PEACE V: Salvage Treatment of OligoRecurrent Nodal Prostate Cancer Metastases

A proportion of prostate cancer (PCa) patients develop relapse following curative local treatment. Regional nodal recurrence is an emerging clinical situation since the introduction of new molecular imaging methods in the restaging of recurrent prostate cancer. More specifically, a subgroup of these patients is being diagnosed with a recurrence confined to the regional lymph nodes and limited in number (oligorecurrence) using choline or PSMA PET-CT. As there are no specific treatment recommendations for these type of patients, different treatment approaches are currently used, mostly focusing on local ablative treatments using radiotherapy or surgery. These treatments are coined metastasisdirected therapy (MDT). MDT in combination with or without temporary ADT could delay the subsequent risk of progression, and even cure limited regional nodal recurrences. Consequently, lifelong palliative ADT, with its toxicity and excess in non-cancer mortality might be postponed. The proposed trial randomizes patients with oligorecurrent nodal prostate cancer following primary PCa treatment to either metastasis-directed therapy (MDT) (salvage lymph node dissection, sLND or stereotactic body radiotherapy, SBRT) or MDT plus whole pelvis radiotherapy (WPRT: 45 Gy in 25 fractions).

Sex

Male

Minimum age

18 Years

Inclusion Criteria:

* Histologically proven initial diagnosis of adenocarcinoma of the prostate
* Biochemical relapse of prostate cancer following radical local prostate treatment (radical prostatectomy, primary radiotherapy or radical prostatectomy +/- prostate bed adjuvant/ salvage radiotherapy) according to the EAU guidelines 2016.
* Following radical prostatectomy, patients with a biochemical relapse are eligible in case a nodal relapse is detected in the pelvis even in the absence of prior postoperative prostate bed radiotherapy (adjuvant or salvage).
* In case of a suspected local recurrence following primary radiotherapy, a biopsy should confirm local recurrence and patients with a confirmed local recurrence are eligible in case they also undergo a local salvage therapy. If imaging rules out local relapse, patients are eligible.
* Nodal relapse in the pelvis on choline, PSMA or FACBC PET-CT with a maximum of 3 positive nodal lymph nodes. The upper limit of the pelvis is defined as the aortic bifurcation.
* WHO performance state 0-1
* Age \>18 years
* Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
* Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.

Exclusion Criteria:

* Bone or visceral metastases
* Para-aortic lymph node metastases (above the aortic bifurcation)
* Local relapse in the prostate gland or prostate bed not suitable for a curative treatment
* Previous irradiation of the pelvic and or para-aortic nodes
* Serum testosterone level \<50ng/dl or 1.7 nmol/L at time of randomization
* Symptomatic metastases
* Lymph node metastases in previously irradiated areas resulting in dose constraint violation
* Contraindications to pelvic radiotherapy (chronic pelvic inflammatory bowel disease)
* Contraindications to androgen deprivation therapy
* PSA rise while on active treatment with (LHRH-agonist, LHRH-antagonist, anti-androgen, estrogen
* Previous treatment with cytotoxic agent for PCa
* Treatment during the past month with products known to influence PSA levels (e.g. fluconazole, finasteride, corticosteroids,…)
* Other active malignancy, except non-melanoma skin cancer or other malignancies with a documented disease-free survival for a minimum of 3 years before randomization.

• DERIVEDOst P, Siva S, Brabrand S, Dirix P, Liefhooghe N, Otte FX, Gomez-Iturriaga A, Everaerts W, Shelan M, Conde-Moreno A, Lopez Campos F, Papachristofilou A, Guckenberger M, Scorsetti M, Zapatero A, Villafranca Iturre AE, Eito C, Counago F, Muto P, Duthoy W, Mach N, Fonteyne V, Moon D, Thon K, Mercier C, Achard V, Stellamans K, Goetghebeur E, Reynders D, Zilli T. Salvage metastasis-directed therapy versus elective nodal radiotherapy for oligorecurrent nodal prostate cancer metastases (PEACE V-STORM): a phase 2, open-label, randomised controlled trial. Lancet Oncol. 2025 Jun;26(6):695-706. doi: 10.1016/S1470-2045(25)00197-4. Epub 2025 May 5. PMID 40339593
• DERIVEDMorgan TM, Boorjian SA, Buyyounouski MK, Chapin BF, Chen DYT, Cheng HH, Chou R, Jacene HA, Kamran SC, Kim SK, Kirkby E, Luckenbaugh AN, Nathanson BJ, Nyame YA, Posadas EM, Tran PT, Chen RC. Salvage Therapy for Prostate Cancer: AUA/ASTRO/SUO Guideline Part III: Salvage Therapy After Radiotherapy or Focal Therapy, Pelvic Nodal Recurrence and Oligometastasis, and Future Directions. J Urol. 2024 Apr;211(4):526-532. doi: 10.1097/JU.0000000000003890. Epub 2024 Feb 29. PMID 38421252
• DERIVEDOst P, Siva S, Brabrand S, Dirix P, Liefhooghe N, Otte FX, Gomez-Iturriaga A, Everaerts W, Shelan M, Conde-Moreno A, Lopez Campos F, Papachristofilou A, Guckenberger M, Scorsetti M, Zapatero A, Villafranca Iturre AE, Eito C, Counago F, Muto P, Van De Voorde L, Mach N, Bultijnck R, Fonteyne V, Moon D, Thon K, Mercier C, Achard V, Stellamans K, Goetghebeur E, Reynders D, Zilli T. PEACE V-Salvage Treatment of OligoRecurrent nodal prostate cancer Metastases (STORM): Acute Toxicity of a Randomized Phase 2 Trial. Eur Urol Oncol. 2024 Jun;7(3):462-468. doi: 10.1016/j.euo.2023.09.007. Epub 2023 Oct 9. PMID 37821242
• DERIVEDHuck C, Achard V, Zilli T. Surgical Treatments of Benign Prostatic Hyperplasia and Prostate Cancer Stereotactic Radiotherapy: Impact on Long-Term Genitourinary Toxicity. Clin Oncol (R Coll Radiol). 2022 Sep;34(9):e392-e399. doi: 10.1016/j.clon.2022.05.021. Epub 2022 Jun 15. PMID 35715340
• DERIVEDCorkum MT, Achard V, Morton G, Zilli T. Ultrahypofractionated Radiotherapy for Localised Prostate Cancer: How Far Can We Go? Clin Oncol (R Coll Radiol). 2022 May;34(5):340-349. doi: 10.1016/j.clon.2021.12.006. Epub 2021 Dec 25.