Prostate Cancer
Conditions
Brief summary
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).
Interventions
DEVICEweekly CT or MR online adaptive definitive SBRT
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.
Sponsors
University of Zurich
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This interventional prospective multicenter international study will include 54 patients with regionally metastatic (i.e. cN1 cM0) prostate cancer according to the NCCN criteria (Supplementary File 2). 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.
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
include: * Regionally metastatic prostate cancer (cN1, any T, Gleason 6-10, any PSA) according to NCCN guidelines consisting of ≤ 5 regional lymph node metastases * Good to moderate performance status (WHO 0-2) * Written informed consent. * A PSMA PET and multiparametric MRI is mandatory according to staging guidelines. * Age ≥ 18 years
Exclusion criteria
include: * \>5 regional lymph nodes * Patients with cT4 disease (tumor is fixed or invades adjacent structures other than seminal vesicles such as external sphincter, rectum, bladder, levator muscles, and/or pelvic wall) * Previous radiotherapy to the pelvis or prostate * Previous radical prostatectomy * Large body size that would not fit into the MRI-simulator bore * Presence of distant metastases (i.e. cM1) * Non-regional lymph nodes (M1a): * Bone metastases (M1b) * Other sites (M1c) * Contraindications to CT or MR-adaptive SBRT (e.g., pacemakers, severe claustrophobia). * Severe comorbidities that may interfere with treatment or follow-up (e.g. inflammatory bowel disease). * Significant concomitant diseases (e.g. hepatic dysfunction, cardiovascular disease, etc.). * Inability to follow procedures or insufficient knowledge of project language, inability to give consent. * Participation in a clinical trial which might influence the results of this project. * Enrolment of the investigator, his/her family members, employees and other dependent persons. * Severe genitourinary or gastrointestinal symptoms (e.g. recent urinary retention or diarrhea ≥ grade 3 or obstipation to CTCAE v.6.0). * Severe urinary symptoms (e.g. IPSS \>12 and/or prostate volume \> 80 mL)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility- a successful delivery of CT or MR-informed SBRT per fraction | from Day 1 of treatment up to 7 weeks until end of treatment | 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. |
| Safety - Adverse events | ≥ 3 months to within 1 year after completion of SBRT | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Biochemical progression-free survival | from Day 1 up to 5 years after treatment | 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 |
| Castration-resistant free survival | from Day 1 up to 5 years after treatment | 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 |
| Patients Quality of Life EQ-5D-5L from the European Organisation for Research and Treatment of Cancer | from Day 1 up to end of study until 5 years | 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. |
| Patients Quality of Life QLQ-C30 from the European Organisation for Research and Treatment of Cancer | From Day 1 up to end of study (up to 5 years) | 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. |
| Adverse events | from Day 1 until 5 years or end of Study | Genitourinary and Gastrointestinal toxicity measured with Common Terminology Criteria for Adverse Events (CTCAE) |
| Patients overall survival | from Day 1 until Progression or death whichever comes first until 5 years | defined from the start of therapy until death or censoring |
| Patient overall treatment - Patient treatment workflow duration (time from MRI scan start to completion of treatment) | from Day 1 start of therapy, weekly until end of treatment up to 7 weeks | 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 |
| Other Toxicities | Day 1 of Treatment for up to 5 years or until death whichever comes first | 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. |
| Dosimetry difference | from Day 1 of treatment start until end of treatment up to 7 Weeks | 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 |
| Anatomy changes assessed on magnetic resonance imaging (MRI) | from Day 1 of treatment up to 7 weeks | 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. |
| Comparison of Patient treated and not treated | from Day 1 until 5 Years of study or death | 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. |
| Patient well being and comfort | from Day 1 of treatment to weekly up to 7 weeks | 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 |
| Patient compliance | from Day 1 until 5 Years / end of Study | 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. |
| Physician decision certainty | from Day1 of treatment to weekly up to 7 weeks | 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 |
Countries
Germany, Switzerland
Contacts
CONTACTRadiation Oncology Study Office
STUDY_CHAIRMatthias Guckenberger
Universitätsspital Zürich
PRINCIPAL_INVESTIGATORTiuri Kroese
University of Zurich
PRINCIPAL_INVESTIGATORMatthias Guckenberger
University of Zurich
Outcome results
None listed