Evaluation of prostate-specific antigen as a surrogate marker for response of hormone-refractory prostate cancer to suramin therapy.
OBJECTIVE
We evaluated the surrogate role of serum prostate-specific antigen (PSA) using prospectively collected information from patients with hormone-refractory prostate cancer (HRPC) treated with suramin.


METHODS
Data from 103 patients were analyzed using survival analysis, exploratory analysis, and regression analysis.


RESULTS
There was a significant survival difference between groups of patients with a PSA decrease of < or = 0% or greater than 0% (P = .018). There were no significant overall survival differences between groups of patients with PSA decreases less than 50% or > or = 50% and less than 75% or > or = 75%. Tree-based modeling did not define a specific threshold percentage PSA change as a response criterion. For a response of 1-year survival, sensitivity increased (0.91 v 0.69), but specificity decreased (0.37 v 0.62), with a 75% versus 50% PSA decrease used as classification criterion. Differences between the area under the receiver-operating curves (ROCs) with 50% and 75% PSA decreases as threshold values were small. For a response of 1-year survival, attributable proportions were 0.38 and 0.68, respectively, with 50% and 75% PSA decreases as threshold values. When pretreatment variables were assessed by Cox proportional hazards model, hemoglobin level was the most significant predictor of survival. When percentage PSA change was included in the model, hemoglobin level remained the most significant factor, but percentage PSA change was also a weak, but statistically significant, factor. PSA was a weak, but statistically significant, predictor of survival in Cox proportional hazards model with PSA as a time-variant covariate.


CONCLUSIONS
Reduction in PSA level has weak prognostic significance with respect to survival in HRPC patients, but, currently, PSA reduction cannot be used as a reliable response criterion to evaluate treatment efficacy in individual patients. Prospective, randomized studies, including prospective measurement of other indices related to symptomatic clinical benefits, are required.
Sridhara
R
R
Department of Epidemiology and Preventive Medicine, University of Maryland Cancer Center, Baltimore 21201, USA.
Eisenberger
M A
MA
Sinibaldi
V J
VJ
Reyno
L M
LM
Egorin
M J
MJ
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood*; D019008:Drug Resistance, Neoplasm; D005069:Evaluation Studies as Topic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000188:drug therapy*; D012372:ROC Curve; D012189:Retrospective Studies; D013498:Suramin / Q000627:therapeutic use*; D016019:Survival Analysis
D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D013498:Suramin; D017430:Prostate-Specific Antigen