18F-FDG PET/CT in Early Stage Breast Cancer Comes with Financial Burden

Approximately 13% of women have a lifetime risk of developing breast cancer.¹ Early diagnosis is particularly essential as treatment options are improving, and mortality, morbidity, and costs associated with diagnosis and treatment are decreasing in early stage breast cancer. Accurate staging also is critical for making management decisions and predicting outcomes in individuals with newly diagnosed breast cancer. Staging workups are performed on patients who have an increased likelihood of distant metastases.

Although it is not usually recommended for early stage breast cancer, fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) is used extensively as a metastatic diagnosis for breast cancer.2 While there are insufficient data for assessing the cost-effectiveness of ¹⁸F-FDG PET/CT in early stage breast cancer, there are abundant data on the efficacy of ¹⁸F-FDG PET/CT in patients with symptoms of metastatic breast cancer. In the era of healthcare cost saving initiatives, the cost of ¹⁸F-FDG PET/CT is an essential consideration, particularly in middle- and low-income countries.

Let’s Look at the Data

Data on 970 early stage breast cancer patients (stage I and II) diagnosed between January 2015 and December 2020 at 16 different centers in Türkiye were collected retrospectively. In this cohort, no patients received neoadjuvant systemic therapy. Following the diagnosis of breast cancer, all patients with no symptoms for metastases underwent an ¹⁸F-FDG PET/CT scan. The scan results of the patients and the site of distant metastases were recorded.

In this study, we used the cost of ¹⁸F-FDG PET/CT reimbursement in Türkiye, an upper middle-income country, to evaluate the financial impact on the health system.

Approval of the study was obtained from the Van Yüzüncü Yıl University Ethics Committee. The mean age of patients was 51.6 (SD ± 12.4) years. According to the TNM classification, clinical stages of patients in this cohort were 28.5%, 39.7%, and 31.8% for stage I, stage IIA, and stage IIB, respectively.

¹⁸F-FDG PET/CT scans detected distant metastasis in 22 patients (2.3%). Of these 22 patients, four patients (0.4%) had mediastinal lymph node positivity, one patient (0.1%) had adrenal metastasis, and 17 patients (1.8%) had lung or bone or lung and bone metastases (see Table, this page).

In 22 patients whose ¹⁸F-FDG PET/CT scans showed distant metastasis, 45.5% were luminal type, 50% were HER2-positive, and only one patient was triple negative. Eleven (50%) patients had more advanced disease and 10 out of these 11 patients upstaged to stage IIIA. Four patients had the same stage comparing preoperative clinical/image evaluation and final pathology report, and seven patients were down staged after the final pathology report.

Internal mammary lymph node positivity was detected in eight patients (0.8%) by ¹⁸F-FDG PET/CT scan. Six patients were in stage IIB, and the rest had stage I and IIA.

Physicians Can Do Better: Time to Think about Costs

In 2024, the estimated number of invasive breast cancer cases in the US is ^310,370.1 The overall 5- and 10-year relative survival rates for invasive breast cancer are 91% and 85%, respectively, mostly because two-thirds of these women are diagnosed with localized-stage disease. Despite these facts and National Comprehensive Cancer Network guidelines stating that routine systemic staging is not indicated for nonmetastatic (M0) cancer in the absence of systemic symptoms,² breast care specialists—especially in developing countries—prefer to order ¹⁸F-FDG PET/CT scans during the diagnostic procedures in early stage breast cancer.

Türkiye is a developing country and, based on World Bank data, gross domestic product per capita in 2023 was $11,938.80.³ The National Social Insurance Service was established in Türkiye to cover the majority of the population, including white- and blue-collar workers in the commercial and public sectors. These individuals were financed by payroll earnings, but there has been a surge in insurance companies for healthcare over the previous 2 decades. From 2000 to 2022, healthcare spending rose exponentially, especially in the past 4 years, where healthcare expenditures more than tripled since 2019.⁴

One out of every four women diagnosed with cancer in Türkiye has breast cancer, and according to the Turkish Cancer Statistics report, 19,211 women were diagnosed with breast cancer in a year. Similar to other countries, breast cancer is the most diagnosed cancer among women.⁵ Although guidelines are well known among breast care specialists, it is important to focus on increased testing for breast cancer such as ordering ¹⁸F-FDG PET/CT scans in a developing country where healthcare spending is limited.

¹⁸F-FDG PET/CT is widely used for staging of breast cancer. It is mainly performed to investigate the distant spread of the disease. The cost of these scans in developing, middle-, and low-income countries should be considered, but the fact that the patient is exposed to around 25 mSv of radiation should not be ignored. Furthermore, patients’ fear due to false-positive results (which may necessitate additional tests such as biopsies), as well as patients’ anxiety while waiting for additional tests to confirm the absence of metastasis, should be recognized and managed appropriately.

The cost of the ¹⁸F-FDG PET/CT scan may pose an additional challenge for middle- and low-income countries. For example, in Türkiye, the National Social Insurance Service pays about $145 for each PET/CT scan, whereas private insurance companies pay more ($1,500). Private hospitals or radiology clinics may have considerably greater costs. Because the National Social Insurance Service covers the majority of the costs of breast cancer-related diagnoses and reimburses the cost of every scan, regardless of disease stage, breast care physicians can readily order such a test.

¹⁸F-FDG PET/CT coverage is similar for private insurance companies. Our study demonstrated that, as stated in the guidelines, the effect of the scans is very low in guiding the clinician to decide the stage and treatment plan of early stage breast cancer. In our study, 97% of patients without symptoms showed no evidence of distant metastases. One can estimate that the total cost of ¹⁸F-FDG PET/CT scans for this cohort of patients was up to $1,455,000, depending on the insurance coverage.

Another improper use of the ¹⁸F-FDG PET/CT scan in an upper middle-income country is to conduct the scan after neoadjuvant systemic therapy and before surgery, even if the preoperative neoadjuvant systemic therapy scan is negative for distant metastases (e.g., in stage IIB patients), which doubles the expense.

The use of ¹⁸F-FDG PET/CT in asymptomatic patients should be limited not only because of the radiation dose received by the patient, the patient’s fear of being diagnosed with metastatic breast cancer, and the impact of false positivity on treatment, but also because it adds unnecessary costs to the healthcare system and the patient’s wallet.

Physicians, as well as the government and private insurance sectors in countries coping with exorbitant healthcare costs, should focus on reducing unjustified breast cancer diagnosis and treatment. While these days we’re discussing the financial toxicity of cancer care, we might consider de-escalating unneeded and ineffective diagnostic tools such as ¹⁸F-FDG PET/CT in early stage breast cancer.

Dr. Atilla Soran is a professor of surgery in the Division of Surgical Oncology at the University of Pittsburgh Medical Center Magee-Womens Hospital in Pennsylvania.

References

1. American Cancer Society. Cancer Facts & Figures 2024. Available at: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2024/2024-cancer-facts-and-figures-acs.pdf. Accessed May 2, 2024.
2. National Comprehensive Cancer Network. Breast guidelines. Available at: https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed May 2, 2024.
3. The World Bank in Turkey. Overview. Available at: https://www.worldbank.org/en/country/turkey/overview. Accessed May 2, 2024.
4. Statista. Total health expenditure in Turkey from 2000 to 2022. Available at: https://www.statista.com/statistics/1272834/health-expenditure-in-turkey/. Accessed May 2, 2024.
5. Koçak AT, Arslan S, İlik Y. Posttreatment experiences of breast cancer survivors in Turkey: A qualitative study. Semin Oncol Nurs. 2022; 38(6):151351.