Androgen deprivation decreases prostate specific antigen in the absence of tumor: implications for interpretation of PSA results

Abstract

Background: Prostate-specific antigen (PSA) is used as an outcome measure for relapsed disease in prostate cancer. Nonetheless, there are considerable concerns about its indiscriminate use as a surrogate endpoint for cell growth or survival. We hypothesized that treatment with a luteinizing hormone releasing hormone (LHRH) analog would decrease PSA levels even in the absence of malignant disease. Methods: We determined testosterone and PSA levels in 30 healthy volunteers after a single intramuscular injection of a LHRH depot formulation. Testosterone and PSA levels were quantified by radioimmunoassay and electrochemi-luminescence immunoassay, respectively. Results: After an initial flare-up during the first 3 days testosterone decreased reaching castration levels in 18 of the 30 young men (60%). After the nadir on day 28, testosterone levels increased to normal again. Changes in PSA paralleled those of testosterone. Castration reduced PSA levels by 29% (95% CI 19%-39%) compared to baseline (p < 0.0001). Conclusions: LHRH superagonists decrease PSA levels by testosterone deprivation. Conferring these findings to tumor patients, decreases in PSA after treatment with LHRH analogs might not only reflect disease regression but also a direct testosterone mediated effect on PSA. Thus, PSA levels should be cautiously interpreted when patients receive hormonal therapy.

Predicting castration-resistant prostate cancer after combined androgen blockade

“…Combined androgen blockade reduced PSA values in most patients by more than 80% in the first month [ 13 ]. However, some studies had shown that PSA decline did not indicate tumor cell death, but instead represented AR pathway inhibition and subsequent reduced PSA secretion [ 14 ]. However, a slower PSA reduction following an initial rapid decline is considered representative of tumor load reduction.…”

The microRNA‐193a‐5p induced ROS production and disturbed colocalization between STAT3 and androgen receptor play critical roles in cornin induced apoptosis

“…Accumulating evidence reveals that AR is critically involved in PC progression (Pelekanou & Castanas, 2016; Zarif & Miranti, 2016) and metastasis (Yin et al, 2014), while ADT using luteinizing hormone releasing hormone agonist decreases PSA level by testosterone deprivation (Liu et al, 2017; Wenisch et al, 2014).…”

Managing Nonmetastatic Castration-resistant Prostate Cancer

“…In the setting of nmCRPC, when no disease is detectable by conventional imaging tests, PSA testing indirectly monitors tumour AR signalling activity, which can correlate with disease burden. However, it must be noted that PSA declines are not proven surrogate biomarkers of survival outcome and that downregulation of AR signalling does not always represent tumour cell elimination, and indeed it is well recognised that some aggressive prostate cancers are low PSA secretors [25,26]. In the nmCRPC state, more data are needed to demonstrate that slowing of PSA velocity, or achievement of a greater PSA decline in the nmCRPC state, is associated with meaningful benefit in terms of extending survival or improving quality of life.…”