MRI-guided radiotherapy for localized prostate cancer: clinical evaluation and development of erectile function-preserving treatment

Magnetic resonance imaging (MRI)-guided radiotherapy is a novel form of external beam radiotherapy that utilizes an MR-Linac, a device that integrates an MRI scanner with a linear accelerator. This device enables MRI acquisition before and during radiation dose delivery to improve visualization of the target volume and surrounding tissue. This is especially important for organs prone to shape and position changes during and between the radiation fractions, such as the prostate. The hypothesis is that MRI-guided radiotherapy can deliver the radiation dose with greater accuracy and precision, resulting in less radiation to healthy tissue and better tumor coverage, causing less toxicity and better tumor control. Additionally, this technique makes it possible to increase the dose per fraction, enabling patients to receive treatment in fewer fractions.
This thesis describes the first clinical outcomes of MRI-guided radiotherapy for localized prostate cancer (chapters 2 and 3). These are results from two prospective cohorts in which patient and physician-reported outcomes of patients treated on a 1.5 T MR-linac are registered (the MOMENTUM study) as well as patients receiving conventional treatment for localized prostate cancer such as prostatectomy, CT-guided radiotherapy, and active surveillance (the UPC study). All treatment modalities show different patterns of toxicity, but in all radical treatment groups, a decline in erectile function is reported.
Patients with localized prostate cancer are often eligible for multiple treatment options. Chapter 4 assesses the preferences for the different treatment options for localized prostate cancer. The results show that active surveillance and non-invasive treatments, such as MRI-guided radiotherapy, are the most preferred options by both patients and healthy volunteers.
Chapters 2 and 3 show that erectile function deterioration after radical prostate cancer treatment is a major issue and chapter 4 emphasizes patient preference for non-invasive treatments. These insights have led to the development of neurovascular-sparing MRI-guided radiotherapy. The aim of this treatment is to preserve erectile function after radiotherapy by sparing neurovascular structures surrounding the prostate. The use of MRI during radiotherapy enables us to visualize these structures. Several steps had to be taken before clinical implementation. In chapter 5 to 7, the several steps towards implementation are described. Chapter 5 reports a contouring study showing sufficient interrater agreement of contouring the neurovascular structures by radiation oncologists, chapter 6 proves the planning feasibility of neurovascular sparing MR-guided radiotherapy, and chapter 7 describes the potential treatment population for the treatment.
In chapter 8, the dosimetric advantage of daily recontouring and plan adaptation during MRI-guided neurovascular-sparing radiotherapy is reported, supporting the development of software for fast online auto-contouring and real-time plan adaptation with MRI-guided radiotherapy.
MRI-guided radiotherapy is continually evolving, with ongoing advancements in both technical and clinical innovations. The MOMENTUM and the UPC studies are actively collecting data to evaluate MRI-guided radiotherapy for localized prostate cancer and to compare it to other treatments. Furthermore, neurovascular-sparing MRI-guided radiotherapy is proven to be technically and clinically feasible and the first clinical trial to assess the effectiveness of neurovascular-sparing MRI-guided radiotherapy for localized prostate cancer is currently underway.