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

Bernhard Grubmüller,Daniela Senn,Markus Hartenbach,Wolfgang Wadsak,Marcus Hacker,Sarah Pfaff,Gero Kramer,Karl Hermann Grubmüller,Alexander R Haug,Pascal Baltzer,Harald Eidherr,Shahrokh F Shariat,Markus Mitterhauser,David D’Andrea

doi:10.1007/s00259-018-4236-4

Abstract

PurposeThe first aim of this study was to evaluate 68Ga-PSMAHBED-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).MethodsWe 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.ResultsThe 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).ConclusionTTV 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.

Highlights

Materials and methodsOver recent decades life expectancy of patients with metastatic castration-resistant prostate cancer has been prolonged by the emergence of novel therapies [1,2,3,4,5,6]
PSA prostate-specific antigen, RECIST Response Evaluation Criteria in Solid Tumors considered essential in determining the suitability of a patient for PSMA therapy, and is valuable for, among other things, assessing tumor response rather relying on a simple serum blood marker
The results of the current study suggest that a hybrid imaging technique combining morphological and functional information, such as PSMAHBED-CC conjugate 11 (PSMA 11) Positron emission tomography (PET)/computed tomography (CT)(MRI) may improve response assessment in metastatic castration-resistant prostate cancer (mCRPC) patients

Summary

Introduction

Materials and methodsOver recent decades life expectancy of patients with metastatic castration-resistant prostate cancer (mCRPC) has been prolonged by the emergence of novel therapies [1,2,3,4,5,6]. Prediction and monitoring of response to therapy allows selection of the ideal patients, and changes in therapy early in the resistance phase when necessary. The most commonly used tools for response assessment include cross-sectional abdominopelvic imaging with computed tomography (CT) or magnetic resonance imaging (MRI) according to the Response Evaluation Criteria in Solid Tumors (RECIST) [7], and bone scintigraphy (BS) together with serial assessments of changes in serum levels of prostate-specific antigen (PSA). The current RECIST and even sometimes PSA levels show limited diagnostic and predictive accuracy in this disease state [8, 9]. PET/CT, as a hybrid imaging modality, shows superior diagnostic performance compared with standard imaging allowing accurate response assessment in other tumor types [11, 12]

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