Editor's Note: The 20th International Society for Diseases of the Esophagus (ISDE) conference took place in Edinburgh, Scotland, from September 22nd to 24th, 2024. At the conference, a study by Dr. Krishna Moorthy from the Royal College of Surgeons in the UK on whether prehabilitation can increase the surgical opportunities for esophageal cancer patients was selected for presentation (Abstract No.: S19.02). Oncology Frontier conducted an exclusive interview with Professor Moorthy at the conference venue about this research. The interview content has been organized and the relevant study abstract is attached for reference.

Oncology Frontier: Based on the current research data, what is your opinion on the effectiveness of prehabilitation therapy in in converting borderline operable patients to operable candidates for esophagectomy?

Dr. Krishna Moorthy: So, prehabilitation is a very interesting and an exciting area in esophageal cancer patients, and has been so for quite a few years now. I think there is no dispute about the benefit of prehabilitation in patients undergoing esophagectomy. There are enough randomized controlled trials, studies, and even metaanalysis that show that prehabilitation results in a reduction in post operative complications, mainly post operative pneumonia, which is a very common complication in our patients, but also results in overall reduction in post operative hospital stay and even intensive care unit stay. And that translates to a significant cost savings for hospitals who are treating these patients. However, we all know that a large number of esophageal cancer patients can be considered to be of both borderline fitness and. What does borderline fitness mean? Fitness is mainly measured in different ways. It is subjective, where we ask questions in terms of how much they can do. It’s called exercise tolerance.Or we have performance status, or sometimes we, surgeons, use simple tests like the “stair climb test”. Those are the subjective tests that we use.

But then, objectively, we also have tests like the cardiopulmonary exercise testing. With all this testing, we can identify a group of people who are not very fit, but on the other hand, they are also not so poor in terms of fitness that we can’t rule out surgery altogether. And this group that we identify can be, we can use different measures for this, but let’s just say that the one thing that we all understand is that many of these patients are frail. And frailty, as we all know, is a syndrome that’s associated with mainly elderly people, but can also be seen in younger people now, especially those who are obese, who are sedentary for a long time, and frailties associated with things like slow walking speed, weight loss, etcetera. And we see a lot of this in our patients. So if you look at the research in terms of the effectiveness of prehabilitation in frail patients, the research is actually very positive. That even in frail patients, we can see the benefits of prehabilitation in terms of post operative outcomes and hospital stay.

Oncology Frontier: Could you please elaborate on the methods to evaluate the marginal state of human physical fitness? And what are the specific methods included in prehabilitation therapy?

Dr. Krishna Moorthy: there are different ways to assess people’s borderline fitness. Some of them are clinic based, where we ask patients questions on exercise tolerance. We ask them how far they can walk before they have to stop or they get breathless. We can use a stair climb test that people use in their clinic. But there are more objective tests, such as cardiopulmonary exercise testing, which in many ways is considered to be the gold standard in terms of assessing preoperative fitness. But it is expensive, it is not easily available and accessible. As a result of which, there are other tests that can be applied within a clinic setting, and that one of the most common ones is a six minute walk test. And so the six minute walk test is the one that is most commonly used in most prehabilitation programs to select those people who are considered to have the poorest functional capacity, or let’s say fitness, and our programs are mainly directed towards them. Now, obviously, exercise is an extremely important aspect of prehabilitation programs, but that is because we want to improve their fitness and their functional capacity. And by doing so, we can not only improve the outcomes, such as post operative complications and hospital stay, but we can also make these people more eligible for curative pathway instead of depriving them of curative surgery. So exercise is important, and exercise has to be highly personalized, because many of these patients are elderly, they have not exercised for a long time and they are facing severe symptoms. Many of our patients are on neoadjuvant chemotherapy because of which they will experience side effects. But exercise cannot be seen just in isolation. Exercise has to be seen as part of a multimodal modal approach in our patients. So many of our patients will have dysphagia, they have weight loss, and so the focus on nutrition is extremely important. And many of these patients will also have significant psychological morbidity, for example, anxiety, distress, depression. And unless we address these psychological factors, it will be very difficult to make patients adhere to the exercise program. So all these programs have to be multimodal. And you also have to then also think about other factors that impact on post op outcomes, such as anemia, such as smoking, alcohol intake. And all this can be bundled together within a multimodal prehabilitation program.

Oncology Frontier: How does prehabilitation impact the long-term outcomes of patients who were initially considered borderline operable，such as on survival rates, postoperative complications, or overall improvement in quality of life?

Dr. Krishna Moorthy: We are still at a very early stage in terms of the research evidence of prehabilitation, in terms of long term outcomes and especially survival. It just seems logical that if there are a group of people who are being denied curative surgery based on their fitness for surgery, that if we make them fit, there is a higher chance that they will access that surgery and thus they will be able to, at least, have a chance at cure of esophageal cancer. But we do not have the evidence as yet in terms of prehabilitation influencing survival. But prehabilitation obviously also works in different ways, which is interesting. There is emerging evidence that prehabilitation, because of its impact on people’s overall health, results in better completion of neoadjuvant treatment. So our own research study, as well as others done by our colleagues in the UK have shown, that prehabilitation group patients have a higher chance of completing neoadjuvant treatment as planned, rather than the neoadjuvant treatment stopping prematurely. And that obviously will have a survival benefit because you can then complete the gold standard treatment, that you were intended to have. In other settings, prehabilitation has also been found to improve access to adjuvant chemotherapy in people who had surgery because they have a lower risk of post op complications and thus a lower risk of postoperative health deterioration, and thus they can start their adjuvant chemotherapy on time. But what there is enough evidence on is that prehabilitation definitely improves patient reported health related quality of life throughout the cancer pathway, both during neoadjuvant treatment and even after surgery. There is research that shows that patients who undergone prehabilitation report much better quality of life at the end of surgery, and the anticipated deterioration that we see in quality of life, especially physical function in our patients, is not so much in patients who have undergone prehabilitation.