Post-testosterone recovery PSA slope tracked progression but not metastatic risk

KEY POINTS

• Individual patient data were pooled from two randomized trials, including 461 men with non-metastatic prostate cancer treated with definitive RT plus ADT who recovered testosterone to >50 ng/dL and had at least two PSA measurements within 18 months of recovery. The cohort contributed 1,594 PSA measurements, with median follow-up of 115 months.
• The trials represented different risk groups and ADT durations. One used 6 months of ADT, while the higher-risk trial used 36 months of ADT. PSA kinetics were modeled only after testosterone had recovered above the castrate range.
• For progression-free survival, faster PSA rise was directionally associated with higher risk. Relative to stable PSA, a PSA doubling time of 6 months corresponded to HR 1.20, 12 months to HR 1.10, and 36 months to HR 1.03.
• The primary metastasis-free survival analysis moved in the opposite direction, with PSADT of 6 months corresponding to HR 0.63 and 12 months to HR 0.80. The authors explicitly caution that this should not be interpreted as a protective effect of faster PSA rise.
• When deaths were censored, the direction became more clinically intuitive. For progression, PSADT of 6 months gave HR 1.61 and 12 months HR 1.27, with a 96.3% posterior probability that faster PSA rise increased progression risk.
• For distant metastasis alone, however, only 32 events occurred. PSADT of 6 months yielded HR 1.28 and 12 months HR 1.13, with very wide credible intervals, leaving substantial uncertainty around any association with metastatic risk.
• Cumulative PSA exposure added little prognostic information. PSA AUC showed no clinically meaningful association with either progression-free or metastasis-free survival, suggesting that the rate of PSA change may be more informative than cumulative PSA burden after testosterone recovery.

CLINICAL TAKEAWAY

SOURCE

International Journal of Radiation Oncology, Biology, Physics