Below the Belt Award
David Chen — 2026
Using PET Imaging to Predict Who Benefits from Early Upfront Lutetium-PSMA Therapy in Men with Newly Diagnosed Advanced Prostate Cancer
“Will this treatment work for me?” is a question that patients with prostate cancer and those supporting them often ask when discussing the therapies available with their doctors [1]. This question reaches the heart of the matter for patients with newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC). While representing only 8% of all Australian men diagnosed with prostate cancer [2], patients with mHSPC represent 50% of all prostate cancer deaths [3]. They also experience a shorter survival time of only 33 months after starting standard hormone therapy [4]. Most patients with a lived experience of mHSPC receive only 2-3 treatment lines [5], highlighting the urgency to maximise efficacy
and promptly discontinue futile therapies.
[177Lu]Lu-PSMA-617 (LuPSMA) is a radioactive medicine homing in on prostate cancer cells over-expressing prostate-specific membrane antigen (PSMA) on their cell surface, while sparing healthy tissue. Our group pioneered LuPSMA, and it is now an established treatment in late-stage prostate cancer [6]. While clinical trials have also demonstrated the safety and efficacy of LuPSMA in mHSPC, there is scarce evidence at present to identify which patients will benefit most [7,8]. The aim of our study is to generate reproducible imaging biomarkers from UpfrontPSMA to optimise patient selection, and spare those who will only have marginal improvements but exposure to harmful side-effects [7].
UpfrontPSMA is an ANZUP co-badged, Peter MacCallum Cancer Centre sponsored, multidisciplinary, high-impact clinical trial conducted at over 10 sites around Australia and has paved the way forward in an area of clinical need. It was the first randomised study internationally (The Lancet Oncology, 2024) to demonstrate the benefit of adding LuPSMA to standard-of-care treatment in mHSPC. The study was supported by a Prostate Cancer Research Alliance (PCRA) grant funded by Movember and the Medical Research Future Fund. Consumers representatives include Mr. Barry Elderfield, Mr. Tony Musgrave, and Mr. Lee Naish. Ongoing and new consumer involvement in this Below-the-Belt project will ensure that we address issues that are most pertinent to patients, tackling unmet needs in prostate cancer care.
In UpfrontPSMA, 130 patients with newly diagnosed mHSPC were randomly allocated to receive LuPSMA in addition to standard treatment with docetaxel chemotherapy and androgen deprivation therapy (ADT), or standard treatment alone. In the LuPSMA arm, 41% of men reached a favourable outcome of undetectable prostate-specific antigen (PSA) demonstrating treatment response, whereas only 16% of patients reached the same in the standard arm. Currently, it is unclear why those 41% of men responded most optimally.
In this study, we aim to use UpfrontPSMA patient’s pre-treatment molecular scans known as positron emission tomography (PET) to assess if certain parameters can predict response to LuPSMA treatment or long-term outcomes. All patients received a PSMA and fluorodeoxyglucose (FDG) PET scan before treatment and at 12-weeks after their allocated treatment has begun. There is currently minimal high-quality evidence in understanding cancer distribution, behaviour and genetic changes on PSMA and FDG-PET in mHSPC. UpfrontPSMA offers a unique, world-leading opportunity to describe how mHSPC visualised on a molecular level responds to LuPSMA and standard treatment.
[177Lu]Lu-PSMA-617 (LuPSMA) is a radioactive medicine homing in on prostate cancer cells over-expressing prostate-specific membrane antigen (PSMA) on their cell surface, while sparing healthy tissue. Our group pioneered LuPSMA, and it is now an established treatment in late-stage prostate cancer [6]. While clinical trials have also demonstrated the safety and efficacy of LuPSMA in mHSPC, there is scarce evidence at present to identify which patients will benefit most [7,8]. The aim of our study is to generate reproducible imaging biomarkers from UpfrontPSMA to optimise patient selection, and spare those who will only have marginal improvements but exposure to harmful side-effects [7].
UpfrontPSMA is an ANZUP co-badged, Peter MacCallum Cancer Centre sponsored, multidisciplinary, high-impact clinical trial conducted at over 10 sites around Australia and has paved the way forward in an area of clinical need. It was the first randomised study internationally (The Lancet Oncology, 2024) to demonstrate the benefit of adding LuPSMA to standard-of-care treatment in mHSPC. The study was supported by a Prostate Cancer Research Alliance (PCRA) grant funded by Movember and the Medical Research Future Fund. Consumers representatives include Mr. Barry Elderfield, Mr. Tony Musgrave, and Mr. Lee Naish. Ongoing and new consumer involvement in this Below-the-Belt project will ensure that we address issues that are most pertinent to patients, tackling unmet needs in prostate cancer care.
In UpfrontPSMA, 130 patients with newly diagnosed mHSPC were randomly allocated to receive LuPSMA in addition to standard treatment with docetaxel chemotherapy and androgen deprivation therapy (ADT), or standard treatment alone. In the LuPSMA arm, 41% of men reached a favourable outcome of undetectable prostate-specific antigen (PSA) demonstrating treatment response, whereas only 16% of patients reached the same in the standard arm. Currently, it is unclear why those 41% of men responded most optimally.
In this study, we aim to use UpfrontPSMA patient’s pre-treatment molecular scans known as positron emission tomography (PET) to assess if certain parameters can predict response to LuPSMA treatment or long-term outcomes. All patients received a PSMA and fluorodeoxyglucose (FDG) PET scan before treatment and at 12-weeks after their allocated treatment has begun. There is currently minimal high-quality evidence in understanding cancer distribution, behaviour and genetic changes on PSMA and FDG-PET in mHSPC. UpfrontPSMA offers a unique, world-leading opportunity to describe how mHSPC visualised on a molecular level responds to LuPSMA and standard treatment.
