This interventional prospective multicenter international study will include 54 patients with regionally metastatic (i.e. cN1 cM0) prostate cancer according to the NCCN criteria. Patients will be treated with weekly CT or MR-informed online adaptive SBRT of the prostate and elective pelvic lymph nodes with 5 x 5 Gy. A simultaneous integrated boost (SIB) of involved lymph nodes will be performed. In the case of up to 2 dominant intraprostatic lesion (DIL) a SIB of the DIL can be performed (optional). Importantly, coverage of these DIL volumes must be compromised as needed to respect OAR constraints. This study is classified as risk category A according to ClinO, Art. 61, as stereotactic radiotherapy (SBRT) for regionally metastatic prostate cancer has been extensively evaluated in prospective interventional trials and is considered an established therapeutic modality. Weekly CT- or MR-guided online adaptive SBRT to the prostate and elective pelvic lymph nodes with 5 × 5 Gy is, however, not yet routinely implemented for this specific patient population. A diagnostic high field MRI during radiotherapy, e.g. week 3 is optional. Follow-up is also according to standard of care (except for patient reported outcome measure using QLQ-C30 and QLQ-PR25 and a diagnostic MRI at 9 months after SBRT (optional), and 12 months in the case of an image non-complete response at 9 months (optional).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
54
Patients will be treated with weekly CT or MR-informed online adaptive SBRT of the prostate and elective pelvic lymph nodes with 5 x 5 Gy. A simultaneous integrated boost (SIB) of involved lymph nodes will be performed. In the case of up to 2 dominant intraprostatic lesion (DIL) a SIB of the DIL can be performed (optional). Importantly, coverage of these DIL volumes must be compromised as needed to respect OAR constraints.
University Clinic Heidelberg
Heidelberg, Baden-Würtemberg, Germany
University Hospital Zurich
Zurich, Canton of Zurich, Switzerland
Feasibility- a successful delivery of CT or MR-informed SBRT per fraction
Feasibility will be assessed by recording whether each fraction of stereotactic body radiation therapy (SBRT), guided by computed tomography (CT) or magnetic resonance (MR) imaging, is successfully delivered according to the planned treatment parameters. Successful delivery is defined as completion of the planned fraction without protocol deviations or technical interruptions. Data will be summarized as the proportion of fractions successfully delivered per patient and overall. Every treatment fraction having passed the point of entry into the adaptive workflow will be analyzed for this endpoint.
Time frame: from Day 1 of treatment up to 7 weeks until end of treatment
Safety - Adverse events
The presence of genitourinary or gastrointestinal toxicity of grade ≥ 3 within 1 year after completion of radiotherapy (according to CTCAE v5.0). Treatment-related discontinuation. and Subgroup analyses will be performed for patients with and without regional lymph node metastases (i.e., cN0 versus cN1).
Time frame: ≥ 3 months to within 1 year after completion of SBRT
Biochemical progression-free survival
This will be 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
Time frame: from Day 1 up to 5 years after treatment
Castration-resistant free survival
Castration-resistant free survival defined as cancer progression despite low (castrate) levels of testosterone (\<50 ng/dL). Cancer progression is defined as: * Biochemical progression: ≥2 consecutive PSA rises (at least 1 week apart) * Radiologic progression: appearance of new lesions on imaging
Time frame: from Day 1 up to 5 years after treatment
Patients Quality of Life EQ-5D-5L from the European Organisation for Research and Treatment of Cancer
Quality-of-life will be measured using the EQ-5D-5L 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.
Time frame: from Day 1 up to end of study until 5 years
Patients Quality of Life QLQ-C30 from the European Organisation for Research and Treatment of Cancer
Quality of life will be measured using the EORTC QLQ-C30 questionnaire. This instrument includes functional scales, symptom scales, and a global health status/quality-of-life scale. All scores are linearly transformed to a 1-4 scale. For functional scales and global health status, higher scores indicate better functioning or quality of life, whereas for symptom scales/items, higher scores indicate greater symptom burden.
Time frame: From Day 1 up to end of study (up to 5 years)
Adverse events
Genitourinary and Gastrointestinal toxicity measured with Common Terminology Criteria for Adverse Events (CTCAE)
Time frame: from Day 1 until 5 years or end of Study
Patients overall survival
defined from the start of therapy until death or censoring
Time frame: from Day 1 until Progression or death whichever comes first until 5 years
Patient overall treatment - Patient treatment workflow duration (time from MRI scan start to completion of treatment)
Patient will be asked from the start and end of MRI scan to start and end of treatment respectively, and for all steps from simulation to treatment delivery individually
Time frame: from Day 1 start of therapy, weekly until end of treatment up to 7 weeks
Other Toxicities
Treatment-related toxicities other than the primary toxicity outcomes will be assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE). Other Toxicities will be evaluated during SBRT treatment and throughout follow-up for up to 5 years after completion of treatment or until patient death, whichever occurs first. The type, frequency, and severity (grade) of adverse events will be recorded according to CTCAE v5.0 criteria.
Time frame: Day 1 of Treatment for up to 5 years or until death whichever comes first
Dosimetry difference
Dosimetry difference of the online adaptive plan compared to the original plan recalculated on the imaging of the day. Dosimetry difference is defined as difference in coverage of the planning target volume (PTV) or of one of the organs at risk e.g. bowel or rectum
Time frame: from Day 1 of treatment start until end of treatment up to 7 Weeks
Anatomy changes assessed on magnetic resonance imaging (MRI)
Anatomical changes will be evaluated using serial magnetic resonance imaging (MRI) acquired during treatment and follow-up. Changes in relevant anatomical structures (e.g., target volume and surrounding organs at risk) will be assessed by comparing images obtained at baseline and subsequent imaging time points. Observed anatomical variations will be documented and summarized descriptively.
Time frame: from Day 1 of treatment up to 7 weeks
Comparison of Patient treated and not treated
Comparison of number of patients not treated at all/not treated with all planned fractions in the CT or MR-informed workflow compared to those intended to be treated and categorization of patterns of failure within the CT or MR-informed workflow.
Time frame: from Day 1 until 5 Years of study or death
Patient compliance
Patient compliance will be measured by tracking a scheduled treatment sessions and adherence to the prescribed treatment protocol, including completion of all required procedures and instructions. Data will be collected throughout the treatment period and summarized as the proportion of scheduled sessions attended and procedures completed, as well as reasons for any missed sessions or deviations from the protocol.
Time frame: from Day 1 until 5 Years / end of Study
Patient well being and comfort
Patients will be asked to report their comfort during and after simulation assess with a 0 to 10 numerical rating scales, with 0 representing complete absence of clinical confidence to 10 representing extreme clinical confidence
Time frame: from Day 1 of treatment to weekly up to 7 weeks
Physician decision certainty
clinicians will be asked to report their clinical confidence with a 0 to 10 NRS, with 0 representing complete absence of clinical confidence to 10 representing extreme clinical confidence
Time frame: from Day1 of treatment to weekly up to 7 weeks
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