Persistent prostate-specific antigen expression after neoadjuvant androgen depletion: an early predictor of relapse or incomplete androgen suppression

Urology. 2006 Oct;68(4):834-9. doi: 10.1016/j.urology.2006.04.016.


Objectives: To analyze post-androgen depletion (AD) primary tumors to identify markers of treatment failure because AD does not reduce the probability of prostate-specific antigen (PSA) failure after prostatectomy.

Methods: Tumors removed by radical prostatectomy after 3 months of AD from 21 patients were analyzed for gene expression using oligonucleotide arrays. Differences between patients with and without relapse were identified using a conservative significance criteria of a threefold change and delta 0.68, ensuring a false discovery rate of less than 11%.

Results: At 50 months of follow-up, 7 of the 18 evaluable patients developed a biochemical recurrence. Gleason grade, pretherapy PSA level, T stage, and margin status were similar between the two groups. Patients with recurrence had greater post-AD PSA levels than those without recurrence (0.87 versus 0.19 ng/mL; P = 0.042). Gene expression analysis revealed 35 probe sets overexpressed in tumors from patients who relapsed. Among the highest ranked probe sets were PSA and other androgen-responsive genes. Serum PSA values during AD revealed similar findings. After 40 days of AD, the PSA level in those without recurrence was 1.21 ng/mL versus 4.5 ng/mL in those with recurrence (P = 0.0034). Immunohistochemistry of post-AD tumors also demonstrated a high PSA staining intensity in many tumors that recurred relative to those that didn't.

Conclusions: The results of our study show that early recurrence is associated with expression of androgen-responsive genes. Surprisingly, these could be identified as early as 3 months after the initiation of AD therapy. Whether this represents a failure to abrogate androgen receptor mediated signaling with androgen depletion or early reactivation of signaling is under study.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgen Antagonists / therapeutic use*
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Flutamide / therapeutic use
  • Gene Expression
  • Gene Expression Profiling
  • Goserelin / therapeutic use
  • Humans
  • Male
  • Neoadjuvant Therapy
  • Neoplasm Recurrence, Local
  • Predictive Value of Tests
  • Prostate-Specific Antigen / blood
  • Prostate-Specific Antigen / genetics*
  • Prostatectomy
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / therapy
  • Treatment Failure


  • Androgen Antagonists
  • Antineoplastic Agents, Hormonal
  • Biomarkers, Tumor
  • Goserelin
  • Flutamide
  • Prostate-Specific Antigen