In this JCO PO Article Insights episode, Harold Nathan Tan summarizes findings from the JCO PO article, “Circulating Tumor DNA as a Prognostic Biomarker for Recurrence in Patients With Locoregional Esophagogastric Cancers With a Pathologic Complete Response.”

TRANSCRIPT

Harold Nathan Tan: Welcome to JCO Precision Oncology Article Insights where we explore cutting-edge discoveries in the world of cancer treatment and research. I'm Harold Nathan Tan, your host for today's episode.

Let's dive into a fascinating study published in JCO Precision Oncology entitled, “Circulating Tumor DNA as a Prognostic Biomarker for Recurrence in Patients With Locoregional Esophagogastric Cancers With a Pathologic Complete Response.” This study led by Dr. Eric Michael Lander and colleagues examines a critical question: Can circulating tumor DNA help predict recurrence in patients with esophagogastric cancer who have achieved a favorable pathologic response after treatment? Esophagogastric cancer ranks as the seventh leading cause of cancer-related deaths worldwide. Despite aggressive treatment including neoadjuvant therapy followed by surgery, recurrence remains a grim reality for many patients. Interestingly, even those who achieve a pathologic complete response face a recurrence risk of up to 25%. This highlights a need for better tools to identify high-risk patients post-treatment. Circulating tumor DNA, or ctDNA for short, is emerging as a powerful biomarker in oncology. This minimally invasive blood-based test detects fragments of tumor DNA in the bloodstream, potentially signaling molecular residual disease before any radiographic evidence of recurrence appears.

In this study, researchers focused on patients with locoregional esophagogastric cancer who had undergone neoadjuvant therapy followed by surgery, achieving either a complete or near complete pathologic response. Blood samples were collected postoperatively within a 16-week molecular residual disease window and during routine surveillance. The aim is to determine whether ctDNA positivity correlates with recurrence-free survival. The study analyzed 309 plasma samples from 42 patients across 11 institutions. Detectable ctDNA within the 16-week postoperative window was associated with a significantly higher recurrence risk. Among those with detectable ctDNA, 67% experienced recurrence compared to only 15% for those with undetectable ctDNA. This corresponds to a hazard ratio of 6.2, an alarming figure that underscores the potential for ctDNA as a prognostic tool. But the story doesn't end there. Postoperative surveillance ctDNA testing more than 16 weeks after surgery also proved to be a powerful prognostic indicator. Every patient with detectable ctDNA during surveillance eventually experienced recurrence, while only 7.4% of those with undetectable ctDNA relapse. These findings suggest that ctDNA testing could provide a critical lead time, enabling earlier interventions and personalized treatment strategies.

Now let's talk about the clinical implications. Currently, patients who achieve a pathologic complete response often aren't considered for adjuvant therapies as the absence of visible disease is taken as a sign of remission. However, this study challenges that assumption. By integrating ctDNA testing into routine post-treatment surveillance, clinicians could identify high-risk patients who might benefit from additional therapy even when traditional imaging shows no signs of recurrence. This brings us to the bigger picture. Esophagogastric cancer treatment is evolving rapidly, with trials like CheckMate 577 and ESOPEC offering new insights into perioperative strategies. However, this study highlights a critical gap, the need for personalized, biomarker-driven approaches in the adjuvant setting. ctDNA could fill that gap, offering a non-invasive, dynamic way to monitor patients and guide clinical decisions.

Of course, no study is without its limitations. The authors acknowledge the relatively small sample size and the retrospective nature of their analysis. They also note the variability in ctDNA testing and imaging schedules across institutions. However, the robust association between ctDNA positivity and recurrence-free survival makes a compelling case for further research in larger prospective cohorts.

Looking ahead, what's the next step? The authors call for prospective validation of ctDNA as a prognostic tool, emphasizing its potential to refine risk stratification and optimize treatment strategies. Imagine a future where a simple blood test could dictate not only the need for additional therapies, but also the timing and type of intervention.

As we wrap up, let's reflect on the broader impact of the study. By integrating ctDNA into routine cancer care, we could move closer to a world where treatments are not just effective, but also precisely tailored to each patient's unique biology and disease dynamics.

Thank you for tuning into JCO Precision Oncology Article Insights. Don't forget to subscribe and join us next time as we explore more groundbreaking research shaping the future of oncology. Until then, stay informed and stay inspired.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.

Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

JCO PO Article Insights: ctDNA as a Prognostic Biomarker in EGC

JCO Precision Oncology Conversations