How do you integrate MRD results (positive, negative, or dynamic changes over time) into your clinical decision-making?

Dr. Espinosa: It’s highly dependent on the tumor type, with colon cancer having the most validated data. A negative MRD result is reassuring, but I always correlate it with clinical and imaging findings. A positive result prompts me to monitor more closely and  often  repeat testing to observe trends. A consistent rise in MRD levels often leads me to consider earlier therapeutic intervention or clinical trial enrollment, even before radiological progression. I emphasize to patients that MRD is an evolving technology but a growing asset in our surveillance toolkit.

How do you communicate MRD results to your patients, and are they becoming more aware of this testing?

Dr. Espinosa: Some patients are becoming aware, especially through community outreach or advocacy. When explaining results, I stress that MRD testing is promising but still being validated across different cancers. I present it as a tool alongside imaging and clinical judgment. For negative results, I explain it’s reassuring but not a definitive guarantee. For positive results, I indicate the potential presence of microscopic disease and discuss next steps, often involving repeat testing to confirm trends before significant treatment changes.

Can you share an example of how IO treatment response monitoring has influenced your management decisions?

Dr. Espinosa: I’ve primarily used it to pause treatments. For example, in several stage IV lung cancer patients on checkpoint inhibitors for nearly two years who developed toxicities—liver issues, kidney problems, or significant skin toxicities like pruritus. When the IO treatment response monitoring shows a negative result, I feel much more confident pausing therapy, knowing molecularly the disease appears controlled. In melanoma, if I see a rising trend in ctDNA after two to three tests, even without clear radiologic progression, I start thinking about switching therapy—especially in BRAF-positive patients where we have options like MAP kinase inhibitors.

How do you interpret discordant results where imaging suggests progression but ctDNA is decreasing?

Dr. Espinosa: This is where treatment response monitoring is invaluable. Pseudoprogression is a known phenomenon with immunotherapy. If imaging shows worsening but the patient feels clinically well and ctDNA is decreasing, I use that as evidence to reassure patients that it’s likely pseudoprogression, not true progression. I explain that ctDNA has a very short half-life—about two hours—so it’s a more immediate and reliable marker than imaging alone, which can show inflammation rather than tumor growth.

What is your typical cadence for ordering IO treatment response monitoring and how often are you testing?

Dr. Espinosa: I align it with treatment cycles. Depending on whether I’m using a four-week or six-week checkpoint inhibitor schedule, I order the ctDNA test with labs about two days before treatment. Sometimes results are back in time for the visit, and that real-time feedback is very reassuring for both me and the patient.

What has your experience been with the Tempus IO TRM offering, particularly regarding scheduling, logistics and turnaround time?

Dr. Espinosa: It’s been excellent. Once the tumor signature is established, subsequent turnaround times are excellent, typically under a week. The ability to access results through the Tempus app on my phone is incredibly convenient — I can pull up results live during a patient visit and have the discussion immediately.

In your experience, how has IO treatment response monitoring impacted your ability to predict long-term outcomes, like relapse-free survival or overall survival?

Dr. Espinosa: It’s still early for me personally to assess long-term survival outcomes. However, what I have consistently observed is that ctDNA trends are predictive of early progression. If the ctDNA starts rising consistently over two or three measurements, it usually precedes clinical or radiographic progression. So it’s been very helpful for earlier intervention decisions, even if I don’t yet have mature survival data in my own patient cohort.

How do you envision the role of MRD evolving in the next few years?

Dr. Espinosa: I believe it will fundamentally reshape oncology practice. For cancers that reliably shed ctDNA, MRD will likely enable more precise treatment tailoring, potentially reducing overtreatment in the adjuvant setting and allowing for earlier intensification of therapy for low-volume disease. I anticipate it following a similar trajectory to Oncotype DX in breast cancer, where validated biomarkers guide treatment de-escalation. I’m optimistic that within 3-5 years, MRD will be integrated into standard guidelines for cancers like colon, melanoma, and lung.

What is the most critical investment you’d like to see for MRD and IO TRM testing in the next five years?

Dr. Espinosa: For MRD, the priority is validation, validation, validation across all tumor types, with robust data on endpoints like progression-free and overall survival. For IO TRM, the focus should be on integration into standard clinical practice and payer acceptance, making it a routine tool to reduce over-reliance on imaging alone.