Diagnostic accuracy of carbonic anhydrase IX–targeted PET/CT for detection of clear cell renal cell carcinoma in patients with renal masses: a systematic review and meta-analysis of diagnostic test accuracy studies
Ralph P. Emerson, Girish Kumar Parida, Kanhaiyalal AgrawalObjective
The preoperative differentiation of clear cell renal cell carcinoma (ccRCC) from other renal masses remains challenging. Carbonic anhydrase IX (CAIX) is a highly specific target for noninvasive ccRCC imaging. We conducted a systematic review and meta-analysis to determine the diagnostic accuracy of CAIX-targeted PET/computed tomography (CT) for differentiating ccRCC from non-ccRCC renal masses.
Methods
A comprehensive search of PubMed, Embase, Scopus, and Registers (up to 30 September 2025) was supplemented by a bibliographic review. Studies evaluating CAIX-PET/CT against histopathologically were included. Of 528 records, five studies (
Results
For the detection of histopathologically confirmed ccRCC (vs. non-ccRCC renal masses), the pooled sensitivity was 85.5% [95% confidence interval (CI): 81.6–88.7] and specificity of 86.5 (95% CI: 80.4–90.9). The hierarchical summary receiver operating characteristic model yielded an area under the curve of 0.894. Exploratory subgroup analysis suggested a potential difference in diagnostic performance between the tracer subtypes.
Conclusion
This review provides low-certainty evidence that CAIX-targeted PET/CT is a highly accurate, noninvasive tool for differentiating ccRCC from non-ccRCC renal masses in presurgical populations. Clinically, its high positive predictive value (94.6%) strongly ‘rules in’ disease, while its modest negative predictive value (~69%) limits its ability to ‘rule out’ malignancy. Further studies are warranted to validate these findings in broader clinical cohorts and for small-molecule agents.