Solange Peters, MD: Well, early-stage non—small cell lung cancer is actually treated in what we call the curative setting, meaning that the aim of the treatment is to definitely get rid of the tumor. This very often implies some kind of multimodality treatments. The patient can have surgery. The majority of the patients would also need some chemotherapy afterwards. If the patient cannot have surgery, many patients receive radiation and chemotherapy as the curative treatment in order to cure locally, but also to potentially cure the small cells at a distance, micrometastases, at the same time.

Suresh Senan, MD: For early-stage non—small cell lung cancer, the standard treatment is considered to be surgery in patients who are fit. So, this involves a lobectomy and lymph node dissections according to the guidelines. And in an expert’s hands, it is good results. However, many of our patients are elderly. They may have had malignancies before, and they may not want to accept the risks associated with surgery. In such patients, the standard of care is still stereotactic radiotherapy. High-precision treatments, which can be delivered in between 3 to 8 treatments, and stereotactic radiotherapy have also been shown to be superior in terms of local control and overall survival compared with conventionally-fractionated radiotherapy, which could take about 5 to 6 weeks to deliver. So currently the 2 options available to patients are surgery and stereotactic radiotherapy. And in fact, it’s the patient risk factor and preferences that will increasingly play a role in deciding between the 2. There are ongoing trials with head-to-head comparisons between the 2 modalities. But it will take a number of years before these trials are completed.

The dose of stereotactic radiotherapy, which is recommended in the guidelines, is more than 100 gray, biologically equivalent. So, despite giving it in 3 fractions or 5 fractions, finally the dose necessary is considered to be more than 100 gray. That’s something that is safe to deliver in tumors in the lung periphery. However, as the tumor is more closely located to the middle of the chest, closer to the blood vessels, then the doses sometimes have to be compromised. So, in patients with the peripheral lung tumor, the standard recommended dose is a biological dose of more than 100 gray, which is necessary for cure.

There are currently 3 ongoing studies where surgery’s being compared to stereotactic radiotherapy in patients with early-stage non—small cell lung cancer. The STABLE-MATES trial in North America has been open for a while. It’s for borderline-operable patients. The term borderline means that patients have a higher risk if they undergo surgery. There are other studies. The Veterans Administration trial, or VALOR, which is a large randomized trial for all patients with peripheral tumors from the Veterans Administration, that will be a phase III definitive trial accruing a few hundred patients. And there’s a smaller trial going on in China in patients who are at standard risk for surgical complications. So, these 3 trials will inform us about the comparative for the merits of either treatment in this population.

Solange Peters, MD: The role of chemotherapy in early-stage disease is, of course, to help treat the local tumor, but more importantly to treat or prevent the emergence of tumor cells at distance, what we call micrometastases. So, what you don’t see on a CT scan or a PET CT, but that potentially exist. So, in that setting, if you would deliver surgery first, all the patients with lymph node involvement or aggressive pattern of tumors will need 3 months of adjuvant chemotherapy. The group in Spain, Enriqueta Felip and colleagues, have shown that you can also give the chemotherapy before. The results are more or less the same. Probably the compliance is better when you give it before surgery, but it was never really adopted by the community because it also implies that when you start with chemotherapy, you have a staging of the tumor, which is after chemotherapy, so you might miss some of the potential invasion of lymph nodes and so on. So, your staging might be a little bit less common to interpret right. You can give neoadjuvant or adjuvant, but it’s more classically adjuvant.

When you cannot perform surgery in a patient and you have to give radiotherapy, the same concern of micrometastasis exists, meaning that if you want to prevent the emergence of a distant disease as a relapse, you have to deliver chemotherapy, too, ideally at the same time of the radiotherapy because both act in a synergistic manner. But if you cannot, one after the other.

Transcript Edited for Clarity