Concordance between Response Assessment Using Prostate-Specific Membrane Antigen PET and Serum Prostate-Specific Antigen Levels after Systemic Treatment in Patients with Metastatic Castration Resistant Prostate Cancer: A Systematic Review and Meta-Analysis

Abstract

Prostate-specific membrane antigen positron emission tomography (PSMA PET) has recently gained interest as a promising tool for treatment response evaluation in metastatic castration-resistant prostate cancer (CRPC). We performed a systematic review and meta-analysis assessing the concordance between response evaluation using PSMA PET and serum prostate-specific antigen (PSA) level after systemic treatment and the association between PSMA PET and overall survival in metastatic CRPC patients. PubMed, Embase, and Cochrane library databases were searched until August 2020. Studies that reported the concordance between PSMA PET and PSA response were included. PSMA PET and PSA response evaluation were dichotomized into response vs. non-response to construct two-by-two contingency tables; an ≥30% increase in PSMA PET according to PET Response Criteria in Solid Tumors 1.0 and as an increase in serum PSA level of ≥25% as per Prostate Cancer Working Group 3 guidelines were defined as non-response. The percent agreement rates were pooled using random-effect model. Ten studies (268 patients) were included. The concordance rates ranged 0.50–0.84 with a pooled proportion of 0.73 (95% confidence interval 0.67–0.79). Patients were treated with 177Lu-PSMA therapy in five, chemotherapy in three, 223Ra in one, and more than one type in one study. Various PET parameters were used: the most widely evaluated was PSMA tumor volume (PSMA-TV). Similar proportions were found across different therapeutic agents, PET response parameters, and regarding directionality of discordance (PSA response/PSMA non-response vs. PSMA response/PSA non-response). Two studies reported that a decrease in PSMA-TV was associated with better overall survival. PSMA PET and PSA response assessments were discordant in nearly a fourth of metastatic CRPC patients. Further studies are warranted to establish the clinical meaning of this discordance and define appropriate management for such clinical situation.

Evaluation of Tumor Burden Response to Single-cycle of Lu-177 PSMA Treatment with Whole Body Scintigraphic Planar Images in Prostate Cancer Patients

“…It has been determined in previous studies that there may be a concordance between PSMA expression and PSA response. (20,21). In our study, agreement was found in the percentage change of PSA and sum values in 13 (24%) patients.…”

PSMA Expression Predicts Early Biochemical Response in Patients with Metastatic Castration-Resistant Prostate Cancer under 177Lu-PSMA-617 Radioligand Therapy

“…Moreover, in the present study, response was assessed only using the PSA change after two cycles of 177 Lu-PSMA-RLT. Although easily to obtain in clinical routine and demonstrating a high predictive value for later outcome [13], Han et al recently revealed significant discordance between PSA and follow-up PSMA-PET/CTs for response assessment pooling 10 different studies [35]. Nonetheless future studies should also include follow-up PSMA-PET/CTs for response assessment (including early biochemical response and OS) to further define the value of changes in PET parameters, such as delta values of PSMA-TV, TL-PSMA or occurrence of new metastases for subsequent outcome.…”

PSMA-Targeted Radiopharmaceuticals for Prostate Cancer Diagnosis and Therapy

“…Response to therapy has not been definitively established as an indication for PSMA PET, but at least one older meta-analysis shows a concordance of 73% between PSA levels and PSMA PET tumor volume as per the PET Response Criteria in Solid Tumors (PERCIST) 1.0 36 . In the specific case of detection after primary radiotherapy, there is a reported detection rate of 66%–83% below the Phoenix threshold of PSA 2 ng/mL, 37 consistent with other studies of recurrence described above.…”