Original article
PSA response to neoadjuvant androgen deprivation is an independent prognostic marker and may identify patients who benefit from treatment escalation

https://doi.org/10.1016/j.urolonc.2013.10.019Get rights and content

Abstract

Purpose

To determine whether pPSA, defined as the prostate-specific antigen (PSA) measurement after initiation of androgen deprivation therapy (ADT) but prior to the start of radiotherapy (RT), is an independent predictor of biochemical relapse-free survival (bRFS). We also sought to determine the effect, if any, of factors affecting bRFS for patients who did not achieve pPSA<0.5 ng/mL.

Methods and materials

A total of 105 patients with National Comprehensive Cancer Network intermediate- or high-risk prostate cancer treated with neoadjuvant ADT (median = 3.9 mo) and external beam RT had pPSA data available and met the inclusion criteria. Pretreatment and treatment characteristics were included in a Cox proportional hazards model to determine effect on bRFS.

Results

Median follow-up was 5.4 years. On multivariable analysis, pPSA≥0.5 ng/mL was associated with worsened bRFS (hazard ratio [HR] = 2.7, P = 0.013). For the subgroup of patients with at most 1 high-risk factor, pPSA remained a statistically significant prognostic factor. For patients within this subgroup who had pPSA≥0.5 ng/mL, the addition of pelvic RT was associated with a trend toward improved outcome (HR = 0.609, P = 0.083).

Conclusion

For patients with intermediate- or high-risk prostate cancer receiving neoadjuvant ADT, achieving pPSA<0.5 ng/mL was associated with improved rates of bRFS. Additionally, pPSA measurement may identify patients who may be able to benefit from escalated treatment such as pelvic RT.

Introduction

The addition of neoadjuvant androgen deprivation therapy (ADT) to radiotherapy (RT) has been shown to improve rates of biochemical control and biochemical relapse-free survival (bRFS) compared with RT alone for patients with intermediate- or high-risk features [1]. However, neoadjuvant ADT does not appear to improve outcome when combined with radical prostatectomy [2], indicating a unique interaction between ADT and RT. Current theories regarding the mechanism of this interaction include inhibiting the antiapoptotic effects of testosterone and increased T cell-mediated immune response [3].

Given this unique relationship between ADT and RT, the prostate-specific antigen (PSA) response to induction phase of ADT has been suggested as a possible prognostic indicator. Retrospective studies indicate that patients who exhibit a more profound PSA response as a result of ADT experience improved biochemical and clinical outcomes [4], [5], [6], [7]. Most recently, McGuire et al. [4] have put forth that the pPSA, defined as the post-ADT, pre-RT PSA, is an independent predictor of bRFS for patients with high-risk disease, with pPSA<0.5 ng/mL being associated with improved bRFS.

In this study, we sought to confirm the role of pPSA, particularly pPSA<0.5 ng/mL, as a prognostic indicator in a group of intermediate- and high-risk patients treated with a variety of modern RT techniques, including hypofractionation. We also sought to determine which factors affected bRFS for patients not reaching the pPSA<0.5 ng/mL threshold.

Section snippets

Inclusion criteria

The records of every patient receiving external beam RT for clinically localized prostate cancer at UAB since 1999 were reviewed. All patients meeting the following criteria were included in the analysis: biopsy-proven National Comprehensive Cancer Network intermediate- or high-risk prostate cancer (T category of 2b or greater, PSA>10 ng/mL, or Gleason≥7) [8], clinically localized disease, no previous treatment before ADT, definitive external beam RT, and a recorded PSA value at least 30 days

Pretreatment and treatment characteristics

A total of 741 charts were reviewed with 105 patients meeting the inclusion criteria. The median age was 66.8 years at the start of RT. Median follow-up was 5.4 years, calculated from the initiation of ADT. All patients were found to be free of metastatic disease; 71 (68%) were classified as high risk and 34 (32%) as intermediate risk. The median length of neoadjuvant ADT was 3.9 months and the median total length of ADT was 24 months. All but 4 patients received at least 2 months of

Discussion

Based on the results of multiple prospective trials, neoadjuvant ADT is commonly added to dose-escalated external beam RT for patients with both intermediate- and high-risk prostate cancer. Despite the widespread use of neoadjuvant ADT, no consensus has been reached regarding measurement of the PSA response during the induction phase. PSA response to ADT has recently been reported as a predictor of long-term outcome in a group of high-risk patients treated with dose-escalated external beam RT,

Conclusion

For patients with intermediate or high-risk prostate cancer receiving neoadjuvant ADT, achieving pPSA<0.5 ng/mL is associated with improved rates of bRFS. For patients receiving neoadjuvant ADT, pPSA appears to be a stronger predictor of outcome than initial PSA. Additionally, pPSA measurement may be useful in identifying patients who may be able to benefit from escalated therapy, though this should be confirmed by prospective research.

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