Standard guidelines for treating metastatic prostate cancer are based on conventional imaging (CT/bone scan). The panel argues that PSMA PET-positive biochemical recurrence represents a different, earlier disease state. This necessitates new treatment paradigms, like definitive therapy durations, not covered by current guidelines.

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.

The PSMAaddition trial's inclusion criterion of just one PSMA-avid lesion is criticized as biologically arbitrary. A patient could qualify for systemic therapy while having 90% of their tumor volume not expressing the target. This highlights a critical need for more sophisticated biomarkers to truly identify patients who will benefit from targeted radioligand therapy.

While PSMA PET scans are more sensitive, they create a clinical dilemma because pivotal trials defining treatment efficacy were based on conventional imaging (CT/bone scans). This forces oncologists to either re-image patients with older technology to match trial criteria or make treatment decisions based on PET data that lacks a clear evidence-based framework for response assessment.

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 Pluvicto (lutetium) is approved for six cycles, clinicians are retreating relapsed patients who previously responded well. This common practice occurs in a "data-free zone," driven by the lack of better options and the logic that a previously effective drug may work again in a patient selected for prior response.

Clinicians are viewing PSMA PET scans as a quantitative tool, not just a binary test. Patients with very "bright" scans (high SUV, e.g., >10) may be the ideal candidates for Lutetium-PSMA radioligand therapy, suggesting avidity predicts the magnitude of benefit.

While ideally a PSMA PET scan would be used early in biochemical relapse, practical limitations like long wait times force a pragmatic approach. Clinicians delay scans until PSA levels are higher (e.g., >0.5) to increase the probability of a positive, actionable result, thereby conserving limited "PET slots" for patients where the scan will most likely change management.

An expert expressed disappointment with Lutetium's efficacy in the metastatic hormone-sensitive setting, suggesting its benefit is lower than expected. A potential flaw in trial design was starting hormonal agents first, which can lower PSMA expression, thereby potentially reducing the radioligand's target and diminishing its therapeutic effect.