Combined biology-guided radiotherapy and Lutetium PSMA theranostics treatment in metastatic castrate-resistant prostate cancer

Mathieu Gaudreault; David Chang; Nicholas Hardcastle; Price Jackson; Tomas Kron; Michael S Hofman; Shankar Siva

doi:10.3389/fonc.2023.1134884

Combined biology-guided radiotherapy and Lutetium PSMA theranostics treatment in metastatic castrate-resistant prostate cancer

Front Oncol. 2023 Mar 13:13:1134884. doi: 10.3389/fonc.2023.1134884. eCollection 2023.

Authors

Mathieu Gaudreault^{1

2}, David Chang^{2

3}, Nicholas Hardcastle^{1

2

4}, Price Jackson^{1

2}, Tomas Kron^{1

2

4}, Michael S Hofman^{2

5}, Shankar Siva^{2

3}

Affiliations

¹ Department of Physical Sciences, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
² Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia.
³ Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
⁴ Centre for Medical Radiation Physics, University of Wollongong, Wollongong, NSW, Australia.
⁵ Molecular Imaging and Therapeutic Nuclear Medicine, Cancer Imaging, Prostate Cancer Theranostics and Imaging Centre of Excellence (ProsTIC), Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Abstract

Background: Lutetium-177 [¹⁷⁷Lu]-PSMA-617 is a targeted radioligand that binds to prostate-specific membrane antigen (PSMA) and delivers radiation to metastatic prostate cancer. The presence of PSMA-negative/FDG-positive metastases can preclude patients from being eligible for this treatment. Biology-guided radiotherapy (BgRT) is a treatment modality that utilises tumour PET emissions to guide external beam radiotherapy. The feasibility of combining BgRT and Lutetium-177 [¹⁷⁷Lu]-PSMA-617 for patients with PSMA-negative/FDG-positive metastatic prostate cancer was explored.

Materials and methods: All patients excluded from the LuPSMA clinical trial (ID: ANZCTR12615000912583) due to PSMA/FDG discordance were retrospectively reviewed. A hypothetical workflow where PSMA-negative/FDG-positive metastases would be treated with BgRT whilst PSMA-positive metastases would be treated with Lutetium-177 [¹⁷⁷Lu]-PSMA-617 was considered. Gross tumour volume (GTV) of PSMA-negative/FDG-positive tumours were delineated on the CT component of the FDG PET/CT scan. Tumours were deemed suitable for BgRT if (1) normalised SUV (nSUV), defined as the ratio of maximum SUV (SUVmax) inside the GTV to mean SUV inside a 5 mm/10 mm/20 mm margin expansion of the GTV, was larger than a pre-specified nSUV threshold and (2) there was no PET avidity inside the margin expansion.

Results: In 75 patients screened for Lutetium-177 [¹⁷⁷Lu]-PSMA-617 treatment, 6 patients were excluded due to PSMA/FDG discordance and 89 PSMA-negative/FDG-positive targets were identified. GTV volumes ranged from 0.3 cm³ to 186 cm³ (median GTV volume = 4.3 cm³, IQR = 2.2 cm³ - 7.4 cm³). SUVmax inside GTVs ranged between 3 and 12 (median SUVmax = 4.8, IQR = 3.9 - 6.2). With nSUV ≥ 3, 67%/54%/39% of all GTVs were suitable for BgRT within 5 mm/10 mm/20 mm from the tumour. Bone and lung metastases were the best candidates for BgRT (40%/27% of all tumours suitable for BgRT with nSUV ≥ 3 within 5 mm from the GTV were bone/lung GTVs).

Conclusions: Combined BgRT/Lutetium-177 [¹⁷⁷Lu]-PSMA-617 therapy is feasible for patients with PSMA/FDG discordant metastases.

Keywords: BgRT; LuPSMA; PSMA; mCRPC; theranostics.

Grants and funding

This work is funded in part by the Peter MacCallum Cancer Centre Foundation. NH acknowledges support from Varian Medical Systems. Shankar Siva is supported by the Victorian Cancer Council Colebatch Fellowship. MH acknowledges philanthropic/government grant support from the Prostate Cancer Foundation (PCF) funded by CANICA Oslo Norway, NHMRC Investigator Grant and a Prostate Cancer Research Alliance funded by Movember and the Australian Government Medical Research Future Fund (MRFF). PJ is partially supported through a fellowship from the PCF. This research is partially funded by RefleXion Medical. The funders had no role in study design or manuscript writing.