Benefits and harms of implementing [18F]FDG-PET/CT for diagnosing recurrent breast cancer: a prospective clinical study

Marianne Vogsen, Jeanette Dupont Jensen, Oke Gerke, Anne Marie Bak Jylling, Jon Thor Asmussen, Ivar Yannick Christensen, Poul-Erik Braad, Peter Thye-Rønn, Katrine Lydolph Søe, Marianne Ewertz, Malene Grubbe Hildebrandt, Marianne Vogsen, Jeanette Dupont Jensen, Oke Gerke, Anne Marie Bak Jylling, Jon Thor Asmussen, Ivar Yannick Christensen, Poul-Erik Braad, Peter Thye-Rønn, Katrine Lydolph Søe, Marianne Ewertz, Malene Grubbe Hildebrandt

Abstract

Background: [18F]-fluorodeoxyglucose-positron emission tomography/computed tomography ([18F]FDG-PET/CT) has been implemented sporadically in hospital settings as the standard of care examination for recurrent breast cancer. We aimed to explore the clinical impact of implementing [18F]FDG-PET/CT for patients with clinically suspected recurrent breast cancer and validate the diagnostic accuracy.

Methods: Women with suspected distant recurrent breast cancer were prospectively enrolled in the study between September 2017 and August 2019. [18F]FDG-PET/CT was performed, and the appearance of incidental benign and malignant findings was registered. Additional examinations, complications, and the final diagnosis were registered to reflect the clinical consequence of such findings. The diagnostic accuracy of [18F]FDG-PET/CT as a stand-alone examination was analyzed. Biopsy and follow-up were used as a reference standard.

Results: [18F]FDG-PET/CT reported breast cancer metastases in 72 of 225 women (32.0%), and metastases were verified by biopsy in 52 (52/225, 23.1%). Prior probability and posterior probability of a positive test for suspected metastatic cancer and incidental malignancies were 27%/85% and 4%/20%, respectively. Suspected malignant incidental findings were reported in 46 patients (46/225, 20.4%), leading to further examinations and final detection of nine synchronous cancers (9/225, 4.0%). These cancers originated from the lung, thyroid, skin, pancreas, peritoneum, breast, kidney, one was malignant melanoma, and one was hematological cancer. False-positive incidental malignant findings were examined in 37/225 patients (16.4%), mainly in the colon (n = 12) and thyroid gland (n = 12). Ten incidental findings suspicious for benign disease were suggested by [18F]FDG-PET/CT, and further examinations resulted in the detection of three benign conditions requiring treatment. Sensitivity, specificity, and AUC-ROC for diagnosing distant metastases were 1.00 (0.93-1.0), 0.88 (0.82-0.92), and 0.98 (95% CI 0.97-0.99), respectively.

Conclusion: [18F]FDG-PET/CT provided a high posterior probability of positive test, and a negative test was able to rule out distant metastases in women with clinically suspected recurrent breast cancer. One-fifth of patients examined for incidental findings detected on [18F]FDG-PET/CT were diagnosed with clinically relevant conditions. Further examinations of false-positive incidental findings in one of six women should be weighed against the high accuracy for diagnosing metastatic breast cancer. Trial registration Clinical.Trials.gov. NCT03358589. Registered 30 November 2017-Retrospectively registered, http://www.ClinicalTrials.gov.

Keywords: Accuracy; Distant metastases; Incidental findings; Recurrent breast cancer; [18F]FDG-PET/CT.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Flowchart of 238 women referred for [18F]FDG-PET/CT due to suspicion of first distant recurrent breast cancer, 2017–2019
Fig. 2
Fig. 2
Prior and posterior probabilities for metastatic breast cancer, any metastatic cancer, and incidental malignancies according to [18F]FDG-PET/CT
Fig. 3
Fig. 3
Illustration of the pathway for 225 patients after [18F]FDG-PET/CT and biopsy/follow-up, reflecting the results of the scan and final diagnostic workup. Footnotes: Metastatic breast cancer (MBC). *Ten patients suspected of MBC were also suspected of incidental findings. †A final diagnosis was not obtained due to an impossible biopsy procedure or the result of the biopsy being inconclusive
Fig. 4
Fig. 4
[18F]FDG-PET/CT in a 40-year-old woman with previous breast cancer who underwent [18F]FDG-PET/CT due to bone pain. [18F]FDG-PET/CT showed incidental focal [18F]FDG-uptake in the thyroid gland that revealed papillary thyroid carcinoma stage T2N1M0. A: Maximum intensity projection and B: axial section of the neck region of [18F]FDG-PET/CT. The red arrows show the incidental focal uptake in the left thyroid gland, and the green arrow shows incidental benign physiologic uptake in the right ovary

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