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Meta-Analysis
. 2024 Dec;52(1):225-236.
doi: 10.1007/s00259-024-06860-1. Epub 2024 Aug 14.

Identifying the primary tumour in patients with cancer of unknown primary (CUP) using [18F]FDG PET/CT: a systematic review and individual patient data meta-analysis

Jeroen R J Willemse  1   2 , Doenja M J Lambregts  1   2 , Sara Balduzzi  3 , Winnie Schats  4 , Petur Snaebjornsson  5   6 , Serena Marchetti  7 , Marieke A Vollebergh  8 , Larissa W van Golen  9 , Zing Cheung  9 , Wouter V Vogel  9   10 , Zuhir Bodalal  1   2 , Sajjad Rostami  1   2 , Oke Gerke  11   12 , Tharani Sivakumaran  13   14 , Regina G H Beets-Tan  1   2   15 , Max J Lahaye  16   17
Affiliations
Meta-Analysis

Identifying the primary tumour in patients with cancer of unknown primary (CUP) using [18F]FDG PET/CT: a systematic review and individual patient data meta-analysis

Jeroen R J Willemse et al. Eur J Nucl Med Mol Imaging. 2024 Dec.

Abstract

Purpose: In this systematic review and individual patient data (IPD) meta-analysis, we analysed the diagnostic performance of [18F]FDG PET/CT in detecting primary tumours in patients with CUP and evaluated whether the location of the predominant metastatic site influences the diagnostic performance.

Methods: A systematic literature search from January 2005 to February 2024 was performed to identify articles describing the diagnostic performance of [18F]FDG PET/CT for primary tumour detection in CUP. Individual patient data retrieved from original articles or obtained from corresponding authors were grouped by the predominant metastatic site. The diagnostic performance of [18F]FDG PET/CT in detecting the underlying primary tumour was compared between predominant metastatic sites.

Results: A total of 1865 patients from 32 studies were included. The largest subgroup included patients with predominant bone metastases (n = 622), followed by liver (n = 369), lymph node (n = 358), brain (n = 316), peritoneal (n = 70), lung (n = 67), and soft tissue (n = 23) metastases, leaving a small group of other/undefined metastases (n = 40). [18F]FDG PET/CT resulted in pooled detection rates to identify the primary tumour of 0.74 (for patients with predominant brain metastases), 0.54 (liver-predominant), 0.49 (bone-predominant), 0.46 (lung-predominant), 0.38 (peritoneal-predominant), 0.37 (lymph node-predominant), and 0.35 (soft-tissue-predominant).

Conclusion: This individual patient data meta-analysis suggests that the ability of [18F]FDG PET/CT to identify the primary tumour in CUP depends on the distribution of metastatic sites. This finding emphasises the need for more tailored diagnostic approaches in different patient populations. In addition, alternative diagnostic tools, such as new PET tracers or whole-body (PET/)MRI, should be investigated.

Keywords: Cancer of unknown primary; Meta-analysis; Molecular imaging; Oncology; [18F]FDG PET/CT.

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Conflict of interest statement

Declarations. Ethical approval: This is a systematic review and individual patient data meta-analysis, for which ethical approval is not required. Consent to participate: Not applicable. Consent to publish: Not applicable. Competing interests: The authors have no relevant financial or non-financial interests to disclose.

Figures

Fig. 1
Fig. 1
PRISMA flowchart depicting the process of identifying relevant studies and inclusion of patients. aExcluding conference proceedings for which no full text is available by default
Fig. 2
Fig. 2
QUADAS-2 results: an overview of 31 studies with full-text availability
Fig. 3
Fig. 3
Forest plot of pooled detection rates of [18F]FDG PET/CT across different patient subgroups according to the most predominant metastatic site. LN lymph nodes; TP true positives
Fig. 4
Fig. 4
Sankey diagram: patients were grouped by metastatic sites on the left side. Flows and their relative sizes represent connections to the final diagnosis after [18F]FDG PET/CT and follow-up (true primary tumours or confirmed CUP). aThoracic lymph nodes; blymph nodes (not specified); cabdominopelvic lymph nodes. Figure created using https://sankeymatic.com/
See this image and copyright information in PMC

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