Combined Fixed-duration Systemic Treatment and Metastasis-directed Radiotherapy for Oligometastatic Hormone-sensitive Prostate Cancer

Background and objective: It is unclear whether "total therapy" (androgen deprivation therapy [ADT] with or without an androgen receptor pathway inhibitor [ARPI], metastasis-directed therapy, and local therapy to the prostate if de novo) may lead to long-term durable remission in oligometastatic hormone-sensitive prostate cancer (omHSPC). This study aims to evaluate the outcomes after the completion of total therapy in patients with omHSPC.

Methods: A retrospective single-institution cohort of consecutive patients with omHSPC identified on conventional or molecular imaging treated with total therapy was assembled. All patients had prostate-specific antigen ≤0.1 ng/ml at the completion of systemic therapy. Kaplan-Meier and Cox regression models were used to evaluate the key outcomes of interest: clinical progression-free survival (cPFS), eugonadal progression-free survival (PFS), and time to restart of ADT (TTrADT).

Key findings and limitations: Eighty-nine patients were included, of whom 23 were with de novo omHSPC; the median number of metastases was 1, and detection of disease by molecular imaging was performed in 43 patients (48%). Forty-nine patients (55%) received ADT + ARPI doublet and 40 (45%) received ADT alone. At a median follow-up of 37 mo, there were 46 cPFS events; 3-yr cPFS rate was 45% (95% confidence interval 33-56) and the median eugonadal PFS was 12 mo. The median TTrADT was 47 mo, and 60% had not restarted ADT at 3 yr. Duration of systemic therapy ≥12 mo was the only significant predictor of better outcomes.

Conclusions and clinical implications: Of the patients receiving total therapy for omHSPC, 45% remained progression free at 3 yr after completing therapy, hinting at the potential for long-term remission and possible cure with this strategy in a subset of patients with omHSPC. Prospective trials evaluating this approach are needed.

Patient summary: In this report, we looked at outcomes in men who had received a fixed duration of hormonal therapy along with radiotherapy to metastatic sites (and prostate radiotherapy or surgery in those with newly diagnosed disease) for oligometastatic prostate cancer. We found that nearly half of the patients had no evidence of cancer recurrence at 3 yr after completing therapy, and 60% had not resumed any therapy at this time point.