Cancer Screening Breakthroughs: Implications for Clinical Practice

Transcript:

Jon O. Ebbert, MD: Exciting data. When we think about bringing this to clinical practice, what implications does it have on future clinical practice?

Tom Beer, MD, FACP: Well, I think both DETECT-A and PATHFINDER [NCT04241796] demonstrate that this is possible. These are feasibility studies. And with that goal in mind, they demonstrated that one can evaluate a blood-based multicancer early-detection [MCED] test and one can detect cancers directly as a consequence of the MCED test that likely would not have been detected otherwise. We also saw that cancers for which no standard-of-care screening is available can be detected with this MCED test. The accuracy of the tissue of origin prediction was impressive in patients with a true positive result. Its impact on the overall work-up is less clear at this point because, of course, it was also reported for those with a false-positive result, where no cancer was ultimately identified. So we’re still trying to better understand what is the most efficient way to evaluate an MCED test and whether or not a tissue-of-origin prediction is helpful when all patients are considered.

More work needs to be done. Studies are ongoing to further define the performance of the test in prospective studies of the intended-use population; that includes greater socioeconomic, ethnic, and racial diversity. So more to come. But I would say both DETECT-A and PATHFINDER succeeded in demonstrating the feasibility of MCED test testing and provided a launching pad, if you will, for additional efforts in this area.

Elizabeth O’Donnell, MD: It’s really provocative. And Dr Buchanan, following up on kind of these initial results, can you tell us a little bit about the longitudinal analyzes from DETECT-A, and what do the follow-up data of the false-positive tell us and reveal?

Adam H. Buchanan, MS, MPH, CGC: Since the original DETECT-A data were published in 2020, we’ve continued to follow that cohort of individuals. So there are nearly 10,000 women who started the study, ages 65 to 75 [years]. And of those in the initial publication, there were 98 who had what was deemed at the time a false-positive result. That means that they had a positive MCED test and then upon further work-up on diagnostic imaging and so forth, no cancer was detected. So we wanted to understand among those individuals whether there were any future cancer diagnoses and whether there was kind of any reassurance or a return of those individuals to usual care after a positive test and negative further work-up.

So we found that in those 98, 96 did not have evidence of cancer approximately 4 years after their enrollment in the study. And those remaining 2, we did have 1 with a breast cancer and 1 was an ovarian cancer. And each of those was diagnosed a little over 2 years after they enrolled in the study. So the breast cancer was a stage IA, the ovarian cancer was a stage IIIC. So one of the challenges here is determining whether a false positive occurs because he you reach the limits of detection and you just were unable to pick up a tumor that was present or whether there was something that has developed in the interim and that’s unanswered with a follow-up data that we have. But one could speculate based on those 2 cancers in their staging. So I think one of the key takeaways there is that it did seem to be largely reassuring that we have these data several years after an initial positive test that was considered at the time to be a false positive, that there was no further development of cancer in these participants with negative work-up. So highlights the importance of getting work-up after a positive MCED test.

Elizabeth O’Donnell, MD: And what about the patients who were true positives? What about their long-term clinical outcomes?

Adam H. Buchanan, MS, MPH, CGC: Similar questions there. We wanted to follow for a period of time and understand whether that detection might occurred through the use of the MCED had favorable outcomes. And so this analysis was focused on the 26 individuals who have their cancer diagnosed through the DETECT-A study and the use of the MCED test. In those 26, we pulled electronic health records for all roughly 4 years after their enrollment, and we found that 13 of the 26 were in remission at the time of that data extraction. And of those 13, 7 had a tumor type for which there was not standard-of-care screening. Among those 13, as one might imagine, they were more early-stage cancers than later-stage cancers, to stages I, II, and III.

And most of the individuals who had surgery for curative intent were in remission at the time of the analysis. So there were 14 of those 26 who had surgical treatment, and 12 of those 14 were in remission. And I think one of the other questions that is percolating in the field right now is about overdiagnosis and early-stage cancers with MCEDs. And I couldn’t answer that question with the data that we have here, but it does raise an interesting series of questions to follow up on. There were 5 individuals who had stage I disease who were in remission at the time of our analysis. And each of those 5 had some indication that it could be a more aggressive tumor. For example, there was an ovarian tumor that was 19 cm in measurement. The uterine cancer was [sarcoma], which is typically more aggressive. So there was some indication there that some of those early-stage tumors that were detected through the MCED test are ones that do bear treatment rather than a watchful waiting approach there, and then mitigate some of those concerns about proper diagnosis and treatment.

Elizabeth O’Donnell, MD: Right. And how do you pull this all together? What are the potential implications of all these findings?

Adam H. Buchanan, MS, MPH, CGC: So there are a couple of main implications, I would say. One is the question of when do you stop following up on a positive test? And so this false-positive data analysis indicates that it seems reasonable to return patients to usual care after a negative diagnostic work-up. That doesn’t answer that question, of course, but it gives some credence to that and sets up further larger studies along those lines and also, I think, emphasizes the importance of early detection and particularly detection that can lead to treatment with curative intent, which is a long-term goal of cancer screening. And I think what we a true positive highlights that as well.

Jon O. Ebbert, MD: Right. So the DETECT-A and PATHFINDER really demonstrated feasibility. It really provided an opportunity for us to look at foundational knowledge in this space. But MCED itself continues to evolve, doesn’t it?

Transcript is AI generated and edited for readability.