The research will study 99mTc-PSMA SPECT/CT and 68Ga-PSMA PET/CT in patients with carcinoma of the prostate as two tests that use different radionuclides and imaging methods. No time restriction is assigned on eligible primary studies.
Inclusion criteria:
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a)
Cross-sectional studies, case-control studies, cohort studies, and historical cohort studies.
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b)
Studies in which histopathology analysis or clinical and imaging follow-up or comparison with reference standards were used as reference standard.
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c)
Only studies in which a 2 × 2 table could be constructed for true-positive, true-negative, false-positive, and false-negative values.
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d)
When data or subsets of data were presented in more than one article, the article with the most detail or the most recent article will be chosen.
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e)
Studies that are published or retrievable in the English language and are available in electronic databases.
Exclusion criteria:
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a)
Narrative reviews and experimental and interventional studies
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b)
Letters to editors, commentaries, and editorials.
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c)
Duplicates of same studies
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d)
Grey literature
This review will be reported in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2015 Statement) [12, 13].
Study characteristics
The PICOS is as follows:
Participants: Men with prostate cancer
Intervention: None
Comparator: 99mTc-PSMA SPECT/CT and 68Ga-PSMA PET/CT
Outcome: The primary outcome is diagnostic accuracy of 99mTc-PSMA SPECT/CT and 68Ga-PSMA PET/CT in prostate cancer patients. The measurable secondary outcomes are sensitivity, specificity, and accuracy of 99mTc-PSMA SPECT/CT and 68Ga-PSMA PET/CT in intermediate and high-risk prostate cancer patients.
Study designs: Observational/randomized controlled trials
Information sources
The search will employ topic-based strategies appropriately designed for the following databases: AJOL, CINAHL, Cochrane Library, Embase, Google Scholar, PubMed, ResearchGate, Scopus, and Web of Science.
Search strategy
This will include MeSH terms, text words, and entry terms as shown in Table 1.
Data extraction and management
Data extraction
For all eligible studies, basic characteristics which include study design, recruiting place and time, and inclusion criteria will be extracted. Details of the participants to be recorded will be age and serum prostate-specific antigen (PSA). SPECT/CT and PET/CT test details (CT technique, radiopharmaceutical uptake time, definition of positive imaging test) and details of reference standards used in the study will be summarized. Outcome data in terms of Tc-99m PSMA SPECT/CT and 68Ga-PSMA PET/CT and pathological results (positive/negative) for biopsies on the basis of per-patient or per-node, as the case may be, will be extracted into 2 × 2 contingency tables. All relevant, searched, and retrieved items will be exported to Endnote version 7 and screened before being exported to Microsoft Excel. The exported studies will then be retrieved for full-text reading to enable snowballing search on the references contained in the journal articles. Where necessary, authors may be contacted for additional information.
Selection process
Two independent reviewers will search information sources independently and assess identified studies for inclusion and exclusion. Studies for eligibility will be reviewed by another independent reviewer to check that all eligibility criteria are met.
Data items (measurable outcomes)
These will include number of cases, true-positive, true-negative, false-negative, and false-positive.
Data for subgroup analysis will include comparison of the pooled estimated sensitivity, specificity, and accuracy of 99mTc-PSMA SPECT/CT and 68Ga-PSMA PET/CT in patients with intermediate and high-risk prostate cancer.
Quality assessment
The Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2) will be used to assess the quality of the studies. The domains to be assessed will include patient selection, index test, reference standard, participant flow, and timing [14].
Risk of bias
Higher scores suggest lower risk of bias in the study’s methodology.
Heterogeneity and publication bias shall be assessed at study level while the method of testing or reporting shall be assessed at the outcome level. Any study with extreme bias will be excluded following consensus decision by the reviewers.
Data synthesis
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a.
Studies that passed the methodological quality assessment using the QUADAS-2 tool will be extracted.
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b.
Meta-analysis will contain the following:
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i.
Diagnostic accuracy of the two imaging methods as determined by combined or pooled estimate of sensitivity and specificity, likelihood ratio (LHR), and pooled diagnostic odd ratio (DOR).
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ii.
Correlation between sensitivity and specificity will be determined by performing a bivariate meta-analysis to assess the possible effect of threshold effect.
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iii.
Sub-population of study subjects, i.e., the intermediate and high-risk prostate cancer groups as categorical data while the two different test methods will be used as moderators.
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c.
Quantitative analysis of the eligible studies will be performed using the OpenMeta (Analyst) software [15]. Sub-group estimates will be compared using a random effects meta-regression model. The degree of heterogeneity in included studies will be analyzed by Cochran chi-square statistic and its p value, I2 and Ʈ2. A random effect model will be used if a significant heterogeneity is observed (p<0.05). The pooled accuracy and subgroups analysis will be reported in forest plots.
Presentation and reporting of results
The study selection process will be summarized in a flow diagram. Tables of search strategy, quality scores, risk of bias, and list of eligible studies will be included. Quantitative data such as accuracy, 95 % CI, P values, and relative weights assigned to studies and heterogeneity tests will be included in the forest plots.
