Evaluation of post radiotherapy PSA as a prognostic and predictive biomarker in high risk prostate cancer: A secondary analysis of RTOG 0521.

384 Background: RTOG 0521 was a randomized trial of radiotherapy (RT) and 24 months of androgen deprivation (ADT) with and without docetaxel (D) in high risk prostate cancer. We sought to evaluate whether post RT PSA was prognostic of outcomes and predictive of the benefit of D. We hypothesized that patients with a higher post RT PSA derive a benefit from D while those with a lower post RT PSA would derive no benefit. Methods: Patients treated on RTOG 0521 received 72-75.6 Gy in 40-42 fractions 8 weeks after starting ADT. In the experimental arm, D was started 28 days after RT. Per protocol, a PSA was to be drawn within 28 days after completion of RT (PRT-PSA). Hazard ratios (HRs) for PRT-PSA (>/≤ median level) were estimated by Cox proportional hazards regression for overall survival (OS) and Fine-Gray competing risks regression for prostate specific mortality (PCSM) and distant metastasis (DM), adjusting for baseline characteristics. As a sensitivity analysis for non-proportional hazards, HRs were estimated with follow up censored at 10 years. Results: PRT-PSA was available in 276/563 patients (114/281 in ADT alone and 162/282 in the ADT+D arm). PRT-PSA was drawn at a median of 15 days from the completion of RT and 120 days from randomization. 25% of patients had a PRT-PSA >0.1 ng/L. Patients with PSA >0.1 ng/mL had worse OS (HR 2.39, 95% confidence interval [CI] 1.51-3.79), PCSM (HR 3.78, 95% CI 1.87-7.62), and DM (HR 3.54, 95% CI 1.99-6.31) (all p<0.001). Baseline characteristics including Gleason score, T-stage, pretreatment PSA, performance status, and age were similar between patients with a PRT-PSA >0.1 and ≤ 0.1 ng/mL. In patients with PRT-PSA >0.1 ng/mL, there was no benefit seen with the addition of D to ADT alone in terms of OS (HR 1.06, p=0.88), PCSM (HR 0.97, p=0.96), or DM (HR 1.16, p=0.75). In patients with PRT-PSA ≤0.1 ng/mL, there was a benefit from the addition of D to ADT alone in terms of OS (HR 0.55, p=0.03) and PCSM (HR 0.36, p=0.02) but no significant benefit in terms of DM (HR 0.74, p=0.40). Results were similar in the sensitivity analysis for patients with PRT-PSA >0.1 ng/mL (OS HR 1.36, p=0.42; PCSM HR 1.71, p=0.39) and patients with PRT-PSA ≤0.1 ng/mL (OS HR 0.41, p=0.003; PCSM HR 0.26, p=0.006). Conclusions: PRT-PSA was prognostic of OS, DMFS, and DM in patients with high risk prostate cancer treated with RT and long term ADT +/- D. Despite having a worse prognosis, patients with PRT-PSA >0.1 ng/mL did not benefit from the addition of D while those with PRT-PSA ≤ 0.1 ng/mL had an OS and PCSM benefit from D. Clinical trial information: NCT00288080 . PRT-PSA (ng/mL) ADT, event/total ADT+D, event/total Adjusted HR (95% CI) Adjusted HR (95% CI)-10 y OS ≤0.1 28/79 31/127 0.55 (0.32-0.95) 0.41 (0.23-0.73) >0.1 21/35 18/35 1.06 (0.51-2.19) 1.36 (0.64-2.88) PCSM ≤0.1 13/79 7/127 0.36 (0.15-0.87) 0.26 (0.10-0.67) >0.1 15/35 11/35 0.97 (0.29-3.21) 1.71 (0.51-5.70) DM ≤0.1 14/79 16/127 0.74 (0.37-1.50) 0.75 (0.37-1.50) >0.1 16/35 16/35 1.16 (0.47-2.85) 1.09 (0.43-2.75)

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