Updates in Systemic Therapy for Non-Metastatic Lung Cancer - Episode 3

Role of Postoperative Radiotherapy in Early Stage NSCLC

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Benjamin P. Levy, MD: Let’s move on to radiation. As Dr Zhang has discussed, there may or may not be a role for postoperative radiation therapy for patients with resected lung cancer. We have some interesting data that have come out of ESMO [European Society for Medical Oncology Congress] 2020 suggesting that maybe we should pump the brakes on radiation postresection. Dr Leal, can you walk us through these data that are just coming out of ESMO—the LUNG ART study?

Ticiana Leal, MD: The role of postoperative radiation has been controversial. We have typically thought about using postoperative radiation in patients with positive margins in complete resection, and for patients who had, for whatever reason, incomplete nodal dissection. Then patients with N2 disease. At our institution, if patients had single-station N2 disease, a lot of times we would actually not proceed with postoperative radiation. So the study, in my opinion, is practice changing.

The LUNG ART study was presented at ESMO 2020. This is a phase 3 trial that looked at mediastinal PORT [postoperative radiotherapy] vs no PORT, 54 Gy and 27 to 30 fractions, for patients with complete resection with nodal exploration and N2 positivity. In this study, prior neoadjuvant chemotherapy was not allowed. The main end point of this trial was disease-free survival. The trial enrolled 500 patients with completely resected non–small cell lung cancer with N2 histology.

These patients were randomized 1:1. Results showed there was no improvement in disease-free survival, which was a primary end point for patients who received PORT vs no PORT. The difference here was 22 months for the patients who received no PORT vs 40.5 months for patients who received PORT. And the hazard ratio was 0.85.

Importantly, there was no difference in overall survival. There was a slight decrease in number in terms of mediastinal relapse in the patients who received PORT vs no PORT. But importantly, there was also increased toxicity, including grade 5 events. More cardiopulmonary mortality was seen in the patients who received PORT.

In my mind, this was a very well-designed study. It really answered the question that we have for worried about for years, and will help me decide not to use PORT in patients with completely resected N2-positive non–small cell lung cancer in the adjuvant setting.

Benjamin P. Levy, MD: Yeah, it was certainly a surprise on the heels of some retrospective data that would suggest that postoperative radiation therapy can lead to improved survival, specifically with resected N2 disease. Now we have a nicely designed phase 3 trial showing that’s not necessarily the case.

Dr Salgia, does this change your practice? Does it change your enthusiasm or likelihood for referral to radiation oncology with incidental N2 disease, or even N2 disease found at the time of resection?

Ravi Salgia, MD, PhD: Absolutely, Dr Levy, and beautifully summarized, Dr Leal. As soon as that data came out, our whole group got an email from our radiation oncologist. “Look at this study on PORT.” We all chimed in as well, and so did our surgical colleagues. This is clearly practice changing, and we have to take this into account. N2 disease is still pretty tough to treat, but now we will not be referring for radiation based on this study. Very nicely done.

Benjamin P. Levy, MD: Dr Naidoo, what are your thoughts on this?

Jarushka Naidoo, MBBCh: I totally agree. Postoperative radiation to the chest, to the mediastinum, does not come with a “get out of jail free” card. These are patients who have already undergone surgery, have already undergone adjuvant chemotherapy. So this would be welcomed news for patients—to hear that their treatment journey had to come to a close and they didn’t need further thoracic radiation.

Benjamin P. Levy, MD: Yes. I would echo the sentiments that have just been relayed. N2 is such a challenging disease. There is a high rate of recurrence. We think that modalities that are instituted will lead to outcomes that are improved, and we’re learning that 1 of our main modalities that we’ve generally deployed in this setting is actually a negative study.

Dr Zhang, does that change how you would monitor these patients? Let’s say you have a patient with an N2-resected lung cancer and you’re giving 4 cycles of chemotherapy, but you can’t give radiation. They’re at high risk of relapse. Would you decrease the interval of the scans for these patients? What would your monitoring strategy be after chemotherapy?

Jun Zhang, MD, PhD: That is a tough question. At this moment, with no clear data, especially regarding survival benefits and additive toxicities, I would say this study is a very beautiful answer for a question that has haunted us for almost 20 years.

Without clear evidence of the benefit, I would just monitor the same way as what we’re doing. But of course if a patient shows worrisome symptoms, we can always scan earlier.

Transcript Edited for Clarity