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

Abstract

BackgroundLutetium-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 methodsAll 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.ResultsIn 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).ConclusionsCombined BgRT/Lutetium-177 [177Lu]-PSMA-617 therapy is feasible for patients with PSMA/FDG discordant metastases.

PSMA Radioligand Therapy in Prostate Cancer

“…The authors proposed that biology-guided radiotherapy could be feasible and even associated with PSMA-RLT in patients with PSMA/FDG discordant metastases. 39 Hotta et al 40 retrospectively evaluated the parotid gland uptake visually and quantitatively in the baseline images of 237 patients treated with either 177 Lu-PSMA-617 or 177 Lu-PSMA-I&T. Most patients (92.4%) presented intermediate to high uptake. PSA50, PSA-PFS and OS presented positive correlation with uptake in salivary glands either in a visual or quantitative scale ( P < 0.005), with good interreader reproducibility (k = 0.68).…”

“…Gaudreault et al 39 evaluated 6 patients that were excluded from the LuPSMA trial with a total of 89 PSMA-negative/FDG-positive targets identified. Median gross tumor volume (GTV) of 4.3 cm 3 , and median SUV max of 4.8 were found in 18 F-FDG PET/CT.…”

“…Approximately 53% of all GTVs were suitable for biology-guided radiotherapy with bone, and lung metastases considered the best suited for biology-guided radiotherapy. The authors proposed that biology-guided radiotherapy could be feasible and even associated with PSMA-RLT in patients with PSMA/FDG discordant metastases 39 …”

What should be the future direction of development in the field of prostate cancer with lung metastasis?

“…In recent years, some reports have shown promising results in the treatment of PCLM patients using 177Lu-PSMA radioligand therapy (Lu-PRLT)[ 31 , 32 ]. However, PCLM patients who are PSMA(-)/fluorescein Di-β-D-galactopyranoside (FDG)(+) may not benefit from Lu-PRLT[ 33 ]. Therefore, some researchers have combined biologically guided radiation therapy with Lu-PRLT for PSMA(-)/FDG(+) PCLM patients and found this combination therapy to be beneficial[ 33 ].…”

“…However, PCLM patients who are PSMA(-)/fluorescein Di-β-D-galactopyranoside (FDG)(+) may not benefit from Lu-PRLT[ 33 ]. Therefore, some researchers have combined biologically guided radiation therapy with Lu-PRLT for PSMA(-)/FDG(+) PCLM patients and found this combination therapy to be beneficial[ 33 ]. Moreover, there have been case reports suggesting that the combination of stereotactic body radiation therapy and androgen deprivation therapy (ADT) can confer benefits in terms of biochemical response and disease-free survival in PCLM patients[ 34 ].…”