title: Prognostic Factors for Prostate Cancer Endpoints Following Biochemical Failure: A Review of the Literature.
abstract: OBJECTIVE
  In the setting of biochemical failure (BCF) following primary treatment for prostate cancer, additional discrimination between clinically significant and non-clinically significant biochemical recurrence is critical in defining robust surrogate endpoints for prostate cancer and guiding salvage management decisions. We reviewed the literature to determine which prognostic factors are most significant for predicting prostate cancer-specific survival (PCSS), metastases-free survival (MFS), and/or overall survival (OS) after BCF.
  
  
  METHODS
  A search of PubMed from 1980 to 2013 yielded 999 studies that examined prognostic factors predictive for PCSS, MFS, and/or OS in prostate cancer patients with BCF following primary treatment. Eligibility criteria for inclusion were: 1) examined a prostate cancer population in the setting of BCF without overt clinical relapse following primary treatment with radical prostatectomy or radiotherapy; 2) based analyses on patient parameters obtained prior to the initiation of salvage therapies; and 3) determined clinical prognostic factors that were significant prognostic measures for at least one of three clinically relevant endpoints: OS, PCS, or MFS.
  
  
  RESULTS
  Nineteen eligible studies reported on 8,040 patients that experienced BCF from 1981-2013. The initial primary therapy was variable: radical prostatectomy alone (n=8), radiotherapy alone (n=4), radiotherapy/radical prostatectomy ± adjuvant therapy (n=5), and multiple treatment arms (n=2). There was also heterogeneity in which outcomes were assessed: PCSS (n=14), MFS (n=7), and OS (n=5). The prognostic factors most commonly found to be significant on multivariate analyses were PSA doubling time (PSADT), time to biochemical failure (TTBF), pathological Gleason score (pGS), and age.
  
  
  CONCLUSIONS
  Risk stratification in prostate cancer post-BCF is challenging because of limited predictive modeling that can determine which patients will optimally benefit from salvage therapy. Our systematic literature review has identified PSADT, TTBF, pGS, and age as the leading prognostic factors for the prediction of PCSS, MFS, and OS after BCF. We plan to leverage the Canadian ProCaRS database to perform predictive modeling using the putative findings in the present study in order to propose potential evidence-based surrogate endpoints for prostate cancer in the setting of BCF.
authors.affiliation: Radiation Oncology, London Health Sciences Centre.
authors.forename: Tim
authors.initials: T
authors.lastname: Nguyen
authors.affiliation: London Health Sciences Centre.
authors.forename: R Gabriel
authors.initials: RG
authors.lastname: Boldt
authors.affiliation: Department of Oncology, London Health Sciences Centre; Schulich School of Medicine & Dentistry, Western University, London, Ontario, CA.
authors.forename: George
authors.initials: G
authors.lastname: Rodrigues
keywords: biochemical failure; biochemical recurrence; clinical endpoints; clinical outcomes; predictor; prognostic factor; prostate cancer; psa; survival