Predictors of Time to Metastasis in Castration-resistant Prostate Cancer.
OBJECTIVE
To investigate predictors of time to metastasis among men treated with androgen deprivation therapy for nonmetastatic prostate cancer who developed castration-resistant prostate cancer (CRPC) within the Shared Equal Access Regional Cancer Hospital cohort.


METHODS
This is a retrospective analysis of 458 nonmetastatic CRPC men. Metastases were detected in routine bone scans or other imaging tests. Predictors of time to metastasis were analyzed using proportional hazards model with CRPC as time zero.


RESULTS
A total of 256 (56%) men were diagnosed with metastatic disease over a median follow-up of 36 months. Metastasis-free survival was 79%, 65%, 52%, 47%, and 41% at 1, 2, 3, 4, and 5 years after CRPC, respectively. In multivariable analysis, Gleason score 8-10 (hazard ratio [HR] = 1.61; P = .026), receiving primary localized treatment (HR = 1.38; P = .028), higher prostate-specific antigen (PSA) levels at CRPC diagnosis (logPSA HR = 1.64; P < .001), and PSA doubling time ≤6 months (HR = 1.42; P = .040) were independently associated with shorter time to metastasis. Race, year of CRPC, age, and time from androgen deprivation therapy to CRPC were not associated with metastasis.


CONCLUSIONS
Among nonmetastatic CRPC men, nearly 60% developed metastatic disease during the first 5 years, with most of the metastasis occurring within the first 3 years. Higher Gleason score, receiving primary treatment, higher PSA, and shorter PSA doubling time were independently associated with shorter time to metastasis. Therefore, these variables can be used to stratify patients according to metastasis risk.
Department of Urology, Mayo Clinic, Rochester, MN. Electronic address: moreira.daniel@mayo.edu.
Daniel M
DM
Moreira
Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC; Urology Section, Veterans Affairs Medical Center, Durham, NC.
Lauren E
LE
Howard
Urology Section, Veterans Affairs Medical Center, Durham, NC.
Katharine N
KN
Sourbeer
Urology Section, Veterans Affairs Medical Center, Durham, NC.
Hiruni S
HS
Amarasekara
Urology Section, Veterans Affairs Medical Center, Durham, NC.
Lydia C
LC
Chow
Urology Section, Veterans Affairs Medical Center, Durham, NC.
Dillon C
DC
Cockrell
Urology Section, Veterans Affairs Medical Center, Durham, NC.
Brian T
BT
Hanyok
Urology Section, Department of Surgery, Veterans Affairs Medical Center, Greater Los Angeles, Los Angeles, CA; Department of Urology, University of California at Los Angeles Medical Center, Los Angeles, CA.
William J
WJ
Aronson
Division of Urology, Department of Surgery, University of California at San Diego Medical Center, San Diego, CA.
Christopher J
CJ
Kane
Urology Section, Division of Surgery, Veterans Affairs Medical Centers, Augusta, GA; Division of Urologic Surgery, Department of Surgery, Medical College of Georgia, Augusta, GA.
Martha K
MK
Terris
Division of Urology, Department of Surgery, Oregon Health & Science University, Portland, OR.
Christopher L
CL
Amling
Departments of Urology and Epidemiology & Biostatistics, University of California, San Francisco, CA; Urology Section, Department of Surgery, Veterans Affairs Medical Center, San Francisco, CA.
Matthew R
MR
Cooperberg
Amgen Inc., Royal Oaks, MI.
Alex
A
Liede
Urology Section, Veterans Affairs Medical Center, Durham, NC; Division of Urology, Department of Surgery, Cedars Sinai Medical Center, Los Angeles, CA.
Stephen J
SJ
Freedland
D000368:Aged; D000369:Aged, 80 and over; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists / Q000037:antagonists & inhibitors; D006801:Humans; D008297:Male; D009919:Orchiectomy; D011379:Prognosis; D064129:Prostatic Neoplasms, Castration-Resistant / Q000556:secondary* / Q000628:therapy; D012189:Retrospective Studies; D013997:Time Factors
D007987:Gonadotropin-Releasing Hormone