BTOG 2021 | Surgical considerations in a peri-operative therapy era

Good morning. So, I’m Rory Beattie. I’m a thoracic surgeon based at The Royal Victoria Hospital in Belfast. So, I’m talking about the surgical considerations in the peri-operative area. I think the main thing here is, there’s lots of great emerging evidence role of TKIs and immunotherapy in surgical patients, but when you look at papers referencing surgical outcomes centers in between 20 and 40 patients in each publication, and burdens in the UK and worldwide really are unlikely to have much experience in managing these patients unless they’re linked to a center that’s been involved in one of the studies.

So understandably, we are presented with these patients, there’ll be some concerns, nervousness in offering them a lung resection, that immunotherapy in particular can be linked with quite marked inflammation leading to fibrosis in or around mediastinal structures, and then there’d be concerns like pneumonitis and surgical approaches for these patients as well.

So we’ll be talking about how feasible minimally invasive surgery is, the surgical outcomes, the longer-term surgical outcomes for immunotherapy and TKIs. And then we’ll be going through, aside from the classic neoadjuvant stage, we’ll be talking about those patients who were initially surgically inoperable and presented to surgeons after a strong response to either immunotherapy, TKIs for salvage resection, and whether or not that’s justified.

But anyway, immunotherapy can be associated with a strong inflammatory response. The studies to date, there’s been some struggle to complete these operations minimally invasively, and there’s a quite high thoracotomy rate for us. The operations are longer or take longer than a standard [inaudible]ectomy. They can be associated with extended infection, so with [inaudible] we’ve looked at the outcomes from Austin and Zurich, and there was quite a high rate of pneumonectomies or extended resections. Despite the difficult surgery, the operations are safe. So, then the last series, the 30-day mortality is zero.

Surgeons can be concerned about the high radiology influence for resection. For immunotherapy, it’s very hard to correlate the radiological response with the pathological response. So, radiology doesn’t have much of a role as to why surgery is going to be difficult or not.

The TKI therapy seems to be a bit different. There’s some paper out showing that those who have a radiological response to therapy do have a higher VATS resection rate, do have a quicker, more straightforward operation. So, the two are a bit different, but either way, it’s VATS or open surgery if surgery is possible.

A common question may be, for immunotherapy in particular, what interval between immunotherapy and surgery? So, the study seemed to have an interval in two to six weeks, and that seems to be reasonable. The concern would be if you leave it longer, the inflammatory response turns to fibrosis, leading to a more difficult operation. The TKIs are different. There’s a similar interval in the literature, two to six weeks. But they do not seem to be associated with this fibrosis.

The last scenario is probably one that surgeons in the UK would be a bit more familiar with, these patients who’ve been given immunotherapy or TKIs for inoperable disease and had a great response to it. In fellowship in Boston, I combined the Boston [inaudible] experience, and we had nearly 50% of our patients were stage-IIIb or IV and we had one-year survival of 90%, and recurrence-free survival of 54%.

There’s a new paper out there from Japan that concludes patients who’ve been given TKI for surgically inoperable disease, and then on to salvage lung resection. They have a three-year survival of 75%, although the progression-free survival is sitting around 23%. But when you look at these patients that have survived, on average it would be higher, 85% have survived three years after starting on TKI. So, there is a thought for the patients that need TKI, you’re converting into a more chronic disease, and surgery may have to wait.

When you do a search on clinicaltrials.gov or neoadjuvant immunotherapy and lung resection you’re getting 23 trials currently recruiting. We’re going to hear a lot more about this for both immunotherapy and TKIs. Surgeons are going to be increasingly asked to go for a lung resection. It’s important we know the data behind it, we know how it may affect our operation, and we understand that these operations can be performed safely. It’s all about improving the results for the current patients who are considered for surgery. It’s about improving the results for the current group of what we consider a surgical patient, but also perhaps offering surgery to some patients that are previously surgically inoperable.