A MORE OBJECTIVE STAGING OF ADVANCED PROSTATE-CANCER - ROUTINE RECOGNITION OF MALIGNANT ENDOCRINE STRUCTURES - THE ASSESSMENT OF SERUM TPS, PSA, AND NSE VALUES

Bone scans, serum tissue-specific polypeptide antigen (TPS), prostate specific antigen (PSA), and neuronspecific enolase (NSE) were assessed in a total of 80 hormonally treated prostate cancer patients. Thirty-nine patients were free of osseous lesions; in 8 subjects, 3 or fewer scintigraphic hot spots were found; in 29 patients, more then 3 bone lesions were recorded. In 3 patients, a partial contribution of endocrine cell cancer structures was found, while in one patient, a homogenous small cell carcinoma was detected at autopsy. Measurement of the serum PSA test showed a clear-cut rise from stage DO subjects to stage D2 patients, with a small number of bone lesions (greater than or equal to 3). However, a relative decrease in the mean PSA level was measured with further progression in a number of hot spots in bone (>3). Androgen threshold that is critical for the induction of the PSA (and PAP) expression seems to differ markedly in various cell subpopulations that arise during adenocarcinoma dedifferentiation. This fact explains not only the rise in serum PSA in the majority of progressive and previously castrated subjects after an initial period of hormonal responsiveness, but also a relative decline of androgen-dependent PSA expression with further tumor progression. Localized disease was accompanied with normal or just slightly elevated TPS concentration. In metastatic tumors, serum TPS values revealed a steady increase with the progression in bone. These data seem to reflect not only an increase in tumor proliferation rate with progressively transformed genome, but also the rise in the number of proliferating cells. The presence of nonepithelial transformed tumor structures, such as small cell cancer within a bulk of adenocarcinoma, reduces or normalizes numerical serotests values of both TPS and PSA even during tumor progression. The extent of such decline depends upon the bulk of the endocrine component. The assessment of the above parameters, especially when associated with elevated plasma NSE concentrations, may help in distinguishing an advanced adenocarcinoma with and without elements of malignant neuroendocrine structures. The proposed approach, modified by applying corresponding organ-specific markers, may be checked for its possible general use in staging protocols of various heterogeneous tumors. (C) 1994 Wiley-Liss, Inc.