The impact of time to prostate specific antigen nadir on biochemical recurrence and mortality rates after radiation therapy for localized prostate cancer

PURPOSE: To investigate the effect of time to prostate-specific antigen (PSA) nadir (TTN) after radiation therapy (RTx) for prostate cancer (PCa) on biochemical recurrence (BCR) and overall survival (OS) rates.

PATIENTS AND METHODS: We analyzed 2,506 patients treated with RTx (external beam radiotherapy, brachytherapy or combinations) between years 2000 and 2021. Kaplan Meier and multivariable Cox regression models tested BCR-free survival and OS after stratification according to TTN (≤24 vs. 24.1-60 vs. >60 months). Similar analyses were performed after stratification according to absolute PSA values at nadir (<0.01 vs. 0.01-0.1 vs. 0.11-0.4 vs. >0.4 ng/ml). Finally, we repeated analyses after setting the time point of PSA nadir as the beginning of follow up in survival analyses.

RESULTS: 10-year BCR-free survival rates were 55.5, 81.7 and 91.1% and OS rates were 71.5, 79.4 and 96.1% for TTN ≤24 months, 24.1 month-60 month and >60 months, respectively. Longer TTN was an independent predictor for BCR-free survival and OS (all P<0.001). However, after accounting for lead-time bias, in multivariable analyses, this association remained only significant for BCR-free survival (P≤0.03), but not for OS (P≥0.1). Finally, compared to a PSA nadir of <0.01 ng/ml, PSA nadir of 0.01-0.1 ng/ml, 0.11-0.4 ng/ml as well as >0.4 ng/ml were independent predictors for shorter BCR-free survival (P≤0.02), but not OS (P≥0.08).

CONCLUSION: Shorter time to TTN and high PSA values at nadir are indicative of early treatment failure (BCR) and OS. However, after accounting for lead-time bias, this effect only remained valid for BCR.