Outcomes with metastasis-directed therapy (MDT) and fixed-duration systemic therapy in oligometastatic hormone-sensitive prostate cancer (omHSPC).
Authors: Ravi Praful , Huang Jiaming , Xie Wanling , Whelpley Bridget , Kelly Emma , McGregor Bradley Alexander , Wei Xiao X. , Kilbridge Kerry L. , Viswanathan Srinivas Raghavan , Taplin Mary-Ellen , Sweeney Christopher , King Martin T. , Huynh Mai Anh , Choudhury Atish Dipankar 
Published: March 2023

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Background: Intensification of systemic therapy beyond ADT, with use of novel hormonal agents (NHAs), and radiotherapy (RT) to the prostate have a proven survival benefit in mHSPC. MDT has shown benefit in delaying need for ADT in omHSPC in phase 2 trials. Combination of fixed-duration systemic therapy with MDT (and RT to the prostate in de novo mHSPC) may produce long-term remission and treatment-free survival in selected patients with omHSPC. Methods: Patients with de novo or recurrent omHSPC treated at our institution between 2010-2020 with MDT (+/- prostate RT if de novo) and a fixed duration of systemic therapy completed by September 2022 were identified. There was no limit on number of metastases as long as all sites could be treated with MDT in the view of the treating physician. Oligometastases were defined as bone or soft tissue lesions beyond the pelvic lymph nodes identified on conventional scans (CT, bone scan, MRI) or PET (fluciclovine or PSMA). The primary outcome was freedom from biochemical recurrence (BCR), defined as PSA of >0.02 (if the patient had undergone prior radical prostatectomy) or >2+nadir (if the patient underwent RT) after completion of systemic therapy. Testosterone recovery was defined as serum testosterone >150ng/dL attained after completion of systemic therapy. BCR-free survival after completion of systemic therapy was estimated using the Kaplan Meier method. Results: 32 patients were included. Median age at diagnosis of mHSPC was 67 (range 52-78). 12 patients (38%) had de novo mHSPC while 20 (63%) had oligorecurrent HSPC. Detection of omHSPC was by conventional scans in 23 patients (72%) and by PET only in 9 (28%), and median number of oligometastases was 1 (range 1-6). Median PSA at start of therapy for omHSPC was 8.2ng/mL (range 0.4-1244), with systemic therapy most commonly comprising of ADT and a NHA (abiraterone, enzalutamide, apalutamide, n=26 [82%]); 6 patients (19%) had ADT alone. Median duration of systemic therapy was 24 months (range 6-36), with 3 men (9%) having received prior systemic therapy for mHSPC. MDT consisted of external beam RT (EBRT, n=10, 31%), EBRT + stereotactic body radiotherapy (SBRT, n=8, 25%), or SBRT alone (n=14, 44%). At a median follow-up of 44 months (range 24-127) and 20 months (2-103) after start and completion of systemic therapy respectively, 9 patients (28%) had BCR and 23 (72%) remained free of BCR, of whom 13 (57%) had testosterone recovery. The estimated 2-year BCR-free survival after completion of systemic therapy was 73% (95% CI 51-86). Conclusions: In this carefully selected cohort of men with omHSPC, estimated 2-yr BCR-free survival after completion of therapy was >70% with ~2 years of ADT +/- NHA along with MDT +/- prostate RT (if de novo). Longer follow-up is needed to determine whether this translates to a durable treatment-free remission, and possibly cure, in these patients with omHSPC.