Novel use of Y-90 radioembolization could transform prostate cancer treatment

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radioembolization
Sam Mouli

In an entirely new endeavour for Yttrium-90 (Y-90) radioembolization, investigators from Northwestern University, Chicago, USA, have used the technique for the treatment of prostate cancer. “This is a new use for radioembolization, and an entirely new, more targeted treatment for prostate cancer,” Sam Mouli, who is leading the research group, tells Interventional News.

Sandeep Bagla (Prostate Centers USA and Vascular Interventional Partners NOVA, Falls Church, USA), course director of the STREAM meeting, which focuses on research at the vanguard of prostatic artery embolization (PAE) and musculoskeletal embolization, says of this novel use of Y-90: “It is the most cutting edge application of embolization going on right now, with extensive future long-term potential.”

The research team, led by Sam Mouli, set out to examine the potential role of intra-arterial radiotherapy in the setting of a large prostate and prostate cancer. “Radiotherapy has been a cornerstone of treatment for locally advanced prostate cancer for the last 30 years,” Mouli explains. “Despite several advances in the understanding and treatment of prostate cancer over this time, current therapies continue to be limited by significant toxicities, including risks of urinary, bowel, and erectile dysfunction following treatment. Patients continue to seek novel therapies that not only provide oncologic benefit, but also maximise quality of life.

“We posited that we could use our experience with Y-90 radioembolization in the treatment of liver cancer, and adapt it to what we have learned from our PAE programme.”

Prostate gland shrunk in early animal testing

The research team utilised the same canine model that they had initially used to study PAE, this time investigating the potential role of Y-90 radioembolization for the treatment of prostate cancer in a dose escalation study. They specifically looked into radiation changes to the prostatic tissues, as well as the effects of radiation on surrounding organs, such as the bladder and rectum, in addition to the erectile nerves, vasculature, and soft tissues.

Mouli describes the thought processes underpinning this early study: “External beam radiotherapy and transperineal brachytherapy are limited by nontarget radiation delivered to tissues surrounding the prostate, which is the source of the adverse event profile seen with current therapies. We hypothesised that targeted intra-arterial delivery of Y-90 microspheres could mitigate these off-target effects, while still delivering high-dose radiotherapy to the prostatic tissues.”

Utilising the techniques learned from both PAE for benign prostatic hyperplasia (BPH), and Y-90 radioembolization for liver malignancies, half of the prostates of the 14 animals included in the pr-clinical feasibility study were treated with Y-90 radioembolization, while the untreated contralateral sides were used as the control.

In this cohort, imaging follow-up performed at specific time-intervals demonstrated prostate gland size reduction in a dose-dependent fashion starting at two weeks’ post-embolization, continuing to three months post therapy. There were no clinical adverse events throughout the follow-up period. In addition, the investigators report no evidence of nontarget embolization or of any radiation damage to the surrounding bladder, rectum, and erectile tissues on MRI and pathologic analysis.

Expounding on the perceived importance of these early data, Mouli enthuses: “By demonstrating feasibility and safety in this model, we have shown that Y-90 microspheres can be safely delivered to prostatic tissues delivering highly targeted radiation without the off-target damage seen with current approaches. Additionally, given the radio-isotope characteristics of Y-90, this potentially offers a single-stage treatment option for patients. Current radiotherapy often requires multiple treatments over several weeks to deliver radiation safely.

Radioembolization tailored to treat the radiosensitive prostate

Radiation is a standard of care therapy for prostate cancer. However, Mouli says, current radiotherapy approaches are challenged by technical considerations, such as limited dosing due to the proximity of surrounding structures, and difficulty of brachytherapy seed placement in larger glands. He believes that radioembolization can overcome these limitations, while also delivering higher therapeutic doses with minimal off-target effects.

“Our initial results have been incredibly promising,” he comments, “demonstrating both feasibility and safety in an animal model. Of note, explant analysis demonstrated no radiation injury or scarring to adjacent tissue, and validated the initial hypothesis of using radiotherapy delivered trans-arterially: it maximises delivery to the gland and minimises non-target radiation. Our next step would be preparing a clinical study in men with unresectable, locally advanced prostate cancer in 2021. Similar to the current paradigm for Y-90 radioembolization, treatment volume-based dosimetry would be utilised to determine radiation dosing.”

However, Mouli also cautions that investigating new therapeutic options can be challenging: “The bar is very high when comparing to the standard of care,” he says. “Once demonstrating safety and feasibility pre-clinically, clinical translation requires collaboration between various medical specialties as well as industry support. Northwestern University is a highly collaborative enterprise, and we have a strong relationship with Boston Scientific, the sponsors of our Y-90 study. We will work together to move this therapy forward through the next phases of clinical trial testing.”

The future of embolization: “The field is advanced”

Mouli and Bagla belong to a generation of interventional radiologists enthusiastic about the potential of embolization in several guises. Mouli expands: “As interventional radiologists interested in advancing the science, we are always looking for ways to expand areas of clinical success into other organs. What 20 years of radioembolization research has shown is that the traditional dogmatic thinking of radiation dose limits no longer holds when radiotherapy is performed trans-arterially. It turns out that with microcatheter technique, 3D imaging, and proper patient selection, in fact doses much higher than can be delivered externally can be delivered to organs safely, in a single-setting. This is now being demonstrated by our current canine model, has been used in the kidney, spleen and, soon, in the brain. The radioembolization platform is quite simple to use, and when combined with modern imaging and contemporary state-of-the-art techniques, the field is advanced. Ultimately, the patients benefit.”


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