There's a growing recognition that the molecular profile of a primary tumor can differ significantly from its metastases. To guide treatment more accurately, the preferred practice is to biopsy an accessible metastatic lesion when possible, as this better reflects the biology of the active disease being treated.

To preserve treatment options, oncologists employ a tactical approach to re-testing. They avoid re-biopsying a tumor with a known positive biomarker to prevent a negative result from jeopardizing drug coverage. Conversely, they are more likely to re-biopsy a previously negative tumor at recurrence, hoping to find a new, actionable mutation.

Unlike invasive tissue biopsies that sample a single site, liquid blood biopsies provide a comprehensive, real-time snapshot of mutations across all metastatic sites. This is crucial for identifying acquired mutations and guiding timely treatment decisions.

Oncologists co-order tissue and liquid biopsies for new pancreatic cancer patients. This is crucial because tissue samples are insufficient for genomic testing in roughly 20% of cases, making the liquid biopsy an essential backup for treatment planning.

The standard of care for pancreatic cancer includes ordering both germline (inherited) and somatic (tumor-specific) genetic tests at the initial patient visit. This "point-of-care" approach is crucial for identifying targetable mutations early on.

While re-biopsying at disease progression is the "by-the-book" standard to confirm biomarkers like HER2, clinicians acknowledge it is often skipped. The difficulty of obtaining tissue and the desire to provide patients with potential treatment options create a gap between guidelines and clinical reality.

When an oncologist anticipates an initial sample (e.g., cytology) will likely have insufficient tissue for NGS testing, they proactively initiate a biopsy of a second site with interventional radiology. This parallel-path approach avoids waiting for the first test to fail, significantly reducing time to diagnosis and treatment.

A common clinical practice—biopsying the primary tumor to guide treatment for metastatic disease—is considered biologically flawed. Metastases can have vastly different molecular and immune profiles from the primary tumor and from each other. Experts advocate for re-biopsying metastatic sites when feasible to get a more accurate profile of the progressing disease.

Performing dual analysis with both liquid and tissue biopsies at metastatic diagnosis establishes a comprehensive baseline. This strategy helps differentiate between clonal and later-acquired mutations, enabling more accurate interpretation of subsequent ctDNA monitoring for resistance.