Klinikum rechts der Isar, Technische Universität München Contribution of PSMA-PET compared to morphological imaging with regard to detection rate in prostate cancer patients with biochemical recurrence after radical prostatectomy AUA 2015 PD 32: #15-1538 Dear chairmen, dear colleagues! In the next talk I want to present you our results with PSMA-PET imaging in recurrent prostate cancer patients. Tobias Maurer1, Veronika Beck1, Ambros J. Beer2, Michael Souvatzoglou2, Konstantin Holzapfel3, Hubert Kübler1, Jürgen E. Gschwend1, Hans-Jürgen Wester4, Bernhard Haller5, Markus Schwaiger2, Matthias Eiber2 1Department of Urology, 2Department of Nuclear Medicine, 3Department of Radiology, 4Department of Pharmaceutical Radiochemistry, 5Institute of Medical Statistics and Epidemiology Klinikum rechts der Isar, Technische Universität München

Methods Pts. with BCR (n=474) PET/CT PET/MRI no RPX PSA <0.2 ng/ml CRPC Pts. (n=332) PSMA-PET/CT (n=256) PSMA-PET/MR (n=76) In this analysis we included 474 consecutive patients with biochemical recurrent prostate cancer. We excluded patients who did not receive radical prostatectomy upfront, whose PSA was below 0.2 ng/ml or who presented already with CRPC - leaving 332 patients for analysis 256 patients were examined with PSMA-PET/CT and 76 patients received PSMA-PET/MRI. Median PSA of all patients was 1.7ng/ml. Pts. characteristics Age (years, median) 71 (46 - 88) PSA (ng/ml, median) 1.67 (0.2 – 63.0) Gleason-Score (median) 7 (range: 5 – 9) 2

Results: Detection rate 68Ga-PSMA-PET/CT 68Ga-PSMA-PET/MR 10/23 25/35 67/71 122/127 Pts. 13/26 9/12 13/16 21/22 Pts. We analysed the detection rate according to PSA value at the time of examination for PSMA-PET/CT and PET/MRI separately. For this, we chose PSA-ranges from 0.2 – 0.5, 0.5 - 1, 1 - 2 and above 2ng/ml. In general, positive findings were seen in roughly 50% of patients with PSA of 0.2-0.5ng/ml, in 75% of patients with PSA of 0.5-1ng/ml and in 90% for PSA from 1-2ng/ml. Over 95% of patients with PSA above 2ng/ml showed positive findings. We could not detect a significant difference between PET/CT and PET/MRI in our patient cohort. However, there might be a potential advantage for PET/MRI at low PSA-values, especially < 0.5ng/ml. In these patients positive findings were more likely to be rated „highly suggestive for prostate cancer“ with PET/MRI as indicated by the larger red bar. no significant difference between PET/CT and PET/MR potential advantage (higher diagnostic certainty) for PET/MR at PSA<0.5ng/ml (due to functional MR sequences?) 3

Results: 68Ga-PSMA-PET vs. morphology (CT / MR) positive findings only in: additional lesions in: 21.4% (71/332) 6.3% (21/332) 28.9% (96/332) 2.7% (9/332) 28.9% 2.7% Next, we compared the detection rate of PSMA-PET to morphological imaging. We analysed in how many patients only one imaging component showed positive findings. We also examined if additional lesions were visible by PSMA-PET on one side or CT and MRI on the other side. In almost 30% of all patients only PSMA-PET revealed positive findings. CT or MRI on the other hand detected suspicious findings that when PSMA-PET showed no abnormal findings in less than 3%. Additional lesions were seen in 21.4% by PSMA-PET vs. 6.3% by CT or MRI. Findings that were only detected by PSMA-PET were mostly LN metastases followed by local recurrent tumor. Findings that were only detected by CT or MRI were mostly local recurrent tumor. 4

Difficult intraoperative localization of small metastatic LN However, those small metastatic LN might be difficult to detect intraoperatively - especially if they are also located atypically. 5

Maurer et al., AUA 2015, May 19th, MP 82: #15-1546 PSMA-radioguided surgery for intraoperative detection 1. Injection of 110-150MBq 111In-labeled PSMA-ligand approx. 24h prior to surgery 2. Intraoperative detection by gamma probe with acoustic and visual feedback Just recently, also PSMA-ligands for intraoperative use have been developed at our institution. We use for PSMA-radioguided surgery a PSMA-ligand that is labeled with the gamma-emitting isotop Indium-111. This tracer is injected intravenously 24h prior to surgery and then intraoperatively suspicious LN can be detected with a gamma probe. Maurer et al., AUA 2015, May 19th, MP 82: #15-1546 6

Maurer et al., AUA 2015, May 19th, MP 82: #15-1546 89_clip0 PSMA-radioguided surgery: Intraoperative acoustic feedback This short video sequence shows the intraoperative detection of an obviously suspicious LN by PSMA-radioguided surgery. Maurer et al., AUA 2015, May 19th, MP 82: #15-1546 7

Maurer et al., AUA 2015, May 19th, MP 82: #15-1546 89_clip0 PSMA-radioguided surgery: Acoustic feedback – ex vivo The next video shows ex-vivo measurements of resected tissue specimens. Also LN that are not enlarged but harbour metastatic prostate cancer cells can be detected. With this method of PSMA-radioguided surgery we could detect metastatic deposits that were as small as 2mm. Maurer et al., AUA 2015, May 19th, MP 82: #15-1546 8

Conclusion 68Ga-PSMA-PET hybrid-imaging shows high detection rates in recurrent PCa at low PSA values PET/MR might be advantageous in patients with PSA <0.5 ng/ml 68Ga-PSMA-PET hybrid-imaging might replace other tracers like 18F-FDG or choline derivatives in future clinical practice Thus, we conclude that PSMA-PET hybrid imaging shows high detection rates in recurrent prostate cancer after radical prostatectomy even at low PSA values. For the most part these enhanced detection rates can be attributed to the PSMA-PET component. In patients with PSA <0.5ng/ml PET/MR might be advantageous. At the bottom you see PET/CT images of two patients that were examined at our hospital roughly 3 years ago. These examinations were done with 11C-choline. At that time we started to use the new PSMA-PET tracer and examined those patients again a few weeks later. Thus, we also think that PSMA-PET imaging might replace other tracers like FDG or choline derivatives in future clinical practice. Thank you for your attention! 11C-choline PET/CT 68Ga-PSMA PET/CT 11C-choline PET/CT 68Ga-PSMA PET/MR 9