A prostate-specific antigen doubling time of &lt;6 months is prognostic for metastasis and prostate cancer-specific death for patients receiving salvage radiation therapy post radical prostatectomy

Corey Foster,Yeohan Song,Skyler B Johnson,Daniel A Hamstra,Howard M Sandler,Todd M Morgan,Benjamin Foster,Darren Li,Felix Y Feng,Ganesh S Palapattu,Mark Shilkrut,William C Jackson,Matthew Schipper

doi:10.1186/1748-717x-8-170

Abstract

BackgroundThe ideal prostate-specific antigen (PSA) doubling time (PSADT) threshold for identifying patients at high-risk for poor clinical outcome following salvage radiation therapy (SRT) has not been well established. We sought to assess what PSADT threshold is most clinically prognostic in this setting.Methods575 patients who received SRT at a single institution for biochemical recurrence after radical prostatectomy were retrospectively reviewed. We assessed the impact of pre-SRT PSADT on biochemical failure (BF), distant metastasis (DM), prostate cancer-specific mortality (PCSM), and overall mortality (OM). Kaplan-Meier methods, hazard ratio (HR) assessment, and Cox Proportional Hazard models were used to assess the discriminatory ability of various PSADT thresholds.ResultsSufficient data to calculate PSADTs were available for 277 patients. PSADT was prognostic for BF, DM, PCSM, and OM on univariate analysis regardless of threshold. HR assessment identified 6 months as a strong threshold. No statistically significant difference was observed in BF, DM, PCSM, or OM between patients with PSADT <3 (n=40) and 3–6 months (n=61) or between 6–10 (n=62) and >10 months (n=114). However significant differences were seen in BF (HR:2.2, [95%CI: 1.4-3.5], p<0.01) and DM (HR:2.2, [95%CI: 1.2-4.3], p=0.02) between a PSADT of 3–6 and 6–10 months. On multivariate analysis a PSADT <6 months predicted BF (HR:2.0, [95%CI: 1.4-2.9], p=0.0001), DM (HR:2.0, [95%CI: 1.2-3.4], p=0.01), and PCSM (HR:2.6, [95%CI: 1.1-5.9], p=0.02).ConclusionsA pre-SRT PSADT <6 months was a strong predictor of outcomes in our data set, including PCSM. The most common nomogram for SRT uses a 10-month PSADT threshold for assigning points used to assess BF following SRT. If validated, our findings suggest that a PSADT threshold of <6 months should be considered for stratification of patients in future clinical trials in this setting.

Highlights

The ideal prostate-specific antigen (PSA) doubling time (PSADT) threshold for identifying patients at high-risk for poor clinical outcome following salvage radiation therapy (SRT) has not been well established
Conclude that PSA doubling time (PSADT) alone is not sufficient to identify patients most likely to benefit from SRT in regard to all clinical end-points; it does identify those at the greatest risk for prostate cancer-specific mortality (PCSM) who may have the most to gain if there is no evidence of metastatic disease
A PSADT

Summary

Introduction

The ideal prostate-specific antigen (PSA) doubling time (PSADT) threshold for identifying patients at high-risk for poor clinical outcome following salvage radiation therapy (SRT) has not been well established. Up to 30% of these patients will eventually experience biochemical failure (BF) as manifested by a rising prostatespecific antigen (PSA) [2]. A rising PSA after RP can be indicative of local recurrence, distant disease, or both. Many patients who experience BF post-RP will go on to receive salvage external beam radiation therapy (SRT). It is likely that many of the patients who experience biochemical failure (BF) after SRT represent a subset of patients who harbor micrometastatic disease at the time of SRT.

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Discussion

Conclusion