Online Adaptive Stereotactic Body Radiotherapy for Localized Prostate Cancer (X-SMILE)

NCT06834152 | Recruiting

• 1 other identifier: RAO-24-014
• Study Type: observational
• Target: 75
• Locations: 2 countries
• Sites: 3

Brief Summary

The aim of this phase II international multicenter study is to evaluate the safety, feasibility, and efficacy of CT or MRI-adaptive SBRT, delivered in five weekly fractions, in patients with newly diagnosed localized prostate cancer who have lower urinary tract symptoms and/or prostatic hyperplasia.

Conditions

Localized Prostate Carcinoma; Prostate Cancer (Adenocarcinoma); Prostate Hyperplasia; Lower Urinary Track Symptoms

Keywords

radiotherapy; SBRT; MRI; CT; stereotactic radiotherapy; localized prostate cancer; lower urinary tract symptoms; prostate hyperplasia; prostate cancer

Outcome Measures

Primary Outcomes (1)

• acute grade ≥ III urogenital toxicity

  The primary endpoint is acute grade ≥ III urogenital toxicity ≤3 months after completion of radiotherapy (according to the NCI CTCAE V5 or RTOG) or treatment discontinuation related to treatment.

  ≤ 3 months after completion of radiotherapy

Secondary Outcomes (9)

• Gastrointestinal toxicity of grade ≥3

  ≤ 3 months after completion of radiotherapy

• Mortality

  ≤1 year after initiation of radiotherapy

• Urogenital and gastrointestinal toxicities

  ≤ 5 years after completion of radiotherapy

• Biochemical progression-free survival

  ≤ 5 years after completion of radiotherapy

• Hormonal therapy-free survival

  ≤ 5 years after completion of radiotherapy

Study Arms (2)

Pilot study

For our pilot study, we assumed that around 3% of patients would have grade 3 acute urogenital toxicity (i.e. 1 patient). The rate of treatment discontinuation within 3 months was considered negligible. Our aim was to show with high probability, that the event rate was below a clinically acceptable threshold, which was set at 20%. Under the null hypothesis, this design with an alpha of 0.05 and power of 80% results in an expected number of cases of 30. Dropouts prior to treatment start will be replaced.

Radiation: radiotherapy

Validation Cohort

For our validation study, we assume that around 3% of patients will have grade 3 long-term urogenital toxicity (i.e. 2 patients). The rate of treatment discontinuation within 3 months is considered negligible. Our aim is to show with high probability, that the event rate is below a clinically acceptable threshold, which is set at 12%. Under the null hypothesis, this design with an alpha of 0.05 and power of 80% results in an expected number of cases of 75. Dropouts prior to treatment start will be replaced.

Radiation: radiotherapy

Interventions

radiotherapy RADIATION

Patients with prostate cancer in the medium or high risk range who are planned to receive definitive CT or MRI-adaptive SBRT.

Pilot study; Validation Cohort

Eligibility Criteria

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

Study Population

This international multicenter prospective phase II study, conducted in collaboration with several academic hospitals in Switzerland and Germany, will include patients with histologically confirmed intermediate to (very) high risk localized prostate cancer with lower urinary tract symptoms and/or prostate hyperplasia. These patients are planned to receive weekly CT or MRI online adaptive SBRT for localized prostate cancer.

You may qualify if:

• histologically confirmed localized prostate cancer
• planned treatment is SBRT according to standard of care and consists of definitive CT or MRI online adaptive SBRT of the prostate according to the PACE trial which includes a total dose to clinical target volume 1 (CTV1, i.e. prostate and proximal 1 cm of the seminal vesicle) of 40.0 Gy in 5 weekly fractions (single dose of 8.0 Gy) and total dose to planning target volume 1 (PTV1) of 37.5 Gy in 5 weekly fractions (single dose of 7.5 Gy) with a compromise for bowel sparing allowed. For patients with unfavorable intermediate to very high-risk disease (according to NCCN guidelines) a total dose to the planning target volume 2 (PTV2, i.e. proximal 1-2 cm of the seminal vesicle) of 32.5 Gy in 5 weekly fractions (single dose of 6.5 Gy) will be delivered.
• intermediate to (very) high risk localized prostate cancer (≤ cT3a and Gleason score ≤ 9 and/or PSA ≤ 20 ng/ml)
• prostate volume \> 60 cc and/or IPSS \> 12;

You may not qualify if:

• Very high risk localized prostate cancer with indication for ADT and ARPI (i.e. Gleason ≥ 8 and cT3a)
• Involvement of seminal vesicles (cT3b)
• Contraindications against definitive CT or MRI-adaptive radiotherapy of the prostate, e.g. inflammatory bowel disease (IBD); previous radiotherapy in the pelvis, previous local radiotherapy of the prostate, contraindication for MRI or CT;
• Patients with severe genitourinary symptoms (e.g. recent urinary retention ≥ grade 3 according CTCAE v.5.0);
• Lymph node metastases or distant metastases (i.e. no localised prostate cancer);
• Participation in a clinical trial which might influence the results of this project.

Sponsors & Collaborators

• University of Zurich: lead

Study Sites (3)

Klinik für Radioonkologie und Strahlentherapie, Universitätsklinikum Heidelberg

Heidelberg, Baden-Wurttemberg, 69120, Germany

NOT YET RECRUITING

Klinik und Poliklinik für Strahlentherapie und Radioonkologie, Universitätsklinikum LMU

Munich, Bavaria, 81377, Germany

NOT YET RECRUITING

University Hospital Zurich, Department of Radio-Oncology

Zurich, Canton of Zurich, 8090, Switzerland

RECRUITING

Related Publications (1)

• Kroese T, Andratschke N, Belka C, Corradini S, Marschner S, Liermann J, Horner-Rieber J, Fink C, Debus J, Silvia F, Tanadini-Lang S, Pouymayou B, Mencarelli A, Fesslmeier D, Schiess A, Guckenberger M, Mayinger M. Online adaptive stereotactic body radiotherapy for localized prostate cancer in patients with lower urinary tract symptoms and/or prostate hyperplasia (X-SMILE). Radiat Oncol. 2025 May 28;20(1):90. doi: 10.1186/s13014-025-02653-4.

  PMID: 40437508 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms; Adenocarcinoma; Prostatic Hyperplasia; Lower Urinary Tract Symptoms

Interventions

Radiotherapy

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Matthias Guckenberger, Prof. Dr. med.

  University of Zurich

  STUDY CHAIR

• Tiuri E. Kroese, MD, PhD

  University of Zurich

  PRINCIPAL INVESTIGATOR

• Matthias Guckenberger

  University of Zurich

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Radiation Oncology Study Office

CONTACT

+41442554108; RAO_akademischesoffice@usz.ch

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2025
• First Posted: February 19, 2025
• Study Start: March 1, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): June 30, 2031
• Last Updated: February 9, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Beginning 9 months and ending 36 months after article publication.
• Access Criteria: Proposals to access study data should send request to matthias.guckenberger@usz.ch. To gain access, data requesters must sign data access agreement.

Locations

CH (1); DE (2)