Examining the Promise of Multicancer Early Detection Tests: Need for a Multidisciplinary Clinic

In this third episode of OncChats: Examining the Promise of Multicancer Early Detection Tests, Toufic A. Kachaamy, MD, of City of Hope, Madappa Kundranda, MD, PhD, of Banner MD Anderson Cancer Center, and Niloy Jewel J. Samadder, MD, of Mayo Clinic, underscore the need for a multidisciplinary clinic to appropriately interpret multicancer early detection (MCED) test results.

Kachaamy: Fantastic comments. From your answer, 2 immediate questions come to mind. I’d love to hear the conversation between you and Dr Kundranda about this. [Say] you have a positive test. Is the oncologist the first person who’s going to see these patients? These tests are commercially available and now offered by the primary care physicians. What is, in your [opinion], the next step when you have a positive test? Is it the oncologist involvement or is it going to be in a primary care [setting]? Who is a team of people who understand these tests? We currently don’t have that [many who do understand]. That’s question number one. I’ll tell you question 2 after I hear [what you have to say].

Samadder: I think oncologists would be overwhelmed if this testing was done in vast populations, 2% were positive, and all of them were sent to a medical oncologist for further workup. I think we need a new paradigm. At Mayo, and I think other expert centers, [we’re] all coming to this idea that [we’re] going to have to set up an MCED clinic, so a multicancer early detection clinical program [that is] probably staffed by a combination of general internists as well as nurse practitioners who have defined algorithms based on the tissue of origin signal of what kind of diagnostic workup needs to occur [to make] a reasonable diagnosis.

About half to 60% of patients with a positive MCED test will have a cancer diagnosis and those [patients] are then referred into oncology for systemic therapy or for surgery. For the other 40% of patients with a positive MCED test, but the diagnostic workup is negative, I’ll give you an example. You have a positive MCED tissue of origin signal for gastrointestinal [GI] cancer. Well, you may do an upper endoscopy, a colonoscopy, a CT enterography to look at the small bowel, an MRI or MRP to look at the pancreas, or even a PET CT. But what about if all that workup is negative at identifying a GI malignancy? What do you do then? I think that is one of the big scares [for] both the patients and referring providers. This is where I think a MCED clinic can apply a logical algorithmic care pathway to identify those who have cancer at the first iteration.

Also, those who had a positive MCED test, but negative diagnostic workup, can be referred into essentially a multispecialty tumor board, similar to what oncologists already do but with radiologists, oncologists, gastroenterologists, [and] urologists, [which can inform] what the next part of workup would be, or [whether it] would only be surveillance imaging. What would be the next step for a patient with a positive test but negative diagnostic workup? Let me hand it over to my colleague, Dr Kundranda to [get his thoughts on this].

Kundranda: No, Dr Samadder. I think you hit on the key parts of this, which is, especially in the context of the positive test, where do you start? In our cancer center, this is not any different from when a patient has an elevated tumor marker, but then you’ve done this whole workup, and then everything [in] that diagnostic workup has been negative, right? Once we hammer out the nuances of [the MCEDs] then we really get to the crux of the thing, which is what is truly the positive predictive value on these randomized studies. Then, we will have a better idea in terms of how many of these [we can] just surveil with one modality or another, or in some cases, a multimodality way of surveilling [which could be] a combination of imaging with some invasive testing.

We, as an institution, tend to work together, whether it’s the internal medicine team, or whether it is our other colleagues within surgical medical gastroenterology and radiation oncology. Certainly, this is exciting, right? For me, as a medical oncologist, most of us, unfortunately, who deal with gastrointestinal malignancies realize that most cases that are diagnosed are at a later stage. More than two-thirds of the cases are incurable—even in 2023. As such, having something in terms of early detection, wherein...sometime in the near future, most of these cases that are detected early can be intervened upon, [can potentially improve] not just survival, but also quality of life, [by] preventing life-altering therapies, including surgeries. The key question is, in the interim, where is the best place to house it? [We are] truly looking at this as a multidisciplinary approach.

Previously, the same question was asked when we had tissue samples that were run with next-generation sequencing [NGS] about a decade ago. Most of you will remember that, right? The biggest concern that patients and physicians had was, if you have a testing that’s done, you have a NGS [panel with] about 800 genes [that are] run, and if you come up with these results, who’s going to be able to interpret that? The solution to that was to create a molecular tumor board. Similarly, as MCEDs evolve and as the data evolve, having a multidisciplinary clinic—you can call it an MCED clinic or whatever [you want to] label it as—would be the way to go.

Kachaamy: [In] oncology, there is [a] shift from less stage IV to more workup. Is this what I'm hearing?

Kundranda: I think all of us are involved in that initial workup, whether it is directly in the oncology clinic, or whether it’s an internal medicine clinic that sits right by the oncology clinic, and you work together as a team. Most of our internal medicine doctors attend our multidisciplinary tumor boards because this, for them, is where they diagnose the patient with cancer, and they want to know what’s happening next.

Samadder: You don’t know what the impact [on] oncology is. The theory, and you made a great point, is surrogate end points that we can look at. One of the surrogate end points could be, does technology like this lead to stage shifting? So, instead of the current mix of stage I, II, III, and IV cancers of whatever organ, by introducing such a test, do you stage shift it down? We don’t know that. That is [one] theory, but that could be a surrogate end point that could be reached in a shorter period than any kind of mortality outcome.

Check back on Wednesday for the next episode in this series.