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 advent of highly sensitive PSMA PET imaging identifies metastases in many patients previously considered to have only biochemical relapse (BCR). However, experts argue against a knee-jerk reaction to treat. Many of these patients, particularly those with slow PSA doubling times, can be safely observed, challenging the assumption that visible disease always requires immediate intervention.

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.

The NCI working group asserts that PSA doubling time, especially a rate under six months, remains the key indicator of high-risk biochemically recurrent (BCR) prostate cancer. This biological marker of aggressiveness is considered more prognostically significant than the presence of lesions on a highly sensitive PSMA PET scan.

An NCI working group coined "PSMA positive BCR" to classify patients with biochemical relapse (BCR) who have findings on a modern PSMA PET scan. This formally recognizes this group is distinct from both conventionally-defined metastatic patients and traditional BCR patients, necessitating unique clinical trial designs and treatment strategies.

For patients with conventionally negative imaging but positive PSMA PET scans (oligometastatic disease), continuous intensified therapy may be overtreatment. A new paradigm involves metastasis-directed therapy followed by a short course of escalated treatment, then stopping to observe. This "time-limited" approach balances efficacy with reducing long-term treatment burden.

The NCI Working Group argues against equating PSMA PET-positive biochemically recurrent (BCR) prostate cancer with traditional metastatic disease. They propose the term "PSMA positive BCR" to emphasize that traditional prognostic factors still apply and the natural history is distinct and often more indolent.

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.

For biochemically recurrent (BCR) prostate cancer, which is often indolent, trials should not wait years to study treatment reduction. The NCI group universally agreed that de-escalation strategies—such as intermittent therapy—should be the default design from the outset, prioritizing quality of life and avoiding overtreatment.