title: Stage at presentation and survival outcomes of patients with Gleason 8-10 prostate cancer and low prostate-specific antigen.
abstract: OBJECTIVE
  To evaluate outcomes for men with high Gleason score and low prostate-specific antigen (PSA) prostate cancer. Low PSA levels among men with Gleason 8-10 prostate cancer may be owing to cellular dedifferentiation rather than low disease burden. We hypothesized that men with Gleason 8-10 prostate cancer and low PSA levels have increased risk for advanced disease and worse survival.
  
  
  METHODS
  Men diagnosed from 2004 to 2007 with Gleason 8-10 prostate adenocarcinoma in the National Cancer Data Base were included. Patients were stratified by PSA levels at diagnosis: 0.1 to 3.9, 4.0 to 9.9, 10.0 to 19.9, and≥20.0ng/ml. Outcomes were clinical TNM category, pathologic stage (for prostatectomy patients), and overall survival (OS). Kaplan-Meier analysis and Cox proportional hazards models were used.
  
  
  RESULTS
  A total of 37,283 patients were included. Men with PSA levels of<4.0ng/ml were more likely than those with PSA levels of 4 to 9.9ng/ml to present with clinical T3-4 disease (15% vs. 10%, P<0.001), nodal (4% vs. 2%, P<0.001) and distant (5% vs. 3%, P<0.001) metastasis. However, among patients treated with prostatectomy, lower PSA levels were not associated with increased likelihood of pathologic T3-4 disease or nodal metastasis. Six-year OS was 89.1% (PSA: 0.1-3.9ng/ml) vs. 91.0% (PSA: 4.0-9.9ng/ml) for prostatectomy (log-rank P<0.001), and 75.8% vs. 81.0% for radiotherapy (P<0.001). Multivariable analyses showed OS of patients with PSA levels of 0.1 to 3.9ng/ml to be similar to those with PSA levels of 10 to 19.9ng/ml.
  
  
  CONCLUSIONS
  Patients with Gleason 8-10 cancer and PSA levels of<4.0ng/ml have more aggressive disease than those with PSA levels of 4 to 9.9ng/ml; these low PSA cancers behave more like those with PSA levels of 10 to 19.9ng/ml. Further study is needed to evaluate potential biological differences in these patients with low PSA-producing cancers.
authors.affiliation: Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC.
authors.forename: Aaron D
authors.initials: AD
authors.lastname: Falchook
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Neil E
authors.initials: NE
authors.lastname: Martin
authors.affiliation: Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC.
authors.forename: Ramsankar
authors.initials: R
authors.lastname: Basak
authors.affiliation: Department of Urology, University of North Carolina at Chapel Hill, Chapel Hill, NC; University of North Carolina-Lineberger Comprehensive Cancer Center, Chapel Hill, NC.
authors.forename: Angela B
authors.initials: AB
authors.lastname: Smith
authors.affiliation: University of North Carolina-Lineberger Comprehensive Cancer Center, Chapel Hill, NC; Department of Medicine, Division of Hematology/Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC.
authors.forename: Matthew I
authors.initials: MI
authors.lastname: Milowsky
authors.affiliation: Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC; University of North Carolina-Lineberger Comprehensive Cancer Center, Chapel Hill, NC; Sheps Center for Health Services Research, University of North Carolina at Chapel Hill, Chapel Hill, NC. Electronic address: Ronald_chen@med.unc.edu.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Chen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy / Q000401:mortality*; D011471:Prostatic Neoplasms / Q000097:blood / Q000401:mortality* / Q000473:pathology*; D015996:Survival Rate
chemical_list: D017430:Prostate-Specific Antigen
keywords: High-risk prostate cancer; NCDB; PSA; Survival