Adding ADT to SBRT improves progression-free survival in oligorecurrent HSPC

Data from the phase 2 RADIOSA trial (NCT03940235) demonstrated that the addition of short-course androgen deprivation therapy (ADT) to stereotactic body radiotherapy (SBRT) improved progression-free survival (PFS) vs SBRT alone in patients with metachronous oligorecurrent hormone-sensitive prostate cancer (HSPC).¹

The data were published in Lancet Oncology.

In the ADT plus SBRT arm, the median time for testosterone recovery to non-castrate levels was 9 months.

In total, the study enrolled 105 patients who were randomly assigned 1:1 to receive the combination of ADT plus SBRT (n = 53) or to SBRT alone (n = 52). Of those, 3 patients were lost to follow-up, thus leaving 51 patients in each arm who were eligible for assessment of the primary end point, which was clinical PFS.

At a median follow-up of 31 months, 60 patients (59%) across both study arms experienced a progression event. This included 49% of patients (25 of 51) in the combination arm and 69% of patients (35 of 51) in the SBRT alone arm. The median clinical PFS was 32.2 months (95% CI, 22.4–not reached) with ADT plus SBRT vs 15.1 months (95% CI, 12.4–22.8) with SBRT alone (HR, 0.43; 95% CI, 0.26–0.72; P = .0010).

In a post-hoc analysis of the data, the clinical PFS at 1 year was 96% (95% CI, 91-100) in the ADT plus SBRT arm and 63% (95% CI, 51-78) in the SBRT alone arm. At 2 years, clinical PFS was 61% (95% CI, 48-78) and 33% (95% CI, 21-50), respectively.

The authors also reported, “Biochemical progression was reported as the first event in 66 (65%) of 102 patients: 40 (78%) of 51 patients enrolled in the SBRT group vs 26 (51%) of 51 patients in the SBRT and ADT group.”

Overall, the median biochemical PFS was 26.8 months (95% CI, 16.8–33.8). with the combination vs 12.6 months (95% CI, 9.6-13.4) with SBRT alone (HR, 0.40; 95% CI, 0.24–0.66; P = .0002). Post-hoc data showed a biochemical PFS rate of 92% (95% CI, 87-100) in the ADT plus SBRT arm and 54% (95% CI, 43-70) in the SBRT alone arm at 1 year. At 2 years, these rates were 54% (95% CI, 40-71) and 23% (95% CI, 13-39), respectively.

Among all patients, the median time to castration-resistant disease was 27.8 months (IQR, 18.8-32.8). Overall survival (OS) at 1 and 2 years was 100% and 95%, respectively.

In the ADT plus SBRT arm, the median time for testosterone recovery to non-castrate levels was 9 months (IQR, 9-12). Eugonadal PFS was 21.8 months (95% CI, 12.3–not reached) in the ADT plus SBRT arm.

Regarding safety, 43% of patients in the combination arm reported a grade 1 adverse event (AE). There was 1 instance of a grade 3 AE, which was a genitourinary acute toxicity (left ureter stenosis) in the combination arm. All AEs were resolved by last follow-up. No grade 4 AEs nor any treatment-related deaths were reported.

In total, the open-label, phase 2 RADIOSA trial enrolled 105 men with metachronous oligometastatic HSPC at a single site in Milan, Italy. The median age at enrollment was 70 years (IQR, 65-75). The median prostate-specific antigen level at diagnosis was 7.48 ng/mL (IQR, 5.70–13.46) in the ADT plus SBRT arm and 8.72 ng/mL (IQR, 5.64–12.35) in the SBRT alone arm.

To be eligible for enrollment, patients needed to have histologically confirmed adenocarcinoma of the prostate, biochemical progression after radical local prostate treatment, nodal relapse in the pelvis, extra-regional nodal relapse, and bone metastases with at least 3 lesions. Patients also needed to have an ECOG performance score of 0-1.

SBRT was delivered as 30 Gy in 3 fractions every other day. Patients in the combination arm received ADT for 6 months with a luteinizing hormone-releasing hormone analogue within 1 week before the start of SBRT. The primary end point was PFS. Secondary end points included biochemical PFS, OS, and safety.²

Overall, the authors concluded, “To the best of our knowledge, our study represents the first randomised effort to report the superiority, in terms of clinical progression-free survival, of SBRT and a short of course ADT compared with SBRT alone in metachronous oligorecurrent hormone-sensitive prostate cancer...Considering that almost all patients in the combined treatment group achieved testosterone recovery at 1 year, the results support that this short term (intermittent) combined approach is an optimal option in selected patients with metachronous oligorecurrent hormone-sensitive prostate cancer."

REFERENCES

1. Marvaso G, Carrao G, Zaffaroni M, et al. ADT with SBRT versus SBRT alone for hormone-sensitive oligorecurrent prostate cancer (RADIOSA): a randomised, open-label, phase 2 clinical trial. Lancet Oncol. 2025. 26(3):300-311. doi:10.1016/S1470-2045(24)00730-7

2. Radioablation with or without Androgen DeprIvation Therapy in Metachronous Prostate Cancer OligometaStAsis (RADIOSA). ClinicalTrials.gov. Last updated June 28, 2023. Accessed March 10, 2025. https://clinicaltrials.gov/study/NCT03940235