PSMA PET in patients with prostate cancer Thomas Hope, MD Assistant Professor of Radiology, UCSF Abdominal Imaging and Nuclear Medicine Co-director, PET/MRI Chief of MRI, San Francisco VA Medical Center PSMA prostate specific membrane antigen expressed on 90-95% of prostate cancer cells increased expression with higher gleason score prostate cancer cell PSMA imaging agent Ga-68 PSMA-11 prostate specific membrane antigen Binds the extracellular domain prostascint bound the intracellular Has been demonstrated to have a higher sensitivity than fluorocholine in patients with biochemical recurrence chelator HBED-CC binding site Ga-68 PSMA versus F18-choline Study 1: 37 patients, mean PSA of 11-86% + on PSMA, 70% + on choline Choline PET PSMA PET Study 2: 38 patients, mean PSA of 1.7-66% + on PSMA, 32% + on choline Afshar-Oromieh EJNMMI 2014, Afshar-Oromieh EJNMMI 2015, Eiber JNM 2015 Afshar-Oromieh 2014, EJNMMI Morigi 2015, JNM 1
DCFPyL Changing prostatectomy population More high risk prostatectomies are being performed Biggest issue that imaging can solve in primary preprostatectomy patients is the detection of nodal metastases Presence of nodes indicates poor cancer specific disease control Nodal metastases Carroll and Cooperberg, JAMA 2015 Biano et al, Urology 2005 PSMA in preprostatectomy patients 130 patients with intermediate to high risk prostate cancer All underwent prostatectomy 66% sensitivity by patient 74% sensitivity by region 72 year old man with Gleason 4+4 Maurer et al, Journal of Urology, 2016 2
72 year old man with Gleason 4+4? low risk intermediate risk high risk When should we intervene? How to interpret PET and MRI together for the primary tumor? what if MR negative and PET positive, or vice versa When should we not intervene? How do we manage patients with nodal metastases that are within the surgical field? 72 year old man with Gleason 4+4 8 mm node Status post RP, PSA of 20 negative MRI and CT 69 year old man status post RP PSA = 0.67 Disease site 1: right humerus Disease site 2: left internal iliac node Converted biopsy from showed ADT/systemic prostate to targeted adeno radiation 3
Biochemical recurrence Post RP: PSA increase from 0.5 to 0.9 Disease site 1: right pelvic side wall node 1 Disease site 2: right pelvic side wall node 2 % patients with disease Percent of patients with disease detected by PSMA PET at UCSF 125% 100% 75% 50% 25% 0% n=12 n=23 0-0.2 0.2-0.5 0.5-1.0 1.0-1.5 1.5-2.0 >2.0 PSA range n=14 n=93 % patients with disease Percent of patients with disease detected by PSMA PET at UCSF 125% 100% 75% 50% 25% 0% n=12 n=23 0-0.2 0.2-0.5 0.5-1.0 1.0-1.5 1.5-2.0 >2.0 PSA range n=14 Eiber 2015 n=93 Effect on change in management Based on 126 surveys from referring clinicians before and after patients were imaged using PSMA PET at UCSF: 52% of patients had a major change in management: 16 patients were converted from ADT to radiation treatment 15 patients were converted from active surveillance to radiation treatment 3 patients were converted from radiation to ADT Detection of oligometastatic disease converts patients to radiation treatment Recurrence after radiation therapy PSA of 10 two nodes seen on CT Disease site 1: left pelvic side wall 4
Oligometastatic patient... PSMA vs NaF PET on Lupron brachytherapy RP + LND tax/carbo 2/2016: cyberknife 4/2016: 0.04 12/2015: 0.26 6/2016: 0.13 1/2016: 0.6 Prostate PET/MRI: pre-prostatectomy patients PET/MRI for prostate recurrence T-stage N-stage M-stage DWI PSMA PET NX: not assessed N0: no nodes N1: 1 or more nodes M0 vs M1 T2 T3a T2: confined to gland T3a: ECE T3b: SVI T4: adjacent organs post-gadolinium T2 weighted imaging Role of MRI Role of PET/CT 5
The time spent on dedicated MR imaging is not wasted time from the PET perspective whole body PET (3 minutes per bed) pelvis PET (15 minutes) PSMA clinical trials PSMA clinical trials Access Current protocols being developed at most sites Indiana Memorial Sloan Kettering NYU Stanford UCSF UCLA University of Iowa University of Michigan University of Wisconsin UT Southwestern Vanderbilt Access Current protocols being developed at most sites Accuracy (FDA) CTN PSMA protocols Includes change in management 2-3 year timeline PSMA clinical trials Theranostics Access Accuracy (FDA) Outcomes (CMS?) The use of a compound for both diagnostics and therapeutics Imaging: Ga-68 Current protocols being developed at most sites CTN PSMA protocols Includes change in management Australia protocol (not funded!!) None yet in US Therapy: Lu-177 Y-90 PSMA I&T Schottelius 2015, EJNNMI Research 6
PET Lu-177-PSMA-617 PSA response after 177 Lu-PSMA response after 1 cycle response after 2 cycles Posttherapy 40% response rate 57% response rate Kabasakal 2015, EJNMMI Rahbar 2016, JNM Summary 1. PSMA is overexpressed on prostate cancer cells and 68 Ga-PSMA-11 has a high sensitivity for detection ax PSMA 2. PSMA PET has important roles in staging patients prior to prostatectomy and at biochemical recurrence Thank you! Fused 3. Moving forward we need to design trials to evaluate outcomes and therapeutic options targeting PSMA PSMA PET thomas.hope@ucsf.edu T1 7