Philippa Cheetham, MD: We’re hearing about how years ago, patients used to have a whole lung removed, and then we got a bit more sophisticated and were able to remove part of the lung and do a lobectomy. But in many cancers now, we are becoming even more focused on that tumor with targeted therapy, with laser therapy, with cryotherapy, and with more targeted radiation therapy that you’ve talked about. Do you think that we will move away from lobectomy? Removing a whole lobe of a lung is still a major operation. Do you see more of a role for targeting directly into the center of the tumor without even removing the lobe?
Evan C. Osmundson, MD, PhD: I would say in the future, yes. I think there are some limitations. One of the advantages of a lobectomy is that they’re able to take lymph nodes out as well and sample those. And so, for any in-transit lymph nodes that were not sampled initially, if there’s disease in those, they are removed. That leads to the improved regional control of lobectomy. I think that perhaps with the addition of improved systemic agents for patients with high-risk early-stage lung cancer, we may move towards a more focused therapy. But as far as it stands right now in lung cancer, lobectomy in operative patients is the standard of care.
Philippa Cheetham, MD: You’ve talked already about early-stage disease versus late-stage disease. Once a patient has a lobectomy and the lymph nodes are sampled, if those lymph nodes come back positive, does that mean to you that the patient is in a late-stage category? How do you categorize the patients?
Evan C. Osmundson, MD, PhD: Traditionally, anything that is less than stage 4 is considered curable. That is evolving, of course.
Philippa Cheetham, MD: Define stage 4 for our patients.
Evan C. Osmundson, MD, PhD: Stage 4 is disease essentially outside the thorax, when the cancer has moved outside of the thorax to other distant organs. Traditionally, anything below stage 4 has been considered potentially curable. Of course, it’s an evolving landscape, and there are some interesting data in oligometastatic patients where you can have significant long-term survival in those cases with appropriate therapy.
Philippa Cheetham, MD: Dr. Horn, we’re hearing a lot in other cancers that we may give patients chemotherapy without evidence of metastatic disease. We’re giving them adjunctive, adjuvant, or neoadjuvant therapy for bladder cancer, where the patients will be given chemotherapy before the bladder is removed, even if there’s no evidence of disease outside the bladder. That has been shown to improve survival. And we’re seeing this more and more with other cancers. Do you think there’s any role in patients who have localized disease for giving them some belt and braces—immunotherapy, systemic treatment, chemotherapy—to kill off microscopic cells that Dr. Sandler’s team may not be able to detect? We assume they’re localized, but they may in fact have microscopic cancer cells traveling around the body that we can’t see. Is there any role for systemic treatment in patients with localized disease?
Leora Horn, MD, MSc: There definitely is a role. For patients who have had surgery, and their tumors were either larger than 4 cm or had lymph node involvement, those patients were generally treated with 4 cycles of adjuvant chemotherapy. Right now, there’s no role for immunotherapy or targeted therapy, but that’s being explored in the context of clinical trials. There are also trials that have been completed that looked at neoadjuvant therapy, so chemotherapy before surgery, in patients with stage 1 to stage 3 disease, also showing a small survival benefit. There are trials that are looking at neoadjuvant immunotherapy as well as targeted therapy in patients with early-stage disease. One of the benefits of therapy before surgery is that it gives us a better idea of the biology of the cancer. Is this a tumor that responds to chemotherapy, immunotherapy, or targeted therapies? And it can also potentially make the tumor a little bit smaller, making surgery easier.
Philippa Cheetham, MD: Easier, yes.
Leora Horn, MD, MSc: However, if a medical oncologist is thinking about that up front, the patient needs to see the surgeon first. The surgeon needs to be part of that discussion of “Yes, if you give chemotherapy first, I do think I can operate on this patient.” We should never go forward with chemotherapy and radiation therapy and say, “Oh, halfway through we’ll have you go see a surgeon.” A surgeon needs to be part of that upfront decision making for that patient.
Philippa Cheetham, MD: Up front, absolutely. Now, we know that these patients with lung cancer who present with a tumor in 1 lung of course have 2 lungs, and given their risk factors that led to them to getting lung cancer in the first place—if it’s going to affect the right lung—the left lung is clearly at increased risk. Do you think in the future, we may be treating high-risk patients who are already at high risk of developing lung cancer or who maybe even had cancer diagnosed and treated in 1 lung? Might we give them some preventative immunotherapy to stop the never-developing cancer in the other side? Do you think that we may move towards getting in there before a cancer diagnosis is even made?
Leora Horn, MD, MSc: That’s a great question. I think that everyone wants to use immunotherapy everywhere, but it’s a cautionary tale. They’re not the panacea we thought they were going to be. They only work in a subset of patients, and they have toxicities. Especially in patients where our goal is to cure, for a patient who develops a severe toxicity—such as pneumonitis, which is inflammation in the lung, or colitis, which can manifest as persistent diarrhea—those toxicities are pretty debilitating and can often last for months or years in patients in terms of recovery. So, I think the biggest lesson we know from once you have 1 lung cancer is that there’s about a 2% risk per year of developing another lung cancer. And so, those patients should continue to be screened after surgery and completing their chemotherapy regularly, because of that higher risk.