title: External beam radiotherapy with dose escalation in 1080 prostate cancer patients: definitive outcome and dose impact.
abstract: BACKGROUND
  The aim of this paper was to report definitive outcome of prostate cancer patients treated with dose escalation during a period of 12.5 years.
  
  
  METHODS
  From October 1999 to March 2012 we treated 1080 patients affected by prostate cancer, using External Beam Radiotherapy (EBRT). The mean age was 69.2 years. Most of the patients (69%) were staged as cT2, Gleason Score (GS)<7; the mean iPSA 18 ng/mL; the rate of clinical positive nodes was 1%. Our intention to treat was the following: for low risk patients 72 Gy; for intermediate risk patients 75.6 Gy and for high-very high risk patients 79.2 Gy in 1.8 Gy/day fractions. From 2008 we changed the fractionation scheme and the doses were the following: for low risk patients 74 Gy and for intermediate and high-very high risk patients 78 Gy in 2.0 Gy/day fractions. Whole pelvis irradiation was performed in high-very high risk patients with 43.2-50.4 Gy in 1.8 Gy per day. The mean follow-up was 81 months.
  
  
  RESULTS
  For the whole population at 5 and 10 years, the prostate cancer specific overall survival (CSOS) was 96.7% and 92.2% respectively; the clinical disease free survival (CDFS) 88% and 77%; the biochemical disease free survival (BDFS) 75% and 58.5%. The 5 and 10 years CSOS was 98% and 96% respectively for low risk, 96% and 92% for intermediate risk and 89% and 82% for high-very high risk patients. In intermediate and high-very high risk groups at 5 and 10 years the CSOS was 95.2% and 89.2% respectively, the CDFS 84.5% and 70% and the BDFS 70% and 51% respectively. In high-very high risk patients at 5 and 10 years the CSOS were respectively 89% and 82% the CDFS was 78% and 61% and BDFS was 61% and 34%. In whole patient population the BDFS was related with the dose level (P=0.006) as well as the CDFS (P=0.003) with a cut off of 75.6 Gy. In the subgroup of intermediate plus high-very high risk patients the BDFS and the CDFS were dose-related with a cut off of 75.6 Gy (P=0.007 and P=0.0018 respectively). Finally, in the subgroup of high-very high risk patients we found that the CSOS, the BDFS and the CDFS were related to the dose level with a cut-off of 77.7 Gy (P=0.017; P=0.006 and P=0.038, respectively). Overall gastrointestinal (GI) acute and late G2 toxicities were respectively 5 % and 3.8%; GI acute and late >G3 toxicities were respectively 0.5% and 0.9%; acute and late >G2 genitourinary (GU) toxicities were respectively 10.5% and 2.6%; finally GU acute and late >G3 toxicities were respectively 0.6% and 0.5%.
  
  
  CONCLUSIONS
  The dose escalation is not relevant for the outcome in low risk patients that can benefit from relatively moderate doses (72-74 Gy). For intermediate and high-very high risk patients the dose becomes significant to levels above 75.6 Gy; particularly in high-very high risk doses >77.7 Gy correlate with an improved outcome. Patients receiving dose >77.7 Gy presented a higher rate of overall GI and GU toxicity, but the number of grade >2 remains low. Our results, consolidated by a long follow-up, corroborate the literature data, confirming that 3D-CRT can allow a safe dose escalation without significantly increasing the severe toxicity.
authors.affiliation: Department of Radiotherapy, Candiolo Cancer Institute, Candiolo, Turin, Italy - elisabetta.garibaldi@ircc.it.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Garibaldi
authors.forename: Domenico
authors.initials: D
authors.lastname: Gabriele
authors.forename: Angelo
authors.initials: A
authors.lastname: Maggio
authors.forename: Elena
authors.initials: E
authors.lastname: Delmastro
authors.forename: Monica
authors.initials: M
authors.lastname: Garibaldi
authors.forename: Sara
authors.initials: S
authors.lastname: Bresciani
authors.forename: Cinzia
authors.initials: C
authors.lastname: Ortega
authors.forename: Michele
authors.initials: M
authors.lastname: Stasi
authors.forename: Pietro
authors.initials: P
authors.lastname: Gabriele
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use; D004307:Dose-Response Relationship, Radiation; D005500:Follow-Up Studies; D041981:Gastrointestinal Tract / Q000528:radiation effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D014566:Urogenital System / Q000528:radiation effects
chemical_list: D000726:Androgen Antagonists