Abstract
Introduction
The risk for metastasis at primary diagnosis of breast cancer is about 4%. The German guidelines give clear indications on when, who, and how to stage breast cancer patients. Ideally, this should be done via computerized axial tomography (CAT) scan of the thorax and abdomen and an additional bone scan. But daily practice shows that the way health-care providers handle staging recommendations can vary. To objectify adherence to guidelines we started a nation-wide survey.
Methods
Between July and September 2020, we sent out a survey via email to all certified and noncertified breast centers and in addition to all Departments of Obstetrics and Gynecology in Germany. We asked for timing of staging, conditions that cause staging, and the applied method. In case we did not get any reply, we sent out a reminder.
Results
A total of 220 certified breast centers, 28 noncertified breast centers, and 48 Departments of Obstetrics and Gynecology who care for breast cancer patients took part in our survey. A general pretherapeutic staging was performed in 16.4%, 39.3%, and 66.7% of all institutions and a general postoperative staging was performed in 4.1%, 0%, and 6.3% of each institutional type, respectively. In terms of the applied method, 75% of all certified breast centers used a CAT scan and bone scan, while 23.3% primarily used chest X-ray, ultrasound of the abdomen (27.7%), or MRI. As a potential reason for using X-ray and ultrasound, the presence of a “low-risk” breast cancer was mentioned.
Summary
Although certified breast centers show the highest adherence to current guidelines, some still perform a general staging or do not use the recommended staging method. The low probability of primary metastatic breast cancer and the use of a reasonable exposure to radiation warrant a critical discussion.
Keywords: Breast cancer, Staging, Guidelines, Medical care, Outcome
Introduction
Breast cancer is the most common cancer of women in western civilization and accounts for about 70,000 new cases in Germany alone. Due to tremendous improvement and individualization of breast cancer therapy the 5-year survival rate improved over the last decades and is to date about 87% [1]. But health-care providers did not just aim to improve treatment, they also gained knowledge about side effects due to diagnostic measures and therapy for breast cancer, which can have long-lasting effects and should, therefore, be kept at the minimum level possible. Last but not least, medical resources are not infinite and should be used wisely [2, 3].
Thus, to optimize breast cancer patients' care, national guidelines, such as the “S3-Leitlinie Mammakarzinom” or the recommendations by the AGO (Arbeitsgemeinschaft Gynäkologische Onkologie, working group of gynecological oncology) “Kommission Mamma” are frequently updated to incorporate the most recent evidence-based medicine [4, 5]. One recommendation that has changed over time is the use of radiation imaging for detecting distant metastases. Up to the year 2012, it was recommended to perform a general pretherapeutic staging for all breast cancer patients using chest X-ray, ultrasound of the abdomen, and a bone scan. However, the probability of primarily metastasized breast cancer is about 4% for all newly diagnosed breast cancer patients and decreases further in node-negative patients to below 1% [6]. So, staging habits at that time caused a high number of unnecessary examinations, which in turn caused unnecessary exposure to radiation, psychological stress in case of false-positive results that needed further imaging, and financial burden on the health-care system [7, 8, 9].
This led to the decision to recommend staging only for patients at higher risk of metastases and those who will undergo chemotherapy. The preferred method to stage breast cancer patients was also changed from chest X-ray and abdominal ultrasound to a computerized axial tomography (CAT) scan of the thorax and abdomen [5]. The reason for this proposal is the higher sensitivity of the latter, although only data of a direct comparison between conventional staging and PET/CT exist [10, 11].
Despite these recommendations, staging habits may vary in daily practice. In a nationwide survey in 2007, König [12] found out that 36.5% of all certified breast centers performed a general preoperative staging and 21.2% a general postoperative staging regardless of the clinical stage. Already back then, data were available showing that a general staging is not indicated for all breast cancer patients [13]. However, staging recommendations had just changed at that time and data about current habits are missing. So, the aim of this study was to evaluate and compare the staging habits of all certified breast centers, all noncertified breast centers, and those Departments of Obstetrics and Gynecology that do not run a breast center but care for breast cancer patients occasionally. In addition, we asked board-certified gynecologists who work in outpatient gynecological practices (“gynäkologische Praxis”) about their experience of staging habits of different institutions.
Materials and Methods
We identified the contact information of all Departments of Obstetrics and Gynaecology in the register of the Federal Office of Statistics and also searched for breast centers on the homepage of the German Society of Senology. Between July and September 2020, we sent out a survey via email to all abovementioned institutions. We asked for timing of staging, conditions that cause staging, and the applied methods (please see online suppl. material for details; www.karger.com/doi/10.1159/000521967). In case we did not get any reply after 4 weeks, we sent out a reminder via email and another one if we did not get a reply after the first reminder. The contacted institutions had different options to send back the questionnaire: via fax, letter, and email.
After surveying the abovementioned institutions, we developed a new questionnaire aiming to question gynaecologists who work in a private practice. We searched the homepage of the Association of Statutory Health Insurance Physicians and randomly chose private practices all over Germany. We, thus, contacted 30 private practices per state. They were also contacted via email and received a reminder if they did not reply to the initial correspondence. They were also given the opportunity to reply via fax, email, and letter.
Results
In total, we contacted 613 institutions. Of these, 316 institutions sent back a completed questionnaire; 9 replied that they did not want to take part in the survey. Of the 316 completed questionnaires, 20 were not suitable for evaluation because we were not able to read the handwriting, the quality of the copy was too poor, or too few questions were answered to be considered. Thus, a total of 296 questionnaires were available for final analysis. These included answers from 220 (74.3%) certified breast centers, 28 (9.5%) noncertified breast centers, and 48 (16.2%) Departments of Obstetrics and Gynecology that do not run a breast center but occasionally care for breast cancer patients. Of those institutions with a certified breast center affiliated with a university hospital, 14 of 24 took part in our study.
The following questions were asked to find out the time point of staging in each institution. The participants had the following choices: in general preoperative, preoperative in case of a positive nodal status, in case of a certain tumor biology (HER2-enriched, triple-negative), preoperative in case of a certain tumor stage, in general postoperative, postoperative in case of a certain tumor biology (HER2-enriched, triple-negative), or postoperative in case of a certain tumor stage. Multiple answers were eligible. The results in percentage refer to each category.
A general preoperative staging is performed in 36 (16.4%) of the certified breast centers, 11 (39.3%) of the noncertified breast centers, and 32 (66.7%) of those departments which occasionally treat breast cancer patients. In case of a positive nodal status, 144 (65.5%), 15 (53.6%), and 15 (31.3%), respectively, organized a staging. Aggressive tumor biology is a cause for staging in 167 (75.9%), 19 (67.9%), and 17 (35.4%) of the institutions, respectively. If the primary tumor is estimated to be larger than 2 cm (T2), 53 (24.1%), 4 (14.3%), and 5 (10.4%) recommend staging to their patients, respectively. Staging is also recommended by 206 (93.6%), 26 (92.6%), and 36 (75%) of the institutions before neoadjuvant chemotherapy is applied, respectively.
A general postoperative staging is performed in 9 (4.1%), 0, and 3 (6.3%) of all participating institutions, respectively. When postoperative histology reveals a positive nodal status, 116 (52.7%), 9 (32.1%), and 9 (18.8%) of the institutions perform staging, respectively. Aggressive tumor biology leads to postoperative staging in 63 (28.6%), 5 (17.9%), and 6 (12.5%) institutions, respectively. If postoperative histology reveals a tumor of 2 cm or larger, 31 (14.1%), 3 (10.7%), and 1 (2.1%) of all participants would recommend staging, respectively.
The next question of the survey evaluated the applied method used for staging. Participants were able to chose between CAT scan of the thorax and abdomen, bone scan, chest X-ray, ultrasound of the abdomen, MRI, tumor marker, or PET scan. Multiple answers were eligible.
A CAT scan of the thorax and abdomen is used by 211 (95.9%), 28 (100%), and 36 (75%), and a bone scan by 217 (98.6%), 28 (100%), and 43 (89.6%) of the participants, respectively. Alternatively, 48 (21.8%), 11 (39.3%), and 23 (47.9%) of the institutions, respectively, stated that they sometimes use ultrasound of the abdomen, and 36 (16.4%), 10 (35.7%), and 23 (47.9%), respectively, of all who answered use chest X-ray for staging in case of a so-called “low-risk” breast cancer. They added this information to the comment field without further specification.
A total of 119 institutions use MRI for staging, whereas 102 institutions made specific comments when to use MRI: 54 (45.4%) use it for additional imaging of the breast in case of lobular invasive histology to rule out multicentricity, 27 (22.7%) use MRI for individual evaluation that cannot be achieved with other imaging, and 21 (17.7%) use it for further evaluation in case of inconclusive results from other imaging. PET-CT is only used in 7 (2.4%) of all institutions.
The following paragraph presents the results from surveying medical doctors specialized in gynecology and obstetrics who run a private practice. We sent out questionnaires to a total of 481 private practices, of those 107 (22%) took part in our survey, and their answers were used for final analysis. Staging habits were perceived as “consistent” by 55 (51%) and as “inconsistent” by 52 (49%) of the respondents. Of those who perceived staging habits as inconsistent, 17 (33%) reported that habits varied within a certain hospital that they referred their patients to, 35 (67%) stated that the indications for staging were used differently in different institutions, and 24 (46%) saw differences in the methods used for staging.
We further asked these gynecologists about their understanding of staging indications: 51 (48%) would stage every breast cancer patient preoperatively, 10 (9%) would stage postoperatively in general. In case of planned chemotherapy, 31 (29%) would perform staging examinations. With regard to postoperative findings, staging would be recommended by 41 (38%) in case of positive nodal status and 30 (28%) in case of a tumor stage ≥T2.
Discussion and Conclusion
In this nationwide survey, we aimed to evaluate staging habits for breast cancer patients in German breast centers and Departments of Obstetrics and Gynecology. We asked about indication and timing of staging and the imaging methods used. In addition, we also questioned gynecologists who work in a private practice to figure out their comprehension of staging recommendations.
Establishing clinical guidelines has significantly standardized and improved breast cancer treatment, and these guidelines are supposed to make sure that every patient receives the same standard of care. Adherence to guidelines is associated with improved survival in breast cancer patients [14, 15]. Nationwide guidelines are usually set up by leading experts on this field who in turn evaluate the current evidence of a certain topic. Ideally, guidelines facilitate decision-making for health-care providers, too [16]. However, a recent study showed that adherence to guidelines is not always self-evident and that a substantial proportion of breast cancer patients do not receive the recommended care [17]. Comparing our results on the indication for staging with current guideline recommendations, we also found that a relevant percentage of the participating institutions do not follow recommendations when they declare to perform preoperative staging in general. This percentage ranged from 16.4% of all certified breast centers to 66.7% of all Departments of Obstetrics and Gynecology who occasionally treat breast cancer patients. On the other hand, aggressive tumor biology and/or the necessity for a neoadjuvant chemotherapy led to staging in most breast centers (certified and noncertified) as recommended by clinical guidelines, but only in 35.4% and 75% of those institutions that do not have a breast center, respectively. These results underline the rationale for treating breast cancer patients in specialized breast centers.
Interestingly, also the method of staging showed deviation from guideline recommendations. Indeed, on the one hand, most institutions use CAT scan of the thorax and abdomen and a bone scan for staging as recommended, but, on the other hand, 21.8–47.9% of all institutions use ultrasound of the abdomen and 16.4–47.9% a chest X-ray for staging in “low-risk” breast cancer patients. Most institutions did not further specify what they mean by “low-risk” breast cancer, some participants explained it as “hormone receptor-positive, HER2-negative” patients in the comments. There is evidence that different breast cancer subtypes are associated with different metastatic patterns, showing that bone metastases are most common in HR*/HER2− breast cancer, and HER2-enriched breast cancers often lead to brain and liver metastases [18]. However, at the time of diagnosis of breast cancer, only about 4% of all patients have distant metastases, regardless of tumor stage and biology [19]. Therefore, detecting distant metastases is a rare event anyhow and regardless of the tumor biology: if we have an indication for staging, we should use the most sensitive method for detection.
This leads to the question whether it matters if we use CAT scan or conventional imaging methods, e.g., chest X-ray and abdominal ultrasound. In fact, no data exist regarding the comparison of conventional imaging methods with CAT scan in terms of clinical impact and cost effectiveness [20]; yet, Barrett et al. [19] demonstrated that CAT scan was the only modality in which the true-positive rate was higher than the false-positive rate and that CAT scan also had a lower false-positive rate than ultrasound and bone scintigraphy. Even with CAT scan staging, the false-positive rate is up to 10% and this, in turn, leads to further imaging or invasive diagnostic examinations. This is the main reason why staging should be performed with good indication only [21].
What are the reasons for health-care providers to deviate from guideline recommendations? One reason might be the fact that some patients do explicitly ask for staging examinations because they feel more comfortable with “knowing” that they are free of distant metastases. Although this fact seems very comprehensible from a patient's point of view, we have to keep in mind that most patients overestimate the risk for metastases at an early stage of disease and that they are also not aware of the likelihood of false-positive and false-negative results [22]. Thorough patient information is therefore mandatory.
Furthermore, some health-care providers might just not be aware of the current recommendations. It seems likely that this is the reason why clinical practice in Departments of Obstetrics and Gynecology without a breast center deviates most from staging recommendations. Educational interventions can improve adhearence to guidelines [23]. After all, we need to consider that the respondent rate of 53% is a limitation of our study. We all know how challenging it is to take extra time for external projects like this survey, but focusing on a higher respondent rate in future projects will lead to an improved quality of research.
Our second part of the survey focused on gynecologists who work in a private practice and who are responsible for guidance of breast cancer patients. They are responsible for referral to a breast center and they provide follow-up care after primary treatment. By asking them about their impression of staging habits, we aimed to gain a different perspective on the topic. The main findings are that about half of the colleagues who took part in the survey feel that staging is applied inconsistently, either in terms of indication or in terms of the methods used. Thereby, they underline the results we reviewed from the first survey, although it has to be considered that only 22% of the private practices that had been contacted took part in our survey.
In conclusion, the results of our survey show deviation from current guidelines but also confirm that adherence is best in certified breast centers. With regard to the methods applied for staging, there seem to be varying opinions regarding CAT scan and conventional imaging that should be addressed in future expert meetings. Since the adoption of guidelines takes time, it would be of great interest to repeat this survey within the next 5 years for possible changes in the adaption of guideline recommendations for staging in the different qualified institutions which offer treatment of breast cancer.
Statement of Ethics
In advance, the project was presented to the ethics committee of the Ärztekammer Nordrhein who did not find any ethical concerns and waived further assessment of the survey as well as the need for written informed consent.
Conflict of Interest Statement
The authors have no conflicts of interest to declare.
Funding Sources
Funding of this study was not necessary so no funding source exists.
Author Contributions
M.K., A.K., and V.K. have made substantial contributions to the conception and the design of the study. M.J. and V.K. were responsible for data acquisition. M.K., V.K., and C.F. made substantial contributions to analysis and interpretation of data. All authors were involved in drafting and revising the manuscript for intellectual content and final approval of the version to be published.
Data Availability Statement
All data generated or analysed during this study are included in this article. Further enquiries can be directed to the corresponding author.
Supplementary Material
Supplementary data
Acknowledgement
We want to thank all the colleagues for their time and consideration in taking part in our survey.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Supplementary data
Data Availability Statement
All data generated or analysed during this study are included in this article. Further enquiries can be directed to the corresponding author.