Natural history of rising serum prostate-specific antigen in men with castrate nonmetastatic prostate cancer.
OBJECTIVE
To describe the natural history of nonmetastatic prostate cancer and rising prostate-specific antigen (PSA) despite androgen deprivation therapy.


METHODS
The 201 patients in this report were the placebo control group from an aborted randomized controlled trial to evaluate the effects of zoledronic acid on time to first bone metastasis in men with prostate cancer, no bone metastases, and rising PSA despite androgen deprivation therapy. Relationships between baseline covariates and clinical outcomes were assessed by Cox proportional hazard analyses. Covariates in the model were baseline PSA, Gleason sum, history of bilateral orchiectomies, regional lymph node metastases at diagnosis, prior prostatectomy, time from androgen deprivation therapy to random assignment, time from diagnosis to random assignment, and PSA velocity.


RESULTS
At 2 years, 33% of patients had developed bone metastases. Median bone metastasis-free survival was 30 months. Median time to first bone metastases and overall survival were not reached. Baseline PSA level greater than 10 ng/mL (relative risk, 3.18; 95% CI, 1.74 to 5.80; P < .001) and PSA velocity (4.34 for each 0.01 increase in PSA velocity; 95% CI, 2.30 to 8.21; P < .001) independently predicted shorter time to first bone metastasis. Baseline PSA and PSA velocity also independently predicted overall survival and metastasis-free survival. Other covariates did not consistently predict clinical outcomes.


CONCLUSIONS
Men with nonmetastatic prostate cancer and rising PSA despite androgen deprivation therapy have a relatively indolent natural history. Baseline PSA and PSA velocity independently predict time to first bone metastasis and survival.
Smith
Matthew R
MR
Massachusetts General Hospital, Cox 640, 100 Blossom St, Boston, MA 02114, USA. smith.matthew@mgh.harvard.edu
Kabbinavar
Fairooz
F
Saad
Fred
F
Hussain
Arif
A
Gittelman
Marc C
MC
Bilhartz
David L
DL
Wynne
Chris
C
Murray
Robin
R
Zinner
Norman R
NR
Schulman
Claude
C
Linnartz
Ronald
R
Zheng
Ming
M
Goessl
Carsten
C
Hei
Yong-Jiang
YJ
Small
Eric J
EJ
Cook
Richard
R
Higano
Celestia S
CS
D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D001859:Bone Neoplasms / Q000517:prevention & control / Q000556:secondary*; D004164:Diphosphonates / Q000627:therapeutic use*; D018450:Disease Progression; D004311:Double-Blind Method; D005500:Follow-Up Studies; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D010919:Placebos; D011237:Predictive Value of Tests; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000032:analysis*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D016019:Survival Analysis; D000077211:Zoledronic Acid
D000726:Androgen Antagonists; D014408:Biomarkers, Tumor; D004164:Diphosphonates; D007093:Imidazoles; D010919:Placebos; D000077211:Zoledronic Acid; D017430:Prostate-Specific Antigen