Journal of Cancer Diagnosis
Open Access

Uterine cancer; Putative characteristics; Positive predictive values; Postmenopausal haemorrhage

Introduction

In the UK, uterine cancer is the fourth most prevalent disease in women, with 7700 new diagnosis and 1700 fatalities each year. The prevalence is gradually rising, especially in postmenopausal women. Although trophoblastic malignancies and tumours of the uterine muscle can also develop, endometrial cancer typically develops first [1]. Despite the cervix being technically a part of the uterus, uterine cancer has different risk factors than cervical cancer and may also have different symptoms. Uterine cancer five-year survival rates have increased to about 75%. The UK lags behind other European nations in terms of survival, with an estimated 100 more uterine cancer deaths per year than the average European death rate or 240 more than the greatest European survival rate. There have been reports of uterine cancer diagnostic delays in several European nations.

Contrary to cervical cancer, there is no screening method for uterine cancer, thus a woman must exhibit symptoms before the illness can be diagnosed. Women with symptoms typically go to their family doctor or general practitioner (GP) first in the UK and many other high-income nations [2]. Uterine cancer is uncommon at the level of a single general practitioner therefore this limits their ability to diagnose it personally. Primary care studies have not examined the complete spectrum of uterine cancer symptoms, while secondary care studies have emphasised the significance of postmenopausal bleeding. 1.7% of women who reported this symptom in a primary care study went on to acquire a relevant malignancy in the next two years [3]. In the influential National Institute for Health and Clinical Excellence (NICEnow the National Institute for Health and Care Excellence) Referral recommendations for suspected cancer (2005), only postmenopausal bleeding and pelvic tumours are listed as potential indicators of uterine cancer. These guidelines for gynaecological cancer were all supported by evidence of grade C or lower [4]. There is a need for better counselling because less than 10% of women who are referred with these symptoms actually have uterine cancer. Additionally, 34% of women who have uterine cancer do not exhibit one of these alarm symptoms, which causes delays in diagnosis [5]. Thus, the sensitivity and specificity of the recommendations in the NICE guidance are both generally poor, with the low sensitivity possibly explaining the UK’s dismal statistics regarding uterine cancer mortality. This study set out to identify the characteristics of uterine cancer in primary care (where the clinical issue of choosing the right women for the investigation exists) and to calculate the cancer risk associated with each characteristic.

Method

Data sources

Data from the General Practice Research Database (GPRD; now the Clinical Practice Research Datalink) in the UK were used for this case-control research. The GPRD keeps an anonymized duplicate of the medical records kept by participating practises; these records include all consultations, reported symptoms, investigations, and diagnoses for the patient [6, 7]. Validation and data quality are subject to strict controls. Similar techniques have been employed in a number of cancer diagnosis studies in the past.

Discussion

The clinical characteristics of uterine cancer in primary care have never been studied before. The majority of the symptoms described from studies conducted in secondary care were, as was expected, similarly substantially linked to uterine cancer in primary care [8]. Except for postmenopausal bleeding, the probability of uterine cancer with these characteristics was, however, quite low, indicating the rarity of uterine tumours and the fact that many of the symptoms are typical of benign illnesses. Women who presented with various symptoms had a higher probability of an underlying uterine malignancy.

This extensive study makes use of primary care data. This is crucial: because primary care chooses the women for the project, primary care data must be utilised to examine the selection process [9]. Of the primary care longitudinal patient databases, the GPRD is the largest and most well-established. Its validity has been thoroughly established and it has been utilised in almost 1000 research articles. Additionally broadly representative of the population in the UK is the patient population in the database. Additionally, laboratory findings are sent directly to the database, preventing transcription errors and enabling for the use of the local normal range to spot anomalous results.

The correctness of the histology-based diagnoses in these patients could not be verified, nor could the staging be established. The majority of cases, however, had numerous records of uterine neoplasms. Such a terrible condition is unlikely to be recorded wrongly on a regular basis [10]. The study’s biggest flaw, however, is that it was dependent on GPs accurately recording patients’ symptoms. All symptoms could be found in the main field of the records, but some symptoms might also be found in the so-called “free-text” region of the GPRD, which is inaccessible. Fortunately, a recent ovarian cancer study found that there wasn’t much hidden information in these categories. Underrecording, however, is only significant when the fraction of underrecording is substantially higher in either cases or controls when calculating likelihood ratios and PPVs.

Only 17.6% of women with uterine cancer reported consulting their GP at least three times before diagnosis, according to data from the National Cancer Patient Experience Survey [11]. Women with uterine cancer visited their doctors about twice as frequently as controls, though this excess is less extreme than seen in many other cancers. This might be the case because, unlike certain other malignancies, such ovarian cancer, with less distinctive symptoms, the likelihood of gynaecological cancer is taken into account early on in a woman with atypical vaginal bleeding.

Endometrial cancer is identified in 5-6% of women with postmenopausal bleeding, according to recent research of secondary care clinics in the UK. In this study, 4% of postmenopausal bleeding cases were reported from primary care. This is consistent with a recent article that claims that two-thirds of women with postmenopausal haemorrhage were referred right away, albeit it does not address the reason for the other one-lack thirds of referral [12]. Only 63% of the women with uterine cancer in this study had any prior history of irregular vaginal bleeding, which is comparable to the 66% found in a big Danish secondary care study [13]. Similar to the link with elevated glucose revealed in the current study, an association between diabetes and uterine cancer has also been described in the past. Finally, primary care studies of lung, pancreatic, and ovarian cancer as well as secondary care studies of ovarian cancer have revealed an increased platelet count.

This investigation uncovered more major uterine cancer symptoms. The additional symptoms may help identify women with uterine cancer earlier, especially if they are numerous. This is perhaps the biggest benefit of the research. There were two significant combinations: haematuria with anaemia, or vaginal discharge. For both of these, the PPV among women under 55 years old is >2% [14]. In this investigation, it was unable to determine if the reported haematuria was a real symptom or was mistaken for vaginal bleeding. But this is a crucial tip for general practitioners: women describing haematuria may not be at risk for urological malignancy; instead, it could be gynaecological.

Another problem is that GPs are not required to refer all women who exhibit one of the symptoms simply because the risks of uterine cancer have been published in this way. Using such clinical decision support, doctors of general practise can and do reassure patients when the danger is low and conduct investigations when the risk is higher. This was proven in the authors’ study of instruments used in colorectal and lung cancer.

Compared to the UK, other European nations have greater uterine cancer survival rates. Some of this might be a result of past research on symptomatic women [15]. GPs may use the information from this study to help them decide whether women need an immediate investigation. Although there may be further conclusive diagnostic techniques, such as biomarkers, in this area, they will still need people to be chosen for testing, and they should probably use the results. The primary care findings from this study will be used in the upcoming UK NICE referral guidance revision.

Conclusion

The significance of various characteristics, particularly postmenopausal haemorrhage, for uterine cancer is confirmed by this study. A key risk factor is haematuria. The findings of this study could help GPs choose which women to look into further, and they should help the NICE revise its recommendations for GP referrals.

1. Evans T, Sany O, Pearmain P, Ganesan R, Blann A, et al. (2011) Differential trends in the rising incidence of endometrial cancer by type: data from a UK population-based registry from 1994 to 2006. Br J Cancer 104:1505–1510.

Google Scholar, Crossref, Indexed at

2. Office for National Statistics (2010) Mortality Statistics: deaths registered in England and Wales (Series DR).

Google Scholar

3. Abdel-Rahman M, Stockton D, Rachet B, Hakulinen T, Coleman MP, et al. (2009) What if cancer survival in Britain were the same as in Europe: how many deaths are avoidable? Br J Cancer 101(suppl 2):S115–S224.

Google Scholar, Crossref, Indexed at

4. Robinson KM, Ottesen B, Christensen KB, Krasnik A (2009) Diagnostic delay experienced among gynecological cancer patients: a nationwide survey in Denmark. Acta Obstet Gynecol Scand 88:685–692.

Google Scholar, Crossref, Indexed at

5. Vandborg M (2011) Reasons for diagnostic delay in gynecological malignancies. Int J Gynecol Cancer 21:967–974.

Google Scholar, Crossref, Indexed at

6. Brand A (2007) The woman with postmenopausal bleeding. Aust Fam Physician 36:116–120.

Google Scholar, Indexed at

7. Parker C, Hippisley-Cox J, Coupland C, Vinogradova Y (2007) Rectal and postmenopausal bleeding: consultation and referral of patients with and without severe mental health problems. Br J Gen Pract 57:371–376.

Google Scholar, Indexed at

8. Burbos N (2010) Predictive value of urgent referrals for women with suspected gynecologic malignancies. Gynecol Oncol 116 (3 suppl 1):S53.

Google Scholar, Crossref

9. Khan NF, Harrison SE, Rose PW (2010) Validity of diagnostic coding within the General Practice Research Database: a systematic review. Br J Gen Pract.

Google Scholar, Crossref, Indexed at

10. Herrett E, Thomas SL, Schoonen WM, Smeeth L, AJ (2010) Validation and validity of diagnoses in the General Practice Research Database: a systematic review. Br J Clin Pharmacol 69:4–14.

Google Scholar, Crossref, Indexed at

11. Hamilton W, Kernick D (2007) Clinical features of primary brain tumours: a case-control study using electronic primary care records. Br J Gen Pract 57:695–699.

Google Scholar, Indexed at

12. Hamilton W, Lancashire R, Sharp D, Peters TJ, Cheng KK, et al. (2008) The importance of anaemia in diagnosing colorectal cancer: a case-control study using electronic primary care records. Br J Cancer 98:323–327.

Google Scholar, Crossref, Indexed at

13. Hamilton W (2009) The CAPER studies: five case-control studies aimed at identifying and quantifying the risk of cancer in symptomatic primary care patients. Br J Cancer 101(suppl 2):S80–S86.

Google Scholar, Crossref, Indexed at

14. Knottnerus JA (2002) The evidence base of clinical diagnosis (BMJ Books, London).

Google Scholar, Crossref, Indexed at

15. Cancer Research (2013) UK Cancer incidence statistics.