title: Radiation dose and late failures in prostate cancer.
abstract: OBJECTIVE
  To quantify the impact of radiation dose escalation on the timing of biochemical failure (BF) and distant metastasis (DM) for prostate cancer treated with radiotherapy (RT) alone.
  
  
  METHODS
  The data from 667 men with clinically localized intermediate- and high-risk prostate cancer treated with three-dimensional conformal RT alone were retrospectively analyzed. The interval hazard rates of DM and BF, using the American Society for Therapeutic Radiology and Oncology (ASTRO) and Phoenix (nadir + 2) definitions, were determined. The median follow-up was 77 months.
  
  
  RESULTS
  Multivariate analysis showed that increasing radiation dose was independently associated with decreased ASTRO BF (p < 0.0001), nadir + 2 BF (p = 0.001), and DM (p = 0.006). The preponderance (85%) of ASTRO BF occurred at < or =4 years after RT, and nadir + 2 BF was more evenly spread throughout Years 1-10, with 55% of BF in < or =4 years. Radiation dose escalation caused a shift in the BF from earlier to later years. The interval hazard function for DM appeared to be biphasic (early and late peaks) overall and for the <74-Gy group. In patients receiving > or =74 Gy, a reduction occurred in the risk of DM in the early and late waves, although the late wave appeared reduced to a greater degree.
  
  
  CONCLUSIONS
  The ASTRO definition of BF systematically underestimated late BF because of backdating. Radiation dose escalation diminished and delayed BF; the delay suggested that local persistence may still be present in some patients. For DM, a greater radiation dose reduced the early and late waves, suggesting that persistence of local disease contributed to both.
authors.affiliation: Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111-2497, USA.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Morgan
authors.forename: Alexandra L
authors.initials: AL
authors.lastname: Hanlon
authors.forename: Eric M
authors.initials: EM
authors.lastname: Horwitz
authors.forename: Mark K
authors.initials: MK
authors.lastname: Buyyounouski
authors.forename: Robert G
authors.initials: RG
authors.lastname: Uzzo
authors.forename: Alan
authors.initials: A
authors.lastname: Pollack
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal; D012189:Retrospective Studies; D016879:Salvage Therapy; D013997:Time Factors; D017211:Treatment Failure
chemical_list: D017430:Prostate-Specific Antigen