title: Molecular staging by RT-pCR analysis for PSA and PSMA in peripheral blood and bone marrow samples is an independent predictor of time to biochemical failure following radical prostatectomy for clinically localized prostate cancer.
abstract: Radical prostatectomy should ideally be curative for all patients with clinically localized prostate cancer (PrCa), yet a sizeable proportion of them eventually relapse. We examined in this setting the feasibility of pre-operative risk stratification for early post-operative relapse using reverse transcriptase polymerase chain reaction (RT-PCR) for prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) transcripts in preoperative bone marrow (BM) biopsies and peripheral blood (PBL) samples. Nested RT-PCR for PSA and PSMA transcripts were performed in RNA from BM biopsies and PBL samples prospectively obtained from 111 men newly diagnosed, by trans-rectal ultrasound (TRUS)-guided biopsy, with clinically localized PrCa and scheduled to undergo radical prostatectomy, according to their respective doctors' recommendation. Molecular analysis for each sample (PBL or BM) was considered positive only if both PSA and PSMA transcripts were detectable. Serial serum PSA level measurements served for biochemical follow-up and detection of biochemical failure (PSA >0.2 ng/ml). PBL and BM RT-PCR molecular staging delineated three groups of patients (a) PBL-BM- (72 patients, 65%), (b) PBL+BM+ (29 patients, 26%), and (c) PBL+BM- (10 patients, 9%). These three groups corresponded to low, high, and intermediate risk for early post-prostatectomy recurrence (median time to biochemical failure of >38, 8, and >28 months, respectively). Multivariate analysis confirmed that molecular staging status was independent predictor of disease-free survival, after adjusting for PSA levels and Gleason score. In clinically localized PrCa, combined PSA/PSMA RT-PCR in PBL and BM is an independent predictor of time to biochemical failure following radical prostatectomy.
authors.affiliation: Department of Experimental Physiology, Medical School, University of Athens, Goudi-Athens, Greece.
authors.forename: Constantine S
authors.initials: CS
authors.lastname: Mitsiades
authors.forename: Peter
authors.initials: P
authors.lastname: Lembessis
authors.forename: Antigone
authors.initials: A
authors.lastname: Sourla
authors.forename: Constantine
authors.initials: C
authors.lastname: Milathianakis
authors.forename: Athanassios
authors.initials: A
authors.lastname: Tsintavis
authors.forename: Michael
authors.initials: M
authors.lastname: Koutsilieris
mesh_terms: D000954:Antigens, Surface / Q000097:blood*; D001853:Bone Marrow / Q000378:metabolism; D018572:Disease-Free Survival; D005240:Feasibility Studies; D043425:Glutamate Carboxypeptidase II / Q000097:blood*; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood* / Q000473:pathology / Q000601:surgery; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D017211:Treatment Failure
chemical_list: D000954:Antigens, Surface; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; D017430:Prostate-Specific Antigen