Evaluation of PSMA-PET Biology-Guided Radiotherapy Sequential Boost to the PSMA-avid Subvolume in the Prostate Region in Low-Volume Advanced Prostate Cancer

Abstract

Biology-guided radiation therapy (BgRT) is a new technology that aims to deliver radiation based on detecting positron emissions in real time. BgRT combined with prostate specific membrane antigen (PSMA) PET/CT imaging may be an attractive option for prostate cancer patients with low-volume pelvic nodes and distant metastases since all lesions may be treated during the same session. This study investigates the feasibility of BgRT sequential boost to the PSMA-avid subvolume (PAS) in the prostate region. The ratio of standard uptake value (SUV) to background SUV is quantified, with specific focus on adjacent bladder uptake.Patients enrolled in the ProPSMA prospective single-institution clinical trial underwent Ga-68-PSMA-11 PET scan at the time of prostate cancer diagnosis. Those with pelvic node or distant metastases were selected for analysis. PAS gross target volume (GTV) was delineated on the PET component of a PET/CT acquisition by using a PET edge tool in commercially available software. Three dimensional shells of thickness 5 mm, 10 mm and 20 mm were created by expanding the GTV to characterize the uptake background and to determine suitability of BgRT based on these tracking zones. Normalized SUV (nSUV) was calculated as the ratio of SUVmax in the GTV to SUVmean of the adjacent shell. Lesions with nSUV larger than 3 were defined to be suitable for BgRT. An increase in nSUV with increasing shell thickness indicates absence of uptake surrounding the GTV.From the ProPSMA patient cohort of 89 patients, 24 patients had at least one pelvic nodal or distant metastases. PAS GTV volume ranged from 1 cc to 147 cc (median = 25 cc, IQR = 12 cc - 62 cc). GTV SUVmax varied from 6.4 to 80 (median = 21.5; IQR = 14 - 33). nSUV ranged from 3.4 to 21.2 (median = 6.4; IQR = 4.9 - 8.5), from 4.1 to 20.9 (median = 8.6; IQR = 6 - 10.5), and from 2.8 to 31.4 (median = 8.2; IQR = 5.4 - 13.8) in 5 mm, 10 mm, and 20 mm shell, respectively. Moreover, 100%, 100%, and 96% of lesions had nSUV greater than 3 in a shell thickness of 5 mm, 10 mm, and 20 mm, respectively. nSUV increased from the 5 mm shell to the 10 mm shell in 75% of patients and from the 10 mm shell to the 20 mm in 46% patients, indicating the absence of bladder uptake.An nSUV greater than 3 was achieved in more than 95% of all GTVs for all shell thicknesses investigated in this study, which suggests that PSMA-guided BgRT is a feasible modality for sequential boost directed at the dPSMA-avid subvolume in the prostate region. If bladder proximity impacts geometric specificity of BgRT delivery or if greater tumor-to-background contrast is desired, additional refinements may be required. These may include modifications to the BgRT algorithm that enable masking of the bladder. Clinical trial number ACTRN12617000005358.