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.

For patients with biochemically recurrent prostate cancer, the decision to treat hinges on PSA doubling time. A doubling time of over two years carries a low risk of metastasis, often warranting observation. Conversely, a doubling time under three months indicates a high risk of metastasis within three years, necessitating intervention.

A PSA doubling time of less than three months acts as a surrogate marker for death from prostate cancer. This powerful heuristic doesn't predict exact lifespan, but it signifies that the cancer's mortality risk has surpassed all other potential causes of death for that individual, signaling extreme high risk.

The standard practice of using rising PSA to trigger early salvage radiotherapy after surgery is complicated by the PROTEUS protocol's neoadjuvant hormone therapy. This approach muddies the interpretation of biochemical recurrence, making it difficult for clinicians to know when or if to intervene with salvage treatment, potentially leading to worse outcomes.

The advent of highly sensitive PSMA PET imaging is changing the management of biochemically recurrent prostate cancer. Rather than relying on fixed PSA thresholds from older trials like EMBARK to restart therapy, clinicians now use PET imaging at lower PSA levels to guide decisions, aiming to extend treatment-free intervals.

When PSA levels rise after initial treatments, patients face the difficult realization that their cancer is likely a chronic condition to be managed, not a disease to be cured. This existential moment requires a fundamental shift in their approach and expectations for the rest of their lives.

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.

Landmark clinical trials (CONDOR, SPOTlight) demonstrate that PSMA PET imaging effectively identifies recurrent prostate cancer in a high percentage of patients even with very low PSA levels. This challenges the traditional paradigm of waiting for higher PSA thresholds before imaging, enabling earlier and more precise intervention.

For high-risk biochemically recurrent prostate cancer, intermittent androgen deprivation therapy (ADT) is the standard of care, not continuous therapy. This approach significantly improves quality of life, bone health, and metabolic health while effectively delaying progression to metastatic disease for years. Continuous therapy is vehemently discouraged in this setting.