[Antiplatelet therapy can unmask an inherited bleeding disorder. Aspirin-like defect of platelets does not protect against atherosclerosis].

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.