RIsk aDapted Stereotactic Radiotherapy vs. standarD of Care Radiotherapy in Patients With Prostate Cancer in the Adjuvant or saLvage sEtting With or Without Lymph Node Irradiation (RIDDLELN) - A Phase III Trial

NCT07830511 | Not Yet Recruiting Phase 3

• 1 other identifier: RIDDLELN - A Phase III trial
• Study Type: interventional
• Target: 206
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to determine whether stereotactic body radiotherapy (SBRT) delivered in five fractions is non-inferior to standard-of-care mildly hypofractionated radiotherapy in terms of patient-reported quality of life in adults with prostate cancer who require adjuvant or salvage radiotherapy after radical prostatectomy. The trial includes patients with or without a macroscopic recurrence in the prostate bed and allows irradiation of the regional lymphatic drainage when clinically indicated. The main questions it aims to answer are:

• Is SBRT non-inferior to standard-of-care radiotherapy regarding urinary (GU) quality of life, measured by the change in the EPIC-26 GU domain score from baseline to 24 months after radiotherapy?
• Is SBRT non-inferior to standard-of-care radiotherapy regarding bowel (GI) quality of life, measured by the change in the EPIC-26 GI domain score from baseline to 24 months after radiotherapy? Researchers will compare SBRT delivered as 6 Gy × 5 fractions to the prostate bed with standard-of-care radiotherapy delivered as 2.625 Gy × 20 fractions (total dose 52.5 Gy) to determine whether the substantially shorter SBRT treatment provides non-inferior patient-reported urinary and bowel outcomes. When clinically indicated, treatment of the lymphatic drainage and a simultaneous integrated boost to macroscopic recurrence or involved lymph nodes may also be delivered. Participants will:
• Be randomly assigned in a 1:1 ratio to receive either five-fraction SBRT or 20-fraction standard-of-care radiotherapy.
• Receive radiotherapy to the prostate bed, with additional irradiation of the regional lymphatic drainage and/or a boost to macroscopic disease or involved lymph nodes when clinically indicated.
• Complete questionnaires assessing quality of life, urinary symptoms, and sexual function, including EPIC-26, IPSS, and IIEF-5.
• Undergo clinical assessments, PSA measurements, assessment of treatment-related adverse events, and radiological imaging when clinically indicated.
• Attend follow-up assessments at 3, 6, 12, 18, and 24 months after radiotherapy and then annually for up to 5 years. A total of 206 participants are planned for the trial. In addition to the primary quality-of-life outcomes, researchers will assess acute and late toxicity, biochemical recurrence-free survival, progression-free survival, time to further anti-cancer therapy, prostate cancer-specific survival, and overall survival.

Conditions

Prostate Cancer (Post Prostatectomy); Prostate Cancer; SBRT

Keywords

SBRT; Prostate Cancer

Outcome Measures

Primary Outcomes (2)

• Change in EPIC-26 urinary (GU) domain score from baseline to 24 months

  Patient-reported quality of life in the urinary (genitourinary, GU) domain, measured with the validated EPIC-26 (Expanded Prostate Cancer Index Composite) questionnaire. The outcome is the change in the GU domain score from pre-treatment (baseline) to 24 months after radiotherapy, compared between the SBRT and standard-of-care arms in a non-inferiority framework.

  Baseline and 24 months after radiotherapy

• Change in EPIC-26 bowel (GI) domain score from baseline to 24 months

  Patient-reported quality of life in the bowel (gastrointestinal, GI) domain, measured with the validated EPIC-26 questionnaire. The outcome is the change in the GI domain score from pre-treatment (baseline) to 24 months after radiotherapy, compared between the SBRT and standard-of-care arms in a non-inferiority framework.

  Baseline and 24 months after radiotherapy

Secondary Outcomes (3)

• Acute adverse events and serious adverse events ((S)AEs)

  From start of radiotherapy up to 3 months of follow-up

• Biochemical recurrence-free survival (bRFS)

  From inclusion up to 5 years of follow-up

• Progression-free survival (PFS), including clinical and local PFS

  From inclusion up to 5 years of follow-up

Study Arms (2)

Study Intervention

EXPERIMENTAL

Stereotactic body radiotherapy (SBRT) to the prostate bed, 6 Gy per fraction in 5 fractions on consecutive working days (EQD2 64.3 Gy at α/β 1.5), completed within approximately one week. If a macroscopic recurrence is present, an optional simultaneous integrated boost (SIB) up to 6.8 Gy per fraction over 5 fractions may be added. If treatment of the lymphatic drainage is indicated (e.g. Roach score above 20% and/or node-positive disease), a SIB of 5 Gy per fraction over 5 fractions is delivered to the lymphatic drainage, and involved lymph nodes may receive up to 6.8 Gy per fraction over 5 fractions. Concomitant androgen deprivation therapy is permitted at the treating physician's discretion.

Radiation: Stereotactic body radiotherapy (SBRT) to the prostate bed

Control Arm

ACTIVE COMPARATOR

Standard-of-care (SOC) radiotherapy to the prostate bed, 2.625 Gy per fraction in 20 fractions (total 52.5 Gy; EQD2 61.95 Gy) on consecutive working days, over approximately four weeks. If a macroscopic recurrence is present, an optional simultaneous integrated boost (SIB) up to 3 Gy per fraction over 20 fractions to a cumulative total of 60 Gy may be added. If treatment of the lymphatic drainage is indicated (e.g. Roach score above 20% and/or node-positive disease), a SIB of 2.2 Gy per fraction over 20 fractions is delivered to the lymphatic drainage, and involved lymph nodes may receive up to 3 Gy per fraction over 20 fractions. Concomitant androgen deprivation therapy is permitted at the treating physician's discretion.

Radiation: Standard-of-care radiotherapy (SOC) to the prostate bed

Interventions

Stereotactic body radiotherapy (SBRT) to the prostate bed RADIATION

SBRT to the prostate bed, 6 Gy per fraction in 5 fractions on consecutive working days (EQD2 64.3 Gy at α/β 1.5), completed within approximately one week. Optional simultaneous integrated boost (SIB) up to 6.8 Gy per fraction over 5 fractions to a macroscopic recurrence. If treatment of the lymphatic drainage is indicated (e.g. Roach score above 20% and/or node-positive disease), SIB of 5 Gy per fraction over 5 fractions to the lymphatic drainage, with involved nodes boosted up to 6.8 Gy per fraction over 5 fractions. Delivered as image-guided intensity-modulated radiotherapy. Administered to the experimental arm.

Study Intervention

Standard-of-care radiotherapy (SOC) to the prostate bed RADIATION

SOC radiotherapy to the prostate bed, 2.625 Gy per fraction in 20 fractions (total 52.5 Gy; EQD2 61.95 Gy) on consecutive working days, over approximately four weeks. Optional simultaneous integrated boost (SIB) up to 3 Gy per fraction over 20 fractions to a cumulative total of 60 Gy to a macroscopic recurrence. If treatment of the lymphatic drainage is indicated (e.g. Roach score above 20% and/or node-positive disease), SIB of 2.2 Gy per fraction over 20 fractions to the lymphatic drainage, with involved nodes boosted up to 3 Gy per fraction over 20 fractions. Delivered as image-guided intensity-modulated radiotherapy. Administered to the control arm.

Control Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed prostate cancer treated with radical prostatectomy (≥ 6 months since radical prostatectomy)
• Indication for adjuvant or salvage radiotherapy (e.g. persisting or rising PSA, macroscopic recurrence, R1 resection, pT3b) at the discretion of the treating physician
• Androgen deprivation therapy allowed at the discretion of the treating physician
• WHO performance status 0-1
• Age ≥ 18 years
• Indication for treatment of the locoregional lymphatic drainage at the discretion of the treating physician allowed (not mandatory)
• Personally signed and dated written informed consent

You may not qualify if:

• Inability to follow the procedures of the study (e.g. due to language problems, psychological disorders, dementia)
• Comorbidities which predispose to significant radiotherapy toxicities (e.g. inflammatory bowel disease), at the discretion of the treating physician
• Prior radiotherapy to the intended treatment site

Sponsors & Collaborators

• Robert Förster: lead
• Swiss Cancer League: collaborator

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Radiosurgery

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Christina Schroeder, MD

  Cantonal Hospital Winterthur

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Robert Prof. Dr. med. Förster, MD

CONTACT

004152 266 26 53; study-coordination-radiotherapy@ksw.ch

Nidar Batifi, MSc

CONTACT

004152 266 5361; nidar.batifi@ksw.ch

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr. med.

Model Details: Parallel-group, two-arm randomised controlled trial. Participants are randomised in a 1:1 ratio to one of two treatment arms: the experimental arm (stereotactic body radiotherapy, SBRT, to the prostate bed) or the control arm (standard-of-care radiotherapy to the prostate bed). Each participant receives only the treatment of their allocated arm, and the two arms run in parallel and are compared against each other. Randomisation is stratified by concomitant androgen deprivation therapy, irradiation of the lymphatic drainage, and planned boost to a macroscopic recurrence. The trial follows a non-inferiority design; no crossover between arms is planned.

Study Record Dates

• First Submitted: September 15, 2026
• First Posted: September 21, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): September 1, 2031
• Study Completion (Estimated): September 1, 2034
• Last Updated: September 21, 2026

Record last verified: 2026-09