Time for PHOENIX to rest in the ashes: Prostate-specific membrane antigen positron emission tomography guided reassessment of biochemical recurrence after radiotherapy

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For nearly two decades, the Phoenix criteria (a rise of 2ng/mL above the nadir PSA following radiotherapy) have served as the universal standard for defining recurrence in prostate cancer (PCa) patients after definitive treatment with radiotherapy. However, the advent of prostate-specific membrane antigen positron emission tomography (PSMA-PET) has redefined the diagnostic landscape, challenging the adequacy of PSA-only thresholds and enabling earlier and more price detection of disease relapse. This review evaluates the literature regarding PSMA-PET positivity across PSA levels—including those below the Phoenix criteria threshold—and correlates them with diagnoses of biochemical recurrence (BCR) in men with PCa treated with radiotherapy, aiming to challenge the framework for defining PCa recurrence in this population. We conducted a narrative review of recent prospective trials, cohort studies, and systematic reviews/meta-analyses assessing PSMA-PET-guided detection of BCR, summarising reported detection rates across PSA strata and key effect estimates from the existing literature. Detection rates were evaluated according to PSA levels, risk stratification systems, and guideline recommendations. The eleven studies reviewed revealed that PSMA PET had significant relapse detection rates at multiple PSA strata below the Phoenix threshold, with detection rates of 54% (PSA 0.2–0.49 ng/mL), 80% (PSA 0.5–0.99 ng/mL), and 88% (PSA 1–1.99 ng/mL), and pooled rates reaching 99% at PSA 2–5 ng/mL. A review of the latest international guidelines demonstrated widespread endorsement of routine PSMA-PET use in the diagnostic pathway of men with BCR following radiotherapy, underscoring its value for earlier disease relapse detection, precise localisation, and expedient intervention. Post-radiotherapy, the Phoenix definition for BCR appears increasingly misaligned with contemporary clinical practice, given that up to 90% of men show PSMA-PET evidence of recurrence before reaching its PSA threshold of 2 ng/mL. Furthermore, PSMA-PET has undoubtedly improved the detection, management, and therapeutic outcomes of men with biochemical relapse subsequent to radiotherapy. Our findings support a shift toward recurrence definitions that integrate PSA kinetics with PSMA-PET as precise and timely tool to diagnose disease relapse and improve prostate cancer care following radiotherapy. Simple Summary: Biochemical recurrence after radiotherapy remains a critical challenge in prostate cancer management, with current definitions relying on PSA thresholds stipulated by the Phoenix criteria that may not accurately reflect true disease recurrence. This review investigates the increasing role of contemporary PSMA-PET/CT in redefining the investigation of men with biochemical relapse after radiotherapy. By conducting a comprehensive review of recent literature, the authors assess the diagnostic performance of PSMA-PET compared to the historic threshold stipulated by the Phoenix criteria. The aim is to determine whether PSMA-PET can provide earlier and more precise identification of recurrence, potentially improving patient selection for subsequent . These findings may support a paradigm shift in how recurrence is defined and managed for men with prostate cancer treated with radiotherapy.

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