Next-generation prostate-specific antigen test: precursor form of prostate-specific antigen

Abstract

An urgent need exists to develop a more sophisticated screening system in order to improve diagnostic accuracy of clinically significant cancer and also to reduce the drawbacks of prostate-specific antigen (PSA) screening including overdetection and overtreatment. The most promising next-generation PSA test, which can improve the management of prostate cancer, may be proenzyme PSA (proPSA) or precursor PSA (pPSA). proPSA has pro-leader peptide sequences of seven or less amino acids and previous studies demonstrated that [-2]proPSA, which contains only a 2-amino-acid propeptide leader, could be more useful not only to distinguish between men with and without cancer, but also between tumors with aggressive features with performance exceeding other classical PSA-related indices including ratio of free PSA to total PSA (%f-PSA) and PSA density. Recently, it was demonstrated that baseline [-2]proPSA-related indices were independent factors to predict pathological reclassification at one year or several years after entering active surveillance. Furthermore, a retrospective study suggested that [-2]proPSA might be a useful predictive marker for future developing clinically manifested prostate cancer as well as aggressive tumors. ProPSA-related indices may have the potential for developing a more ideal risk classification for men at risk for prostate cancer, with a screening system maintaining the sensitivity of detecting clinically significant prostate cancer while saving cost, individualized treatment strategies, and follow-up procedures of active surveillance or active treatments. At a minimum, proPSA will be one of the most important new markers on the prostate cancer management in the near future.

Screening for prostate cancer: History, evidence, controversies and future perspectives toward individualized screening

“…65,67,85,[106][107][108][109][110][111][112] The future perspectives on prostate cancer management, including screening, and diagnostic and treatment systems for prostate cancer, might not only be aimed at decreasing the mortality of prostate cancer, but also aimed at achieving a significant increase in QALY with acceptable ICER. Countermeasures against overdetection according to widely available biomarkers, including proenzyme PSA 113 and magnetic resonance imaging-targeted biopsy, 114 and those against overtreatment by appropriate introduction of an active surveillance strategy, should be considered concomitantly with the establishment of an individualized screening system based on the baseline PSA concentration at a certain age. Subsequent appropriate diagnostic and treatment strategies, including appropriate clinical staging, minimally invasive intervention for the early stage of prostate cancer, individualized multimodal treatment for the advanced stage of prostate cancer and breakthrough in the field of CRPC treatment, would be very important.…”

Comprehensive assessment for novel prostate cancer markers in the prostate‐specific antigen era: Focusing on Asians and Asian countries

“…Prostate cancer cells lack a basal cell layer and invade blood vessels in the prostate, and [‐2]proPSA is relatively stable in serum compared with other forms of proPSA. Therefore, the diagnostic accuracy of [‐2]proPSA‐related indices has been investigated more than other forms of proPSA in clinical studies …”

Delivering on the promise of cancer biomarkers in the clinic

“…For example, in prostate cancer, increased levels of prostate specifc antigen (PSA) in the blood, in combination with other clinical characteristics, are used to aid in diagnosis and staging. 4,5 Recent advancements in high throughput genomic, proteomic, and even metabolomic technologies has driven the identifcation of DNA, RNA, protein, and metabolite biomarkers that are potentially informative in the diagnosis of cancer. Use of next-generation sequencing technologies can be particularly useful in establishing a diagnosis in metastatic tumors, for which there is frequent ambiwww.jcso-online.com Features guity.…”