title: Extreme-risk prostate adenocarcinoma presenting with prostate-specific antigen (PSA)>40 ng/ml: prognostic significance of the preradiation PSA nadir.
abstract: OBJECTIVE
  To examine the impact of patient, disease, and treatment characteristics on survival outcomes in patients treated with neoadjuvant androgen deprivation therapy (ADT) and radical external-beam radiotherapy (RT) for clinically localized, extreme-risk prostate adenocarcinoma with a presenting prostate-specific antigen (PSA) concentration of >40 ng/ml.
  
  
  METHODS
  A retrospective chart review was conducted of 64 patients treated at a single institution between 1991 and 2000 with ADT and RT for prostate cancer with a presenting PSA level of >40 ng/ml. The effects of patient age, tumor (presenting PSA level, Gleason score, and T stage), and treatment (total ADT duration and pre-RT PSA level) characteristics on rates of biochemical disease-free survival (bDFS), prostate cancer-specific survival (PCSS), and overall survival (OS) were examined.
  
  
  RESULTS
  Median follow-up time was 6.45 years (range, 0.09-15.19 years). Actuarial bDFS, PCSS, and OS rates at 5 years were 39%, 87%, and 78%, respectively, and 17%, 64%, and 45%, respectively, at 10 years. On multivariate analysis, the pre-RT PSA level (≤0.1 versus >0.1 ng/ml) was the single most significant prognostic factor for bDFS (p=0.033) and OS (p=0.018) rates, whereas age, T stage, Gleason score, and ADT duration (≤6 versus >6 months) were not predictive of outcomes.
  
  
  CONCLUSIONS
  In prostate cancer patients with high presenting PSA levels, >40 ng/ml, treated with combined modality, neoadjuvant ADT, and RT, the pre-RT PSA nadir, rather than ADT duration, was significantly associated with improved survival. This observation supports the use of neoadjuvant ADT to drive PSA levels to below 0.1 ng/ml before initiation of RT, to optimize outcomes for patients with extreme-risk disease.
authors.affiliation: British Columbia Cancer Agency, Vancouver Island Centre, Radiation Therapy Program, Victoria, British Columbia, Canada.
authors.forename: Abraham S
authors.initials: AS
authors.lastname: Alexander
authors.forename: Aminudin
authors.initials: A
authors.lastname: Mydin
authors.forename: Stuart O
authors.initials: SO
authors.lastname: Jones
authors.forename: Jennifer
authors.initials: J
authors.lastname: Christie
authors.forename: Jan T W
authors.initials: JT
authors.lastname: Lim
authors.forename: Pauline T
authors.initials: PT
authors.lastname: Truong
authors.forename: Charles M
authors.initials: CM
authors.lastname: Ludgate
mesh_terms: D000230:Adenocarcinoma / Q000097:blood* / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant / Q000379:methods; D018572:Disease-Free Survival; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D011879:Radiotherapy Dosage; D012189:Retrospective Studies
chemical_list: D000726:Androgen Antagonists; D017430:Prostate-Specific Antigen