Multicenter, prospective evaluation of circulating tumor DNA testing in metastatic hormone-sensitive prostate cancer

There are few established prognostic biomarkers in metastatic hormone-sensitive prostate cancer (mHSPC). Assesment of circulating tumor DNA (ctDNA) provides information on both circulating volume (tumor fraction, TF) and genomic data. A multicenter prospective study evaluated ctDNA testing in mHSPC. Results before androgen deprivation therapy initiation have now been published. The primary objective was to evaluate the association between TF and overall survival (OS) and time to metastatic disease (TTCRPC). Among 72 patients with evaluable baseline ctDNA samples, 46 (64%) had positive TF. Compared with patients with negative ctDNA TF, more patients with positive ctDNA TF had de novo (87% versus 39%; p<0.001) and high-volume disease (80% versus 46%; p=0.01). At a median follow-up of 20.8 months, median OS was not reached among those with negative ctDNA TA and was 33 months among those with positive ctDNA TF (HR 3.33; p=0.03), and median TTCRPC was not reached versus 13 months (HR 3.43; p=0.004). Negative baseline TF was associated with an undetectable 7-month PSA. ctDNA was also potentially prognostic in high-volume disease and those who received doublet therapy. The authors conclude that in this diverse cohort, a positive ctDNA TF at baseline was associated with worse outcomes in mHSPC and may potentially complement other risk stratification tools.