|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
© 2003 American Society for Clinical Oncology Provider Delay Among Patients With Breast Cancer in Germany: A Population-Based Study
From the German Centre for Research on Ageing, Department of Epidemiology, Heidelberg; University of Ulm, Department of Epidemiology, Ulm; and Saarland Cancer Registry, Saarbrücken, Germany. Address reprint requests to Volker Arndt, The German Centre for Research on Ageing (DZFA), Department of Epidemiology, Bergheimer Strasse 20, D-69115 Heidelberg, Germany; email: arndt{at}dzfa.uni-heidelberg.de.
Purpose: Delaying the diagnosis and initiation of treatment of cancer is likely to result in tumor progression and a worse prognosis. We examined sources and consequences of provider delay among female breast cancer patients in a population-based study in Germany. Patients and Methods: Three hundred eighty women, who were ages 18 to 80 years and who had invasive breast cancer, were interviewed with respect to the diagnostic process. Provider delay was defined as time from first presentation to a health care provider until initiation of cancer treatment. Results: Median provider delay was 15 days and did not substantially differ by the specialty of first consulted physician. Delays in the diagnostic work-up were mainly because of erroneous initial suspicion of a benign breast disease or because of time constraints by patients or physicians. Provider delay over 3 months was found in 11% of all breast cancer cases and was associated with patient characteristics such as higher education (odds ratio [OR] = 2.6; 95% confidence interval [CI], 1.3 to 5.4), full-time employment (OR = 2.5; 95% CI, 1.1 to 5.5), family history of breast cancer (OR = 2.8; 95% CI, 1.2 to 6.2), and presenting with a non–breast symptom (OR = 4.3; 95% CI, 1.7 to 10.9). The association between duration of diagnostic work-up and stage at diagnosis was U shaped, with the highest proportions of metastasized breast cancer tumors among women with very short (< 7 days) or very long (> 3 months) duration. Conclusion: Diagnostic work-up is within reasonably short time limits among most patients with breast cancer in Germany. Although the association between delay and tumor stage seems to be complex, any delay in diagnostic work-up should be kept to a minimum.
BREAST CANCER is an important health concern for women in many countries, and delaying the diagnosis and initiation of treatment is likely to result in tumor progression and a worse prognosis. Two types of delay in diagnosis and treatment of cancer are commonly distinguished:1 (1) patient delay, which covers the period from first onset of symptoms to first medical consultation; and (2) provider delay, which covers the period from first consultation to definite diagnosis or treatment. There is quite substantial evidence that among breast cancer patients, delay of more than 3 months is associated with poorer survival,2 and it is well recognized that delay in diagnostic work-up and initiation of treatment is likely to result in psychosocial stress for the patients.3–5 However, the prognostic effect of provider delay is less clear.6,7 Past reports from various European countries and North America indicate that median provider delay varies between 2 and 4 weeks.8–11 It has been reported that younger age,8–10,12–14 presentation with a breast symptom other than a lump,8,10,13,15,16 and false-negative biopsies17 may increase the likelihood of provider delay. Most past studies addressing diagnostic delay in breast cancer patients relied on chart review or tumor registry data and, thus, were limited by the subset of variables available. Additional potential factors, such as patient’s history of benign breast disease or breast cancer screening, family history, and socioeconomic factors like employment status, have not been addressed to date. Therefore, we initiated a population-based study in Germany to address the following objectives: (1) to study the extent and nature of provider delay in breast cancer patients; (2) to identify determinants of long provider delay by studying a broader set of patient and provider characteristics than earlier studies; and (3) to study the association between provider delay and stage at diagnosis.
Study Design and Study Population Details of the study design as well as results with respect to patient delay have already been described.18,19 In brief, we conducted a population-based, state-wide study on the diagnostic process, risk factors, and prognosis among patients with various forms of cancer from Saarland, Germany (Verlauf der diagnostischen Abklärung, VERDI). Saarland is a state in southwest Germany covering a population of approximately 1 million inhabitants. For the purpose of this analysis, all women aged 18 to 80 years, with sufficient German language skills and with primary and invasive breast cancer, diagnosed between October 1, 1996, and February 28, 1998, were eligible. Potential study participants were identified by their clinicians during first hospitalization. With the exception of two hospitals that did not offer inpatient cancer treatment, all the other 34 hospitals from the study region participated in the recruitment. Overall, 458 patients were deemed suitable for participation by their treating physicians and were reported to the study center after they had given written informed consent. Fifty-four women did not meet the inclusion criteria for the following reasons: noninvasive tumor (n = 14), recurrent tumor (n = 13), age over 80 years (n = 7), duplicate report (n = 2), date of diagnosis outside study period (n = 14), or living outside study region (n = 4). Three women died before the interview, and 14 eligible women with breast cancer withdrew their consent to participate in study. Seven women with missing information on stage had to be excluded because stage was a major end point for this analysis. Thus, the final study population comprises 380 breast cancer patients and represents approximately 50% of all new incident cases during the recruitment period. The study participants did not substantially differ from the source population of all female breast cancer patients from Saarland in terms of basic demographic characteristics with the exception of a slightly higher proportion of younger women.
Data Collection
Measure of Provider Delay
Statistical Methods Unlike patients in many others countries, many patients in Germany directly consult an outpatient specialist rather than presenting their symptoms to a general physician or family practitioner first. Therefore, we were interested to see whether the diagnostic work-up of breast cancer cases is faster when women directly consult a gynecologist instead of any other primary health care provider (including general physician).
The bivariate associations between these factors and provider delay were tested with the Finally, we were interested to see whether a longer duration of diagnostic work-up (provider delay) is associated with advanced disease and, thus, probably a worse prognosis for the patients. Tumor stage was categorized as local, regional, or distant according to tumor-node-metastasis staging scheme.26 Local disease included all patients with T1–T3 and N0/M0, regional disease included all patients with N1–N3/M0 or T4/N0/M0, and distant disease included all patients with M1 disease. For this study, the small number of distant disease patients (n = 14) was combined with the regional disease patients (n = 168) to represent late-stage disease in contrast with early-stage (local) disease. The association between provider delay and tumor stage was examined for all tumors together and after stratification by tumor differentiation to control for differences in the tumor growth of low- (grade 1 and 2) and high-grade (grade 3 and 4) tumors.27
Table 1  lists some basic characteristics of the study population (N = 380). The mean age of all women was 58.0 years. Over three quarters of all tumors were detected because of symptoms noticed by the patients. Almost 18% of all breast cancer cases were identified through a screening examination, and 7% of all cases were diagnosed as a result of the diagnostic work-up of some other disease. A lump in the breast detected either by the patient or by her physician was the trigger for further diagnostic work-up in 64% of all our study participants. Other symptoms of the breast, such as an inverted nipple, skin edema, peau d’orange, and nipple discharge or bleeding, were found less often (23%) than the main symptom of a breast lump. At time of diagnosis, over 52% of all breast cancer tumors were confined to the breast tissue; in 44% of all patients, involvement of regional lymph nodes was found, and 4% of all patients already showed clinical evidence of distant metastases.
Details of the diagnostic work-up are listed in Table 2 . Gynecologists were the primary physicians in 249 (66%) of 380 women. This proportion varied according to whether the diagnostic work-up started as a result of a screening examination (81%), because of symptoms (65%), or incidentally (39%). Other major primary consultants include general practitioners (n = 74), specialists of internal medicine (n = 26), and radiologists (n = 17; data not shown).
Almost all women who consulted a gynecologist directly received a mammography, ultrasound, or biopsy of the breast the day of first consultation. Fifty percent of these women were told the breast cancer diagnosis within 12 days and were admitted to a hospital for further treatment within 2 weeks after first consultation. In total, it took, on average, three outpatient consultations and two outpatient physicians (usually one gynecologist and one radiologist). The diagnostic work-up of women with breast cancer who first consulted a general physician or a specialist other than a gynecologist did not markedly differ; the median duration until a diagnosis was told to the patient was also 12 days, and breast cancer therapy started within 14 days after first consultation. However, in both groups, diagnostic work-up and initiation of treatment took over 1 month in more than a quarter of all women with breast cancer. When we restricted the study population to the symptomatic breast cancer patients, it seemed that diagnostic work-up and initiation of treatment tended to be slightly more timely among women who first consulted a gynecologist.
Forty-six women with breast cancer symptoms reported that it took over 14 days after the first consultation before the first mammography, ultrasound breast examination, or breast biopsy was performed (Table 3
Determinants of Provider Delay In our study population, the median delay between first consultation until initiation of treatment was 15 days. Initiation of treatment started within the first month in almost 73% of all patients, within the second and third month in 16% of patients, and after the third month in 11% of patients (Table 4 ). Bivariate analysis yielded that duration of diagnostic work-up was statistically significantly longer among women with 10 years or more of schooling and women who were working full-time. There were no significant differences in the duration of the diagnostic work-up with respect to patient age, nationality, or health insurance.
Women with a first-degree relative diagnosed with breast cancer showed a different pattern in the duration of diagnostic work-up. Although treatment started within 1 month after first consultation in 65% of these women, there were over 20% for whom 3 months or more elapsed before breast cancer treatment was initiated. Diagnostic work-up tended to be longer in women who underwent a screening mammography during the year preceding the index disease and in women who presented with a symptom other than a lump in the breast.
Education, employment status, family history of breast cancer, mammography history, type of symptom, and mode of detection were identified as statistically significant and independent determinants of provider delay in multivariate analysis (Table 5
The relationship between provider delay and tumor stage is shown in Table 6 . As already described earlier, we combined the relatively small number of patients with distant disease with the number of patients with regional disease to represent late-stage disease in contrast to early-stage (localized) disease.
There was no clear linear association between duration of diagnostic work-up and tumor stage at time of diagnosis when we used the predefined categories of less than 1 month, 1 to 3 months, and more than 3 months. The corresponding proportions of late-stage tumors were 48%, 44%, and 51% and, if anything, indicated a slightly U-shaped association between duration of diagnostic work-up and late-stage diagnosis rather than a linear association. Stratification by tumor grade did not reveal any further evidence for a clear association.
The U-shaped association became more evident when we split up the relatively large group of women diagnosed and treated within 1 month into three groups of almost equal sample size (Fig 1
Negligent procrastination of onset of diagnostic work-up and treatment in cancer patients per se is likely to result in further advanced disease, more invasive surgery, and higher cause-specific mortality. Although it has been repeatedly reported that patient delay of more than 3 months among breast cancer cases is associated with lower survival, the consequences of a long duration delay of diagnostic work-up after the first consultation are less clear, and the sources of this so-called provider delay are more complex. Delay in the diagnostic work-up after the first consultation of a physician may arise from patient noncompliance, provider misdiagnosis, or long waiting times for diagnostic or therapeutic procedures because of limited capacities in the health care system. The terms of provider delay or doctor delay are, therefore, somewhat misleading because they imply that providers or doctors are the sole sources of delaying a prompt diagnosis. Interpreting breast cancer symptoms is problematic because presenting symptoms are similar in both benign and malignant disorders of the breast. In addition, breast cancer symptoms are more common in women diagnosed with benign disease.28 Therefore, it is not surprising to see that a substantial diagnostic delay was caused by false-negative findings or a working hypothesis of a benign disease. However, time constraints presented either by the patient or by physician also were observed and underline the complexity of the phenomenon of provider delay. Mammography, ultrasound, or fine-needle aspiration cytology are the essential diagnostic procedures to perform a work-up on suspicious lumps of the breast. A one-stop examination with mammography, ultrasound, or fine-needle aspiration cytology provides an accurate and effective means of establishing a correct diagnosis (positive predictive value > 0.95) in symptomatic breast patients.29 It is interesting to note, particularly in the light of the actual discussion about referral guidelines,30 that there are virtually no differences in our study with respect to the timeliness of the diagnostic work-up between women who consult a gynecologist first and women who consult another physician first. This is in agreement with a recent study from Sweden,31 in which no difference in provider delay between general practitioners and other physicians was found. Specifically, in the case of breast cancer, it is likely that nongynecologists promptly refer women presenting breast symptoms of unknown dignity to a breast specialist or a radiologist for further specific diagnostic work-up. Burgess et al13 reported that over 80% of all symptomatic breast cancer patients were referred directly to a breast clinic after their first general practitioner visit. In our study, we found a median delay of 15 days between first consultation and onset of treatment. This delay is comparable with the median system delay of 2.6 weeks, as seen by Caplan et al,10 or the 16-day median delay earlier reported by Nichols et al,28 and slightly shorter than the system delay reported by Sainsbury et al7 and Afzelius et al.9 Although treatment was started within 1 month after first consultation in almost three quarters of all breast cancer patients, more than 3 months elapsed between the first consultation and initiation of treatment in 11%. High-risk groups for a delayed diagnostic work-up (> 3 months) seem to be women who presented with a symptom not directly related to the breast, women who were working full-time, better-educated women, and women with a first-degree relative with breast cancer. Presenting with a symptom other than a lump in the breast has been linked to a delayed diagnostic work-up in previous studies.10,13,15,16 However, the finding that full-time working women, who also tended to be better educated in our study sample, are more prone to delay even after first consultation is new and underlines that the timing of the diagnostic work-up also depends on the individual patient’s perceptions of other priorities taking precedence over personal health.32 It is not quite clear why the diagnostic work-up among better-educated women and women with a first-degree relative of breast cancer tended to be longer than average. One might hypothesize that fear of diagnosis and perceived susceptibility by the patient may work as barriers against a quick diagnostic work-up. In a previous analysis looking at determinants of patient delay before first consultation,19 none of these two factors was a determinant of delayed help-seeking behavior before first consultation. Thus, the underlying mechanisms are not fully understood, and the results deserve confirmation by other studies. Young age did not emerge as strong a risk factor for provider delay as it did in some other studies.7,9,10,12–14 Although there was a tendency for a slightly longer diagnostic work-up among younger women in our sample, the differences were not statistically significant. This apparent discrepancy from previous findings may be a result of two reasons. The first reason is time trends. Four of these previous studies7,9,10,14 recruited most of their patients more than 10 years earlier than we did, and changes in the diagnostic work-up of women with breast symptoms, including referral practices, may have changed during the last decade. The second reason is differences in definition of delay. For example, Burgess et al13 defined provider delay as "a failure not to refer a patient after the first attendance." In our sample, 16%, 28%, and 35% of all women under the ages of 50 years, ages 50 to 65 years, and over age 65 years, respectively, were directly referred into a hospital after first consultation (P < .01); however, the differences in initiation of treatment were only marginal. The most important question, however, is whether a long duration of diagnostic work-up results in further advanced disease and ultimately worse survival. Our data indicate a U-shaped association between duration of diagnostic work-up and stage at diagnosis, and thus, at least two different mechanisms may work. First, women with advanced disease have a higher chance of getting diagnosed more promptly because of a clearer clinical picture. This mechanism is in agreement with other studies9,33 that reported a poorer prognosis for breast cancer patients with a short provider delay compared with a long delay. Afzelius et al9 postulated that doctors are capable of distinguishing between more and less aggressive malignancies. However, because we do not see a pure inverse linear relationship between provider delay and stage, a second mechanism might be hypothesized. False-negative findings at the initial examination may delay definite diagnosis and the initiation of treatment and, thus, result in further advanced disease. Probably, the major limitation of our study is the sample size. Despite the sample-size limitation, significant relationships were identified between a number of factors and provider delay. These relationships should be replicated in further, ideally larger, studies, particularly because some of these relationships are not easily explained. In summary, the diagnostic work-up is within reasonably short time limits among most patients with breast cancer in Germany. Delay in the diagnosis of breast cancer is mainly because of the time constraints of patients and physicians and the initial suspicion of a benign breast disease. Although the association between delay and tumor stage seems to be complex, any delay in diagnostic work-up should be kept to a minimum.
We thank Drs Corinna Hetke, Wiebke Michaels, and Marianne Schramm for conducting the interviews; Rolf Friemond, Rainer Müller, Gabriele Berg, Daniela Österle, and Dietlind Wehrhahn for their technical assistance; and the reviewers for their helpful comments.
Supported by grant no. 70-1816 from the German Cancer Foundation (Deutsche Krebshilfe).
1. Facione NC: Delay versus help seeking for breast cancer symptoms: A critical review of the literature on patient and provider delay. Soc Sci Med 36:1521–1534, 1993[CrossRef][Medline] 2. Richards MA, Westcombe AM, Love SB, et al: Influence of delay on survival in patients with breast cancer: A systematic review. Lancet 353:1119–1126, 1999[CrossRef][Medline]
3. Olivotto IA, Bancej C, Goel V, et al: Waiting times from abnormal breast screen to diagnosis in 7 Canadian provinces. CMAJ 165:277–283, 2001 4. Thorne SE, Harris SR, Hislop TG, et al: The experience of waiting for diagnosis after an abnormal mammogram. Breast J 5:42–51, 1999[CrossRef][Medline]
5. Brett J, Austoker J, Ong G: Do women who undergo further investigation for breast screening suffer adverse psychological consequences? A multi-centre follow-up study comparing different breast screening result groups five months after their last breast screening appointment. J Public Health Med 20:396–403, 1998 6. Coates AS: Breast cancer: Delays, dilemmas, and delusions. Lancet 353:1112–1113, 1999[CrossRef][Medline] 7. Sainsbury R, Johnston C, Haward B: Effect on survival of delays in referral of patients with breast-cancer symptoms: A retrospective analysis. Lancet 353:1132–1135, 1999[CrossRef][Medline] 8. Ramirez AJ, Westcombe AM, Burgess CC, et al: Factors predicting delayed presentation of symptomatic breast cancer: A systematic review. Lancet 353:1127–1131, 1999[CrossRef][Medline] 9. Afzelius P, Zedeler K, Sommer H, et al: Patient’s and doctor’s delay in primary breast cancer: Prognostic implications. Acta Oncol 33:345–351, 1994[Medline]
10. Caplan LS, Helzlsouer KJ, Shapiro S, et al: System delay in breast cancer in whites and blacks. Am J Epidemiol 142:804–812, 1995 11. Interdisciplinary Group for Cancer Care Evaluation (GIVIO): Reducing diagnostic delay in breast cancer: Possible therapeutic implications. Cancer 58:1756–1761, 1986[CrossRef][Medline] 12. Montella M, Crispo A, Botti G, et al: An assessment of delays in obtaining definitive breast cancer treatment in Southern Italy. Breast Cancer Res Treat 66:209–215, 2001[CrossRef][Medline] 13. Burgess CC, Ramirez AJ, Richards MA, et al: Who and what influences delayed presentation in breast cancer? Br J Cancer 77:1343–1348, 1998[Medline] 14. Finley ML, Francis A: Risk factors and physician delay in the diagnosis of breast cancer. Prog Clin Biol Res 130:351–360, 1983[Medline] 15. MacArthur C, Smith A: Delay in breast cancer and the nature of presenting symptoms. Lancet 1:601–603, 1981[CrossRef][Medline] 16. Adam SA, Horner JK, Vessey MP: Delay in treatment for breast cancer. Community Med 2:195–201, 1980[Medline] 17. Bates AT, Bates T, Hastrich DJ, et al: Delay in the diagnosis of breast cancer: The effect of the introduction of fine needle aspiration cytology to a breast clinic. Eur J Surg Oncol 18:433–437, 1992[Medline] 18. Arndt V, Sturmer T, Stegmaier C, et al: Socio-demographic factors, health behavior and late-stage diagnosis of breast cancer in Germany: A population-based study. J Clin Epidemiol 54:719–727, 2001[CrossRef][Medline] 19. Arndt V, Sturmer T, Stegmaier C, et al: Patient delay and stage of diagnosis among breast cancer patients in Germany: A population based study. Br J Cancer 86:1034–1040, 2002[CrossRef][Medline] 20. Rothwell JF, Feehan E, Reid I, et al: Delay in treatment for oesophageal cancer. Br J Surg 84:690–693, 1997[CrossRef][Medline] 21. Fisher ER, Redmond C, Fisher B: A perspective concerning the relation of duration of symptoms to treatment failure in patients with breast cancer. Cancer 40:3160–3167, 1977[CrossRef][Medline] 22. Feldman JG, Saunders M, Carter AC, et al: The effects of patient delay and symptoms other than a lump on survival in breast cancer. Cancer 51:1226–1229, 1983[CrossRef][Medline] 23. Gardner B: The relationship of delay in treatment to prognosis in human cancer. Prog Clin Cancer 7:123–133, 1978[Medline] 24. Moritz DJ, Satariano WA: Factors predicting stage of breast cancer at diagnosis in middle aged and elderly women: The role of living arrangements. J Clin Epidemiol 46:443–454, 1993[CrossRef][Medline] 25. Stokes ME, Davis CS, Koch GG: Categorical Data Analysis Using the SAS System. Cary, NC, SAS Institute, 1995 26. Esteban D, Whelan S, Laudico A, et al: Manual for Cancer Registry Personnel, chapter 4. Lyon, France, IARC Technical Report, 1995, p 24 27. World Health Organization: Handbook for standardized cancer registries. Geneva, Switzerland, World Health Organization, 1976 28. Nichols S, Waters WE, Fraser JD, et al: Delay in the presentation of breast symptoms for consultant investigation. Community Med 3:217–225, 1981[Medline] 29. Eltahir A, Jibril JA, Squair J, et al: The accuracy of "one-stop" diagnosis for 1,110 patients presenting to a symptomatic breast clinic. J R Coll Surg Edinb 44:226–230, 1999[Medline]
30. Jones R, Rubin G, Hungin P: Is the two week rule for cancer referrals working? Br Med J 322:1555–1556, 2001 31. Mansson J, Bjorkelund C, Hultborn R: Symptom pattern and diagnostic work-up of malignancy at first symptom presentation as related to level of care: A retrospective study from the primary health care centre area of Kungsbacka, Sweden. Neoplasma 46:93–99, 1999[Medline] 32. Burgess C, Hunter MS, Ramirez AJ: A qualitative study of delay among women reporting symptoms of breast cancer. Br J Gen Pract 51:967–971, 2001[Medline]
33. Mayo NE, Scott SC, Shen N, et al: Waiting time for breast cancer surgery in Quebec. CMAJ 164:1133–1138, 2001 Submitted August 9, 2002; accepted January 23, 2003.
This article has been cited by other articles:
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2003 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
TOP
ABSTRACT
INTRODUCTION
2 test statistic (categorical data) and with the nonparametric Brown-Mood test (medians). Polytomous logistic regression with forward selection (P < .05) using the SAS procedure CATMOD (SAS Institute, Cary, NC)
