Erectile Function PRESERVation in Definitive Radiotherapy for Prostate Cancer by MRI-Enhanced Adaptive Sparing of the Neurovascular Bundle (EF-PRESERVE)
Radiotherapy is a standard and highly effective treatment for prostate cancer that is confined to the prostate gland. One modern approach, called stereotactic body radiotherapy (SBRT), delivers treatment in just five sessions and has been shown to control prostate cancer as well as longer treatment schedules. Large clinical studies have demonstrated excellent cancer control rates after SBRT.
Although SBRT is effective, some men experience worsening erectile function after treatment. Researchers believe that reducing radiation exposure to the nerves and blood vessels involved in erections, known as the neurovascular bundles (NVBs), may help preserve sexual function.
The EF-PRESERVE study is evaluating whether a specialized MRI-guided treatment approach can safely reduce radiation dose to these structures while still delivering effective treatment to the prostate cancer.
Studienübersicht
Status
Bedingungen
Intervention / Behandlung
Detaillierte Beschreibung
Stereotactic body radiotherapy (SBRT) has evolved from an experimental modality into a guideline-supported treatment option for localized prostate cancer. Initial pooled consortium data across 1,100 patients demonstrated high efficacy and acceptable toxicity, which was subsequently confirmed by prospective phase III trials. The HYPO-RT-PC trial established the non-inferiority of 42.7 Gy in seven fractions, while PACE-B showed that 5-fraction SBRT without androgen deprivation therapy (ADT) achieved equivalent 5-year biochemical or clinical failure-free survival compared to conventional or moderately hypofractionated schedules (95.8% vs. 94.6%). Nevertheless, erectile dysfunction remains a frequent late toxicity, with clinician-reported CTCAE Grade more than 2 erectile dysfunction rising from 18% at baseline to 26.4% five years post-SBRT in PACE-B.
To mitigate this functional decline, the EF-PRESERVE study incorporates daily adaptive magnetic resonance imaging (MRI). Because standard cone-beam computed tomography (CBCT) lacks sufficient soft-tissue resolution to visualize structures like the neurovascular bundle (NVB), the ARTEMIS workflow acts as a scaleable alternative to integrated MR-linacs.
Patients are scanned on a dedicated MRI simulator to adjust target and NVB contours daily, then transferred via a dedicated shuttle system directly to a CE-marked CBCT linear accelerator for radiotherapy delivery.
Studientyp
Einschreibung (Geschätzt)
Phase
- Unzutreffend
Kontakte und Standorte
Studienkontakt
- Name: Tiuri Kroese, MD PhD
- Telefonnummer: +41 44 255 41 32
- E-Mail: tiuri.kroese@usz.ch
Studieren Sie die Kontaktsicherung
- Name: Matthias Guckenberger, Prof. Dr. med
- Telefonnummer: +41 44 255 29 30
Studienorte
-
-
-
Zurich, Schweiz
- University Hospital Zurich
-
Kontakt:
- Tiuri Kroese, MD PhD
- Telefonnummer: +41 44 255 41 32
- E-Mail: tiuri.kroese@usz.ch
-
-
Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
Inclusion Criteria:
-
Age ≥18 years
-
Histologically confirmed, low- or intermediate risk localized prostate cancer eligible for definitive prostate SBRT according to NCCN criteria as (Appendix 1):
- cT1-cT2 and
- PSA <20 ng/ml and
- Gleason <8
-
At least at one side the DIL ≥5 mm from the NVB
-
WHO/ECOG performance status 0-2
-
Sexually active patients (i.e. satisfactory penetrative intercourse over the last 4 weeks)
-
Life expectancy >5 years
-
If ADT planned during radiotherapy:
- Only short-course ADT for in total ≤6 months using oral GnRH-antagonists (e.g. Relugolix) for rapid testosterone recovery.
Exclusion Criteria:
-
DIL within <5 mm to NVB at both sides
-
High risk localized prostate cancer according to NCCN criteria as:
- cT3-cT4 or
- PSA ≥20 ng/ml or
- Gleason ≥8
-
Non-localized prostate cancer (i.e. cN1 or cM1)
-
Insufficient erectile function preventing satisfactory penetrative intercourse (i.e. erectile dysfunction CTCAE (v6.0) Grade 3)
-
Sexually inactive patients (i.e. no penetrative intercourse over the last 4 weeks).
-
Previous pelvic radiotherapy (at any time)
-
Previous definitive treatment for prostate cancer (radiotherapy or prostatectomy at any time)
-
Contraindication to repeated MRI
-
Unable to lie in a supine position for estimated 30 min
-
Inability or contraindications to undergo the investigated intervention,
-
Clinically significant concomitant diseases,
-
Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: N / A
- Interventionsmodell: Einzelgruppenzuweisung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
|---|---|
|
Experimental: Adaptive MR-Enhanced SBRT with NVB Sparing
Participants undergo ultra-hypofractionated stereotactic body radiotherapy (SBRT) delivered in 5 fractions. Prior to each fraction, patients are imaged on a MRI simulator to evaluate and adapt target volumes and neurovascular bundle (NVB) contours. Using the ARTEMIS transfer shuttle system, patients are moved directly to a standard C-arm CBCT linear accelerator. The NVB will be spared during radiotherapy delivery while maintaining a minimum target dose of 40 Gy to the dominant intraprostatic lesion (DIL). If clinically indicated, concurrent short-course androgen deprivation therapy (under 6 months) is limited strictly to oral GnRH antagonists (e.g., Relugolix). |
Patients receive daily adaptive ultra-hypofractionated SBRT (5 fractions) utilizing the ARTEMIS workflow. Before each fraction, patients undergo low-field MRI to adapt target and neurovascular bundle (NVB) contours based on daily anatomical changes. Patients are transferred in treatment position to a standard CBCT linear accelerator via a shuttle system. Radiotherapy intentionally spares the NVB (unilaterally or bilaterally depending on tumor proximity) to preserve erectile function, while ensuring the dominant intraprostatic lesion (DIL) receives at least 40Gy. Additional erection-related structures (internal pudendal artery, penile bulb, corpus cavernosum) are contoured for dosimetric analysis. Concurrent short-course ADT (not more than 6 months), if indicated, is restricted to oral GnRH antagonists (Relugolix) to allow rapid testosterone recovery. |
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Proportion of Patients with CTCAE v6.0 Grade ≥2 Erectile Dysfunction at 1 Year Post-SBRT
Zeitfenster: 1 year post-SBRT
|
Evaluates the proportion of sexually active patients who develop clinician-reported moderate to severe erectile dysfunction (defined as CTCAE v6.0 Grade ≥2) 1 year following the completion of adaptive MR-enhanced prostate SBRT with neurovascular bundle (NVB) sparing. The rate will be evaluated against historical controls from the PACE-B trial benchmark. |
1 year post-SBRT
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Patient-Reported Erectile Function Change via IIEF-5 Score
Zeitfenster: Baseline, every 3 months for the first 1 year, and annually thereafter up to 5 years post-SBRT
|
Evaluates changes in patient-reported erectile function using the 5-item International Index of Erectile Function (IIEF-5) questionnaire. Scores range from 5 to 25, with lower scores indicating more severe erectile dysfunction (ED). The mean score change from baseline, the proportion of patients maintaining potency, and the proportion experiencing a clinically meaningful decline (≥4 point drop in IIEF-5 score) will be evaluated across time points. |
Baseline, every 3 months for the first 1 year, and annually thereafter up to 5 years post-SBRT
|
|
Biochemical progression-free survival
Zeitfenster: Baseline, every 3 months for the first 1 year, and annually thereafter up to 5 years post-SBRT
|
Measurement of PSA, biochemical progression is defined according to phoenix criteria. |
Baseline, every 3 months for the first 1 year, and annually thereafter up to 5 years post-SBRT
|
Mitarbeiter und Ermittler
Sponsor
Ermittler
- Hauptermittler: Tiuri Kroese, MD PhD, University Hospital Zurich / University of Zurich
Publikationen und hilfreiche Links
Allgemeine Veröffentlichungen
- King CR, Freeman D, Kaplan I, Fuller D, Bolzicco G, Collins S, Meier R, Wang J, Kupelian P, Steinberg M, Katz A. Stereotactic body radiotherapy for localized prostate cancer: pooled analysis from a multi-institutional consortium of prospective phase II trials. Radiother Oncol. 2013 Nov;109(2):217-21. doi: 10.1016/j.radonc.2013.08.030. Epub 2013 Sep 20.
- Shore ND, Saad F, Cookson MS, George DJ, Saltzstein DR, Tutrone R, Akaza H, Bossi A, van Veenhuyzen DF, Selby B, Fan X, Kang V, Walling J, Tombal B; HERO Study Investigators. Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer. N Engl J Med. 2020 Jun 4;382(23):2187-2196. doi: 10.1056/NEJMoa2004325. Epub 2020 May 29.
- van As N, Griffin C, Tree A, Patel J, Ostler P, van der Voet H, Loblaw A, Chu W, Ford D, Tolan S, Jain S, Camilleri P, Kancherla K, Frew J, Chan A, Naismith O, Armstrong J, Staffurth J, Martin A, Dayes I, Wells P, Price D, Williamson E, Pugh J, Manning G, Brown S, Burnett S, Hall E. Phase 3 Trial of Stereotactic Body Radiotherapy in Localized Prostate Cancer. N Engl J Med. 2024 Oct 17;391(15):1413-1425. doi: 10.1056/NEJMoa2403365.
- Brand DH, Tree AC, Ostler P, van der Voet H, Loblaw A, Chu W, Ford D, Tolan S, Jain S, Martin A, Staffurth J, Camilleri P, Kancherla K, Frew J, Chan A, Dayes IS, Henderson D, Brown S, Cruickshank C, Burnett S, Duffton A, Griffin C, Hinder V, Morrison K, Naismith O, Hall E, van As N; PACE Trial Investigators. Intensity-modulated fractionated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): acute toxicity findings from an international, randomised, open-label, phase 3, non-inferiority trial. Lancet Oncol. 2019 Nov;20(11):1531-1543. doi: 10.1016/S1470-2045(19)30569-8. Epub 2019 Sep 17.
- Nilsson P, Gunnlaugsson A, Beckman L, Widmark A, Fransson P, Hoyer M, Lagerlund M, Kindblom J, Johansson B, Bjornlinger K, Ginman C, Olsson M, Agrup M, Kjellen E, Zackrisson B, Tavelin B, Franzen L, Anderson H, Thellenberg Karlsson C. Ultra-hypofractionated versus conventionally fractionated radiotherapy for localised prostate cancer (HYPO-RT-PC): 10-year outcomes of an open-label, randomised, phase 3, non-inferiority trial. Lancet Oncol. 2026 Mar;27(3):293-301. doi: 10.1016/S1470-2045(25)00656-4. Epub 2026 Feb 5.
- Spratt DE, Srinivas S, Adra N, Ahmed B, An Y, Bitting R, Chapin B, Cheng HH, Cho SY, D'Amico AV, Desai N, Dorff T, Eastham JA, Farrington TA, Gao X, Gupta S, Ippolito JE, Karnes RJ, Kishan A, Kuettel MR, Lang JM, Lee D, Lotan T, McDonald A, Morgan T, Pessoa R, Rais-Bahrami S, Roach M 3rd, Robin T, Rosenfeld S, Scarpato KR, Shabsigh A, Szmulewitz R, Teply BA, Tward J, Valicenti R, VanderWeele D, Wong JK, Kovach E, Freedman-Cass D. Prostate Cancer, Version 3.2026, NCCN Clinical Practice Guidelines In Oncology. J Natl Compr Canc Netw. 2025 Nov;23(11):469-493. doi: 10.6004/jnccn.2025.0052.
- Tutrone R, Saad F, George DJ, Tombal B, Bailen JL, Cookson MS, Saltzstein DR, Hanson S, Brown B, Lu S, Fallick M, Shore ND. Testosterone Recovery for Relugolix Versus Leuprolide in Men with Advanced Prostate Cancer: Results from the Phase 3 HERO Study. Eur Urol Oncol. 2024 Aug;7(4):906-913. doi: 10.1016/j.euo.2023.11.024. Epub 2023 Dec 23.
- Wilke L, Christ SM, Bello RD, Denney E, Fabiano S, Gabrys HS, Kefer K, Mayinger M, Nilo I, Perryck S, von der Grun J, Guckenberger M, Tanadini-Lang S. Safety in MR-enhanced daily adaptive SBRT Radiotherapy using a conventional C-arm linear accelerator: An FMEA approach. Z Med Phys. 2025 Nov;35(4):423-427. doi: 10.1016/j.zemedi.2025.05.002. Epub 2025 Jun 3.
- Teunissen FR, Wortel RC, Hes J, Willigenburg T, de Groot-van Breugel EN, de Boer JCJ, van Melick HHE, Verkooijen HM, van der Voort van Zyp JRN. Adaptive magnetic resonance-guided neurovascular-sparing radiotherapy for preservation of erectile function in prostate cancer patients. Phys Imaging Radiat Oncol. 2021 Sep 21;20:5-10. doi: 10.1016/j.phro.2021.09.002. eCollection 2021 Oct.
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Geschätzt)
Primärer Abschluss (Geschätzt)
Studienabschluss (Geschätzt)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Tatsächlich)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
Andere Studien-ID-Nummern
- EF-PRESERVE
Plan für individuelle Teilnehmerdaten (IPD)
Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?
Arzneimittel- und Geräteinformationen, Studienunterlagen
Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .