title: Initial management of prostate-specific antigen-detected, low-risk prostate cancer and the risk of death from prostate cancer.
abstract: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The recently published Prostate Cancer Intervention versus Observation Trial (PIVOT) did not identify differences in prostate cancer-specific mortality or all-cause mortality among patients with low-risk disease managed conservatively vs those managed definitively; however, recently published data suggest that older men may harbour more aggressive disease than is identified at biopsy owing to sampling error and undergrading. Whether older men with apparent low-risk disease are placed at risk of prostate cancer-specific mortality when managed conservatively remains unknown. The study used population-level data to show that non-curative approaches for older men with low-risk prostate cancer do result in an increased risk of prostate cancer-specific mortality. Differences between our study and the PIVOT trial include the fact that we included a larger sample size, analysed the data using an 'as-treated' approach, and included a healthier cohort of men as evinced by lower 4-year all-cause mortality estimates in our study than in the PIVOT. Our results suggest that older men with apparent low-risk prostate cancer are at risk of undergrading, which probably explains the differences in prostate cancer-specific mortality observed between men managed conservatively vs those managed definitively. Our study suggests that alternative approaches to excluding occult, high grade prostate cancer are needed in such men.
  
  
  OBJECTIVE
  To evaluate whether older age in men with low-risk prostate cancer increases the risk of prostate cancer-specific mortality (PCSM) when non-curative approaches are selected as initial management.
  
  
  METHODS
  The study cohort consisted of 27 969 men, with a median age of 67 years, with prostate-specific antigen (PSA)-detected, low-risk prostate cancer (clinical category T1c, Gleason score ≤6, and PSA ≤10) identified by the Surveillance, Epidemiology and End Results programme between 2004 and 2007. Fine and Gray's competing risk regression analysis was used to evaluate whether management with non-curative vs curative therapy was associated with an increased risk of PCSM after adjusting for PSA level, age at diagnosis and year of diagnosis.
  
  
  RESULTS
  After a median follow-up of 2.75 years, 1121 men died, 60 (5.4%) from prostate cancer. Both older age (adjusted hazard ratio [AHR] 1.05; 95% confidence interval (CI) 1.02-1.08; P < 0.001) and non-curative treatment (AHR 3.34; 95% CI 1.97-5.67; P < 0.001) were significantly associated with an increased risk of PCSM. Men > the median age experienced increased estimates of PCSM when treated with non-curative as opposed to curative intent (P < 0.001); this finding was not seen in men ≤ the median age (P = 0.17).
  
  
  CONCLUSIONS
  Pending prospective validation, our study suggests that non-curative approaches for older men with 'low-risk' prostate cancer result in an increased risk of PCSM, suggesting the need for alternative approaches to exclude occult, high grade prostate cancer in these men.
authors.affiliation: Harvard Radiation Oncology Program, Boston, MA.
authors.forename: Ayal A
authors.initials: AA
authors.lastname: Aizer
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Chen
authors.forename: Jona
authors.initials: J
authors.lastname: Hattangadi
authors.forename: Anthony V
authors.initials: AV
authors.lastname: D'Amico
mesh_terms: D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D060787:Neoplasm Grading; D018579:Patient Selection; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy / Q000379:methods / Q000401:mortality*; D011471:Prostatic Neoplasms / Q000097:blood / Q000401:mortality* / Q000473:pathology*; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D017430:Prostate-Specific Antigen
keywords: active surveillance; non-curative; prostate cancer; prostatectomy; radiation; undergrading