Suitability of PSMA-PET Biology-Guided Radiotherapy for Low Volume Metastases in Newly Diagnosed Prostate Cancer

Abstract

Biology-guided radiation therapy (BgRT) guides radiation therapy in real time based on positron emissions detected during treatment delivery. Protein specific membrane antigen (PSMA) is a positron emission tomography (PET) tracer with superior sensitivity and specificity for prostate cancer detection compared with conventional imaging. This study aims to quantify the ratio of standard uptake value (SUV) to background SUV for patients with low volume prostate cancer metastases, in the context of determining suitability of these lesions for BgRT. A single institutional patient subset from the ProPSMA prospective clinical trial underwent Ga-68-PSMA-11 at the time of prostate cancer diagnosis with suspected localized disease. From this cohort of 84 patients, 15 had at least one metastatic site disease diagnosed, 1 to 11 lesions per patient, with a total of 43 metastatic lesions (12 bones/31 viscerals). Metastatic gross tumor volume (GTV) were delineated on PSMA-PET images by using a patient-specific fixed SUV threshold method. In order to determine the suitability of various BgRT tracking zones, 3D shells of thickness 5 mm, 10 mm and 20 mm were constructed around the GTV to represent adjacent non-tumor background. Normalized SUV (nSUV) was calculated as the ratio of SUVmax in the GTV to SUVmean of adjacent shell. Sensitivity of nSUV to shell thickness variation was reported as the difference between nSUV values obtained for each thickness. GTV SUVmax ranged from 2.9 to 48.0 (median, 12.0; IQR, 5.1 to 19.5). nSUV ranged from 2.4 to 42.6 for 5 mm shell, 2.7 to 47.5 for 10 mm shell and 2.6 to 36.4 for 20 mm shell. Bone metastases had increased SUVmax compared with visceral metastases (SUVmax min/median/max 2.9/15.0/48.0 for bone compared with 2.9/11.0/40.0 for visceral). Furthermore, 90% of lesions had nSUV greater than 2.9 for a shell thickness of 5 mm, 3.1 for a shell thickness of 10 mm, and 3.2 for a shell thickness of 20 mm. Moreover, 100%/93%/84% of lesions would be suitable for BgRT by using nSUV cut-off of 2/3/4 and a shell thickness of 10 mm. nSUV decreased with increasing shell thickness for 17 lesions, indicating high signal in adjacent non-tumor tissue due to the proximity of bladder (5), bowel (4), other lesion (4), vessel (3) and liver (1). This study demonstrates that it is feasible to identify metabolically defined radiotherapy targets in the setting of BgRT. High lesion to background signal was observed for metastases visible on Ga-PSMA-EPT-11, however a subset of metastases had adjacent non-tumor uptake which may require exclusion from emission tracking during BgRT. Trial ID ACTRN12617000005358.