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.
Highlights
Prostate cancer is the most frequently diagnosed cancer in men and the second leading cause of cancer-specific deaths [1]
Studies were included if they satisfied the following patient/index test/comparator/ outcome/study design (PICOS) criteria: (1) patients (P) with metastatic Castration-resistant prostate cancer (CRPC); (2) Prostate specific membrane antigen (PSMA) PET, positron emission tomography/computed tomography (PET/CT) or PET/magnetic resonance imaging (MRI) used as the index test (I); (3) prostate-specific antigen (PSA) used as the comparator (C); (4) concordance between response assessment between PSMA PET and PSA as the outcome (O); and (5) randomized trials or any type of prospective or retrospective cohort studies as the study design (S)
Data for PSMA PET response evaluation were categorized as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) according to PET Response Criteria in Solid Tumors (PERCIST) 1.0 in all the included studies but one using European Organization for Research and Treatment of Cancer (EORTC) classification which set ±30% (PERCIST 1.0) and ±25% (EORTC) changes in size or uptake as cut-offs for discriminating PR/SD/PD, respectively, and were dichotomized to response (CR, PR, and SD) vs. non-response (PD) to build 2 × 2 contingency tables [7,8]
Summary
Prostate cancer is the most frequently diagnosed cancer in men and the second leading cause of cancer-specific deaths [1]. Response assessment for systemic treatments in patients with metastatic CRPC is primarily done using conventional imaging and biochemical testing—that is, Response Evaluation Criteria in Solid Tumors (RECIST) on CT, bone scan, and serum prostate-specific antigen (PSA) [5,6]. A baseline PSMA PET is highly recommended in patients with CRPC for accurate assessing of disease extent (i.e., non-metastatic, oligometastatic vs polymetastatic) [13] and appropriate selection of therapeutic strategy including metastasis-derived therapy or systemic treatment [14].
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