Prostate CancerRE-FOCUSNCT07810660
RE-irradiation for Isolated FOCal Recurrence of Prostate Cancer With Ultrahypofracted SBRT
An observational study of Prostate Cancer, run by European Institute of Oncology.
Trial summary
Prostate cancer (PCa) is one of the most frequently diagnosed malignancies in men worldwide, with the highest prevalence observed in developed countries. Patients affected by localized disease can be treated with several local modalities, including radical prostatectomy (RP), external beam radiotherapy (EBRT) and… Read more about this study
- Who is it for?
- Ages 18 to 80 years, men only
- Conditions the study is for
- Prostate Cancer
- How many people
- 60 participants
- Where
- No sites listed yet
- Study dates
- Sep 2026to 1 May 2030
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- Men only
- No healthy volunteers
- Adult, Older adult
Study population: All enrolled patients will receive standard-of-care CyberKnife-based SBRT to the pelvic target. Androgen deprivation therapy (ADT), including its indication, timing, and duration, will be prescribed at the discretion of the treating radiation oncologist based on clinical judgment and individual patient characteristics.
Who may be able to join
- Age > 18 and < 80 years
- Histologically confirmed adenocarcinoma of the prostate initial diagnosis
- History of a previous adjuvant/salvage RT following prostatectomy or curative RT
- Diagnosis of local recurrence at the restaging imaging in hormone sensitive patients (maximum 1 prostate bed recurrence and 3 intraprostatic recurrences)
- DICOM plan of the previous RT course
- No evidence of greater than grade 2 according to Common Terminology Criteria for Adverse Events (CTCAE) genitourinary (GU) or gastrointestinal (GI) late adverse events from the previous RT course
Show all 9Show fewer
- Eastern Cooperative Oncology Group (ECOG) Performance Status <2
- Good urinary flow (peak flow >10 mL/s) or IPSS < 15
- Written informed consent for treatment and research purpose
Who cannot join
- Evidence of distant metastasis at the restaging imaging
- Patients with current concomitant anticoagulant therapy (antiplatelet therapy is allowed even if it will be temporary suspended before fiducials implant)
- Platelets count < 75'000/uL
- Urethral stricture
- Having received previous different salvage treatments for PCa local relapse
- Development of BCR while on ADT
Show all 9Show fewer
- Concomitant inflammatory bowel disease or other serious systemic comorbidities
- Presence of hip prosthesis
- Impossibility of performing an MRI
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: RE-irradiation for Isolated FOCal Recurrence of Prostate Cancer With Ultrahypofracted SBRT: The RE-FOCUS Study - Pushing the Boundaries of Precision and Efficacy
Prostate cancer (PCa) is one of the most frequently diagnosed malignancies in men worldwide, with the highest prevalence observed in developed countries. Patients affected by localized disease can be treated with several local modalities, including radical prostatectomy (RP), external beam radiotherapy (EBRT) and brachytherapy (BT). Although the advances in treatment strategies, after primary treatment 5 to 60% of men experience biochemical recurrence (BCR).
Read the detailed description
One of the most common sites of recurrence is locally in the prostate gland in case of radiotherapy (RT) as primary treatment, and in the prostate bed in case of surgery as primary treatment. In case of PSA persistence or recurrence after surgery as primary treatment, international guidelines recommend salvage RT as the treatment of choice[7]. But what does international guidelines suggest in case of a clinically confirmed local recurrence after an RT course (either curative or salvage)? This presents a significant clinical challenge, as locally radiorecurrent prostate cancer has emerged as the fourth most common genitourinary malignancy in men, following primary prostate cancer, bladder cancer, and kidney cancer[8]. International guidelines recommend various approaches-from monitoring to local therapy (e.g., surgery, high-intensity focused ultrasound, cryotherapy, re-irradiation) or lifelong castration with androgen deprivation therapy (ADT), with a negative impact on patients' quality of life (QoL) due to the wide range of associated side effects. While salvage prostatectomy has been the traditional curative approach, its high morbidity has driven exploration of alternatives like re-irradiation (re-RT) to improve control and reduce adverse events.
Stereotactic body RT (SBRT) has emerged as a promising, curative, non-invasive salvage option, offering precise re-RT with minimal adverse events, as international guidelines suggest. Valle et al.[9] meta-analysis reported no significant differences in 5-year recurrence-free survival among RP, high-intensity focused ultrasound, cryotherapy, and re-RT techniques via brachytherapy (BT) and SBRT. However, re-RT with SBRT was associated with significantly lower genitourinary (GU) adverse events compared to RP, suggesting equivalent efficacy but potentially lower adverse events with re-RT. Similarly, a systematic review on re-RT for local failure after a prior RT showed a safe toxicity profile and promising overall mortality and biochemical control rates[10].
Furthermore, emerging data suggest that partial-prostate re-RT, targeting only the visible recurrent lesion rather than the entire prostate gland or prostate bed, may further reduce severe adverse events without compromising oncological efficacy.
Despite these promising developments, re-RT remains a complex therapeutic challenge requiring careful patient selection, meticulous dosimetric planning, and multidisciplinary clinical management. The cumulative radiation dose to organs at risk (OARs) from both the first radiotherapy course and the second must be carefully evaluated to minimize the risk of severe late adverse events, while delivering sufficient dose to achieve tumor control. Several SBRT techniques for ultrahypofractionated RT (UHRT, defined as >6 Gy per fraction) have been explored. From the early acute adverse events findings of the PACE-B trial, significantly lower RTOG grade 2 or worse GU adverse events were reported in the treatment arm with CyberKnife. This favorable adverse events likely reflects CyberKnife's capability for intrafraction motion management with digitally reconstructed radiographs (DRRs) throughout delivery and real-time beam corrections when deviations exceed tolerance thresholds, which enhance dose conformality to the target volume while improving dose falloff to adjacent OARs. These technical advantages, combined with demonstrated tumor control rates, should position CyberKnife as the preferred SBRT therapy for locally recurrent PCa following a prior RT course.
- Conditions
- Prostate Cancer
- Keywords
- local recurrence, RE-irradiation
- Medical subject headings
- Prostatic Neoplasms
What is being measured
The primary outcome is the main question the study is designed to answer.
Acute GU adverse events
Acute GU adverse events will be reported as clinician-reported outcomes (according to CTCAE scoring criteria)
Measured: at the end of treatment and 3 months after the end of treatment
Acute GI adverse events
Acute GI adverse events will be reported as clinician-reported outcomes (according to CTCAE scoring criteria)
Measured: at the end of treatment and 3 months after the end of treatment
questionnaire IIEF-5
The patient fills out the questionnaire IIEF-5
Measured: At the baseline and from the end of radiotherapy through study completion, every three months.
questionnaire IPSS
The patient fills out the questionnaire IPSS
Measured: At the baseline and from the end of radiotherapy through study completion, every three months.
questionnaire QLQ-C30
The patient fills out the questionnaire QLQ-C30
Measured: At the baseline and from the end of radiotherapy through study completion, every three months.
Late GU adverse events (CTCAE)
Late GU adverse events will be reported as clinician-reported outcomes (according to CTCAE scoring criteria)
Measured: From 6 months after the end of radiotherapy until the end of the study, every six months.
Late GI adverse events (CTCAE)
Late GI adverse events will be reported as clinician-reported outcomes (according to CTCAE scoring criteria)
Measured: From 6 months after the end of radiotherapy until the end of the study, every six months.
Secondary outcomes (1)
Biochemical progression-free survival (bPFS)
Defined as the time from the end of re-RT to either biochemical recurrence (BCR) or last follow-up. bPFS will be assessed through trimestral PSA evaluation from the end of treatment.
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2026
- Study startSep 2026 (estimated)
- Primary completion1 May 2030 (estimated)
- Study completion1 May 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by European Institute of OncologyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- European Institute of Oncology
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- BARBARA A JERECZEK-FOSSA, MD, PhD, Principal investigator, European Institute of Oncology, Milano. Mi, Italy 20141BARBARA JERECZEK-FOSSA, MD, PhD, Principal investigator, European Institute of Oncology, Milano. Mi, Italy 20141
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07810660
- Sponsor's protocol ID
- UID 5402
- Other IDs
- L2-653
- Acronym
- RE-FOCUS
- Status last verified
- Jul 2026
- First submitted
- 31 Aug 2026
- Last updated
- 9 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- RE-irradiation for Isolated FOCal Recurrence of Prostate Cancer With Ultrahypofracted SBRT: The RE-FOCUS Study - Pushing the Boundaries of Precision and Efficacy
- ClinicalTrials.gov ID
- NCT07810660
- Acronym / sponsor ID
- RE-FOCUS / UID 5402
- Conditions
- Prostate Cancer
- Keywords
- local recurrence, RE-irradiation
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- European Institute of OncologyUniversity, hospital or other
- Study start
- Sep 2026 (estimated)
- Primary completion
- 1 May 2030 (estimated)
- Study completion
- 1 May 2030 (estimated)
- First posted
- 9 Sep 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Prostate cancer (PCa) is one of the most frequently diagnosed malignancies in men worldwide, with the highest prevalence observed in developed countries. Patients affected by localized disease can be treated with several local modalities, including radical prostatectomy (RP), external beam radiotherapy (EBRT) and brachytherapy (BT). Although the advances in treatment strategies, after primary treatment 5 to 60% of men experience biochemical recurrence (BCR).
Detailed description
One of the most common sites of recurrence is locally in the prostate gland in case of radiotherapy (RT) as primary treatment, and in the prostate bed in case of surgery as primary treatment. In case of PSA persistence or recurrence after surgery as primary treatment, international guidelines recommend salvage RT as the treatment of choice[7]. But what does international guidelines suggest in case of a clinically confirmed local recurrence after an RT course (either curative or salvage)? This presents a significant clinical challenge, as locally radiorecurrent prostate cancer has emerged as the fourth most common genitourinary malignancy in men, following primary prostate cancer, bladder cancer, and kidney cancer[8]. International guidelines recommend various approaches-from monitoring to local therapy (e.g., surgery, high-intensity focused ultrasound, cryotherapy, re-irradiation) or lifelong castration with androgen deprivation therapy (ADT), with a negative impact on patients' quality of life (QoL) due to the wide range of associated side effects. While salvage prostatectomy has been the traditional curative approach, its high morbidity has driven exploration of alternatives like re-irradiation (re-RT) to improve control and reduce adverse events.
Stereotactic body RT (SBRT) has emerged as a promising, curative, non-invasive salvage option, offering precise re-RT with minimal adverse events, as international guidelines suggest. Valle et al.[9] meta-analysis reported no significant differences in 5-year recurrence-free survival among RP, high-intensity focused ultrasound, cryotherapy, and re-RT techniques via brachytherapy (BT) and SBRT. However, re-RT with SBRT was associated with significantly lower genitourinary (GU) adverse events compared to RP, suggesting equivalent efficacy but potentially lower adverse events with re-RT. Similarly, a systematic review on re-RT for local failure after a prior RT showed a safe toxicity profile and promising overall mortality and biochemical control rates[10].
Furthermore, emerging data suggest that partial-prostate re-RT, targeting only the visible recurrent lesion rather than the entire prostate gland or prostate bed, may further reduce severe adverse events without compromising oncological efficacy.
Despite these promising developments, re-RT remains a complex therapeutic challenge requiring careful patient selection, meticulous dosimetric planning, and multidisciplinary clinical management. The cumulative radiation dose to organs at risk (OARs) from both the first radiotherapy course and the second must be carefully evaluated to minimize the risk of severe late adverse events, while delivering sufficient dose to achieve tumor control. Several SBRT techniques for ultrahypofractionated RT (UHRT, defined as >6 Gy per fraction) have been explored. From the early acute adverse events findings of the PACE-B trial, significantly lower RTOG grade 2 or worse GU adverse events were reported in the treatment arm with CyberKnife. This favorable adverse events likely reflects CyberKnife's capability for intrafraction motion management with digitally reconstructed radiographs (DRRs) throughout delivery and real-time beam corrections when deviations exceed tolerance thresholds, which enhance dose conformality to the target volume while improving dose falloff to adjacent OARs. These technical advantages, combined with demonstrated tumor control rates, should position CyberKnife as the preferred SBRT therapy for locally recurrent PCa following a prior RT course.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 80 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- All enrolled patients will receive standard-of-care CyberKnife-based SBRT to the pelvic target. Androgen deprivation therapy (ADT), including its indication, timing, and duration, will be prescribed at the discretion of the treating radiation oncologist based on clinical judgment and individual patient characteristics.
Key inclusion criteria (9 listed)
- Age > 18 and < 80 years
- Histologically confirmed adenocarcinoma of the prostate initial diagnosis
- History of a previous adjuvant/salvage RT following prostatectomy or curative RT
- Diagnosis of local recurrence at the restaging imaging in hormone sensitive patients (maximum 1 prostate bed recurrence and 3 intraprostatic recurrences)
- DICOM plan of the previous RT course
Key exclusion criteria (9 listed)
- Evidence of distant metastasis at the restaging imaging
- Patients with current concomitant anticoagulant therapy (antiplatelet therapy is allowed even if it will be temporary suspended before fiducials implant)
- Platelets count < 75'000/uL
- Urethral stricture
- Having received previous different salvage treatments for PCa local relapse
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Acute GU adverse events
Time frame: at the end of treatment and 3 months after the end of treatment
Acute GU adverse events will be reported as clinician-reported outcomes (according to CTCAE scoring criteria)
Acute GI adverse events
Time frame: at the end of treatment and 3 months after the end of treatment
Acute GI adverse events will be reported as clinician-reported outcomes (according to CTCAE scoring criteria)
questionnaire IIEF-5
Time frame: At the baseline and from the end of radiotherapy through study completion, every three months.
The patient fills out the questionnaire IIEF-5
questionnaire IPSS
Time frame: At the baseline and from the end of radiotherapy through study completion, every three months.
The patient fills out the questionnaire IPSS
questionnaire QLQ-C30
Time frame: At the baseline and from the end of radiotherapy through study completion, every three months.
The patient fills out the questionnaire QLQ-C30
Late GU adverse events (CTCAE)
Time frame: From 6 months after the end of radiotherapy until the end of the study, every six months.
Late GU adverse events will be reported as clinician-reported outcomes (according to CTCAE scoring criteria)
Late GI adverse events (CTCAE)
Time frame: From 6 months after the end of radiotherapy until the end of the study, every six months.
Late GI adverse events will be reported as clinician-reported outcomes (according to CTCAE scoring criteria)
1 secondary outcome
Biochemical progression-free survival (bPFS)
Time frame: through study completion, an average of 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2026.
Related trials for Prostate Cancer
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
Active, not recruitingObservational study
MRI Fusion Biopsy vs. Micro-Ultrasound Guided Biopsy
Prostate Cancer
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
Recruiting
Rehabilitation and Sex Therapy to Optimize Recovery After Prostate Cancer Treatment
Prostate Cancer, Urinary Incontinence
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
BARBARA A JERECZEK-FOSSA, MD, PhD principal investigator
European Institute of Oncology, Milano. Mi, Italy 20141
BARBARA JERECZEK-FOSSA, MD, PhD principal investigator
European Institute of Oncology, Milano. Mi, Italy 20141
Questions about this trial
What is this clinical trial studying?
An observational study of Prostate Cancer, run by European Institute of Oncology.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 9 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact BARBARA A JERECZEK-FOSSA, MD, PhD (+39 0257489037, barbara.jereczek@ieo.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Acute GU adverse events (time frame: at the end of treatment and 3 months after the end of treatment). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2026.