While androgen receptor inhibitors such as enzalutamide are potent components of multimodal treatment, metastasis-directed therapy such as PSMA-radioguided surgery (PSMA-RGS) might be an attractive alternative to a subset of BCR-only patients.3 Within a multi-institutional database, we identified 111 PSMA-RGS patients who fulfilled the EMBARK inclusion criteria. After PSMA-RGS, a PSA decline below 0.2 ng/ml was observed in 53/111 patients (47.7%). In these PSA-responders (equivalent to the treatment suspension criterion in EMBARK), the estimated survival rates at 2 years were 49.9% for biochemical recurrence-free survival and 65.2% for treatment-free survival. For comparison, in the EMBARK trial, the median treatment suspension for leuprolide plus enzalutamide was 20 months.
In conclusion, PSMA-guided precision surgery might exploit the full potential of metastases-directed therapies and delay systemic therapies. While pharmaceutical products extend into the early stages, surgery and radiotherapy should be assessed in advanced stages as well.
Written by: Fabian Falkenbach & Tobias Maurer, Martini-Klinik Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
References:
- Freedland SJ, de Almeida Luz M, De Giorgi U, Gleave M, Gotto GT, Pieczonka CM, et al. Improved Outcomes with Enzalutamide in Biochemically Recurrent Prostate Cancer. N Engl J Med 2023;389:1453–65.
- Holzgreve A, Armstrong WR, Clark KJ, Benz MR, Smith CP, Djaileb L, et al. PSMA-PET/CT Findings in Patients With High-Risk Biochemically Recurrent Prostate Cancer With No Metastatic Disease by Conventional Imaging. JAMA Netw Open 2025;8:e2452971.
- Falkenbach F, Lischewski F, Knipper S, Koehler D, Karakiewicz PI, Tian Z, et al. Prostate-specific Membrane Antigen–radioguided Surgery in an EMBARK-like Cohort of Patients with Oligorecurrent Hormone-sensitive Prostate Cancer: Delay in Systemic Treatment. Eur Urol Focus 2025.