Marina Chiara Garassino, MD: I think that the most important thing is to have a multidisciplinary team in your hospital for the locally advanced disease. It is really the key point of the treatment. It is important to have a multidisciplinary team that is composed, at least, of the medical oncologists, so the surgeon and the radiotherapist. And it is also important to have, if it is impossible, the radiologist and also the nuclear medicine physician, because the key points of the right to treatment for locally advanced stages, to treat non—small cell lung cancer, is to define exactly the right staging. And this is the reason why we also include, in our cancer center, the radiologist and the nuclear medicine team because you can exactly define what the volume of the tumor is and what the nodal involvement in the mediastinum is. And this is the key point to decide whether to go with the surgery or to go with chemoradiation or with chemotherapy alone or with radiation alone.

So, I think that in 2018, it is mandatory to have and to discuss in a multidisciplinary team every stage 3 non—small cell lung cancer. And it is also important that the patients are aware that the right treatment can be done only in the centers where a multidisciplinary team is present. And if the multidisciplinary team is not present in the same cancer center or in the same hospital, it is important that every medical oncologist have some referral points in other hospitals for the surgery and the radiation oncologist, because you can decide case by case a totally different approach with the multidisciplinary team. And sometimes in my hospital, we are fighting every time to go with the chemoradiation or go with surgery. Because sometimes there are really tricky decisions.

Solange Peters, MD, PhD: In locally advanced non—small cell lung cancer, only some patients can benefit from surgery. We face again here the problem of heterogeneity of this disease, defining or being defined as locally advanced. Some of these patients can simply not benefit from surgery. I’ll give you an example: When you have positive supraclavicular lymph node, you cannot perform surgery on the lung and resect these lymph nodes. It doesn’t make sense biologically and it’s not anatomically feasible. So, some patients can simply not benefit from surgery. But some selected patients can be operated, can be surgical candidates. In that setting of surgical candidates, in this very precise subgroup of resectable stage 3, we also encompass here the patients with nodal involvement, what’s called N2, on the same side of the tumor. And these patients must be highly selected, and even here, there is a controversy.

There have been 2 randomized trials trying to address the role of surgery versus no surgery when you replace surgery with radiotherapy. And both of them are not able to really show that one modality is better than the other one, or if you want to make a long story short, you need to perform surgery because you could do radiotherapy, which is considered to be a little bit less dangerous in that setting. One of these 2 trials, however—the one from the American Intergroup trial—was showing that if you don’t do a big surgery like or if you just take a lobe out, a lobectomy, in these patients, maybe surgery is a bit more efficient than radiotherapy. But it’s an unplanned retrospective analysis, so it doesn’t close the debate.

It depends really on the country, the region, and the local politics you live in. In my country, for example, in Switzerland, we are very surgical. So, for stage 3 with an N2 disease, we’ve been performing a lot of surgery in resectable patients. But when I was in the United States, for example, these patients had radiotherapy and chemotherapy and no surgery. So, it’s really geographically defined. We all have our own standards of care. I think for the time being, nothing is right and nothing is wrong. In the ESMO guidelines, we have allowed the 2 options. You can choose between surgery or radiotherapy in stage 3 disease always with chemotherapy.

Marina Chiara Garassino, MD: The optimal treatment must be decided in the multidisciplinary team because if you decide that the patient is operable, and this is done with the surgeon, maybe you have to answer the question, go with chemotherapy before or go with neoadjuvant treatment after. In the last 15 years, there are several studies in the neoadjuvant setting and also in the neoadjuvant with chemotherapy or with chemoradiation therapy. However, all the studies, all the trials, are small, and sometimes when they started, they were with other clinics. And so, the results at the end are quite controversial, and still now in 2018, we have no clear answer which is the best sequence for treatment for this kind of patient.

So, what we need is a balance between the toxicities and the aim of why we do something. For example, for the surgeon, it can be important to reduce the tumor volume because it is easier later to operate on the patients. In some cases, this is important also. For example, if you want to reduce very quickly the tumor, maybe also chemoradiotherapy can be an option. But we have also to think that chemoradiation as the adjuvant treatment is quite controversial because it is true that we have more complete responses when we operate the patients. But all the studies, all the trials, were negative to prove a benefit in terms of overall survival and progression-free survival. So, if you have the goal to reduce the tumor and to render it easier for the surgeon, the operation, you can decide which is the most powerful regimen.

In other cases, for example, there are some stage 3 tumors that potentially are operable from the beginning, and in the most disciplinary team, you can decide to go with the operation immediately and then maybe to go with the adjuvant therapy in the second part of the study of the patient. What we know, and it is important, is that we have it in both cases in the neoadjuvant setting. And in the adjuvant setting, we have a reduction of the risk of death, which is very similar. There is the reduction of risk of death, about 5%, if we go in the neoadjuvant and if we go in the adjuvant. What is important is that sometimes it is better to go with the neoadjuvant chemotherapy before the surgery because patients are even better conditioned than after the surgery, and sometimes the chemotherapy is more tolerable than after the surgery. So, again, it is a balance between the toxicities, the conditions of the patients, and what is the big goal that you want to achieve with the treatments that you are going to do.

There are several studies of neoadjuvant chemotherapy, and the overall response rate with chemotherapy ranges between 25% and 40% with all of the regimens. So, there is not a favorable regimen. But you must be also aware that in not only all the cases, you are able to reduce the tumor and then go with the operation. You must be very careful to go with the neoadjuvant because you can resource the chance to operate on the patient in a second part of the life. So, it is always a balance between the medical oncologist and the surgeon, which is the right moment and the right treatment to be done for the patients in that moment.

Transcript Edited for Clarity