Drs. Koshkin, Basu on Clinical Practice Patterns for Adjuvant Therapy of ctDNA-Positive MIBC

Vadim Koshkin, MD, University of California, San Francisco, and Arnab Basu, MD, MPH, FACP, University of Alabama at Birmingham, comment on the best available treatment approach for patients with ctDNA-positive MIBC after surgery.

Dr. Koshkin: I’ll conclude with a final question regarding your current clinical practice patterns. We’ve discussed trial data, ongoing trials, and future trials that you and others are planning. However, considering the available data, let’s say you have a patient with muscle invasive disease who underwent surgery and subsequently tested positive for ctDNA. Based on what you’ve mentioned, it seems you would recommend treatment for such patients. What treatment options would you consider? It’s worth noting that atezolizumab is not approved in the US or elsewhere, and the data from IMvigor010 primarily focused on atezolizumab. Nivolumab is approved, and adjuvant chemotherapy could also be considered for patients who haven’t received it previously.

Dr. Basu: That’s correct.

Dr. Koshkin: What is your typical approach? Do you have a preferred option, or is it a patient-centered decision? How do you handle this situation?

Dr. Basu: Certainly, we need to keep in mind that the data we have is from a pre-planned exploratory analysis. However, it serves as a strong hypothesis generator. When it comes to MRD, the test is designed to have extremely high specificity, and across different disease types, specificity has never been below 97%. In my personal opinion, this level of specificity is comparable to identifying small records on a radiologic scan. Therefore, in my practice, a positive MRD test is equivalent to having a record. This perspective is supported by both the exploratory data and the scientific principles behind the development of the test.

I strongly recommend adjuvant treatment for these patients. If the patient hasn’t undergone neoadjuvant chemotherapy, the decision is relatively straightforward. If the patient is eligible for chemotherapy, I will offer it as an option.

Dr. Koshkin: It’s a personalized approach.

Dr. Basu: Exactly. We will have a discussion, of course. If the patient is open to all options, that’s my go-to strategy. For other patients, I try to offer nivolumab since it has demonstrated improved progression-free survival in all high-risk patients in the adjuvant setting, and it has received approval.

The question sometimes arises regarding MRD-negative patients in the adjuvant setting. Personally, I believe we have reached a point where we don’t need to establish non-inferiority because the test’s sensitivity in the adjuvant setting appears to be exceptionally high. This understanding is further reinforced by accumulating evidence. I feel comfortable advocating for a surveillance approach in that setting. As we gather more real-world data, we will be able to strengthen and support this approach further.

View their other comments on MRD, ctDNA, and Liquid Biomarker Use in Bladder Cancer as well as ctDNA and MRD Considerations for Adjuvant Therapy After Radical Cystectomy.