THE MOST PROMISING SURROGATE END-POINT BIOMARKERS FOR SCREENING CANDIDATE CHEMOPREVENTIVE COMPOUNDS FOR PROSTATIC ADENOCARCINOMA IN SHORT-TERM PHASE-II CLINICAL-TRIALS

Surrogate endpoint biomarkers (SEBs) are needed in clinical chemopreve ntion trials to avoid the excessively long study periods and high cost s associated with the use of cancer incidence reduction as an endpoint , particularly with relatively slow-growing tumors such as prostatic a denocarcinoma. SEBs should be directly associated with the evolution o f neoplasia, and develop with high frequency in abnormal cells of susc eptible individuals. If SEBs can be modified by a particular intervent ion regimen in short-term studies, the rationale for carrying out long -term studies may be strengthened. The consensus panel identified a sm all and manageable group of biomarkers measured in tissue or serum as the most promising; in prostate cancer chemoprevention, including (1) prostate specific antigen (PSA); (2) morphometric markers, such as nuc lear size and roundness; (3) proliferation markers, such as MIB-1 and PCNA; (4) uclear DNA content (ploidy); (5) oncogene c-erbB-2 (HER-2/ne u) expression; (6) angiogenesis; and (7) high-grade prostatic intraepi thelial neoplasia (PIN). Information regarding many of these and other biomarkers is limited, calling for further investigation. Also, these factors, chosen chiefly for their proven or proposed utility as progn ostic factors, may be less useful as SEBs. It was agreed that concurre nt study of numerous markers rather than single markers allows compari son of their relative utility,, including assessment of ease of quanti tation and the sensitivity, specificity, and positive and negative pre dictive value. (C) 1994 Wiley-Liss, Inc.