Insights From: Suresh Senan, MD, VU University Medical Center; Solange Peters, MD, PhD, Centre Hospitalier Universitaire Vaudois
Suresh Senan, MD: In locally advanced resectable disease, the role of radiation versus surgery has been compared in a number of trials. The most common approach used in trials has been to deliver chemotherapy and radiotherapy at the same time before surgery versus an approach including chemotherapy and surgery only.
The reason for exploring concurrent chemoradiotherapy is that it causes downstaging more effectively. So, more tumors are downstaged, potentially making it easier for surgeons to do a complete resection. A metaanalysis of these trials was published last year and showed that actually there was no difference between the 2 in terms of overall survival. And it comes about because the longer-term outcomes are determined by patient factors and fitness and in the short term, the surgical arms often have a slightly increased mortality. But in the intermediate to long term, it sort of balances out.
According to the recommendations, for example, the ESMO, let an expert multidisciplinary team decide on the best treatment sequence. So, if you have very good surgeons, and an expert team with good mortality and complication figures, you’d be more likely to use a bit more surgery in these patients. On the other hand, if you’re a center without expert thoracic surgeons, then standard chemoradiotherapy can be delivered in most oncology centers. So, center expertise cannot simply be translated from one center to another.
Now the Swiss have done an interesting trial because they’re a group with a very long track record of evaluating surgery. So, they asked the questions in the most recent trial, when you are going to operate on a patient? Is it sufficient to give chemotherapy or should you add chemotherapy and radiotherapy beforehand? But what they did is they did not combine the two at the same time; it was not concomitant chemoradiotherapy, but they gave sequentially. They concluded there was no benefit of adding radiotherapy before surgery, but they didn’t ask the question if the surgery was necessary in the first place.
The second point about the Swiss study is they showed that the likelihood of a tumor progressing before surgery and the likelihood of a tumor recurring after surgery was higher in the arm without the radiotherapy. So, I do not think that the Swiss study is likely to change practice or guidelines in the rest of Europe or the world. If you’re going to do induction therapy, the guidelines are clear and the evidence from trials show that giving them both at the same time seems to be the best way. The German ESPA II trial also evaluated the role of surgery, but they gave concurrent chemoradiotherapy to both arms with or without surgery. And the arm randomized to not receiving surgery got a higher dose, and they found no differences in outcomes as well.
Both options are suitable in patients in the hands of an expert team. So, I think we have 2 treatment options but 1 treatment option, chemoradiotherapy alone, can be more widely applicable because chemoradiotherapy followed by surgery does require expert surgical knowledge and postoperative care. And I think they’re both reasonable options in expert hands.
So, at our center, we do concurrent chemoradiotherapy for all patients and in patients who undergo surgery. We do it if the surgeon feels there’s a need to ensure radical resection margins. That’s the first thing. The 2 instances where we use it are, as in any routine fashion, tumors of the superior sulcus where we give all of them chemoradiotherapy to 50 gray before, and in younger, fitter patients where a lobectomy can be performed, then we give a preoperative dose, but that is decided up front in a multidisciplinary tumor board with the surgeon determining that.
If the surgeon is not sure whether he’s going to do surgery, then the tumor board in our experience says, “Well, go to 60 gray.” There’s a likelihood we will not do surgery, but we will review the case. But if the surgeon is confident up front for single-station N2 disease where lobectomy can be performed, we would perform that or discuss that option with the patient. Because all of the evidence from trials tell us they are both good, that both chemotherapy radiotherapy only or chemotherapy radiotherapy with surgery are acceptable and good treatment options.
A metaanalysis in locally advanced non–small cell lung cancer showed that concurrent chemoradiotherapy alone in operable stage 3 disease gave comparable progression-free and overall survival as induction treatment followed by surgery. However, the results of the recent PACIFIC trial, which showed an 11-month improvement in progression-free survival in the patients who underwent immunotherapy for 12 months after completing chemoradiotherapy, calls into question the role of surgery. So, we need surgical data to show that this magnitude of survival benefit can be achieved with surgery alone. My own feeling is that with this very effective tool available now, immunotherapy after standard chemoradiotherapy, it will further entrench the role of nonsurgical treatments in stage 3 non–small cell lung cancer. Because if the 2 are comparable and one approach has made a big breakthrough, clinicians may be more inclined to use the nonsurgical approach in the future.