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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.
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. In our validation cohort 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| radiotherapy | Radiation | Patients with prostate cancer in the medium or high risk range who are planned to receive definitive CT or MRI-adaptive SBRT. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Gastrointestinal toxicity of grade ≥3 | Gastrointestinal toxicity of grade ≥3 within 3 months after completion of radiotherapy (according to CTCAE V5.0 and RTOG) | ≤ 3 months after completion of radiotherapy |
| Mortality |
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Inclusion Criteria:
Exclusion Criteria:
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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.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Radiation Oncology Study Office | Contact | +41442554108 | RAO_akademischesoffice@usz.ch |
| Name | Affiliation | Role |
|---|---|---|
| Matthias Guckenberger, Prof. Dr. med. | University of Zurich | Study Chair |
| Tiuri E. Kroese, MD, PhD | University of Zurich | Principal Investigator |
| Matthias Guckenberger |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Klinik für Radioonkologie und Strahlentherapie, Universitätsklinikum Heidelberg | Not yet recruiting | Heidelberg | Baden-Wurttemberg | 69120 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40437508 | Derived | 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. |
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Individual participant data that underlie the results reported in this trial after de-identification. Other documents may be shared include the study protocol.
Beginning 9 months and ending 36 months after article publication.
Proposals to access study data should send request to matthias.guckenberger@usz.ch. To gain access, data requesters must sign data access agreement.
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| ID | Term |
|---|---|
| D011471 | Prostatic Neoplasms |
| D000230 | Adenocarcinoma |
| D011470 | Prostatic Hyperplasia |
| D059411 | Lower Urinary Tract Symptoms |
| ID | Term |
|---|---|
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D011878 | Radiotherapy |
| ID | Term |
|---|---|
| D013812 | Therapeutics |
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Mortality (related to treatment and/or disease).
| ≤1 year after initiation of radiotherapy |
| Urogenital and gastrointestinal toxicities | Number of urogenital and gastrointestinal toxicities within 5 years after completion of radiotherapy and their severity. | ≤ 5 years after completion of radiotherapy |
| Biochemical progression-free survival | 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), | ≤ 5 years after completion of radiotherapy |
| Hormonal therapy-free survival | Hormonal therapy-free survival (determined from the start of therapy until the start of hormonal therapy, | ≤ 5 years after completion of radiotherapy |
| Overall survival | overall survival (defined from the start of therapy until death or censoring) | 5 years after completion of radiotherapy |
| Quality-of-life questionnaire C-30 from the European Organisation for Research and Treatment of Cancer | 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. | ≤ 5 years after completion of radiotherapy |
| Uroflowmetry (optional) | Uroflowmetry prior to the start of radiotherapy (optional study procedure) | Uroflowmetry ≤ 6 weeks prior to the start of radiotherapy |
| Quality-of-life questionnaire PR25 of the European Organisation for Research and Treatment of Cancer | 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. | ≤ 5 years after completion of radiotherapy |
| University of Zurich |
| Principal Investigator |
| Klinik und Poliklinik für Strahlentherapie und Radioonkologie, Universitätsklinikum LMU | Not yet recruiting | Munich | Bavaria | 81377 | Germany |
|
| University Hospital Zurich, Department of Radio-Oncology | Recruiting | Zurich | Canton of Zurich | 8090 | Switzerland |
|
| D005832 |
| Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D020924 | Urological Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |