The patient population in pivotal trials like EMBARK, defined as non-metastatic by conventional imaging, is being re-evaluated. A UCLA study showed that over 80% of a similar patient group would have been positive on a PSMA PET scan, suggesting the "M0" classification is largely an artifact of older imaging technology and that these patients likely have micrometastatic disease.

In cases of suspected glioma recurrence post-radiation, FET PET imaging can provide a more accurate diagnosis than MRI perfusion, even when MRI findings suggest tumor growth. This allows clinicians to avoid unnecessary changes in therapy based on potentially misleading MRI data.

Unlike cancers that form distinct masses, invasive lobular carcinoma (ILC) grows in a 'single file' or 'creepy crawly' pattern. This subtle infiltration is extremely difficult to detect with standard imaging like mammograms, ultrasounds, MRIs, and even FDG PET-CT, often leading to underestimation of the disease's extent.

FES PET-CT relies on a tracer binding to estrogen receptors. If a patient is on ER modulators or down-regulators (like tamoxifen or fulvestrant), these drugs will block the tracer, causing a false-negative scan. Clinicians must plan for a washout period of several weeks before imaging, which requires careful treatment coordination.

While powerful, FES PET-CT is a specialized tool with key limitations. It is not effective for evaluating disease in the liver, a common site of breast cancer metastasis. Furthermore, it cannot detect any disease that has become estrogen receptor-negative. Therefore, it must be used as part of a broader imaging program, not as a standalone surveillance tool.

NCCN now recommends PSMA PET as a potential replacement for traditional CT, MRI, and bone scans for initial staging of higher-risk prostate cancer and detecting recurrence. This shift is based on PSMA PET's superior sensitivity and specificity for finding micrometastatic disease, positioning it as a more effective frontline tool.

The processing of bone biopsy samples can sometimes result in a false-negative finding for estrogen receptor (ER) status. If clinical suspicion remains high for ER-positive disease, an FES PET-CT can be used as a tiebreaker. A positive FES scan can confirm functional ER presence, overriding the biopsy and drastically altering patient care.

A biopsy can confirm ER-positive tissue, but FES PET-CT demonstrates that these receptors are functional and capable of binding. This distinction is critical, as some tumors may have non-functional receptors or heterogeneous expression. A positive FES scan provides strong evidence that a patient is a good candidate for endocrine therapy.

The introduction of highly sensitive PSMA PET scans means established endpoints like Metastasis-Free Survival (MFS) may no longer be valid. A metastasis detected by PET likely has a different, better prognosis than one found with older imaging, requiring new validation for this key endpoint.