Combined Biology-Guided Radiotherapy and Lutetium PSMA Treatment in Metastatic Prostate Cancer

Abstract

<h3>Purpose/Objective(s)</h3> Biology-guided radiotherapy (BgRT) is a new technology that delivers radiation based on positron emission tomography (PET) signal. Lutetium-177 (¹⁷⁷Lu) prostate-specific membrane antigen (PSMA) is a novel theranostic treatment that demonstrated high response and low toxicities in patients with metastatic castrate-resistant prostate cancer. However, patients may be excluded from this theranostic treatment due to discordance between Gallium-68 (⁶⁸Ga)-PSMA-11 and ¹⁸F-fluorodeoxyglucose (FDG) PET uptake at screening. Using the theranostic treatment alone on these excluded patients would result in untreated FDG-only avid tumor deposits. However, FDG-only avid tumor deposits may be treated with BgRT. This study investigates the feasibility of a combined theranostic/BgRT treatment to excluded patients with discordant uptake. <h3>Materials/Methods</h3> Patients excluded from the LuPSMA clinical trial (ID ANZCTR12615000912583) were retrospectively reviewed. A hypothetical hybrid treatment was considered in which BgRT would supplement ¹⁷⁷Lu-PSMA treatment in discordant FDG-avid tumors. In this treatment, FDG-only avid tumors would be treated with BgRT whereas PSMA-avid tumors would be treated with LuPSMA treatment (100% efficacy was assumed). PSMA PET uptake was mapped to the FDG PET frame of reference using deformable registration between the CT-component of the two PET scans. Gross tumor volume (GTV) of FDG-only avid tumors were contoured on the CT-component of the FDG PET/CT scan by a radiation oncologist. Biological tracking zones (BTZ) for BgRT dose delivery were generated from GTV outer margin expansion of 5 mm / 10 mm / 20 mm. Normalized SUV (nSUV) was calculated as the ratio of the maximum SUV inside the GTV to the mean of SUV inside the outer margin expansions. Tumors were considered suitable to BgRT if nSUV was larger than 3 and if the normal tissue surrounding the tumor was free of any PET signal inside the BTZ. <h3>Results</h3> Of 75 patients screened for LuPSMA treatment, 7 patients had discordant PSMA and FDG uptake, 6 of which had FDG-only avid tumors and were included in this study. In these 6 patients, 89 potential BgRT 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 was between 3 and 12 (median SUVmax = 4.8, IQR = 3.9 – 6.2). With nSUV ≥ 3, 67% / 48% / 28% of all GTVs were free of FDG uptake within 5 mm / 10 mm / 20 mm from the tumor and therefore suitable to BgRT. Bone and lung sites were the best candidates for BgRT (27% / 18% of all tumors were bone / lung GTVs with nSUV ≥ 3 and were isolated from PET uptake within 5 mm). <h3>Conclusion</h3> 67% of FDG-only avid tumors were suitable to BgRT treatment inside a BTZ generated from a margin expansion of 5 mm. BgRT treatment to FDG-only avid tumor in combination with Lutetium PSMA theranostic treatment is therefore feasible.