Abstract
The substantial biological heterogeneity of metastatic prostate cancer has hindered the development of personalized therapeutic approaches. Therefore, it is difficult to predict the course of metastatic hormone-sensitive prostate cancer (mHSPC), with some men remaining on first-line androgen deprivation therapy (ADT) for several years while others progress more rapidly. Improving our ability to risk-stratify patients would allow for the optimization of systemic therapies and support the development of stratified prospective clinical trials focused on patients likely to have the greatest potential benefit. Here, we applied a liquid biopsy approach to identify clinically relevant, blood-based prognostic biomarkers in patients with mHSPC. Gene expression indicating the presence of CTCs was greater in CHAARTED high-volume (HV) patients (52% CTChigh) than in low-volume (LV) patients (23% CTChigh; * p = 0.03). HV disease (p = 0.005, q = 0.033) and CTC presence at baseline prior to treatment initiation (p = 0.008, q = 0.033) were found to be independently associated with the risk of nonresponse at 7 months. The pooled gene expression from CTCs of pre-ADT samples found AR, DSG2, KLK3, MDK, and PCA3 as genes predictive of nonresponse. These observations support the utility of liquid biomarker approaches to identify patients with poor initial response. This approach could facilitate more precise treatment intensification in the highest risk patients.
Highlights
This study reported on the initial 58 patients with metastatic hormone-sensitive prostate cancer (mHSPC) enrolled in MiCoPilot (Table 1)
The prevalence of circulating tumor cell (CTC) was found to be significantly greater in HV patients (52% CTChigh ) than in LV patients (23% CTChigh ; p = 0.03)
Risk stratification of an mHSPC patient currently leans on clinical characteristics
Summary
Other studies enriched for more aggressive tumor subsets by recruiting a larger proportion of men with a higher volume of disease (CHAARTED) [2] or predominantly de novo metastatic disease (STAMPEDE, LATITUDE) [3,4]. Both of these studies demonstrated a clear benefit for docetaxel, leading to a change in the standard of care. These studies demonstrated the importance of understanding the biology and heterogeneity within a clinical cohort to design optimal clinical trials and, outcomes for patients. Even though abiraterone has a clear survival benefit when initiated within 3 months of ADT starting per LATITUDE and STAMPEDE, when its start is delayed for 7 months and just given to those with a poor PSA response, the benefit is lost [4,5,6]
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