Addition of a Focal Boost in External Beam Radiotherapy for Locally Advanced Prostate Cancer by Online Adaptive MR-guided Radiotherapy

Study Overview
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Brief Summary
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The AFFIRM trial tests the safety and clinical feasibility of MR-guided hypofractionated focal boost radiotherapy for patients with locally advanced prostate cancer. External beam radiotherapy combined with androgen deprivation therapy is considered as the treatment of choice for patients with locally advanced non-metastatic prostate cancer with seminal vesicle invasion.The long-term results of the multicentre phase III study (FLAME trial) showed that addition of an isotoxic focal boost to the intraprostatic lesion improves biochemical disease free survival in intermediate to high-risk patients without impacting toxicity and quality of life. This focal boost strategy is now proven for a conventional fractionation scheme (35 fractions). The current trend in radiotherapy for prostate cancer is (extreme) hypofractionation, reducing the number of fractions. For locally advanced prostate cancer, however, the data on extreme hypofractionation are scarce.

Official Title
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Addition of a Focal Boost in External Beam Radiotherapy for Locally Advanced Prostate Cancer by Online Adaptive MR-guided Radiotherapy

Conditions
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Prostate Cancer, Prostate Neoplasm

Intervention / Treatment
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* Radiation: Ultrahypofractionated MR-guided radiotherapy boost


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men aged 18 years or older with histologically proven prostate carcinoma Imaging stage T3b (as defined on mpMRI) N0M0 Intraprostatic lesion visible on MRI Capable of giving informed consent Exclusion Criteria: History of radiotherapy to the pelvis or transurethral resection of the prostate (TURP) Contraindications for MRI according to the guidelines of the local department of Radiology, inability to lay on a treatment table for 45-60 minutes or severe claustrophobia Absence of pre-treatment PSMA PET CT WHO performance score > 2 International Prostate Symptom Score ≥ 15 PSA > 30 Prostate volume >100c

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MR-guided hypofractionated focal boost radiotherapy<br>External beam MR-guided (MR-linac) radiotherapy to the prostate and seminal vesicles of 5x7Gy (once weekly) with an isotoxic integrated focal boost up to 50Gy to the intraprostatic tumor as visible on multiparametric MR | Radiation: Ultrahypofractionated MR-guided radiotherapy boost<br>* External beam MR-guided (MR-linac) radiotherapy to the prostate and seminal vesicles of 5x7Gy (once weekly) with an isotoxic integrated focal boost up to 50Gy to the intraprostatic tumor as visible on multiparametric MRI.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute gastrointestinal and genitourinary toxicity | Acute gastrointestinal (GI) and genitourinary (GU) Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0). Acute toxicity is defined as toxicity occurring within 90 days after the first radiation treatment (e.g. 60 days after completion of the radiation treatment). | 90 days after start of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Late GI and GU toxicity (CTCAE v5.0) | assessed between 90 days and up to 5 years after the first radiation treatment | from 90 days after start of treatment up to 5 years | 
| Quality of life | using the EORTC QLQ-C30 questionnaires | from baseline up to 5 years after completion of treatment | 
| Quality of life | using the EORTC QLQ-PR25 questionnaires | from baseline up to 5 years after completion of treatment | 
| Biochemical disease free survival | measuring the PSA concentration using the Phoenix definition for biochemical recurrence | up to 5 years after completion of treatment | 
| Overall survival |  | up to 5 years after completion of treatment | 
| Prostate cancer specific survival |  | up to 5 years after completion of treatment | 
| Distant metastasis free survival |  | up to 5 years after completion of treatment |