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.

The effectiveness of radioligand therapy is counterintuitive: as tumors shrink and PSMA binding sites decrease, less radiation is delivered to the cancer. The VISION trial showed the first two doses delivered more radiation to the tumor than the subsequent four, questioning the value of a fixed, prolonged treatment schedule.

Unlike traditional chemotherapy, radioligand therapy's toxicity may be inversely correlated with tumor volume. In low-burden disease, fewer cancer cells act as a 'sink' for the drug, potentially leading to higher radiation exposure and side effects in healthy, PSMA-expressing tissues like salivary glands.

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.

An innovative strategy for solid tumors involves using bispecific T-cell engagers to target the tumor stroma—the protective fibrotic tissue surrounding the tumor. This novel approach aims to first eliminate this physical barrier, making the cancer cells themselves more vulnerable to subsequent immune attack.

A practical method to monitor radioligand therapy is a post-treatment SPECT scan. Since the therapeutic agent is radioactive, a simple planar scan about 24 hours after injection can visually confirm where the drug was delivered. This provides real-time feedback, beyond PSA levels, to potentially adapt treatment.

The Rampart study's use of the Leibovic score for risk stratification is a key strength. Unlike traditional TNM staging, this score more heavily weights tumor grade, which clinicians find to be a more granular and clinically relevant predictor of recurrence risk than just tumor size.

The intensity and volume of FET PET activity serve as a powerful prognostic marker in glioma patients. Even when imaging suggests treatment-related changes rather than active tumor, elevated PET signals still correlate with a worse overall outcome, providing an additional layer of risk stratification.

Regularly scheduled FET PET scans over extended periods help clinicians confidently monitor fluctuating lesions. This longitudinal data provides the reassurance needed to be patient and avoid prematurely escalating treatment for what may ultimately prove to be benign, treatment-related changes.