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EAU 2025

EAU 2025: High-Volume De Novo Metastatic Hormone-Sensitive Prostate Cancer: Local Treatment Matters

(UroToday.com) The 2025 European Association of Urology (EAU) Annual Meeting held in Madrid, Spain was host to the clinically relevant questions in the management of advanced, hormone-sensitive prostate cancer: Thematic session. Dr. Karim Fizazi delved into why local treatment still matters for high-volume de novo metastatic hormone-sensitive prostate cancer.


Dr. Fizazi highlighted that in patients with high-volume de novo metastatic hormone-sensitive prostate cancer (mHSPC), a key concern is managing severe local symptoms of metastatic disease. He presented data from two institutions over the past decade, evaluating the prevalence of local symptoms in mHSPC patients at baseline and upon progression to mCRPC. Two-thirds of mHSPC patients experienced local symptoms, while in mCRPC, a separate study found that 78% had local symptoms, including 29% with acute urinary retention, 45% with pelvic pain, and 14% with hematuria.

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Similarly, in mHSPC, 17% of patients required TURP, 4% underwent palliatrive radiotherapy, and 4% needed stents or nephrostomy tubes. The need for these interventions is significantly higher in mCRPC, as shown below.

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Radiation therapy can help prevent local progression in mCRPC. Solid data from the PEACE-1 study confirmed that in both high-volume and low-volume mHSPC, upfront RT reduces the risk of severe GU symptoms, including the need for TURP, stents, nephrostomy, or prostatectomy.1

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Moreover, based on PEACE-1 data, local radiation therapy is likely synergistic with Abiraterone acetate in both low- and high-volume mHSPC. This benefit also translates into improved endpoints such as radiological progression free survival (rPFS) and castration resistant disease-free survival.

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The prevention effect of RT was recently confirmed by other groups. The HORRAD trial in the Netherlands, showed that in 432 patients with mCSPC there were fewer local events with radiation therapy (50 vs 30, p=0.04), and time to local interventions was longer in the radiation therapy group (HR: 0.61, 95% CI: 0.37-0.99, p=0.04).2 Similarly, data from STAMPEDE in the NHS confirmed the preventive effect of upfront radiotherapy in mHSPC.3

Regarding toxicity and costs, PEACE-1 demonstrated that RT was well tolerated, with Grade 3-4 toxicity rates of 58.8% vs 56.1% (with vs without RT), and <1% had Grade 3-4 rectal hemorrhage. Most toxicities were Grade 1-2 pollakiuria or dysuria. Radiotherapy is generally not expensive, at least in Europe, whereas the cost of managing local symptoms in mCRPC is high. Hospitalization due to local symptoms occurred in 43% of symptomatic patients, and 11 of 263 patients died from local progression.

Dr. Fizazi concluded with a strong message:

  • Prevention is better than cure!
  • Prostate radiotherapy should be part of the standard of care in men with mCSPC.

Presented by: Karim Fizazi, MD, PhD, Medical oOncologist at Institut Gustave Roussy and full professor in Oncology at the University of Paris Saclay in Villejuif, France.

Written by: Julian Chavarriaga, MD – Urologic Oncologist at Cancer Treatment and Research Center (CTIC) via Society of Urologic Oncology (SUO) Fellow at The University of Toronto. @chavarriagaj on Twitter during the European Association of Urology (EAU) 2025 Annual Meeting, Madrid, Spain, Fri, Mar 21 – Mon, Mar 24, 2025.  

References:

  1. Fizazi K, Foulon S, Carles J, Roubaud G, McDermott R, Fléchon A, Tombal B, Supiot S, Berthold D, Ronchin P, Kacso G, Gravis G, Calabro F, Berdah JF, Hasbini A, Silva M, Thiery-Vuillemin A, Latorzeff I, Mourey L, Laguerre B, Abadie-Lacourtoisie S, Martin E, El Kouri C, Escande A, Rosello A, Magne N, Schlurmann F, Priou F, Chand-Fouche ME, Freixa SV, Jamaluddin M, Rieger I, Bossi A; PEACE-1 investigators. Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel 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. 2022 Apr 30;399(10336):1695-1707. doi: 10.1016/S0140-6736(22)00367-1. Epub 2022 Apr 8. PMID: 35405085.
  2. Boevé LMS, Hulshof MCCM, Verhagen PCMS, Twisk JWR, Witjes WPJ, de Vries P, Jeroen A van Moorselaar R, Vis AN, van Andel G. Prostate Cancer-related Events in Patients with Synchronous Metastatic Hormone-sensitive Prostate Cancer Treated with Androgen Deprivation Therapy with and Without Concurrent Radiation Therapy to the Prostate; Data from the HORRAD Trial. Eur Urol. 2025 Mar;87(3):357-363. doi: 10.1016/j.eururo.2024.08.035. Epub 2024 Sep 20. PMID: 39304427.
  3. Parker CC, James ND, Brawley CD, Clarke NW, Hoyle AP, Ali A, Ritchie AWS, Attard G, Chowdhury S, Cross W, Dearnaley DP, Gillessen S, Gilson C, Jones RJ, Langley RE, Malik ZI, Mason MD, Matheson D, Millman R, Russell JM, Thalmann GN, Amos CL, Alonzi R, Bahl A, Birtle A, Din O, Douis H, Eswar C, Gale J, Gannon MR, Jonnada S, Khaksar S, Lester JF, O'Sullivan JM, Parikh OA, Pedley ID, Pudney DM, Sheehan DJ, Srihari NN, Tran ATH, Parmar MKB, Sydes MR; Systemic Therapy for Advanced or Metastatic Prostate cancer: Evaluation of Drug Efficacy (STAMPEDE) investigators. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial. Lancet. 2018 Dec 1;392(10162):2353-2366. doi: 10.1016/S0140-6736(18)32486-3. Epub 2018 Oct 21. PMID: 30355464; PMCID: PMC6269599.