Persistent prostate-specific antigen expression after neoadjuvant androgen depletion: An early predictor of relapse or incomplete androgen suppression Journal Article
| Authors: | Ryan, C. J.; Smith, A.; Lal, P.; Satagopan, J.; Reuter, V.; Scardino, P.; Gerald, W.; Scher, H. I. |
| Article Title: | Persistent prostate-specific antigen expression after neoadjuvant androgen depletion: An early predictor of relapse or incomplete androgen suppression |
| Abstract: | 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. © 2006 Elsevier Inc. All rights reserved. |
| Keywords: | immunohistochemistry; adult; clinical article; human tissue; aged; treatment failure; cancer adjuvant therapy; neoadjuvant therapy; follow up; antigen expression; prostate specific antigen; neoplasm recurrence, local; gene expression; gene expression profiling; tumor markers, biological; relapse; prostate cancer; gleason score; prostate-specific antigen; prostatic neoplasms; goserelin; prostatectomy; androgen antagonists; predictive value of tests; dna microarray; flutamide; antineoplastic agents, hormonal |
| Journal Title: | Urology |
| Volume: | 68 |
| Issue: | 4 |
| ISSN: | 0090-4295 |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 2006-10-01 |
| Start Page: | 834 |
| End Page: | 839 |
| Language: | English |
| DOI: | 10.1016/j.urology.2006.04.016 |
| PUBMED: | 17070363 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 20" - "Export Date: 4 June 2012" - "CODEN: URGYA" - "Source: Scopus" |
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