Flexible Cystoscopy Findings in Patients Investigated for Profound Lower Urinary Tract Symptoms,Recurrent Urinary Tract Infection,and Pain

Abstract

Background and Purpose:

The National Institute of Clinical Excellence published guidelines in 2010 recommending the use of cystoscopy to investigate profound lower urinary tract symptoms (pLUTS), recurrent urinary tract infection (rUTI), and pain in men. Currently, there are no equivalent guidelines for women. We aimed to examine the diagnostic performance of flexible cystoscopy (FC) when it is used in this context in both men and women.

Patients and Methods:

Results of all outpatient FCs undertaken in our department between April 2009 and March 2010 were examined retrospectively. Patients undergoing FC for the investigation of pLUTS, rUTI, or pain were included. Diagnostic performance was calculated, which was defined as the number of patients receiving a diagnosis of a clinically relevant abnormality at FC divided by the total number of patients undergoing FC for this indication.

Results:

Of the 1809 patients who underwent FC during the study period, 113 underwent FC to investigate pLUTS, rUTI, or pain. Diagnostic performance was 11.5% (n=13), being 11.4%, 19.2%, and 0% in those with pLUTS, rUTI, and pain, respectively. Bladder cancer was diagnosed in one (0.9%) patient who underwent FC to investigate pLUTS but also had nonvisible hematuria. Urethral stricture was diagnosed in nine (8.0%) cases and intravesical calculi in four (3.5%) cases.

Conclusion:

Clinically relevant abnormalities were found in 11.5% of patients with pLUTS, rUTI, or pain, supporting recently published NICE guidelines recommending cystoscopy in patients with pLUTS or rUTI. Of the 17 patients who were investigated for pain, none was found to have clinically relevant abnormalities; further studies are needed to define the clinical utility of FC in these cases.

Introduction

L ower urinary tract symptoms (LUTS) are extremely common, with up to 60% of men aged more than 40 years with bothersome symptoms.¹ Consequently, assessment and treatment of these patients constitutes a large proportion of the workload of urology departments. The most common cause of LUTS in the male population is benign prostatic enlargement,² but pathology such as urethral stricture, intravesical calculi, or malignant disease (prostatic or intravesical) can also produce these symptoms.

The National Institute of Clinical Excellence (NICE) published guidelines in May 2010 regarding the assessment and management of LUTS in men.² As yet, no equivalent guidelines have been published regarding the assessment and management of LUTS in women. These guidelines recommend that cystoscopy should comprise part of the investigation of LUTS by a hospital-based specialist if there is a history of profound symptoms (pLUTS), recurrent urinary tract infection (rUTI), sterile pyuria, hematuria, or pain. The guidelines do not provide specific definitions of what constitutes pLUTS or rUTI or what type of pain should go forward to cystoscopy. In cases such as these, visualization of the bladder via flexible cystoscopy (FC) may diagnose pathology such as urethral stricture or bladder calculi and exclude life-threatening disease such as bladder malignancy.

No studies, however, have examined the diagnostic performance of FC in men when it is used to investigate pLUTS, rUTI, pain, or sterile pyuria, the NICE guidelines having been based on level 4 evidence (expert opinion). Studies have examined the clinical utility of FC in women with rUTI, but the data remain inconclusive.³ We therefore aimed to review the findings at FC and ascertain the diagnostic performance of this procedure when it is used for the investigation of pLUTS, rUTI, pain, or sterile pyuria in both men and women.

Patients and Methods

The records of all patients attending the Oxford department of urology for FC between April 1, 2009 and March 31, 2010 were reviewed retrospectively. At the time of cystoscopy, the indication, findings at procedure, and ongoing management were documented on a department-specific proforma. From these completed forms, indication, findings, and initial outcome of FC were recorded. Men and women of any age were included in this study if the primary indication for cystoscopy was LUTS that had failed initial conservative management, rUTI of any frequency or duration, pain at any site or of any nature, or sterile pyuria. The Oxford department of urology deals only with patients over 16 years of age.

The results of imaging studies and subsequently collected histology specimens were recorded via a search of the hospital results systems. Clinic letters for all patients referred for the investigation of pLUTS, rUTI, pain, or sterile pyuria were reviewed to confirm the reason for referral for FC and ascertain final management. Patients were excluded from analysis if records made at the time of FC were either incomplete, illegible, or contained an incorrect hospital number.

Diagnostic performance was defined as the number of patients who were found to have a clinically relevant abnormality at FC (bladder cancer, urethral stricture, or bladder stone) divided by the total number of patients undergoing the procedure for this indication. Microsoft Excel was used for data collection and analysis, and the Fisher exact test used for statistical comparison.

Results

Over the 1-year study period, 1809 patients underwent outpatient FC. Twenty-nine (1.6%) patients were excluded because records made at the time of FC were either incomplete, illegible, or contained an incorrect hospital number. One hundred and thirteen (6.3%) patients underwent FC for the investigation of pLUTS, rUTI, or pain, all of whom were included in the study. No patients were referred with a primary indication of sterile pyuria. Patient demographics are shown in Table 1. The remaining patients (93.7%) underwent FC for the investigation of visible hematuria (n=546), nonvisible hematuria (n=367), bladder cancer follow-up (n=666), or for other indications such as for the investigation of hemospermia or an abnormal imaging or cytology result or for ureteral stent removal (n=88). Clinically relevant abnormalities were found at FC in 13 of the patients included in this study.

Table 1.

Indications and Demographics of Patients Undergoing Flexible Cystoscopy

	All		Male		Female
Indication	Number (%)	Mean age (range)	Number (%)	Mean age (range)	Number (%)	Mean age (range)
All	1780 (100)	65.7 (17–96)	1266 (100)	63.3 (18–96)	514 (100)	66.9 (17–95)
pLUTs	70 (3.9)	59.3 (23–86)	56 (4.4)	60.9 (23–86)	14 (2.7)	52.5 (25–85)
rUTI	26 (1.5)	55.9 (17–87)	11 (0.9)	59.5 (19–87)	15 (2.8)	53.3 (17–76)
P	17 (1)	55.0 (22–78)	13 (1.0)	54.7 (23–78)	4 (0.8)	56 (22–66)

pLUTS=profound lower urinary tract symptoms; rUTI=recurrent urinary tract infection; P=pain.

The calculated diagnostic performance of FC was 11.5%, being 11.4%, 19.3%, and 0% in those referred with a primary indication of pLUTS, rUTI, and pain, respectively. Bladder cancer was diagnosed in one (0.9%) case, urethral stricture in nine (8.0%) cases, and intravesical calculi in four (3.5%) cases (Table 2). All erythematous bladder lesions identified were benign.

Table 2.

Findings at Diagnostic Flexible Cystoscopy in Male and Female Patients

		Total % (n)	pLUTS % (n)	rUTI % (n)	P % (n)
All patients
All		100 (113)	100 (70)	100 (26)	100 (17)
Significant abnormalities	Intravesical calculi	3.5 (4)	2.8 (2)	7.7 (2)	0 (0)
	Urethral stricture	8.0 (9)	7.1 (5)	15.4 (4)	0 (0)
	Malignant bladder lesion	0.8 (1)	1.4 (1)	0 (0)	0 (0)
	Total	11.5 (13)	11.4 (8)	19.2 (5)^a	0 (0)
Benign bladder lesion^b		5.3 (6)	4.3 (3)	3.8 (1)	11.8 (2)
Prostatic obstruction		37.2 (42)	48.6 (34)	7.7 (2)	35.2 (6)
Any abnormality necessitating nonmedical treatment^c		20.4 (23)	18.6 (13)	30.8 (8)	11.8 (2)
No abnormality reported		49.6 (56)	38.6 (27)	73.1 (19)	38.5 (10)
Male patients
All		100 (80)	100 (56)	100 (11)	100 (13)
Significant abnormalities	Intravesical calculi	5 (4)	3.6 (2)	18.2 (2)	0 (0)
	Urethral stricture	8.8 (7)	7.1 (4)	27.2 (3)	0 (0)
	Malignant bladder lesion	0.8 (1)	1.4 (1)	0 (0)	0 (0)
	Total	13.8 (11)	12.5 (7)	36.4 (4)^a	0 (0)
Benign bladder lesion^b		3.8 (3)	1.8 (1)	9.1 (1)	7.7 (1)
Prostatic obstruction		37.2 (42)	48.6 (34)	7.7 (2)	35.2 (6)
Any abnormality necessitating nonmedical treatment^c		20 (16)	19.6 (11)	36.3 (4)	7.7 (1)
No abnormality reported		36.3 (29)	30.4 (17)	45.5 (5)	53.8 (7)
Female patients
All		100 (33)	100 (14)	100 (15)	100 (4)
Significant abnormalities	Intravesical calculi	0 (0)	0 (0)	0 (0)	0 (0)
	Urethral stricture	6.1 (2)	7.1 (1)	6.7 (1)	0 (0)
	Malignant bladder lesion	0 (0)	0 (0)	0 (0)	0 (0)
	Total	6.1 (2)	7.1 (1)	6.7 (1)	0 (0)
Benign bladder lesion^b		9.1 (3)	14.3 (2)	0 (0)	25 (1)
Any abnormality necessitating nonmedical treatment^c		12.1 (4)	14.3 (2)	6.7 (1)	25 (1)
No abnormality reported		81.8 (27)	71.4 (10)	93.3 (14)	75 (3)

One patient had a diagnosis of both urethral stricture and intravesical calculi.

Benign bladder lesions included inflamed urothelium and lesions with abnormal appearance.

These abnormalities included procedures under general anesthesia or intermittent self-catheterization.

pLUTS=profound lower urinary tract symptoms; rUTI=recurrent urinary tract infection; P=pain.

pLUTS

Of the 70 patients who underwent FC for the investigation of pLUTS, one male patient had nonvisible hematuria in addition to pLUTS. None of the remaining patients had hematuria of any sort. The patient with nonvisible hematuria was subsequently found to have a high grade T₁ transitional-cell carcinoma. Flat erythematous intravesical lesions necessitating biopsy were identified in three other patients. Subsequent histology revealed changes in keeping with radiation change in one patient who had had previous treatment for endometrial carcinoma, and chronic inflammation in two patients. Four male patients aged 29, 67, 73, and 75 years were found to have urethral strictures, two of whom had a history of stricture. One 56-year-old woman was found to have urethral narrowing and went on to urethral dilation. Bladder calculi were diagnosed in two men aged 58 and 82 years. One of these had had previous urinary tract imaging with ultrasonography at which the stones were not identified. Two patients were unable to tolerate FC, and therefore the procedure was abandoned. At a later date, the cystoscopies were performed under general anesthesia, and no abnormalities were detected.

Overall, after FC, 18.6% of patients (n=13) went on to surgical intervention. Biopsy, however, revealed only benign changes in three patients, and two patients went on to transurethral resection of the prostate. Therefore, pathology diagnosed as a direct result of FC resulting in a change in management was found in 11.4% (n=8) of all patients and in seven males (12.5%) and in 1 female (7.1%); there was no significant difference between the proportion of men and women who had abnormalities diagnosed (P=1).

rUTI

Bladder calculi were diagnosed in two male patients aged 82 and 87 years. These calculi were visualized at ultrasonography in one case, but in the other, they were visible only on radiography of the kidneys, ureters, and bladder but not reported on ultrasonography of the urinary tract. Urethral strictures were diagnosed in three male patients aged 40, 66, and 87 years; one of these patients had a history of stricture. One patient was found to have a urethral stricture in addition to a bladder calculus. Urethral narrowing was found in one 68-year-old woman who went on to urethral dilation. Clinically relevant abnormalities diagnosed as a direct result of FC were found in 19.2 % (n=5) of these patients, 36.3% (n=4) of males, and 6.7% (n=1) of females; there was no significant difference between the proportion of men and women in whom abnormalities were diagnosed (P=0.13).

Pain

Among the 17 patients who underwent FC for the investigation of pain, none received a diagnosis of a malignant lesion, intravesical stones, or urethral stricture. All patients referred for this indication were experiencing pain in one or more of the urethra, perineum, scrotum, suprapubic, or inguinal regions. Not all pain was associated with micturition. One male patient and one female patient were found to have flat erythematous intravesical lesions without cytologic abnormality. Histology revealed normal tissue in one case and fibrosis and chronic inflammation in the second. The operation notes from these patients made no comment on their bladder capacity. No other abnormalities and no Hunner's ulcers were detected at the time of cystoscopy under general anesthesia. All other flexible cystoscopies in this group had either normal results or revealed prostatic enlargement only. No patients investigated for pain were recorded to have hematuria. After FC, 11.8% of patients went on to bladder biopsy; however, only benign changes were found.

Discussion

In this retrospective study, FC diagnosed relevant pathology in more than 10% of patients who underwent this examination for the investigation of pLUTS or rUTI. No clinically relevant abnormalities were diagnosed, however, in the 17 patients who underwent FC for the investigation of pain. In women, urethral narrowing was only found in the postmenopausal age group, and bladder calculi were only detected in men more than 58 years old. Urethral strictures, however, were found in men between the ages of 29 and 87 years.

Studies have previously examined the value of cystoscopy for the investigation of presentations other than hematuria. In 2004, Kumar and colleagues⁴ retrospectively reviewed the findings of 295 patients who underwent FC for “nonstandard” indications—ie, referrals for reasons other than bladder cancer surveillance or hematuria. They found that cystoscopy altered management in 14.1% of patients, findings similar to ours. Cancer was diagnosed in 6.1% of patients, a figure much higher than that which we observed. No attempt, however, was made to specify what referral criteria made up these nonstandard indications or whether patients also had visible or nonvisible hematuria.

Our study showed that 5% of the patients investigated (6 of 113) had erythematous bladder lesions that were confirmed to be benign. Swinn and associates⁵ found that 1 patient received a diagnosis of malignancy when biopsies were taken from erythematous patches in 23 patients with LUTS alone, and Fernando and coworkers⁶ diagnosed malignancy in 1 patient when biopsies were taken from erythematous patches in 7 patients with LUTS alone. Neither of these studies, however, recorded findings at cystoscopy other than erythematous patches for these patients with LUTS.

Other reports have focused on the use of cystoscopy for the investigation of irritative voiding symptoms in women.^7

–11 These studies have found that in the presence of nonvisible hematuria, women with irritative LUTS may be at increased risk of malignancy but absolute numbers diagnosed are low, with no more 0.6% of patients receiving a diagnosis of malignancy in any of the studies. Again, investigators did not record the presence, or absence, of other positive findings at cystoscopy in these patients.

Malignancy was only diagnosed in 1 of the 113 patients studied here. This gentleman also had a trace of hematuria on urine dipstick test. The reason for referral for FC was the pLUTS experienced by the patient, the nonvisible hematuria being subsequently identified. The patient was therefore included in the pLUTS group for the purposes of this study. It may be that this patient should have been referred for cystoscopy on the basis of the finding of nonvisible haematuria, however. Excluding this patient, no life-threatening diagnoses were made.

In previous studies, between 1% and 14% of women with recurrent UTI have been found to have an abnormality detected at cystoscopy.³ This is comparable with our results; in this study, 6.7% of women with rUTI were found to have an abnormality detected at FC. Abarbanel and associates¹² did not identify any pathology at cystoscopy in 10 men aged 16 to 45 years who had experienced UTI and visible hematuria; no other articles have investigated findings at cystoscopy in older men who have experienced UTI with or without hematuria.

No studies have sought to define the value of cystoscopy in the evaluation of pain, although findings at cystoscopy for suspected interstitial cystitis have been documented.^13,14 Positive findings at these studies include inflammation, ulceration and small bladder capacity. Although the number of patients with isolated pain in our study was small (n=17), our results suggest that very few had stones, strictures, or malignant disease. The role of FC in this population needs further assessment with a particular focus on the diagnosis of interstitial cystitis.

Pathology identified in this study necessitating further surgical intervention included intravesical calculi and urethral strictures. Fifty percent of the bladder calculi diagnosed at FC were also identified using imaging techniques. To our knowledge, there is no literature investigating the sensitivity and specificity of urinary tract ultrasonography in combination with kidneys-ureters-bladder radiography for the detection of bladder calculi in patients with a normal renal tract; our results suggest that sensitivity may be low.

Myers and colleagues¹⁵ compared renal tract ultrasonography with noncontrast CT for the detection of abnormalities in a young population with urinary tract reconstruction. They found that ultrasonographic scan had a sensitivity of only 14% for the identification of bladder calculi (with a specificity of 100%). It may be that this cannot be translated to a normal adult population; however, on the basis of this, and the failure to detect bladder calculi at ultrasonography in 50% of the bladder calculi diagnosed at FC during this study, ultrasound techniques should not be relied on to exclude bladder calculi. However, further investigation of the diagnostic performance of ultrasonography in this context may be useful, however appears twice because the number of patients analyzed here is low.

One of the limitations of this study is that we do not know if all patients presenting to the Oxford department of urology with pLUTS, rUTI, or pain went on to have a FC; referrals for FC were made on the basis of the experiences of eight different consultants. In addition, the numbers of patients studied here is small, reducing the power of statistical comparisons. A larger prospective study would be able to address these limitations.

Conclusions

In our practice, patients with pLUTS, rUTI, or pain received a diagnosis of clinically relevant abnormalities in 11.5% of cases. This study supports recently published NICE guidelines, which recommend FC in patients with pLUTS or rUTI. Of the 17 patients investigated for pain, none was found to have clinically relevant abnormalities; further larger scale studies focusing on the diagnosis of interstitial cystitis are needed to define the clinical utility of FC for this indication.

Footnotes

Disclosure Statement

No competing financial interests exist.

Abbreviations Used

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