PSMA-PET/MRI-Based Focal Dose Escalation in Patients with Primary Prostate Cancer Treated with Stereotactic Body Radiation Therapy (HypoFocal-SBRT): Study Protocol of a Randomized, Multicentric Phase III Trial

Abstract

Technical advances in radiotherapy (RT) treatment planning and delivery have substantially changed RT concepts for primary prostate cancer (PCa) by (i) enabling a reduction of treatment time, and by (ii) enabling safe delivery of high RT doses. Several studies proposed a dose–response relationship for patients with primary PCa and especially in patients with high-risk features, as dose escalation leads to improved tumor control. In parallel to the improvements in RT techniques, diagnostic imaging techniques like multiparametric magnetic resonance imaging (mpMRI) and positron-emission tomography targeting prostate-specific-membrane antigen (PSMA-PET) evolved and enable an accurate depiction of the intraprostatic tumor mass for the first time. The HypoFocal-SBRT study combines ultra-hypofractionated RT/stereotactic body RT, with focal RT dose escalation on intraprostatic tumor sides by applying state of the art diagnostic imaging and most modern RT concepts. This novel strategy will be compared with moderate hypofractionated RT (MHRT), one option for the curative primary treatment of PCa, which has been proven by several prospective trials and is recommended and carried out worldwide. We suspect an increase in relapse-free survival (RFS), and we will assess quality of life in order to detect potential changes.

Feasibility, pitfalls and results of a structured concept-development phase for a randomized controlled phase III trial on radiotherapy in primary prostate cancer patients

“…We present the conduction and results of the CDP, which resulted in the final design and study protocol of the HypoFocal-SBRT study (see Fig. 2 ) and [ 43 ]. To our best knowledge, this is the first publication systematically reporting on these crucial steps including insights into currently available clinical trials.…”

Intraindividual Comparison Between [18F] PSMA-1007 PET/CT and Multiparametric MRI for Radiotherapy Planning in Primary Prostate Cancer Patients

“…Parts of non-PCa tissue within the prostate might likewise be irradiated, which might lead to an increased risk for toxicity. Whether a RT dose escalation on GTVs based on combined PSMA PET and mpMR information is safe and increases the tumor control will be examined by the randomized controlled HypoFocal-SBRT trial in the future ( 26 ). Interestingly, PET had even a higher concordance in laterality of PCa lesion with surgery specimen compared to mpMRI and biopsy cores.…”

Imaging Biomarkers in Prostate Stereotactic Body Radiotherapy: A Review and Clinical Trial Protocol

“…In the primary management of prostate cancer, improved imaging guidance has allowed for radiotherapy advances for prostate cancer, including prostate SBRT and focal boost ( 3 – 6 , 11 ). Ongoing trials are evaluating SBRT with focal boost guided by mpMRI and PSMA-PET (NCT04243941, NCT04402151, and NCT04599699) ( 21 , 59 ). The ARGOS/CLIMBER trial will explore the safety of SBRT with focal boost guided by mpMRI and 18 F-PSMA-1007 PET.…”

“…Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) complements mpMRI and improves the detection and characterization of intraprostatic cancer and nodal disease in the primary setting ( 17 – 20 ). As such, it may improve oncologic outcomes through more accurate delineation of focal boost volumes ( 17 , 18 , 21 ). Additionally, PSMA PET provides better distant staging and can identify extra-prostatic extension, especially among men with higher risk disease ( 22 ).…”