Molecular markers to guide primary radical treatment selection in localized prostate cancer

Abstract

Localized prostate cancer can be effectively treated by surgical or radiotherapy approaches. In selected cases, active surveillance may also be appropriate. The choice of therapy for an individual is dependent on a number of factors but it is well recognized that different therapies may work equally well. Conversely, many patients will fail a particular treatment despite apparently favorable disease characteristics. A priori knowledge of how a tumor will respond to a treatment would be a powerful tool toward tailored therapy. Very little attention has been paid to the role of biomarkers in predicting therapy-specific responses. In this article, the current evidence for the use of tissue biomarkers to guide radical therapy selection in localized prostate cancer is discussed. Treatment failure mechanisms and the future design of research are also considered with regard to how they might inform biomarker discovery and validation in this important area of clinical need.

Keywords::

• biomarker
• predictive
• prostate cancer
• radical prostatectomy
• radiotherapy
• tailored therapy
• treatment specific

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Current choice of radical curative therapy (surgery or radiotherapy) is left to patients and clinicians to decide with few clinical models to help selection.

• No good way of predicting differential response to one treatment or another.

• The choice of treatment has a significant impact on the patient’s quality of life and survivorship.

• Equally the impact of failed primary treatment can be devastating.

• Currently, very little biomarker work addressing this specific issue is in clinical use.

• Despite hundreds of published studies, there is no good evidence that any known biomarker can help radical therapy selection in prostate cancer.

• Each therapy has different mechanisms of therapy response and failure and this has seldom been accounted for in studying biomarkers.

• Current methods of biomarker studies do not facilitate comparative studies between treatment cohorts and assume similar significance in terms of predicting outcomes.

• Technologies and archival bio-repositories already exist to initiate focused studies but require concerted resourcing and efforts to investigate this area.

• Emerging more precise methods of disease characterization at diagnosis will facilitate robust comparable biomarker studies between treatment cohorts in future studies.

• Use of common biomarker profiling platforms, survival end points and well–annotated bio-repositories are needed to address this important issue.

Notes