Surgery Maintains Role in Rapidly Advancing Lung Cancer Treatment Paradigm

Eric Vallieres, MD

Despite practice-changing advancements with immunotherapy and targeted therapy in the treatment of patients with lung cancer, the importance of surgery remains rigid for now, said Eric Vallieres, MD.

In the past few years, thoracic surgery has become more minimally invasive with the use of video-assisted thoracic surgery (VATS) and, more recently, robotics. Smaller incisions and a more visualized scope of the operation site have allowed for patients to return to a normal quality of life (QoL) in dramatically less time.

Vallieres, medical director of the Division of Thoracic Surgery of Swedish Medical Center, explained that in the future, the efficacy of surgery may be enhanced when used in partnership with immunotherapy. For example, ongoing research is looking to determine if adjuvant immunotherapy will have the same impact after the lymph nodes have been removed.

Secondly, in a small phase II trial, investigators evaluated the use of neoadjuvant nivolumab (Opdivo) in patients with untreated, surgically resectable early (stage I, II, or IIIA) NSCLC. Neoadjuvant nivolumab demonstrated an acceptable toxicity profile and had not been associated with delays in surgery. Twenty of the 21 tumors were completely resected, and a major pathological response occurred in 9 of the 20 resected tumors (45%). Although the results are promising, the data are preliminary and follow-up is ongoing.

“For me, as a surgical oncologist, the biggest excitement is how we are going to incorporate immunotherapy into treating our patients,” said Vallieres. “In terms of patients who need fairly large surgeries, can we give them those drugs and then tailor their surgeries down?”

OncLive: What are some recent technological advances made in thoracic surgery?

Could you expand on the postoperative recovery period and QoL outcomes?

In an interview with OncLive during the 16th Annual Winter Lung Cancer Conference^TM, Vallieres highlighted the technological advances of lung cancer surgery and how this impacts the outlook for patients who are candidates for it.Vallieres: First, there is the notion of advanced recovery after surgery. We have data showing that strict application of those programs can result in better care, better results, faster recovery, and less need for narcotics; overall, it is also less expensive. In terms of incisions, the minimally invasive surgical approach has gone from VATS to robotics, which is evolving in its own sphere. There are several different ways of getting there. There is also the idea of operating after immunotherapy; there are little data here on this, but it is out there. Operating after failed radiation therapy is something that we are also seeing more often. The topic of performing surgery in stage IV oligometastatic disease is also something being explored.We have really moved the pendulum in a favorable way in that patients are staying in the hospital for a shorter period than they used to. The way we manage their pain perioperatively and the minimally invasive approaches allow for less surgical trauma in the chest wall. By itself that translates to early recovery, which is easier. Even for open surgery, the way we do it in 2019 is not the way that I was taught 25 years ago. As such, even those patients recover much quicker and better.

Does the advancement with other types of treatment, such as immunotherapy, affect the role of surgery?

This all translates into their ability to be active earlier in the postoperative period, to be ambulating earlier, to be going back to a fairly decent QoL very early after surgery. Now, 2 to 4 weeks after surgery patients are back at baseline and off all pain medication; that is whether we do it on a minimally invasive platform or open. This is a tremendous advancement.Not yet. The adjunct of targeted therapy before or after surgery has not yet been shown to be of value to patients that, we, as surgeons, treat with early-stage disease. With immunotherapy, there is a lot of excitement about adding immunotherapy to a surgery platform—whether we should to do it before or after surgery and for which patients. After surgery, when all the lymph nodes and lymphatics have been removed, would [immunotherapy] have a similar effect? Those are all unanswered questions.

What are the benefits of the robotic approach over VATS and other traditional surgical approaches?

There is excitement about taking a PACIFIC trial type of approach with stage III disease and moving immunotherapy in the backdoor after an approach that would include surgery. Would we able to replicate the improvement [in survival] that PACIFIC has shown? This is all ongoing, but the preliminary studies have been very exciting.That is a million-dollar question. For straightforward lung resections, there are no obvious benefits for robotics over VATS. For the surgeons who are comfortable with doing VATS, there is really not much of a difference. Robotics are still a video-based surgery, but you are using a different field of view and have a different way of controlling your instruments inside the chest. Really, the big difference [between the 2 approaches] may translate [in terms of] the more complex surgeries, but this remains to be seen. There are no randomized studies that have compared 1 platform versus the other. I believe that what keeps your patients in the hospital are not the incisions, but it the air leaks and complications. Whether you do it with a 2019 open approach or a VATS, your patients will be in the hospital about the same period of time if they have no air leaks. The potential is there.

What can be accomplished in this field within the next few years?

Then we have to discuss the cost. There is definitely more of a cost issue with these robotic surgeries, but I am hoping these costs come down as there is more than 1 platform available to do this. We looked at it about 5 or 6 years ago in our own institution. For a robotic lobectomy to make sense, we have to either shave off 1 day of hospitalization, use a lot less staplers during surgery, or both. We will see, but it is exciting, and it is the future.For me, as a surgical oncologist, the biggest excitement lies in how we are going to incorporate immunotherapy into treating our patients. In terms of patients who need fairly large surgeries, can we give them those drugs and then tailor their surgeries down? Secondly, [what role] will immunotherapy [play in] patients who have nodal involvement? For stage III disease—that is potentially reason for surgery—do we give those drugs upfront or after surgery? We are still learning about immunotherapy. To me, this is the most exciting [topic of research]: how will we incorporate immunotherapy into the surgical treatment of our patients?

As our systemic treatments are getting better for stage IV disease, there is evidence that by doing a local therapy with oligometastatic disease, we have to analyze the role of surgery in those patients. Most patients may benefit from radiation, but others may benefit from surgery or a combination of both. However, there will be an increased role for surgery because we have better systemic therapy.

Forde PM, Chaft JE, Smith KN, et al. Neoadjuvant PD-1 blockade in resectable lung cancer. N Engl J Med. 2018;378(21):1976-1986. doi: 10.1056/ NEJMa1716078.

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