Delineating biochemical failure with Ga-PSMA-PET following definitive external beam radiation treatment for prostate cancer

Background and purpose: We investigated the role of Ga-PSMA-PET (PSMA) to determine the location of disease recurrence in those with a rising PSA following definitive external beam radiation treatment (EBRT). Materials and methods: 538 men were treated with image guided EBRT to a dose of 78 or 82 Gy between 2007 and 2014. Patients at least 24 months post EBRT with biochemical failure (nadir + 2) underwent PSMA scanning. Local recurrence (LR) was defined as increased uptake within the prostate or seminal vesicles. Distant disease included lymph node (LN), bone or visceral metastases. Results: 419 men formed the study cohort. Median follow-up was 50 months, 70 patients (17%) had biochemical failure (BF), 13 of whom have died. Of the 57 survivors, 5 had metastases detected on conventional scans; 2 were lost to follow up. 48 men (of 50 candidates) underwent PSMA; in all cases, the PSMA was unequivocally positive. Of the 48 positive scans, 25 patients (52%) failed beyond the prostate – 5 in bones, 16 LN, 3 in both, and 1 in the lungs. Fifteen men (31%) failed within the gland and in either LN (11), bones (3), or both (1). Eight (17%) had an isolated LR, which represents 2% of patients managed with definitive EBRT and followed for at least 2 years. Conclusions: PSMA was positive in all patients with BF. Site of failure following dose-escalated EBRT was generally distant. Isolated LR (on PSMA) occurred in only 8 of 419 patients post-EBRT. Crown Copyright 2016 Published by Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 122 (2017) 99–102 The source of a rising PSA following definitive EBRT may be local, distant or both. This has important implications with respect to salvage versus systemic management options. In this situation, and with a PSA < 10, conventional imaging with CT and bone scan is unhelpful [1]. PSMA has a higher detection rate with a higher specificity than choline-PET [2,3], and is able to evaluate distant metastatic disease in contrast to multi-parametric MRI (mp-MRI). Since 2015, our high risk prostate cancers have been routinely staged with PSMA; and we use PSMA to identify sites of recurrence in men post-prostatectomy, with a rising PSA above 0.2 ng/mL [4]. We have also performed PSMA in those who fail EBRT to determine sites of failure and identify those who may benefit from focal or targeted radiation treatment versus those who are best managed with observation or systemic treatment. In this analysis, we set out to determine whether PSMA was positive in men with BF; if so, to then investigate its role to delineate sites of failure in patients who received definitive image guided and dose-escalated EBRT and who subsequently met the Phoenix definition [5] of BF (nadir + 2). Our hypothesis was that those with LR alone may have had radio-resistant disease based on bulky or hypoxic tumours predicted by factors such as PSA, T stage, dose, and higher core positivity. Methods and materials