Duration of first off-treatment interval is prognostic for time to castration resistance and death in men with biochemical relapse of prostate cancer treated on a prospective trial of intermittent androgen deprivation.
OBJECTIVE
This was an exploratory analysis of a trial of intermittent androgen deprivation (IAD) in men with biochemical relapse (BR) to establish first cycle characteristics prognostic for progression to castration-resistant prostate cancer (CRPC) and death.


METHODS
Men with BR of prostate cancer after radical prostatectomy (RP) or radiation (RT) were treated with androgen deprivation therapy (ADT) comprised of leuprolide and flutamide. After 9 months on treatment, ADT was stopped, and monthly prostate-specific antigen (PSA) levels were observed during the off-treatment interval. When the PSA reached a threshold value (1 ng/mL for RP, 4 ng/mL for RT), ADT was resumed in a new cycle. Patients were treated intermittently in this manner until CRPC, which was defined as > or = two consecutive increasing PSA values while on ADT with castrate testosterone levels.


RESULTS
Seventy-two of 100 patients enrolled onto the study met criteria for this analysis. The duration of the first off-treatment interval (< or = v > 40 weeks) was associated with shorter time to CRPC (hazard ratio = 2.9; 95% CI, 1.1 to 7.7; P = .03) and death (hazard ratio = 3.8; 95% CI, 1.1 to 13.6; P = .04) after adjusting for age, stage, grade, and PSA at diagnosis.


CONCLUSIONS
In patients who completed the first cycle of IAD, a duration of the first off-treatment interval of < or = 40 weeks defines a subset of patients at higher risk of CRPC and death. Conversely, patients with an off-treatment interval of more than 40 weeks have a significantly better long-term prognosis.
Yu
Evan Y
EY
Department of Medicine, Division of Oncology, University of Washington, 825 Eastlake Ave E., Seattle, WA 98109, USA.
Gulati
Roman
R
Telesca
Donatello
D
Jiang
Peter
P
Tam
Stephen
S
Russell
Kenneth J
KJ
Nelson
Peter S
PS
Etzioni
Ruth D
RD
Higano
Celestia S
CS
D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000726:Androgen Antagonists / Q000008:administration & dosage / Q000009:adverse effects; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000009:adverse effects; D001918:Brachytherapy / Q000379:methods; D002369:Castration; D002423:Cause of Death; D017024:Chemotherapy, Adjuvant; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005485:Flutamide / Q000008:administration & dosage / Q000009:adverse effects; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016729:Leuprolide / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D009367:Neoplasm Staging; D011336:Probability; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy / Q000379:methods; D011471:Prostatic Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy; D018570:Risk Assessment; D016879:Salvage Therapy / Q000379:methods*; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D005485:Flutamide; D017430:Prostate-Specific Antigen; D016729:Leuprolide