Upfront [177Lu]Lu-PSMA-617 radioligand therapy prior to radical prostatectomy in men with HR PC

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Published: 16 Mar 2023
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Dr Renu Eapen - Peter MacCallum Cancer Centre, Melbourne, Australia

Dr Renu Eapen speaks to ecancer about her talk at EAU 2023 regarding the LuTectomy study.

LuTectomy is a prospective study of dosimetry, safety and potential benefit of upfront [177Lu]Lu-PSMA-617 radioligand therapy prior to radical prostatectomy in men with high-risk localised prostate cancer.

She discusses the background and results of the study.

Dr Eapen talks about how this can be game changing for the treatment of patients with high-risk localised prostate cancer.

The LuTectomy trial is a phase I/II study and it is looking at the dosimetry, efficacy and safety of lutetium-PSMA therapy given up front prior to radical prostatectomy in men with high-risk localised prostate cancer. It’s really the earliest use of Lu-PSMA in the prostate cancer spectrum.

It was a single series study, non-randomised. It’s really a feasibility proof of concept trial. We recruited twenty men in a staggered fashion; these are all men with high-risk prostate cancer biopsy proven with high-risk features. Six out of the twenty men had pelvic nodal disease but no-one had distant metastasis. They all had high uptake on PSMA-PET scan which was an important inclusion criteria. 

The first cohort of ten men received one cycle of lutetium and the second cohort of ten men received two cycles spaced six weeks apart. Then six weeks after the last cycle they underwent their radical prostatectomy and lymph node dissection. The primary endpoint of the trial is dosimetry, so what dose of radiation we can really deliver to the target tissues that contain tumour, and the important secondary endpoints were biochemical imaging and pathological responses, safety of the treatment – how well it is tolerated, and, importantly, how safe is surgery after this treatment. We also looked at quality of life measures.

The primary endpoint is dosimetry and so we calculated this using a three timepoint SPECT CT. We saw that we could deliver quite significant doses to tumour tissues, so a total of 35Gy to the lesions in general, a median of 35Gy, and that included a median of 38Gy to the lymph nodes and 20Gy to the prostate. The thing to remember, because a lot of people say that these are very low doses, but actually these are very targeted doses. So all of this goes specifically to the cells that express PSMA and that’s the difference and what makes this treatment unique over other forms of treatment such as external beam radiation or brachytherapy. 

We also found that it was very well tolerated. Events were very low grade, most of them were grade 1. No patient had grade 3-5 adverse events. Very small doses delivered to physiological glands so it was a very well tolerated treatment. Surgery was really straightforward; we were pleasantly surprised that all tissue planes were well preserved. The majority of patients, the level of difficulty was as you would expect for a high-risk prostate cancer. They all had routine postoperative care and no-one had any high grade complications and no-one had any complications attributed to the Lu-PSMA.

What it tells us is that further research into this space is really worthwhile. We have demonstrated that Lu-PSMA delivers good doses of targeted radiation. We’ve demonstrated that it is safe and surgery is well tolerated afterwards. But we do need the next trial, the next big randomised trial that really looks at the role of this sort of treatment in the up-front setting. Oncological endpoints were not the aim of this trial and they take a long time in prostate cancer – it takes many years for that to really be apparent. But before we design the next trial the questions we will need to answer are what is the optimal dose of Lu-PSMA? How many cycles do we need to give? How long do we need to wait between the treatment and operating on these patients? Do we need to operate on them at all? And how do we better select these patients for treatment? So these are the sorts of questions over time we will need to answer before this becomes a treatment strategy.

This was a major collaborative effort from a lot of people. The primary investigators of this trial are Declan Murphy and Michael Hofman and they dedicate a lot of their time and energy to completing this trial. Dr John Violet, the late Dr John Violet, our friend and colleague, really came up with the initial vision for this trial and he was the one who was instrumental in getting this set up. We had some great support from our major funders which were the Movember Foundation and the EJ Whitten Foundation as well as Novartis and ANSTO and the Prostate Cancer Foundation for supporting me. So it was really a fantastic collaborative effort.