The utility of prostate‐specific antigen in the management of advanced prostate cancer

Abstract

To review current prostate‐specific antigen (PSA) metrics used in monitoring treatment of advanced prostate cancer, with a specific focus on castration‐resistant prostate cancer (CRPC) therapies. Explore what is known about the correlation between PSA and androgen levels as well as underlying reasons for persistent PSA expression and serum elevation in CRPC, and outline suggestions for use of PSA in managing patients with advanced prostate cancer. A comprehensive search of the PubMed database for English language articles through April 2012 was performed using the following Medical Subject Headings (MeSH) keywords or terms, alone or in combination: ‘prostate cancer’; ‘prostate cancer treatment’; ‘prostate cancer outcomes’; ‘prostate‐specific antigen’; ‘androgen receptor’; ‘advanced prostate cancer’; ‘castration‐resistant prostate cancer’; ‘biomarkers’. Bibliographies of relevant articles were searched for additional references. Relevant medical society and regulatory agency web sites from the USA and Europe were accessed for issued guidance on PSA use. PSA doubling time (PSADT) is a useful metric for determining which patients should be considered for androgen‐deprivation therapy (ADT) after failing local treatment or for second‐line therapies after failing ADT. However, it is not a validated surrogate for survival and no therapy has received regulatory approval based upon PSADT characteristics. PSA nadir and time‐to‐nadir have been identified as possible prognostic markers for patients receiving ADT. There is no universally accepted definition for PSA progression, nor is PSA progression a regulatory‐approved surrogate for clinical progression in drug approval trials. PSA responses to second‐line therapies can vary and are not considered by regulatory agencies as valid surrogates for clinical endpoints, so they must be assessed in the context of each individual therapy and trial design. PSA expression in CRPC is often a reflection of persistent androgen receptor activity. While we can provide guidance for use of PSA monitoring in managing patients with advanced prostate cancer based on the data at hand, there is an urgent need for prospective analyses of refined PSA metrics in conjunction with newer prostate cancer biomarkers in clinical trials to provide stronger evidence for their roles as surrogate endpoints.

Intensity of stromal changes is associated with tumor relapse in clinically advanced prostate cancer after castration therapy

“…Serum PSA response is the most frequently used prognostic marker in patients having tumors with a Gleason score of 6–7 22. However, it is often difficult to correctly evaluate patients who have a better or poorer response to castration therapy.…”

Fibroblasts prolong serum prostate-specific antigen decline after androgen deprivation therapy in prostate cancer

“…2 In patients with PCa undergoing ADT, PSA kinetics are considered an important indicator of the response to ADT; however, the prognostic significance of PSA kinetics remains controversial. 3 Intuitively, most urologists expect that a more rapid PSA decline in response to ADT would be positively associated with extended survival. Clinical studies performed in the 1990s indicated that rapid PSA decline was associated with longer remission periods.…”

“…5,6 Several recent studies have also demonstrated that longer time to PSA nadir after ADT can predict favorable progression-free survival and overall survival in various hormone-naive patient populations based on large, multicenter investigations. 3,7,8 Thus, surprisingly, a rapid decline in PSA expression after ADT strongly appears to indicate more aggressive disease. However, the mechanisms mediating this effect remain unknown.…”

Low-dose docetaxel, estramustine and prednisolone combination chemotherapy for castration-resistant prostate cancer

“…PSA values were dichotomized as ≤20 or >20 ng̸ml in the univariate and multivariate analyses. PSA level was shown to be a potential predictor of CSS (26) and most prediction models define high-risk prostate carcinoma as a presenting PSA level of >20 ng̸ml (27), with high risk defined as the risk of prostate cancer causing metastasis.…”