# Two Decades of Disease Evolution and Biomarker-Guided Clinical Decision Making in Metastatic Prostate Cancer

## TL;DR

This paper describes how tracking genetic changes in a prostate cancer patient over 20 years helped guide effective, personalized treatments as the cancer evolved.

## Contribution

The study highlights the clinical value of longitudinal genomic profiling and advanced imaging in managing metastatic prostate cancer.

## Key findings

- Genomic profiling and liquid biopsies revealed AR amplification, a resistance mechanism in the patient's tumor.
- Bipolar androgen therapy (BAT) reduced AR expression and restored sensitivity to enzalutamide.
- Serial liquid biopsies provided insights into tumor evolution and informed treatment decisions.

## Abstract

Despite significant advances in prostate cancer treatment over the past two decades, metastatic castration-resistant prostate cancer (mCRPC) remains incurable. We present the case of a patient with aggressive prostate cancer diagnosed 20 years ago, underscoring the value of longitudinal genomic profiling and advanced imaging to guide clinical decisions. After multiple treatment failures, genomic analyses of tissue and liquid biopsies revealed dynamic changes in tumor biology and the emergence of resistance mechanisms, particularly AR amplification, identified with a liquid biopsy test and validated by [18F]-FDHT PET scan. This finding guided treatment with bipolar androgen therapy (BAT), which achieved a dramatic clinical response, reduced AR expression, improved symptoms, and restored sensitivity to enzalutamide. This case exemplifies the utility of serial liquid biopsies in uncovering mechanisms of tumor evolution and resistance, and the crucial role of cutting-edge diagnostics in personalized cancer treatment.