In this retrospective study of 203 patients from a bicentric German patient series with EBC and low-risk profile, we found that the detection rate of distant metastases is very low with additional imaging procedures performed at initial diagnosis and consisting of chest radiography, abdominal ultrasonography, and bone scan. The study also showed that this form of staging leads to follow-up imaging in a relatively high number of cases (6.8%). On the other hand, the rate of findings clinically considered false positives is very high in this situation (99.5%).
Staging examinations are important for patients with an initial diagnosis of breast cancer to plan therapy and assess prognosis. However, the rate of metastatic disease is low at initial diagnosis of early breast cancer with low-risk profile [10]. Therefore, there was an ongoing discussion regarding the benefit of whole-body staging in low-risk EBC [11, 12]. In the study by Schneider et al. (2003), distant metastasis was detected in tumors smaller than 1 cm in only 3.9% of cases [13].
In various publications, imaging examination methods were presented individually and only a low detection rate for metastases at the time of initial diagnosis was found for bone scan with 0.5–11% [13, 14, 15], for liver ultrasound with 0.24–3.3% [13, 14, 15] and for chest radiography 0.2–1.2% [13, 14]. In the study by Schneider et al. (2003), few metastases were detected at the pT1 stage; only two of 106 (2.7%) patients at the pT1c stage were shown to have a bone metastasis [13]. This is also confirmed in our collective: distant metastases were detected in only one patient, which corresponds to a detection rate of 0.5%.
Based on these data, current guidelines no longer recommend whole-body staging in patients with early breast cancer [16, 17, 18]. However, the extent to which there are exceptional cases in which staging should be performed despite low-risk carcinoma is unclear. Symptomatic patients should be evaluated in any case. The current S3 guideline only recommends staging (in the case of aggressive tumor biology) if these examinations would have a decisive influence on the therapeutic procedure [17]. The current AGO guideline recommends whole body staging only in cases of high risk for distant metastases and / or symptoms and / or indication for (neo-)adjuvant chemo/antibody therapy [19].
The lack of studies showing an impact of staging on outcome (survival or progression-free survival) is repeatedly pointed out [17]. However, since staging is a diagnostic test, according to the Centre for Evidence-based Medicine, valid data on the diagnostic accuracy of the test are required, not outcome data. The background for this is that there are multiple confounders (different handling of test results/different therapies) between diagnostic test (staging) and outcome. In addition, each test generates new patient groups for whom adequate therapy may not yet have been evaluated. Therefore, the valid assessment of the quality of a diagnostic test via outcome parameters is not reasonably possible in most cases.
Data on diagnostic accuracy are available for many imaging modalities. However, the procedures mainly used in our study are characterized by a relatively low diagnostic accuracy. When procedures with relatively low diagnostic accuracy are used, a high rate of false positive findings occurs. This was also observed in our study. The effect was amplified by the low pretest probability of our low-risk collective. Furthermore, if patients undergo staging via sonography of the upper abdomen, bone scan and chest radiography it often requires the patients to arrange multiple appointments [8]. Whereas the CT thorax/abdomen is logistically easier for the patients, as they already tend to have multiple doctors’ appointments for therapy planning and start of treatment [8].
In this work, we looked for the first time at the resulting follow-up caused by conventional staging in low-risk breast carcinomas. Overall, this work described abnormal chest radiographic findings in 10 (6%) patients and two (1.0%) upper abdominal sonographies requiring clarification. Eighteen (9%) patients had suspicious findings on skeletal scintigraphy, so further follow-up examinations were recommended. Thus, a total of 599 examinations could be performed without evidence of metastasis. The false-positive rate in our collective was 6.8%, with no difference between the respective examination methods.
These diagnostic measures are a burden for the patients concerned, especially the psychological impact caused by this diagnosis and the resulting consequences [18]. Additional radiation exposure may not be without risk either [20]. However, at the current time, there is no evidence that diagnostic imaging causes malignancies.
Three patients in our collective underwent CT thoracic examinations at three-month intervals because the findings did not provide clear evidence of metastasis. Another important issue is also the cost incurred by these diagnostic measures. In the study by Eismann et al. (2013), costs for staging without benefit were calculated at 5–20 million euros/year [21].
Additional resources are wasted by the multitude of unnecessary examinations which could possibly benefit patients for whom these examinations would be more necessary. In addition, it should be mentioned that staging examinations may delay the start of therapy [22].
One possible solution is the use of imaging techniques with better diagnostic accuracy. Because of better sensitivity and specificity, CT thorax/abdomen and a skeletal scintigram have replaced the former staging with X-ray thorax and abdominal ultrasound as basic staging examinations (ESMO 2015/17) [17]. Also debatable would be the use of PET-CT, PET-MRI, or whole-body MRI, which have significantly better diagnostic accuracy compared with the methods used in this study [23].
In this work, only low-risk carcinomas were evaluated, and our collective included all patients with a grading of 1, 2, or 3. Neither the S3 guideline nor the AGO guideline specifically address the importance of staging examinations in G3 carcinomas []. Not all patients in our collective received a complete staging. In some cases, only one or two metastatic sites were investigated. The indication for the respective examination or the omission of an examination can no longer be precisely traced due to the retrospective data evaluation and must be self-critically evaluated as a weakness of the work.