PSA Dynamics, Bounce, and Biochemical Recurrence Definitions After Low-Dose-Rate Brachytherapy for Prostate Cancer: A Narrative Review with Cross-Modality Comparison

Background: Prostate-specific antigen (PSA) dynamics provide the earliest indicator of treatment outcome. Understanding them, including nadir kinetics and PSA bounce, is essential for refining biochemical recurrence (BCR) definitions and guiding clinical decision making. Methods: A literature search was conducted across the PubMed, Scopus, and Web of Science databases. Backward citation chaining of selected references resulted in a final synthesis of 143 studies. Iodine-125 constitutes the primary radioisotope across the reviewed literature. Key Findings: Following low-dose-rate brachytherapy (LDR-BT), a PSA nadir < 0.2 ng/mL is strongly associated with long-term biochemical control. PSA bounce (defined as a rise ≥ 0.2 ng/mL above the current nadir with spontaneous resolution) occurs in approximately 30% to 50% of LDR-BT cohorts, with a median onset of approximately 1.5 years, a median duration of approximately 1 year, and a median amplitude < 1 ng/mL. Up to 18% of bounces exceed 2.0 ng/mL, accounting for nearly half of all early rises triggering the Phoenix criteria. Superior dosimetric parameters are associated with longer time to nadir and lower nadir values. Within LDR-BT cohorts, younger patient age is the most consistent predictor of bounce incidence, whereas between-study variation is primarily driven by differences in treatment modality. LDR-BT and hypofractionated regimens report higher bounce rates than those for conventional external beam radiotherapy, although unadjusted comparisons are confounded. Onset timing is the most useful feature distinguishing between bounce and BCR. Conclusions: Static, single cutoff BCR definitions post-LDR-BT may be suboptimal for surveillance. This observational synthesis suggests a hypothesis-generating, time-windowed approach (Phoenix definition during early follow-up (< 4 years) and an absolute threshold of PSA > 0.2 ng/mL thereafter) that requires prospective validation and is not a recommendation for clinical use.