For on-treatment monitoring, a fixed absolute tumor volume increase (e.g., 50mL) on PSMA-PET is a superior marker of progression than a percentage-based change. Percentage metrics unfairly disadvantage patients with high-volume baseline disease, where a small relative change can represent massive, clinically significant growth.

Experts predict that emerging cell-free DNA (ctDNA) tests for lymphoma will shift treatment from fixed durations to a response-adapted approach. Monitoring minimal residual disease via ctDNA will allow clinicians to tailor the length of therapy based on the quality of response.

There is a growing suspicion that conventional imaging understages many presumed early-stage lobular cancers. Using FES PET-CT upfront could detect small-volume metastatic disease missed by other methods. This would reclassify patients to a metastatic setting, sparing them the morbidity of major local surgeries that would not be curative.

PSMA-PET imaging at baseline can identify who benefits from adding lutetium-PSMA. In the ENZA-P trial, patients with high-volume disease saw a significant survival benefit from the combination. Conversely, those with low-volume disease derived no benefit, suggesting imaging can be used for patient selection.

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 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.

Though EMBARK trial patients were negative on conventional imaging, an analysis suggests over 80% had PSMA PET-detectable disease. This reframes the landmark study, suggesting its findings may apply more to treating low-volume metastatic disease intermittently rather than purely biochemical recurrence.

When a patient becomes ctDNA positive during surveillance after completing adjuvant therapy, the optimal next step is not immediate systemic chemotherapy. Clinicians should instead initiate intensive imaging (e.g., CT, PET) to identify a potential radiographic recurrence, which may be isolated and resectable.