PEACE V: Salvage Treatment of OligoRecurrent Nodal Prostate Cancer Metastases

NCT ID: NCT03569241

Last Updated: 2024-12-09

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 196 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-04-27
• Study Completion Date: 2026-12-31

Brief Summary

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).

Detailed Description

A proportion of prostate cancer (PCa) patients develop a local, regional (N1) or distant (M1) relapse following curative local treatment. For both local and distant relapses, different treatment recommendations are made in the guidelines (EAU guidelines 2016). However, the entity regional nodal recurrence is not mentioned in the guidelines but is an emerging clinical situation since the introduction of choline and more recently PSMA PET-CT 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 metastases, 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) (sLND or SBRT) or MDT plus WPRT. In the recurrent PCa setting, 2 recent trials have suggested a progression-free and even survival benefit of adding temporary ADT to local salvage prostate bed radiotherapy. Consequently, this positive effect might also be applicable for regional recurrences. Although the optimal duration of ADT is unknown, a minimal duration of 6 months of ADT seems advisable in this setting and will be mandatory for both arms.

This trial will improve our insights in the pattern of recurrence following these treatment modalities with the expectation that WPRT will reduce the number of nodal relapses, improving metastasis-free survival and postponing the need for palliative systemic treatments while maintaining quality-of-life. The current phase II trial will try to establish a golden standard in the treatment of oligorecurrent nodal PCa.

Conditions

Prostate Cancer; Prostate Cancer Metastatic; Metastatic Cancer; Oligometastatic Cancer

Keywords

Radiotherapy; metastasis-directed therapy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MDT + ADT

Metastasis-directed therapy (salvage lymph node dissection OR stereotactic body radiotherapy) + 6 months androgen deprivation therapy

Group Type: OTHER

metastasis-directed treatment

Intervention Type: RADIATION

stereotactic body radiotherapy

salvage Lymph Node Dissection

Intervention Type: PROCEDURE

metastasis-directed treatment

androgen deprivation therapy

Intervention Type: DRUG

LHRH-agonist (+ anti-androgen) or antagonist for a duration of 6 months

MDT + WPRT + ADT

Metastasis-directed therapy (salvage lymph node dissection OR stereotactic body radiotherapy) + whole pelvic radiotherapy + 6 months androgen deprivation therapy

Group Type: EXPERIMENTAL

whole pelvic radiotherapy

Intervention Type: RADIATION

addition of prophylactic whole pelvic radiotherapy to a local metastasis-directed treatment

metastasis-directed treatment

Intervention Type: RADIATION

stereotactic body radiotherapy

salvage Lymph Node Dissection

Intervention Type: PROCEDURE

metastasis-directed treatment

androgen deprivation therapy

Intervention Type: DRUG

LHRH-agonist (+ anti-androgen) or antagonist for a duration of 6 months

Interventions

whole pelvic radiotherapy

addition of prophylactic whole pelvic radiotherapy to a local metastasis-directed treatment

Intervention Type: RADIATION

metastasis-directed treatment

stereotactic body radiotherapy

Intervention Type: RADIATION

salvage Lymph Node Dissection

metastasis-directed treatment

Intervention Type: PROCEDURE

androgen deprivation therapy

LHRH-agonist (+ anti-androgen) or antagonist for a duration of 6 months

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Geneva

OTHER

Sponsor Role: collaborator

University Hospital, Ghent

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Piet Ost, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Ghent

Locations

Epworth Healthcare

Melbourne, , Australia

GZA

Antwerp, , Belgium

AZ St-Jan Brugge

Bruges, , Belgium

AZ St-Lucas

Bruges, , Belgium

Institut Jules Bordet

Brussels, , Belgium

University Hospital Ghent

Ghent, , Belgium

AZ Maria Middelares

Ghent, , Belgium

AZ Groeninge

Kortrijk, , Belgium

UZ Leuven

Leuven, , Belgium

CH Mouscron

Mouscron, , Belgium

Humanitas Research Hospital

Milan, , Italy

Vita-Salute San Raffaele University

Milan, , Italy

Istituto Nazionale Tumori IRCCS

Napoli, , Italy

Fondazione IRCCS Policlinico S. Matteo

Pavia, , Italy

Ospedale Sacro Cuore-Don Calabria

Verona, , Italy

Oslo University Hospital

Oslo, , Norway

Cruces University Hospital

Barakaldo, , Spain

Clínica Universitaria IMQ

Bilbao, , Spain

Hospital Ramón y Cajal

Madrid, , Spain

Hospital Universitario La Princesa

Madrid, , Spain

Universitario Quironsalud

Madrid, , Spain

Hospitalario de Navarra

Navarro, , Spain

Hospital Clínico de Santiago

Santiago, , Spain

Hospital Universitari i Politècnic la Fe

Valencia, , Spain

Universitätsspital Basel

Basel, , Switzerland

Universitätsklinik für Radio-Onkologie

Bern, , Switzerland

Hôpitaux Universitaires de Genève

Geneva, , Switzerland

Kantonsspital St. Gallen

Sankt Gallen, , Switzerland

UniversitätsSpital Zürich

Zurich, , Switzerland

Countries

Germany; Netherlands; Australia; Belgium; Italy; Norway; Spain; Switzerland

References

Ost 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.

Reference Type: DERIVED

PMID: 40339593 (View on PubMed)

Ost 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.

Reference Type: DERIVED

PMID: 37821242 (View on PubMed)

Huck 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.

Reference Type: DERIVED

PMID: 35715340 (View on PubMed)

Corkum 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.

Reference Type: DERIVED

PMID: 34961659 (View on PubMed)

Zilli T, Dirix P, Heikkila R, Liefhooghe N, Siva S, Gomez-Iturriaga A, Everaerts W, Otte F, Shelan M, Mercier C, Achard V, Thon K, Stellamans K, Moon D, Conde-Moreno A, Papachristofilou A, Scorsetti M, Guckenberger M, Ameye F, Zapatero A, Van De Voorde L, Lopez Campos F, Counago F, Jaccard M, Spiessens A, Semac I, Vanhoutte F, Goetghebeur E, Reynders D, Ost P. The Multicenter, Randomized, Phase 2 PEACE V-STORM Trial: Defining the Best Salvage Treatment for Oligorecurrent Nodal Prostate Cancer Metastases. Eur Urol Focus. 2021 Mar;7(2):241-244. doi: 10.1016/j.euf.2020.12.010. Epub 2020 Dec 29.

Reference Type: DERIVED

PMID: 33386290 (View on PubMed)

De Bruycker A, Spiessens A, Dirix P, Koutsouvelis N, Semac I, Liefhooghe N, Gomez-Iturriaga A, Everaerts W, Otte F, Papachristofilou A, Scorsetti M, Shelan M, Siva S, Ameye F, Guckenberger M, Heikkila R, Putora PM, Zapatero A, Conde-Moreno A, Counago F, Vanhoutte F, Goetghebeur E, Reynders D, Zilli T, Ost P. PEACE V - Salvage Treatment of OligoRecurrent nodal prostate cancer Metastases (STORM): a study protocol for a randomized controlled phase II trial. BMC Cancer. 2020 May 12;20(1):406. doi: 10.1186/s12885-020-06911-4.

Reference Type: DERIVED

PMID: 32398040 (View on PubMed)

Other Identifiers

EC/2018/0130

Identifier Type: -

Identifier Source: org_study_id