Response assessment using 68Ga-PSMA ligand PET in patients undergoing 177Lu-PSMA radioligand therapy for metastatic castration-resistant prostate cancer

Abstract

Purpose: The first aim of this study was to evaluate ⁶⁸Ga-PSMA^HBED-CC conjugate 11 positron emission tomography (PSMA PET) parameters for assessment of response to ¹⁷⁷Lu-PSMA-617 radioligand therapy (RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC). The second aim was to investigate factors associated with overall survival (OS).

Methods: We retrospectively assessed mean standardized uptake values (SUVmean) and total tumor volumes (TTV) on PSMA PET in 38 of 55 mCRPC patients before and after RLT. PSA testing and PSMA PET/CT(MRI) imaging were performed during the 8 weeks before and the 6 weeks after RLT. PSMA PET and CT(MRI) images were reviewed separately according to the modified PET Response Criteria in Solid Tumors (mPERCIST) and RECIST1.1. The results were compared with PSA responses. Associations between OS and the RECIST evaluation and changes in SUVmean, TTV, and PSA, CRP, LDH, hemoglobin and ALP levels were determined in a univariable survival analysis.

Results: The median PSA level at the time of pretherapy PSMA PET/CT(MRI) was 60.8 ng/ml (IQR 15.4, 264.2 ng/ml). After RLT the median PSA level decreased by 44%, TTV by 45.1%, SUVmean by 25.8% and RECIST by 11.3%. A PSA response was seen in 18 patients (47.4%), stable disease in 12 (31.6%) and progressive disease in 8 (21.1%). Contrary to the changes in SUVmean and the RECIST evaluation, the change in TTV was significantly associated with PSA response (p = 0.15, p = 0.58, and p < 0.001, respectively). After a median follow-up of 17 months (IQR 8.0, 24.2 months), 11 patients (28.9%) had died of their prostate cancer. The changes in both TTV and PSA levels were associated with OS (HR 1.001, 95% CI 1-1.003, p = 0.04, and HR 1.004, 95% CI 1.001-1.008, p = 0.01, respectively), while the changes in SUVmean and the RECIST evaluation were not. The pre-therapy CRP level was also associated with OS (HR 1.07, 95% CI 1.009-1.14, p = 0.02).

Conclusion: TTV on PSMA PET seems to be a reliable parameter for response assessment in mCRPC patients undergoing RLT and might overcome the limitations of RECIST in prostate cancer. Furthermore, the change in TTV was significantly associated with OS in our cohort.

Keywords: Hybrid imaging; Metastatic prostate cancer; PET/CT; PET/MRI; PSMA ligand.

Fig. 1

A 74-year-old patient with castration-resistant metastatic prostate cancer (mCRPC) after treatment with enzalutamide and docetaxel. a⁶⁸Ga-PSMA 11 PET image before the first ¹⁷⁷Lu-PSMA-617 radioligand therapy (RLT) in December 2015 demonstrates extended pelvic, abdominal and thoracic lymph node metastasis. The total tumor volume (TTV) measured semiautomatically as described in Materials and methods is marked red in the maximum intensity projection (MIP) 3D image. The PSA level at the time of imaging was 597 ng/ml, and the TTV was 359 ml. b After three cycles of RLT (7.4 GBq each), the PSA level had significantly decreased (23.1 ng/ml) and the TTV had reduced (43 ml), demonstrating a partial response. The patient received a further three cycles of RLT that resulted in a biochemical complete response (PSA 0.01 ng/ml, January 2018)

Fig. 2

Percentage changes in PSA level from baseline in 38 patients undergoing ¹⁷⁷Lu-PSMA-617 radioligand therapy in relation to the responses measured in terms of PSMA total tumor volume (TTVresponse)

Fig. 3

Kaplan-Meier analysis of overall survival in 38 patients with metastatic prostate cancer undergoing ¹⁷⁷Lu-PSMA-617 radioligand therapy (RLT). a According to PSA response after RLT: blue line patients with biochemical stable disease (SD) or progressive disease (PD); red line patients with a biochemical partial response (PR) or complete response (CR). b According to total tumor volume (TTV) after RLT: blue line patients with stable disease (SD) or progressive disease (PD); red line patients with a partial response (PR) or complete response (CR)