SNMMI 2021: Imaging and Clinical Factors Impacting PSA Response in Patients with Metastatic Castrate Resistant Prostate Cancer Undergoing Lu177-PSMA-617 Therapy

( Beginning with the introduction of docetaxel for metastatic castration resistant prostate cancer (mCRPC) in 2004, there has been a dramatic and rapid proliferation of systemic therapy options in advanced prostate cancer including a number of novel hormonal therapies (including abiraterone acetate and enzalutamide), second-line chemotherapy (cabazitaxel), bone-targeting agents (radium-223) and other targeted agents (including olaparib, rucaparib, and pembrolizumab), each of which has proven survival benefits. Recently, theranostic treatment with prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy, including most notably 177lutetium-PSMA-617 as well as others, has demonstrated promising activity among pre-treated individuals with mCRPC. However, there is no consensus on criteria to determine which patients will benefit the most from these therapeutic approaches. To address this gap, in the Cancer Radiopharmaceutical Therapy session at the Society of Nuclear Medicine & Molecular Imaging (SNMMI) 2021 Annual Meeting, Dr. Sarah Boughdad presented data that aimed to assess characteristics that might affect PSA response in patients undergoing Lu-177-PSMA-617 therapy.

To do so, they examined patients with mCRPC who were eligible for Lu-177-PSMA-617.  These patients were prospectively enrolled at a single center from February 2020 to December 2020. For initial disease characterization, all patients underwent both 68Ga-PSMA and 18F-FDG PET/CT acquired 60 minutes after injection of 2-3.5 MBq/kg of each radiotracer. Those patients who had mismatched lesions (FDG positive but not seen on 68Ga-PSMA PET/CT) were excluded from further evaluation within this context. Using the PET images, patients were characterized in terms of tumor burden (high >20 lesions versus medium < 20 and > 5 lesions) and the appearance of diffuse bone marrow infiltration.

Additionally, the authors collected baseline information including cancer grade (Gleason score ≤ 7 vs > 7) and previous treatments including chemotherapy (1 line versus 2 lines) and novel antiandrogen drugs (abiraterone or enzalutamide vs both). The authors examined PSA serum levels before and during the course of treatment. The Mann-Whitney test was used to compare PSA values before treatment and PSA response after cycles 1 (C1) and 2 (C2).

Among 22 consecutive patients with mCRPC, 19 patients with high uptake on 68Ga-PSMA PET/CT and no discordant lesion on 18F-FDG PET/CT and were treated with at least one cycle of Lu-177-PSMA-617. Three patients were excluded because of liver metastasis only seen on 18F-FDG PET/CT. These 19 patients were administered between 3.9 to 8 GBq of 68Ga-PSMA for C1 (19 pts) and 5.2 to 8.1 GBq for C2 (15 pts), on the basis of patients' laboratory results.


Patients with a high tumor burden on the basis of 68Ga-PSMA PET/CT had significantly higher pre-treatment PSA values (759.8±1923.7 vs 56.6±109.3; p=0.02), however, pre-treatment tumor burden was not associated with PSA response after C1 or C2 (p=0.7 and 0.4, respectively). Similarly, those patients with diffuse bone marrow infiltration on PET images (n=7, 26.8%) had significantly higher PSA levels at baseline (1229.8±2482.4 vs 77.1±92.5; p=0.007) though diffuse bone marrow infiltration did not significantly affect PSA response (-25.8±71.7 vs -32.4±82.3 after C1; p=0.53).


Further, the authors found no evidence of an association between Gleason score or the number of chemotherapy lines and PSA response (p>0.05). However, the nine patients who had received both abiraterone and enzalutamide prior to Lu-177-PSMA-617 therapy had higher PSA values at baseline than those who had received a single line of therapy (963.7±2213.5 vs 77.1±92.5; p=0.035) and showed a lower magnitude of PSA response after C1, though this was not significantly different (-15.2±54.6 vs -51.8±-38.5; p=0.09).

The authors, therefore, concluded that patients with higher tumor burden and those diffuse bone marrow infiltration demonstrated comparable PSA responses to Lu-177-PSMA-617. Additionally, there was evidence that prior therapy, particularly with multiple lines of androgen axis inhibition, may affect treatment response. This may have implications on treatment sequencing and the role of Lu-177-PSMA-617 though they require further validation.

Presented by: Sarah Boughdad, MD, University of Lausanne, Lausanne, Switzerland

Written by: Christopher J.D. Wallis, Urologic Oncology Fellow, Vanderbilt University Medical Center Contact: @WallisCJD on Twitter at the Society of Nuclear Medicine & Molecular Imaging 2021 virtual annual meeting