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

Recruiting

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

• Registration Number: NCT06834152
• Lead Sponsor: University of Zurich

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.

Detailed Description

Background: Stereotactic body radiotherapy (SBRT) for localized prostate cancer has demonstrated non-inferior oncological outcomes and toxicity profiles to conventionally or moderately hypofractioned radiotherapy regimens, while offering the advantage of shorter treatment durations. However, SBRT may not be suitable for all patients, particularly those with lower urogenital tract symptoms and/or prostatic hyperplasia.

Methods: This study aims to evaluate the safety and efficacy of weekly computed tomography (CT) or magnetic resonance image-guided (MRI) online adaptive SBRT in patients with intermediate to (very) high-risk localized prostate cancer who present with lower urinary tract symptoms (International Prostate Symptom Score \[IPSS\] \> 12) and/or have prostate hyperplasia (prostate volume \>60 mL). The primary outcome measure is urogenital toxicity grade ≥3 within 3 months after completion of SBRT (according to CTCAE V5.0 and RTOG) or discontinuation of therapy. Our aim is to show that the event rate is at 3% below a clinically acceptable threshold, which is 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.

Study Timeline

• Study Start: 2024-03-01
• Status Verified: 2025-02
• Study First Submitted: 2025-02-06
• Study First Submitted QC: 2025-02-13
• Last Update Submitted: 2025-02-13
• Study First Posted: 2025-02-19
• Last Update Posted: 2025-02-19
• Primary Completion: 2026-09-01
• Study Completion: 2031-06-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 30

Inclusion Criteria

• 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;

Exclusion Criteria

• 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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
acute grade ≥ III urogenital toxicity	≤ 3 months after completion of radiotherapy	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.

Secondary Outcome Measures

Name	Time	Method
Biochemical progression-free survival	≤ 5 years after completion of radiotherapy	Biochemical progression-free survival (determined from the start of therapy until the occurrence of PSA recurrence according to the Phoenix criteria i.e. post- therapeutic PSA nadir + 2 ng/ml),
Gastrointestinal toxicity of grade ≥3	≤ 3 months after completion of radiotherapy	Gastrointestinal toxicity of grade ≥3 within 3 months after completion of radiotherapy (according to CTCAE V5.0 and RTOG)
Mortality	≤1 year after initiation of radiotherapy	Mortality (related to treatment and/or disease).
Urogenital and gastrointestinal toxicities	≤ 5 years after completion of radiotherapy	Number of urogenital and gastrointestinal toxicities within 5 years after completion of radiotherapy and their severity.
Hormonal therapy-free survival	≤ 5 years after completion of radiotherapy	Hormonal therapy-free survival (determined from the start of therapy until the start of hormonal therapy,
Overall survival	5 years after completion of radiotherapy	overall survival (defined from the start of therapy until death or censoring)
Quality-of-life questionnaire C-30 from the European Organisation for Research and Treatment of Cancer	≤ 5 years after completion of radiotherapy	Quality-of-life measured using the EORTC QLQ-C30 questionnaire during and after treatment; All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high/healthy level of functioning, a high score for the global health status/QoL represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology/problems.
Uroflowmetry (optional)	Uroflowmetry ≤ 6 weeks prior to the start of radiotherapy	Uroflowmetry prior to the start of radiotherapy (optional study procedure)
Quality-of-life questionnaire PR25 of the European Organisation for Research and Treatment of Cancer	≤ 5 years after completion of radiotherapy	Quality-of-life measured using the QLQ-PR25 questionnaire during and after treatment; All of the scales and single-item measures range in score from 0 to 100. A high score for the Sexual Activity and Sexual Functioning scales represents a high level of functioning, whereas a high score for the Urinary, Bowel, and Hormonal Treatment-Related symptoms scales and Incontinence Aid item represents a high level of symptomatology or problems.

Trial Locations

Locations (3)

Klinik für Radioonkologie und Strahlentherapie, Universitätsklinikum Heidelberg; 🇩🇪 Heidelberg, Baden-Württemberg, Germany

Klinik und Poliklinik für Strahlentherapie und Radioonkologie, Universitätsklinikum LMU; 🇩🇪 Munich, Bavaria, Germany

University Hospital Zurich, Department of Radio-Oncology; 🇨🇭 Zurich, Switzerland