Circulating tumor DNA in oligoprogressive prostate cancer treated with SBRT: secondary analysis of the phase 2 TRAP trial

Stereotactic body radiotherapy (SBRT) is increasingly used for oligoprogressive prostate cancer, but the duration of disease control is highly variable. Prespecified secondary analysis of the phase 2 TRAP trial (targeted radiotherapy in androgen-suppresed prostate cancer patients) evaluated time to progression based on circulating tumor DNA (ctDNA) prior to SBRT. The analysis included patients with castration-resistant prostate cancer (CRPC) and 2 or fewer SBRT-treated metastases while continuing an androgen receptor pathway inhibitor (ARPI). Plasma DNA was collected at 1 or 2 timepoints prior to SBRT and tested for ctDNA. The primary endpoint was time to progression, defined as an increase in serum PSA level of 25% or greater from the post-SBRT nadir, radiologic or symptomatic progression, clinican decision to stop ARPI, or death from any cause. Of 77 patients with evaluable blood samples taken prior to SBRT, 19 (24.7%) were in the ctDNA-positive group. The six-month progression-free survival (PFS) rate was 21.1% for the ctDNA-positive group compared with 58.3% for the ctDNA-negative group, with median PFS 3.0 versus 7.8 months (p=0.003), median time to initiation of a new therapy or death 15.3 months versus 29.6 months, and median overall survival 27.2 versus 33.6 months. The authors conclude that these findings suggest that for patients with oligoprogression and no ctDNA, SBRT and continued ARPI could be considered a valid option for prolonging disease control.