complete response rates going into surgery compared with chemotherapy alone. That's led to very promising outcomes at 1 and 2 years, including good progression-free survival and control rates at early time points. 

Immunotherapy has been very exciting for surgery, but it's also been very exciting for non-surgical approaches, particularly the chemoradiation approaches. We know from the PACIFIC trial that the addition of immunotherapy in the consolidation phase relative to chemoradiation alone triples the progression-free survival compared to chemoradiation. We don't see a tripling of progression-free survival or even response rates in the surgical literature. If anything, it looks like immunotherapy is even more helpful in the non-surgical patients, and that's the case in earlier stages. Much of the surgical literature right now is not just stage 3, it also includes stage 1 and stage 2 patients grouped together to have these good response rates. Those patients do very well anyway, regardless of modalities, regardless of immunotherapy, but immunotherapy also helps the non-surgical early-stage patients. A Lancet publication just a few months ago, a randomized trial showing that immunotherapy in addition to [stereotactic body radiation therapy] SBRT dramatically improves the event-free survival relative to SBRT alone.

While immunotherapy has been exciting for the consideration of surgery in this patient population, the truth of the matter is, it's been as exciting or more so in the radiation population. And we don't have long-term data or good data suggesting that patients with surgery do better than patients without surgery, especially when matched, considering surgical patients tend to be younger, healthier, better performance status, less nodal disease burden, which we know is a marker for distant metastatic disease and survival. 

Radiation is also improving, so it's not just immunotherapy that's helping to shift the dynamic between surgery or non-surgery in these patients. We have advances such as intensity-modulated radiation therapy or proton therapy, neither of which were used in the SENTINEL trial showing surgery did not have a benefit in stage 3. We are now able to deliver adaptive radiation therapy with consideration for radioprotectors. There's a new exciting trial with NRG Oncology, NRG-LU008, looking at escalating the dose to the primary tumor with stereotactic treatments, as well as consideration for FLASH radiotherapy.  

There are a lot of horizons to explore for radiation, making the dynamic even better, but for right now in the large majority of our patients, there is not a routine role for surgery and the standard care should be chemoradiation in combination with consolidation immunotherapy.

Source: 

Simone C. Debate: Handling stage 3: Surgical vs. non-surgical approach. Presented at Great Debates & Updates in Lung Cancer; April 27-28, 2024; New York, NY.