title: Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (the ASCENDE-RT Trial): An Analysis of Survival Endpoints for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost to a Dose-Escalated External Beam Boost for High- and Intermediate-risk Prostate Cancer.
abstract: To report the primary endpoint of biochemical progression-free survival (b-PFS) and secondary survival endpoints from ASCENDE-RT, a randomized trial comparing 2 methods of dose escalation for intermediate- and high-risk prostate cancer.
  
  
  
  ASCENDE-RT enrolled 398 men, with a median age of 68 years; 69% (n=276) had high-risk disease. After stratification by risk group, the subjects were randomized to a standard arm with 12 months of androgen deprivation therapy, pelvic irradiation to 46 Gy, followed by a dose-escalated external beam radiation therapy (DE-EBRT) boost to 78 Gy, or an experimental arm that substituted a low-dose-rate prostate brachytherapy (LDR-PB) boost. Of the 398 trial subjects, 200 were assigned to DE-EBRT boost and 198 to LDR-PB boost. The median follow-up was 6.5 years.
  
  
  
  In an intent-to-treat analysis, men randomized to DE-EBRT were twice as likely to experience biochemical failure (multivariable analysis [MVA] hazard ratio [HR] 2.04; P=.004). The 5-, 7-, and 9-year Kaplan-Meier b-PFS estimates were 89%, 86%, and 83% for the LDR-PB boost versus 84%, 75%, and 62% for the DE-EBRT boost (log-rank P<.001). The LDR-PB boost benefited both intermediate- and high-risk patients. Because the b-PFS curves for the treatment arms diverge sharply after 4 years, the relative advantage of the LDR-PB should increase with longer follow-up. On MVA, the only variables correlated with reduced overall survival were age (MVA HR 1.06/y; P=.004) and biochemical failure (MVA HR 6.30; P<.001). Although biochemical failure was associated with increased mortality and randomization to DE-EBRT doubled the rate of biochemical failure, no significant overall survival difference was observed between the treatment arms (MVA HR 1.13; P=.62).
  
  
  
  Compared with 78 Gy EBRT, men randomized to the LDR-PB boost were twice as likely to be free of biochemical failure at a median follow-up of 6.5 years.
authors.affiliation: Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada; BC Cancer Agency-Vancouver Centre, Vancouver, British Columbia, Canada. Electronic address: jmorris@bccancer.bc.ca.
authors.forename: W James
authors.initials: WJ
authors.lastname: Morris
authors.affiliation: Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada; BC Cancer Agency-Vancouver Centre, Vancouver, British Columbia, Canada.
authors.forename: Scott
authors.initials: S
authors.lastname: Tyldesley
authors.affiliation: Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Sree
authors.initials: S
authors.lastname: Rodda
authors.affiliation: Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada; BC Cancer Agency-Centre for the Southern Interior, Vancouver, British Columbia, Canada.
authors.forename: Ross
authors.initials: R
authors.lastname: Halperin
authors.affiliation: Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada; BC Cancer Agency-Vancouver Island Centre, Vancouver, British Columbia, Canada.
authors.forename: Howard
authors.initials: H
authors.lastname: Pai
authors.affiliation: Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada; BC Cancer Agency-Vancouver Centre, Vancouver, British Columbia, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: McKenzie
authors.affiliation: Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada; BC Cancer Agency-Vancouver Centre, Vancouver, British Columbia, Canada.
authors.forename: Graeme
authors.initials: G
authors.lastname: Duncan
authors.affiliation: Department of Radiation Oncology, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
authors.forename: Gerard
authors.initials: G
authors.lastname: Morton
authors.affiliation: Department of Population Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Hamm
authors.affiliation: BC Cancer Agency-Vancouver Centre, Vancouver, British Columbia, Canada; Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Nevin
authors.initials: N
authors.lastname: Murray
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use*; D001918:Brachytherapy / Q000379:methods*; D003131:Combined Modality Therapy / Q000379:methods; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D007987:Gonadotropin-Releasing Hormone / Q000627:therapeutic use; D006801:Humans; D057194:Intention to Treat Analysis; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D015182:Lymphatic Irradiation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010388:Pelvis; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality* / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D000069475:Re-Irradiation / Q000379:methods / Q000706:statistics & numerical data; D013997:Time Factors
chemical_list: D000726:Androgen Antagonists; D007457:Iodine Radioisotopes; D007987:Gonadotropin-Releasing Hormone; D017430:Prostate-Specific Antigen