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

BACKGROUND: Lutetium-177 [(177)Lu]-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 [(177)Lu]-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 [(177)Lu]-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 [(177)Lu]-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 cm(3) to 186 cm(3) (median GTV volume = 4.3 cm(3), IQR = 2.2 cm(3) – 7.4 cm(3)). 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 [(177)Lu]-PSMA-617 therapy is feasible for patients with PSMA/FDG discordant metastases.