Editorial: GI cancer – is the dial shifting?

6 minute read

GI cancer patients haven’t seen the dramatic outcomes that make the news for other cancers, but there is a lot going on.

Drug development and new technologies are opening doors for patients with GI cancer, and management has changed in response to exciting, new data. But research presented at the recent ASCO GI 2024 meeting suggests the way ahead will be complicated.     

A substantial proportion of newly diagnosed patients with cancer each year have GI cancer, accounting for approximately a quarter of all cancer diagnoses each year.

We haven’t seen much significant progress for this group of patients for a long while. It’s not like in melanoma, for instance, when suddenly the curve just changed completely. But now, and thinking on the past few years, it looks like there will be a change in the management of some of these conditions, although it won’t happen overnight and there’s a lot of research yet to be done.

We’ve been traversing the molecular era in clinical oncology for the last 10 to 20 years; increasingly trying to understand the biology of cancer broadly, and in particular the molecular basis of cancers that can be targeted by specific therapeutic approaches. With that has come greater understanding and insights into what drives cancers of the gastrointestinal tract; what works and what doesn’t.

Industry has led many of the opportunities in relation to technology and biomarkers. As a result, drug development, especially with the advent of immuno-oncology, has brought some, though not broadly enormous benefits in various subgroups of GI cancer, with the notable exception of the use of checkpoint inhibitors (CPIs) for patients diagnosed with tumours with a MSI genotype.

The role of immuno-oncology, particularly in the upper GI space (gastric cancer and oesophageal cancer) is becoming clearer though, as the data are maturing. And there are increasingly, encouraging results around the role of CPIs in earlier stages of primary liver cancer.

But that’s not the whole story.

In terms of management, there has been a reframing of some of our practices; a change in clinical algorithms that has required a shift in the way people think, and an understanding of the limitations of what we currently do/don’t do as the case may be. This is not as easy as it sounds. It takes time to understand the real-world impacts of “practice-changing” clinical trials, make further changes to practice and observe these effects.

One example of that is in the treatment of rectal cancer, which affects about a third of people with bowel cancer. In those patients with locally advanced but not metastatic disease, the standard of treatment was radiotherapy with chemotherapy, waiting a few weeks, then operating and removing part of the rectum, or sometimes all of it (leaving the patient with a stoma), and then giving additional chemotherapy if lymph nodes were involved or if the disease was considered high risk.

That was the treatment paradigm for many years. But there are side effects that come with treatment after surgery. There are functional sequalae of removing part or all of the rectum and anus. There were increasing data to suggest that perhaps we could do things differently, and with these findings, the paradigm started to change.

Firstly, we now give all the treatments before surgery – total neoadjuvant treatment (TNT) – rather than adjuvant chemotherapy after surgery. The second change came about because it was observed that in some people who get treatment before surgery, the tumour disappeared completely, at least clinically, and these patients may not need surgery at all. Many surgeons have been very accepting of these findings and have adapted to what is a significant change in practice.

It is important to remember, however, that change does not automatically mean better outcomes. Sobering data presented at the recent ASCO GI Cancer symposium showed that when local recurrence occurs, which it does for a significant percentage of cases, those people had a worse overall outcome. It isn’t just a matter of cutting out the recurrence. Maybe these data were just a blip, but not everything goes the way you hope it will.

It’s too early to predict whether that is going to swing the pendulum back from trying to avoid surgery to again performing more surgery. It will undoubtedly fall somewhere in the middle, where we will have to be able to select the right people in each case – those who need surgery and those who don’t. It isn’t easy to do that at this point in time, but as we understand these issues more, it will become easier.

For some time, there’s been quite an interest in using circulating tumour DNA to guide treatment, particularly in the adjuvant setting and in large part led by Australian investigators at the WEHI and Peter MacCallum Cancer Centre in collaboration with the Australian Gastrointestinal Trials Group (AGITG).

Currently, for example, you might have surgery and be told there’s a 50% or 60% chance of a cure, but a number of people are not cured, and so we give everybody chemotherapy. The beauty of this technology is that maybe we can pick the people that need chemotherapy after surgery, and those that don’t. But data presented at the symposium raised questions about whether this technology is really ready for prime time.

There is a great deal of complexity involved in interpreting various available tests. For instance, some of the data presented showed that, after surgery, participants in the control group were also experiencing a fall in circulating tumour DNA over time, suggesting that elevated levels prior to surgery did not necessarily predict a susceptibility to recurrence or the benefit of treatment.

So, the data are still a little unclear as to how the technology should be used, and there is uncertainty around what tests should be used. This technology isn’t routinely available in Australia yet, other than in research laboratories, but it’s coming, and it will be interesting to see how we use it.

Professor John Zalcberg AO is immediate past head of the Cancer Research Program in the School of Public Health and Preventive Medicine at Monash University and a medical oncologist at Alfred Health. He is also the Editor of Oncology Republic.

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