ctDNA Shaping Real-World Practice — The IMvigor011 Trial

  • Top clinicians weigh in on ctDNA-guided decision-making in bladder cancer.

    • Dr. Jorge Garcia, a medical oncologist who specializes in bladder cancer at University Hospitals Seidman Cancer Center, says IMvigor011 provides compelling evidence that ctDNA can identify which bladder cancer patients truly benefit from adjuvant therapy — and which may safely avoid it, helping reduce over-treatment while intensifying care for those at highest risk.

    • Dr. Gary Steinberg, a leading clinical researcher and urologist at Rush Cancer Center, adds that ctDNA is a more sensitive tool than traditional imaging and represents a turning point toward personalized care — enabling clinicians to better monitor disease and thoughtfully escalate or de-escalate therapy.

In what many describe as a watershed moment for bladder cancer care, leading clinicians from across the country are increasingly incorporating circulating tumor DNA (ctDNA) testing in their practice as a way of determining whether patients need additional therapy.

“The bulk of biomarkers that we have in bladder cancer tend to be prognostic,” says Dr. Jorge Garcia, a medical oncologist who specializes in bladder cancer and serves as the Division Chief of Solid Tumor Oncology at University Hospitals Seidman Cancer Center. “With circulating tumor DNA, we’re taking it to a different level.”

Dr. Garcia points to the phase 3 IMvigor011 trial — in which investigators regularly tested patients for ctDNA after surgery — as compelling evidence showing that ctDNA can identify who truly benefits from adjuvant therapy and who may safely avoid it.

The investigators behind the IMvigor011 trial had those who were ctDNA-negative undergo observation, while ctDNA-positive patients were randomized to receive atezolizumab or placebo. The results showed that patients with detectable ctDNA derived significant benefit from adjuvant immunotherapy, with improvements in both disease-free and overall survival. In contrast, patients who remained ctDNA-negative had excellent outcomes with observation alone — suggesting some may safely avoid additional treatment.

 IMvigor011 Trial Summarized

  • 761 total patients enrolled

  • 250 ctDNA-positive patients randomized

    • 167 → Atezolizumab

    • 83 → Placebo

  • 357 patients remained ctDNA-negative and were monitored

  • Median DFS:

    • 9.9 months with atezolizumab

    • 4.8 months with placebo

While incorporation into prospective trials is ongoing, ctDNA is increasingly being used to guide real-world decision-making — not as a binary test, but as part of a broader clinical conversation.

“What we found out is that patients who had circulating tumor DNA detectable in their plasma had the best benefit from that therapy demonstrating that people who may not have circulating tumor DNA may not need additional therapy,” Dr. Garcia says. “Maybe we are over-treating some of them while some patients who have detectable circulating tumor DNA, may in fact, require additional therapy for us to be able to achieve that goal of cure or complete responses.”


WATCH: DR. GARY STEINBERG ON THE TOP 3 ADVANCES IN BLADDER CANCER CARE

Dr. Gary Steinberg, a leading clinical researcher and urologist at Rush Cancer Center, agrees that ctDNA represents a meaningful step forward and a turning point in bladder cancer.

“This is a very powerful tool that’s much more sensitive and specific than imaging, such as CT scans, PET scans, MRI scans and so forth,” Dr. Steinberg says.

Ultimately, he says, this approach supports a broader shift toward more tailored care. “It’s a real move forward to help us monitor patients and to escalate or de-escalate therapy,” Steinberg adds, emphasizing that avoiding unnecessary treatment matters. “There’s always some side effect and toxicity from any therapy that we use.”