Abstract
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Introduction: PSMA is a membrane glycoprotein highly expressed in prostatic adenocarcinoma especially in poorly differentiated and metastatic setting. Novel therapeutic approaches targeting PSMA showed good results in patients with metastatic castrate resistant prostate cancer (mCRPC) (TheraP trial, ASCO 2020). However, there are no consensus on criteria to determine which patients will benefit the most of peptide receptor radionuclide therapy. We aimed to assess which factors might affect PSA response in patients undergoing Lu-177-PSMA-617 therapy.
Methods: Patients with mCRPC eligible for Lu-177-PSMA-617 from February 2020 to December 2020 were prospectively included in this single-center study. 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. Patients with mismatched lesions FDG positive but not seen on 68Ga-PSMA PET/CT were excluded. PSA serum levels were collected before and during the course of treatment. PET images were analyzed in terms of tumor burden (high >20 lesions versus medium < 20 and > 5 lesions) and the appearance of diffuse bone marrow infiltration. We collected Gleason score (≤ 7 vs > 7) and information on previous treatments: chemotherapy (1 line versus 2 lines) and novel antiandrogen drugs (abiraterone or enzalutamide vs both). Mann-Withney test were used to compare PSA values before treatment and PSA response after cycle 1 (C1) and 2 (C2).
Results: 22 consecutive patients with mCRPC were eligible and 19 patients with a high uptake on 68Ga-PSMA PET/CT and no discordant lesion on 18F-FDG PET/CT received at least one cycle of Lu-177-PSMA-617 with good clinical tolerance. Three patients were excluded because of liver metastasis only seen on 18F-FDG PET/CT. Injected activity was adjusted to patients' lab results ranging from 3.9 to 8 GBq for C1 (19 pts) and from 5.2 to 8.1 GBq for C2 (15 pts). There was a significant difference according to the tumor burden high in 12/19 patients on 68Ga-PSMA PET/CT before treatment by PSA value (759.8±1923.7 vs 56.6±109.3;p=0.02), however it did not affect PSA response after C1 or C2 (p=0.7 and 0.4 respectively). Seven patients (26.8%) with diffuse bone marrow infiltration on PET images had significantly higher PSA levels (1229.8±2482.4 vs 77.1±92.5;p=0.007) though it did not impact PSA response (-25.8±71.7 vs -32.4±82.3 after C1;p=0.53). There was no difference in PSA response according to Gleason score or the number of chemotherapy lines (p>0.05). Conversely, 9 patients (47.4%) who had both abiraterone and enzatulamide prior to Lu-177-PSMA-617 therapy had higher PSA values in comparison to those who had only one of those drugs (963.7±2213.5 vs 77.1±92.5;p=0.035) and showed a lower decrease in PSA after C1 (-15.2±54.6 vs -51.8±-38.5;p=0.09). Conclusion: Patients with higher tumor burden or those diffuse bone marrow infiltration had significant differences in PSA levels before treatment, but had similar PSA response to patients with lower tumor burden or without bone marrow infiltration. Previous treatments especially novel antiandrogen drugs might influence PSA response and question the timing for initiating Lu-177-PSMA-617 therapy in mCRPC patients. Further investigations will be done in this population of patients for which recruitment is still ongoing.
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