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Prostate Radiotherapy in Patients with Metastatic Hormone-Sensitive Prostate Cancer: A Systematic Review and Meta-Analysis of Randomised Controlled Trials - Beyond the Abstract

In our recent systematic review and meta-analysis of randomized controlled trials, we evaluated the role of local prostate radiotherapy (RT) in patients with synchronous metastatic hormone-sensitive prostate cancer (mHSPC).1 

None of the included randomized trials (HORRAD,2 STAMPEDE,3 and PEACE-14 met their primary endpoints of demonstrating a statistically significant overall survival benefit from local RT. Our pooled analysis confirmed that RT did not significantly prolong overall survival in the overall study population (HR 0.92; 95% CI 0.85–1.00), and although a potential effect was suggested in patients with low metastatic burden (HR 0.74; 95% CI 0.51–1.06), it did not reach conventional levels of statistical significance. However, local RT was associated with delayed development of castration resistance (HR 0.76; 95% CI 0.70–0.82), and in both HORRAD and PEACE-1 trials, there was evidence that it reduces the risk of prostate cancer–related local adverse events

The changing therapeutic landscape in patients with mHSPC complicates interpretation. The benefit of RT observed in earlier analyses may be diminished when combined with intensified systemic regimens, including androgen receptor pathway inhibitors. PEACE-1 demonstrated that systemic intensification modifies the relative effect of local RT, underlining the need for refined selection strategies. Importantly, the current “low-volume” definition, defined by the CHAARTED criteria,5 may not adequately identify those patients most likely to benefit, and these selection criteria urgently need to be redefined in the context of modern systemic therapies and advanced imaging. PSMA-PET imaging, dynamic treatment-response markers, and genomic profiling are likely to provide the tools needed to refine patient selection.

In conclusion, local prostate RT does not improve OS in unselected patients with synchronous mHSPC but may still play a role as part of a multimodal strategy to delay resistance to androgen deprivation and prevent local complications. Until ongoing studies clarify its role in the era of systemic treatment intensification, RT should be used selectively within shared decision-making, emphasizing patient-specific disease characteristics and preferences.

Written by: Navid Roessler,1,2 Marcin Miszczyk,1,3 and Shahrokh F. Shariat1,4-9

  1. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
  2. Department of Urology, Medical University Center Hamburg-Eppendorf, Hamburg, Germany.
  3. Collegium Medicum, Faculty of Medicine, WSB University, Dąbrowa Górnicza, Poland.
  4. Department of Urology, Semmelweis University, Budapest, Hungary.
  5. Department of Urology, University of Texas Southwestern, Dallas, TX, USA.
  6. Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic.
  7. Hourani Center for Applied Scientific Research, Al-Ahliyya Amman University, Amman, Jordan.
  8. Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria.
  9. Research Center for Evidence Medicine, Urology Department, Tabriz University of Medical Sciences, Tabriz, Iran.
References:

  1. Roessler N, Miszczyk M, Dematteis A, Zattoni F, Fazekas T, Carletti F, Reitano G, Matsukawa A, Alfarhan AR, Cormio A et al: Prostate radiotherapy in patients with metastatic hormone-sensitive prostate cancer: A systematic review and meta-analysis of randomised controlled trials. Clin Transl Radiat Oncol 2025, 54:101009.
  2. Boevé LMS, Hulshof M, Vis AN, Zwinderman AH, Twisk JWR, Witjes WPJ, Delaere KPJ, Moorselaar R, Verhagen P, van Andel G: Effect on Survival of Androgen Deprivation Therapy Alone Compared to Androgen Deprivation Therapy Combined with Concurrent Radiation Therapy to the Prostate in Patients with Primary Bone Metastatic Prostate Cancer in a Prospective Randomised Clinical Trial: Data from the HORRAD Trial. Eur Urol 2019, 75(3):410-418.
  3. Parker CC, James ND, Brawley CD, Clarke NW, Hoyle AP, Ali A, Ritchie AWS, Attard G, Chowdhury S, Cross W et al: Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial. Lancet 2018, 392(10162):2353-2366.
  4. Bossi A, Foulon S, Maldonado X, Sargos P, MacDermott R, Kelly P, Fléchon A, Tombal B, Supiot S, Berthold D et al: Efficacy and safety of prostate radiotherapy in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design. Lancet 2024, 404(10467):2065-2076.
  5. Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M, Wong YN, Hahn N, Kohli M, Cooney MM et al: Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med 2015, 373(8):737-746.
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