The role of liquid biopsies in management of advanced prostate cancer

A newly published paper in Science Translational Medicine has added to our understanding of the future potential of liquid biopsies (e.g., blood, plasma, and similar samples) in the management of progressive forms of prostate cancer. However, we need to be very clear that — at least as yet — there is no proven demonstration that the use of these types of liquid biopsy technique can be associated to change in long-term outcomes for individual patients.

The new paper by Romanel et al. reports data from an international research team on the levels of expression of specific androgen receptors in blood plasma among a cohort of 97 men with castration-resistant prostate cancer (CRPC) over time while they were being treated with abiraterone acetate (Zytiga).

The available data show that:

  • Four specific androgen receptor amplifications were present from the initiation of treatment, and the levels of these androgen receptors appeared to be correlated with the development of abiraterone resistance over time.
  • Detection of these androgen receptor amplifications have the potential to help guide the use of drugs like abiraterone acetate in men with CRPC over time and to avoid the use of abiraterone acetate in the treatment of men who appear to have abiraterone-resistant disease prior to initiation of such treatment.
  • There were, however, also some new mutations to androgen receptors that became evident over time.

The current “state of the art” in the application of this type of liquid biopsy technique was discussed in this Reuters commentary yesterday, which addressed both the study by Romanel et al. and another study on sequential liquid biopsies in a single female patient with advanced breast cancer.

A key quote in the Reuters commentary comes from Dr. Nick Turner of the Institute of Cancer Research in the UK, who stated that:

What is really missing at the moment is the hard evidence that using liquid biopsy and treating patients on that basis improves hard endpoints like how long the patient lives. The field really needs those studies to change practice.

While there is no doubt at all that liquid biopsies have massive potential in the management of cancer patients (and prostate cancer patients specifically) over time, we are still missing the most important thing that we need to know: Does the use of liquid biopsies significantly change important outcomes for patients, such as overall survival, cancer-specific survival, time to metastasis, and quality of life? Without impact on key outcomes like these, the value of liquid biopsies may be limited to the research setting as opposed to regular clinical practice.

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