Experts find a positive circulating tumor DNA (ctDNA) test more useful for informing a decision to start adjuvant therapy. A negative result is considered less helpful and doesn't provide the same level of reassurance or definitively rule out treatment, as the pivotal clinical trial was designed to address the ctDNA-positive scenario.
Advanced diagnostic tools like the Signatera ctDNA test and certain approved therapies like adjuvant nivolumab are not available or reimbursed in many countries, including Italy. This access barrier renders many cutting-edge treatment strategy discussions from the US irrelevant for a large part of the global oncology community.
Experts caution against making definitive clinical decisions based on subgroup analyses, such as the apparent lack of benefit for upper tract disease in an adjuvant immunotherapy trial. These analyses are hypothesis-generating, and conflicting results between different endpoints (e.g., DFS vs. OS) demonstrate they can be misleading.
An expert would not offer just the adjuvant portion of the EV-Pembro regimen to a patient who went straight to surgery, even though the full perioperative (neoadjuvant + adjuvant) regimen is approved. This highlights a strict adherence to trial data, where the lack of specific evidence for a purely adjuvant application prevents off-label use.