Stratifying Patients with Haematuria into High or Low Risk Groups for Bladder Cancer : a Novel Clinical Scoring System

Haematuria is a common presentation of bladder cancer (Messing, 2007; Madeb and Messing, 2008). As such, patients with haematuria should be assessed thoroughly for the presence of this malignancy. A full urologic assessment of a patient with haematuria includes repeated urinalysis, urine culture, upper urinary tract imaging, cystoscopic examination (CE) and urinary cytology (Grossfeld et al., 2001). CE requires specialized endoscopic equipment and a well-trained team of medical personnels to perform it


Introduction
Haematuria is a common presentation of bladder cancer (Messing, 2007;Madeb and Messing, 2008).As such, patients with haematuria should be assessed thoroughly for the presence of this malignancy.A full urologic assessment of a patient with haematuria includes repeated urinalysis, urine culture, upper urinary tract imaging, cystoscopic examination (CE) and urinary cytology (Grossfeld et al., 2001).CE requires specialized endoscopic equipment and a well-trained team of medical personnels to perform it method to assess the bladder for cancer (Grossfeld et al., 2001;Messing, 2007).To date, there is no single test that can replace the list of investigations that a patient with haematuria has to go through.Neither is there a method that can safely exclude the presence of bladder cancer in a patient with haematuria, without the use of CE (Khadra et al., 2000;Grossfeld et al., 2001;Messing, 2007;Lotan et al., 2009).
Delays in the treatment of bladder cancer have been shown to be detrimental to the survival outcome

Stratifying Patients with Haematuria into High or Low Risk Groups for Bladder Cancer: a Novel Clinical Scoring System
Guan Hee Tan 1 *, Shamsul Azhar Shah 2 , Ho Sue Ann 3 3 , Lim Chun Shen 3 , Nurudin Al-Fahmi Abdul Galib 3 , Praveen Singam 1 , Christopher Ho Chee Kong 1 , Goh Eng Hong 1 , Badrulhisham Bahadzor 1 , Zulkifli Md Zainuddin 1 (Wallace et al., 2002;Gore et al., 2009).Bearing in when detected and treated at an early stage, this usually compels us to perform the investigations as soon as possible (Grossman et al., 2005;Messing, 2007;Madeb and Messing, 2008).This compulsion places a substantial also means that certain patients who really harbour bladder cancer could be diagnosed later simply because they did not receive an early assessment.Therefore, it would be useful to identify the patients with haematuria who are at a higher risk of having bladder cancer.This group of patients can then be assessed earlier and hopefully improve the detection rate of early stage bladder cancer.The aim of this study was to develop a scoring system to stratify patients with haematuria into high or low risk for having bladder cancer.

Materials and Methods
This was a cross-sectional study of all adult patients who were referred to the Urology Unit of Universiti Kebangsaan Malaysia Medical Centre for haematuria from the year 2001-2011.Only patients who had full urologic assessment for haematuria were included (Grossfeld et al., 2001).The patients with incomplete data of their assessment or had bladder cancer diagnosed outside of the study period were excluded.The patients were chosen from the Urology Unit database and their data were collected from the hospital records.Data on patient demography and the presence of common risk factors for bladder cancer in each of them were recorded.The variables that were taken into account were age, gender, presence of gross haematuria, and history of smoking and version 20.Univariate analysis was performed to determine the association each of these risk factors have with bladder cancer within this study population.A scoring system was designed by including variables that were symptoms was given a score according to the magnitude of their association with bladder cancer.This meant that, the greater the odds ratio obtained for the variable, the larger the score assigned to it in the scoring system.The accuracy of the scoring system was determined by the area under the receiver operating characteristic (ROC) curve.The most suitable cut-off point was decided.The This study was carried out after obtaining approval from the Research and Ethics Committee of Universiti Kebangsaan Malaysia.

Results
Between the years 2001 and 2011, 405 cases of haematuria were referred the Urology Unit for further management.Out of these, 325 cases were included while 80 cases were excluded from the study due to incomplete were investigated for haematuria were diagnosed to have respectively.
The average age of patients in the bladder cancer group was 62.5±11.4years.This was slightly older than the patients who did not have bladder cancer, whose male patients who had haematuria were at a greater risk Smokers or ex-smokers with haematuria were also noted to be more at risk of bladder cancer compared to non-smokers patients with either microscopic or gross haematuria.
patients with gross haematuria in the bladder cancer group.The odds ratio of patients with gross haematuria having bladder cancer over those with microscopic haematuria probability of having bladder cancer among patients with A scoring system to predict the probability of having bladder cancer among patients with haematuria was proposed.The scoring system had 4 clinical parameters, namely age, gender, history of smoking and whether the haematuria was gross or microscopic in nature.The total (Figure 1).A score of 10 or more places the patient at a higher risk of harbouring bladder cancer.By using the cut-off value of 10, this scoring system had a sensitivity Discussion urologist for further assessment and management.They could either present with gross haematuria that is visible to the naked eye, or microscopic haematuria that is detected by urinalysis or urinary microscopy.While most cases of haematuria have benign aetiologies, a fair proportion management of patients with haematuria, the authors haematuria.They devised an algorithm of management in which it was recommended that all visible haematuria  and symptomatic non-visible haematuria be evaluated haematuria and over the age of 40 years also warranted a urologic evaluation in this algorithm (Kelly et al., 2000).Bladder cancer most commonly presents with haematuria, and indeed bladder cancer is the commonest malignancy detected in patients with either macroscopic or microscopic haematuria (Grossfeld et al., 2001;Edwards (Edwards et al., 2006).
were diagnosed with bladder cancer and they accounted for the majority of all patients with malignancies (Khadra et al., 2000;Edwards et al., 2006).Cha et al reported a of patients with haematuria, which is quite close to the prevalence found in the present study (Cha et al., 2012).
bladder cancer than those with microscopic haematuria.
haematuria have bladder cancer (Buntinx and Wauters 1997;Messing 2007).These figures show that not only should gross haematuria be taken seriously, even microscopic haematuria cannot be treated lightly.They warrant a thorough urologic assessment to exclude malignancies of the urinary system, and in particular bladder cancer.A complete urologic evaluation for a patient with haematuria includes repeated urinalysis, urine culture, upper urinary tract imaging, cystoscopic examination (CE) and urinary cytology (Grossfeld et al., 2001).CE is the most reliable method to assess the bladder for cancer (Khadra et al., 2000;Grossfeld et al., 2001;Messing, 2007).There are urine-based tumour marker detection to diagnose bladder cancer in patients with haematuria (Messing, 2007;Lotan et al 2009).However the sensitivity of such methods for the detection of bladder cancer is only 2007).
Several nomograms have been developed to quantify the risk of bladder cancer in patients presenting with haematuria (Lotan et al., 2009;Cha et al., 2012).They usually combine clinical risk factors with an investigation such as a urine-based tumour marker or urinary cytology.While they have improved accuracy over either tumour markers or urinary cytology alone, they can underestimate the probability of bladder cancer (Lotan et al., 2009).To date, there is no single test that can replace the list of investigations that a patient with haematuria has to go through.Neither is there a non-invasive method other than CE that can safely exclude the presence of bladder cancer in a patient with haematuria (Khadra et al., 2000;Grossfeld et al., 2001;Messing, 2007;Lotan et al., 2009).
detected at an early stage (Grossman et al., 2005;Messing, 2007;Madeb and Messing, 2008).The 5-year survival mucosa.But any delay in the treatment was shown to have a detrimental effect on the survival of T1 bladder cancer (Wallace et al., 2002).Once there is muscle invasion, the al., 2005).Delays before radical cystectomy for muscleinvasive bladder cancer can further worsen the survival outcome of this group of patients (Gore et al., 2009).This usually compels us to perform the investigations as soon as possible.
The need for early diagnosis and treatment of bladder cancer places a substantial burden on the urology units because of the need for CE.Although CE is considered equipment and well-trained medical personnel to perform be cleaned and sterilised before being used for the next patient.Hence, there is a limit to the number of patients who can be assessed at any one session.This potentially results in late diagnosis for some patients who really harbour bladder cancer because they could not be assessed early enough.Therefore, it would be useful to identify the patients with haematuria who are at a higher risk of having bladder cancer.This group of patients can then be assessed earlier and hopefully improve the detection rate of early stage bladder cancer.
The aforementioned nomograms could be used to identify patient who are more at risk of having bladder cancer.However, the need for specialised test kits or urinary cytology limits the feasibility of adopting these nomograms in many urology units.The scoring system that was developed in the present study aims to utilise only clinical parameters to risk stratify these patients into high to use.The 4 parameters used were age, gender, history of cigarette smoking, and the presence of gross haematuria.They were each given scores based on the strength of their association with bladder cancer.For instance, the presence of gross haematuria was given the greatest score because it was strongly related to the diagnosis of bladder cancer Although the mean age of the bladder cancer and nongeneral trend that bladder cancers are found in the more advanced age patients was still evident here.A cut-off age of 50 years was chosen because numerous studies have considered ages above this to be a risk factor for bladder cancer (Messing et al., 1987;Alishahi et al., 2002;Madeb and Messing, 2008).The male gender, history of cigarette smoking and gross haematuria are all known to confer a greater risk of bladder cancer (Summerton et al., 2002;Grossman et al., 2005;Lotan et al., 2009).This this study.Gross haematuria seemed to be the risk factor most heavily associated with bladder cancer, followed by history of cigarette smoking and gender.Even though not included in the development of this scoring system.detecting bladder cancer among patients with haematuria.A patient with score of 10 or more is at a higher risk haematuria and bladder cancer will be correctly scheduled of all patients who present with haematuria and do not have bladder cancer can be given later appointments for assessment.This will allow the resources of the urology unit to be channeled to patients who are more likely to require early attention.and undergo early urologic evaluation will have bladder cancer.This seems to be an acceptable yield since no extra investigation tools are needed to stratify the patients.Equally useful is that patients who are considered low-risk based on the scoring system, can be informed that there cancer.This can provide them reassurance and comfort, while waiting for full urologic evaluations to be carried out.
The retrospective nature of this study limits the completeness of the data obtained for analysis.Every effort was made to ensure that only patients with complete This study also has the inherent problem of retrospective studies in which selection bias occurs.Nevertheless, we tried to reduce this effect by including the majority of the patients in our database through diligent search of critical information in every patient's medical records.Although the current performance of this scoring system seems impressive, we recognise the need for prospective validation.The validity of this scoring system is being evaluated with prospectively collected data, currently ongoing in our institution.
or any other currently available nomogram cannot replace the standard urologic evaluation of patients with haematuria.The scoring system created in the present study is only intended to assist urologists and medical practitioners in deciding the urgency of assessment that the patients need.The quest for a non-invasive and reliable method in diagnosing bladder cancer continues.Until then, CE remains the best tool we have for this purpose.Nevertheless, we can improve the survival outcome of this end that scoring systems and nomograms can play a role by identifying those at a greater risk for timely urologic evaluation. of bladder cancer that demands serious attention.Early detection of bladder cancer is known to confer survival patients with haematuria into high or low risk for bladder this way can help identify the high-risk patients for early urologic evaluation.

Figure 1 .
Figure 1.An Area Under the Receiver Operating Characteristic Curve of 80.4% Demonstrates that the Scoring System has Good Accuracy

Table 1 . The Scoring System for Stratifying Patients with Haematuria into High or Normal Risk for Bladder Cancer
*Total score of 10 or more indicates high risk for bladder cancer