Original article Delineating biochemical failure with 68 Ga-PSMA-PET following definitive external beam radiation treatment for prostate cancer George Hruby a,e,f,⇑ , Thomas Eade a,e,f , Andrew Kneebone a,e,f , Louise Emmett d , Lesley Guo a , Bao Ho c,d , Ed Hsiao b , Geoff Schembri b , Julia Hunter a , Carol Kwong a a Department of Radiation Oncology; b Department of Nuclear Medicine and PET, Royal North Shore Hospital; c Department of Nuclear Medicine, St Vincent’s Hospital; d University of New South Wales; e University of Sydney; and f Genesis Cancer Care, Sydney, Australia article info Article history: Received 15 September 2016 Received in revised form 29 November 2016 Accepted 30 November 2016 Available online xxxx Keywords: PSMA-PET Biochemical failure Prostate cancer abstract Background and purpose: We investigated the role of 68 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 bio- chemical failure (BF), 13 of whom have died. Of the 57 survivors, 5 had metastases detected on conven- tional 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 Ó 2016 Published by Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology xxx (2016) xxx–xxx 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 delin- eate 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 Study cohort All patients at our centre are enrolled onto an ethics approved, prostate cancer patient database. 538 men were treated with image guided EBRT to a dose greater than 78 Gy between 2007 and 2014. For this study, we identified 419 patients treated to at least 78 Gy and followed for at least 24 months post completion of EBRT. Men with BF (n = 70), and without evident disease on http://dx.doi.org/10.1016/j.radonc.2016.11.023 0167-8140/Crown Copyright Ó 2016 Published by Elsevier Ireland Ltd. All rights reserved. ⇑ Corresponding author at: Department of Radiation Oncology, RNSH, St Leonards, NSW 2065, Australia. E-mail address: george.hruby@health.nsw.gov.au (G. Hruby). Radiotherapy and Oncology xxx (2016) xxx–xxx Contents lists available at ScienceDirect Radiotherapy and Oncology journal homepage: www.thegreenjournal.com Please cite this article in press as: Hruby G et al. Delineating biochemical failure with 68 Ga-PSMA-PET following definitive external beam radiation treat- ment for prostate cancer. Radiother Oncol (2016), http://dx.doi.org/10.1016/j.radonc.2016.11.023