title: The number of risk factors is the strongest predictor of prostate cancer mortality: multi-institutional outcomes of an extreme-risk prostate cancer cohort.
abstract: OBJECTIVE
  To report treatment outcomes in a cohort of extreme-risk prostate cancer patients and identify a subgroup of patients with worse prognosis.
  
  
  METHODS
  Extreme-risk prostate cancer patients were defined as patients with at least one extreme-risk factor: stage cT3b-cT4, Gleason score 9-10 or PSA > 50 ng/ml; or patients with 2 or more high-risk factors: stage cT2c-cT3a, Gleason 8 and PSA > 20 ng/ml. Overall survival (OS), cause-specific survival (CSS), clinical-free survival (CFS), and biochemical non-evidence of disease (bNED) survival are the four outcomes of interest in a population of 1341 patients.
  
  
  RESULTS
  With a median follow-up of 71.5 months, 5- and 10-year bNED survival, CFS, CSS and OS for the entire cohort were 77.1 % and 57.0, 89.2 and 78.9 %, 97.4 and 93.6 %, and 92.0 and 71.3 %, respectively. On multivariate analysis, PSA and clinical stage were associated with bNED survival. PSA and Gleason score predicted for CFS, whereas only Gleason score predicted for OS. When a simplified model was performed using the "number of risk factors" variable, this model provided the best distinction between patients with ≥2 extreme-risk factors and patients with 2 high-risk factors, showing a hazard ratio (HR) of 1.737 (p = 0.0003) for bNED survival, HR 1.743 (p = 0.0448) for OS and an HR of 3.963 (p = 0.0039) for the CSS endpoint.
  
  
  CONCLUSIONS
  Patients presenting at diagnosis with two extreme-risk criteria have almost fourfold higher risk for prostate cancer mortality. Such patients should be considered for more aggressive multimodal treatments.
authors.affiliation: Department of Radiation Oncology, Hospital Universitario Cruces, Plaza Cruces Gurutzeta 12, 48903, Barakaldo, Spain. agomeziturriaga@gmail.com.
authors.forename: A
authors.initials: A
authors.lastname: Gomez-Iturriaga
authors.affiliation: Department of Radiation Oncology, Hospital Doce de Octubre, Madrid, Spain.
authors.forename: Á
authors.initials: Á
authors.lastname: Cabeza
authors.affiliation: Department of Radiation Oncology, Hospital General de Valencia, Valencia, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Pastor
authors.affiliation: Department of Radiation Oncology, Hospital Germans Trias i Pujol, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Jove
authors.affiliation: Department of Radiation Oncology, Instituto Valenciano de Oncologia, Valencia, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Casaña
authors.affiliation: Department of Radiation Oncology, Hospital Clínico Universitario, Santiago de Compostela, Spain.
authors.forename: A G
authors.initials: AG
authors.lastname: Caamaño
authors.affiliation: Department of Radiation Oncology, Instituto Valenciano de Oncologia, Valencia, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Mengual
authors.affiliation: Department of Radiation Oncology, Hospital Universitario San Joan, Reus, Tarragona, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Henríquez
authors.affiliation: Department of Radiation Oncology, Hospital Infanta Cristina, Badajoz, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Muñoz
authors.affiliation: Department of Radiation Oncology, Hospital Ramón y Cajal, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Hervás
authors.affiliation: Department of Radiation Oncology, Hospital Gregorio Marañon, Madrid, Spain.
authors.forename: C G-S
authors.initials: CG
authors.lastname: Segundo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; 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*; D011471:Prostatic Neoplasms / Q000097:blood / Q000401:mortality* / Q000473:pathology*; D012042:Registries; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D017430:Prostate-Specific Antigen
keywords: Androgen deprivation; Extreme risk; Multimodal treatment; Prostate cancer; Radiotherapy; Survival