RE-irradiation for Isolated FOCal Recurrence of Prostate Cancer With Ultrahypofracted SBRT (RE-FOCUS)

September 4, 2026 updated by: European Institute of Oncology

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).

Study Overview

Status

Not yet recruiting

Conditions

Prostate Cancer

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 Type

Observational

Enrollment (Estimated)

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: BARBARA A JERECZEK-FOSSA, MD, PhD
Phone Number: +39 0257489037
Email: barbara.jereczek@ieo.it

Study Contact Backup

Name: GIULIA MARVASO, MD
Phone Number: +39 0257489037
Email: giulia.marvaso@ieo.it

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

Adult
Older Adult

Accepts Healthy Volunteers

Sampling Method

Non-Probability Sample

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.

Description

Inclusion Criteria:

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
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

Exclusion Criteria:

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
Concomitant inflammatory bowel disease or other serious systemic comorbidities
Presence of hip prosthesis
Impossibility of performing an MRI

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	at the end of treatment and 3 months after the end of treatment
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)	at the end of treatment and 3 months after the end of treatment
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	At the baseline and from the end of radiotherapy through study completion, every three months.
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	At the baseline and from the end of radiotherapy through study completion, every three months.
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	At the baseline and from the end of radiotherapy through study completion, every three months.
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)	From 6 months after the end of radiotherapy until the end of the study, every six months.
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)	From 6 months after the end of radiotherapy until the end of the study, every six months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biochemical progression-free survival (bPFS) Time Frame: through study completion, an average of 1 year	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.	through study completion, an average of 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

European Institute of Oncology

Investigators

Principal Investigator: BARBARA A JERECZEK-FOSSA, MD, PhD, European Institute of Oncology, Milano. Mi, Italy 20141
Principal Investigator: BARBARA JERECZEK-FOSSA, MD, PhD, European Institute of Oncology, Milano. Mi, Italy 20141

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

September 1, 2026

Primary Completion (Estimated)

May 1, 2030

Study Completion (Estimated)

May 1, 2030

Study Registration Dates

First Submitted

August 31, 2026

First Submitted That Met QC Criteria

September 4, 2026

First Posted (Actual)

September 9, 2026

Study Record Updates

Last Update Posted (Actual)