title: Molecular load of pathologically occult metastases in pelvic lymph nodes is an independent prognostic marker of biochemical failure after localized prostate cancer treatment.
abstract: OBJECTIVE
  Thirty percent of patients treated with curative intent for localized prostate cancer (PC) experience biochemical recurrence (BCR) with rising serum prostate-specific antigen (sPSA), and of these, approximately 50% succumb to progressive disease. More discriminatory staging procedures are needed to identify occult micrometastases that spawn BCR.
  
  
  METHODS
  PSA mRNA copies in pathologically normal pelvic lymph nodes (N0-PLN) from 341 localized PC patients were quantified by real-time reverse-transcriptase polymerase chain reaction. Based on comparisons with normal lymph nodes and PLN with metastases and on normalization to 5 x 10(6) glyceraldehyde-3'-phosphate dehydrogenase mRNA copies, normalized PSA copies (PSA-N) and a threshold of PSA-N 100 or more were selected for continuous and categorical multivariate analyses of biochemical failure-free survival (BFFS) compared with established risk factors.
  
  
  RESULTS
  At median follow-up of 4 years, the BFFS of patients with PSA-N 100 or more versus PSA-N less than 100 was 55% and 77% (P = .0002), respectively. The effect was greatest for sPSA greater than 20 ng/mL, 25% versus 60% (P = .014), Gleason score 8 or higher, 21% versus 66% (P = .0002), stage T3c, 18% versus 64% (P = .001), and high-risk group (50% v 72%; P = .05). By continuous analysis PSA-N was an independent prognostic marker for BCR (P = .049) with a hazard ratio of 1.25 (95% CI, 1.001 to 1.57). By categorical analysis, PSA-N 100 or more was an independent variable (P = .021) with a relative risk of 1.98 (95% CI, 1.11 to 3.55) for BCR compared with PSA-N less than 100.
  
  
  CONCLUSIONS
  PSA-N 100 or more is a new, independent molecular staging criterion for localized PC that identifies high-risk group patients with clinically relevant occult micrometastases in N0-PLN, who may benefit from additional therapy to prevent BCR.
authors.affiliation: New York University Cancer Institute, New York University Medical School, 160 E 34th St, 8th Floor, New York, NY 10016, USA. anna.ferrari@nyumc.org
authors.forename: Anna C
authors.initials: AC
authors.lastname: Ferrari
authors.forename: Nelson N
authors.initials: NN
authors.lastname: Stone
authors.forename: Ralf
authors.initials: R
authors.lastname: Kurek
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Mulligan
authors.forename: Roy
authors.initials: R
authors.lastname: McGregor
authors.forename: Richard
authors.initials: R
authors.lastname: Stock
authors.forename: Pamela
authors.initials: P
authors.lastname: Unger
authors.forename: Ulf
authors.initials: U
authors.lastname: Tunn
authors.forename: Amir
authors.initials: A
authors.lastname: Kaisary
authors.forename: Michael
authors.initials: M
authors.lastname: Droller
authors.forename: Simon
authors.initials: S
authors.lastname: Hall
authors.forename: Heiner
authors.initials: H
authors.lastname: Renneberg
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Livak
authors.forename: Robert E
authors.initials: RE
authors.lastname: Gallagher
authors.forename: John
authors.initials: J
authors.lastname: Mandeli
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D018450:Disease Progression; D006801:Humans; D008207:Lymphatic Metastasis / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D017430:Prostate-Specific Antigen; D011471:Prostatic Neoplasms / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D017430:Prostate-Specific Antigen