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Timing of Radiographic Progression Relative to Prostate-Specific Antigen Kinetics in Patients with Metastatic
Akinori Nakayama1, Erika Ikezoe1, Minoru Inoue1
1Department of Urology, Dokkyo Medical University Saitama Medical Center, 2-1-50 Minamikoshigaya, Koshigaya, Saitama 343- 8555, Japan.
Purpose:
Prostate-specific antigen (PSA) progression does not always coincide with radiographic progression in patients with metastatic castration-sensitive prostate cancer (mCSPC) receiving upfront androgen receptor signaling inhibitor (ARSI) therapy. We evaluated the timing of radiographic progression according to predefined PSA kinetic periods.
Materials And Methods:
We retrospectively reviewed 82 consecutive patients with synchronous mCSPC treated with upfront ARSI therapy between April 2018 and May 2024. The median follow-up duration was 23 months (interquartile range [IQR], 14-38). PSA kinetics were categorized into three predefined periods: pre-PSA nadir (treatment initiation to PSA nadir), post-PSA nadir/before PSA progression (PSA nadir to PSA progression), and post-PSA progression. Radiographic progression events were classified according to these PSA kinetic periods.
Results:
During follow-up, 33 patients (40%) experienced PSA progression and 26 (31.7%) developed radiographic progression. Among the 26 radiographic progression events, 1 (3.8%) occurred during the pre-PSA nadir period, 7 (26.9%) during the post-PSA nadir/before PSA progression period, and 18 (69.2%) during the post- PSA progression period. Overall, 25 of 26 radiographic progression events (96.2%; 95% confidence interval [CI]: 81.1%-99.3%) occurred after PSA nadir. The only patient who developed radiographic progression before PSA nadir was subsequently diagnosed with small-cell carcinoma of the prostate. PSA nadir levels and time to PSA nadir were comparable between patients who developed radiographic progression before and after PSA progression.
Conclusion:
Radiographic progression before PSA nadir was uncommon in this cohort, whereas a substantial proportion of progression events occurred after PSA nadir but before PSA progression. These findings suggest that PSA nadir may serve as a useful temporal reference point for radiographic surveillance during upfront ARSI therapy. However, these observations should be considered hypothesis-generating and require validation in larger prospective multicenter studies.