Correlation between the International Prostate Symptom Score, Ultrasound Features and Maximum Flow Rate in Cameroonian Patients with Benign Prostatic Hypertrophy

Background: Benign prostatic hypertrophy is the non-malignant stromal and epithelial proliferation of the prostate gland, with or without associated anatomical enlargement of the gland and clinical symptoms. Symptomatic Benign prostatic hypertrophy may cause obstructive symptoms, irritative symptoms or both obstructive symptoms include a sensation of incomplete bladder emptying, straining to void, urinary hesitancy and weak stream while irritative symptoms include dysuria, nocturia, urinary frequency and urinary urgency. A quantitative measure of the severity of lower urinary tract symptoms due to benign prostatic hypertrophy can be obtained using the International Prostate Symptoms Score. Ultrasonography is useful for helping to determine bladder and prostate size in patients with urinary lower urinary tract symptoms. Uroflowmetry is a non-invasive test that assesses voiding func-tion. It provides valuable data on the voided volume, time is taken to reach maximum flow rate and average flow rate. The goal of this study was to im-prove prostatic enlargement suggestive of benign prostatic hypertrophy taking into account clinical, uroflowmetry and ultrasound findings. Results: A study population of 103 participants was recruited. The mean age of patients was 63.17 ± 10.26 years. Concerning the International Prostate Symptoms Score, the mean total, voiding (obstructive) and storage (irritative) scores were 14.6 ± 6.2, 8.5 ± 4.1 and 6.05 ± 2.7 respectively. The mean maximum flow rate was 13.44 ± 3.88 mL/s. The mean prostate volume was 53.71 ± 16.46 ml. A majority of patients have an enlarged prostate 1.5 to 2 times (46 to 60 mL) the upper limit for normal value. The intravesical prostatic protrusion was present in eighty-three (80.58%) and absent in 20 (19.42%). Above a prostate volume of 60 mL, 91% to 100% of our patients had intravesical prostatic protrusion. There was strong evidence (p < 0.001) that a change from no intravesical prostatic protrusion to intravesical prostatic protrusion grade 1 increased the chances of having a low maximum flow rate with a crude odds ratio of 7.98. The adjusted odds ratio after multivariate analysis was 5.26 and this remained statistically significant (p = 0.03). Conclusion: the measure of intravesical prostatic protrusion is superior to the prostate volume in the assessment of maximum flow rate and thus the follow up of patients with benign prostatic hypertrophy. This measure which is non-invasive, easy to measure, easily ac-cessible, and cost effective may be a useful tool in predicting voiding dysfunction and acute urinary retention.


Introduction
Benign prostatic hypertrophy (BPH) refers to the non-malignant enlargement of the prostate gland. Post mortem studies show a histologic prevalence of about 10% for men in their 30s, 20% for men in their 40s, going up to 50% to 60% for men in their 60s and 80% to 90% for men in their 70s and 80s [1]. It is one of the most prevalent diseases in elderly men with an incidence of 20% amongst 40 to 60 years old and 90% in men above 80 years old [2]. It is fundamental to differentiate between histologic BPH, macroscopic BPH and clinical BPH. While histologic BPH represents microscopic stromal and epithelial hyperplasia, macroscopic BPH represents an anatomical enlargement of the prostate gland from stromal and epithelial proliferation and is otherwise referred to as benign prostatic enlargement. Clinical BPH is when this is associated with symptoms [3]. Lower urinary tract symptoms (LUTS), although not exclusive to BPH, are known to be the most common clinical presentation of BPH. However, not all men with BPH develop LUTS.
Lower urinary tract symptoms in BPH are due to bladder outlet obstruction (BOO). The international prostate symptom score (IPSS) is a validated scoring system recognised by the American Urology Association to evaluate lower uri- This symptom score has 7 questions on symptoms and 1 on the quality of life.
The seven symptoms include 4 obstructive symptoms (incomplete emptying, intermittency, weak stream and straining) and 3 irritative symptoms (frequency, urgency and nocturia) [4]. Park et al. [5] in Korea and Eze et al. [6] in Nigeria showed a positive correlation between IPSS and IPP.
Uroflowmetry is a non-invasive test that assesses voiding function. Urinary flow is calculated through a flow meter, usually fitted in a commode or urinal. It provides valuable data on the voided volume, time is taken to reach maximum flow rate and average flow rate [7]. The gold standard for assessing BOO is however by pressure flow study. Pressure flow studies are invasive and have as potential complications dysuria, bleeding, urinary tract infection, sepsis and acute urinary retention [8]. However, prostate volume (PV) and intravesical protrusion (IPP) have been shown in previous studies not only to have a parallel correlation but to equally have a good correlation with bladder outlet obstruction [9]. In pressure flow studies carried out in Brazil and Singapore, IPP was shown to predict the extent of BOO [10] [11]. Meanwhile, Bassem et al. in Egypt demonstrated no correlation of the total, obstructive or irritative symptoms score with objective parameters including average flow rate, maximum flow rate (Qmax), post void residual urine and prostate size [4]. The relationship between PV and BOO has been shown to be controversial [12].
Through this study, we sought to determine the relationship between the prostate volume and intravesical prostatic protrusion, and show which one best correlates with the IPSS and maximum flow rate amongst patients with clinical BPH at the Yaounde Gynaeco-Obstetric and Paediatric Hospital. From this, we also sought to determine the usefulness of the ultrasound scan measures in the evaluation and follow up of these patients in the absence of complete urodynamic studies in a low-income country like ours.

Study Design and Participants
This is a hospital-based cross-sectional analytic study carried out over a period of five months (May 1st 2020 to September 30 th 2020) at the Yaounde Gynaeco-Obstetric and Paediatric Hospital, which is a tertiary hospital in Cameroon.

Procedure
Clinical data including uroflowmetry and biological was collected by a senior resident in urology and a urologist during out-patient consultations. The patients were then given appointments for ultrasonography. Ultrasonography was conducted by a senior resident in radiology, and a radiologist. Data collected in- The variables in our study therefore included clinical data (patient's age, international prostate symptom score, presence or absence or acute urinary retention), ultrasound measures (intravesical prostatic protrusion, post-void residual volume, prostate volume), and uroflowmetry (maximum flow rate). Structured questionnaires were pretested on 10 participants. Each questionnaire was labelled with a code rather than the patient's name to ensure confidentiality.

Results
A total of one hundred and fifty-eight (158) patients were reviewed. Of this, 55 were excluded from the study following exclusion criteria as stipulated above leaving a study population of 103 participants (Figure 1).

Socio-Demographic Characteristics of the Study Population
The mean age of our study participants was 63.17 ± 10.26 years (range 42 -103) with the median being 63 years. The most represented age was 60 to 69 years, representing 44.7% of the study participants ( Figure 2).

Clinical Features
The mean total, voiding (obstructive) and storage (irritative) scores plus or   minus standard deviation were 14.6 ± 6.2, 8.5 ± 4.1 and 6.05 ± 2.7 respectively. Table 1 lists the results of symptom score. A majority (57.3%) of our patients had moderate symptoms as shown on the table below. A majority of patients were mostly unsatisfied (score of 4) with their symptoms. No patient was delighted (score of 0) Data on AUR was missing in 3 of the 103 study participants. Ten (10%) had a history of AUR.

Uroflowmetry
The uroflow measure evaluated in our study was the maximum flow rate (Qmax). 8 of our patients had in dwelling catheters and so did not do a uroflowmetry. The mean Qmax was 13.44 ± 3.88 mL/s (range: 6.8 -20.4 mL/s). Of the 95 patients assessed, 22 (23.16%) had an abnormally low Qmax.

Ultrasound Features
The ultrasound features evaluated in our study included prostate volume, intravesical prostatic protrusion and post void residual volume.

Association between Variables
There was no association between the age of the patient and the intravesical prostatic protrusion. There was no association between patient age and prostate volume. As seen in Table 3   protrusion, the p-value was 0.11 so we cannot conclude on any relationship between these two variables.
Eight of the 103 patients had an in dwelling catheter so their Qmaxcould not be evaluated. There was no evidence of any association between the prostate volume and the maximum flow rate. Table 4 shows the correlation of individual symptoms, total voiding (obstructive) symptoms, and storage (irritative) symptoms scores relative to the objective parameters from transrectal ultrasonography (PV, IPP and PVR) and uroflowmetry (Qmax).
Logistic regression was used to find the odds of causing a low Qmax (<10 mL/s) amongst the variables which had a significant association with low Qmax (IPSS grade and IPP grade). (Table 5) Univariate analysis showed strong evidence (p < 0.001) that an increase from mild to moderate IPSS increased the probability of having a low Qmax with a crude odd ratio of 4.4. However, this relationship was not statistically significant, after adjusting the odd ratio through multivariate analysis. There was also strong evidence (p < 0.001) that a change from no IPP to IPP grade 1 increased the chances of having a low Qmax with a crude odds ratio of 7.98. The adjusted odds ratio after multivariate analysis was

Discussion
The mean age of our patients was 63.17 ± 10.3 years and the minimum age was 42. This is similar to the mean age of 64.6 ± 10.2 years and minimum age of 40 reported by Agbo et al. in Nigeria [13]. In our study, we observed a continuous rise in the patients with BPH from the 40 -49 age group to the 60 -69 age group.
Roehrborn [1], Lepor [2], Vuichoud [14] and Berry [15]. The drop in the number of patients after 70 years old in our study does not mean a fall in the incidence of BPH after this age. This is rather in line with the small proportion of ageing population in our setting owing to the life expectancy.
A majority of our patients presented with a moderate IPSS score. The mean total, voiding (obstructive) and storage (irritative) scores plus or minus standard deviation were 14.6 ± 6.2, 8.5 ± 4.1 and 6.05 ± 2.7 respectively. This is similar to the 16.7 ± 7.6, 9.8 ± 3.5 and 6.9 ± 3.3 reported by Agbo et al. [13]. Wadie et al. in Egypt [4] reported slightly higher scores of 17.53 ± 6.65, 10.15 ± 4.6 and 7.38 ± 4. Variations observed by different authors may be explained by differences in sample size, differences in delay between start of symptoms and consultation, and differences in the method of administration of the IPSS questionnaire. Ten of one hundred patients (10%) had acute urinary retention. This is about ten times the 0.7% reported by McNeill et al. [16] in a meta-analysis of 11 European studies and twice the 5.1% reported in Spain by Hunter et al. [17] This may be explained by the high proportion (80.6%) of patients with intravesical prostatic protrusion amongst our patients and the fact that IPP is associated with acute urinary retention.
The mean prostate volume amongst our patients was 53.71 ± 16.46 ml. Wadie et al. in Egypt [4], Sigdel et al. [18] in Nepal, and Lin et al. [19] in Taiwan reported a much smaller mean prostate volume of 39.7 ± 22.3 ml, 42.9 ± 18.3 ml and 39.1 ± 20.1 ml respectively. Wadie et al. [4] included all men who presented with LUTS whereas we included only patients with BPH in our study. Agbo et al. [13] reported higher mean prostate volume with a very wide standard deviation of 70.1 ± 50.3 ml.
We observed that although our patients and those of Agbo et al. [13] [13], Lin et al. [19] and Sigdel et al. [18] respectively. This might have been influenced by the fact that up to 7.8% of our patients had an indwelling catheter due to acute urinary retention and so their PVR was not evaluated. This population of patients is expected to have high PVR so not including them might have dampened our mean PVR.
Increasing the prostate volume increased the relative proportion of patients with intravesical prostatic protrusion. Furthermore, above a prostate volume of 60 mL, 91% to 100% of our patients had intravesical prostatic protrusion. This suggests that the occurrence of intravesical prostatic protrusion increases with increasing prostate size. This finding was however not statistically significant so we cannot conclude any relationship between prostate size and intravesical protrusion. While some authors [9] [13] [20] [21] have reported a parallel relationship between PV and IPP, a recent study by Lee et al. in 2017 reported a controversial relationship [12]. We found no correlation between the International prostate symptom score and the prostate volume or the intravesical prostatic protrusion. This is similar to findings of several other authors [21] [22] [23]. As stated by Wadie et al. [4] who reported similar results, such results should not be surprising as this scoring system assigns nominal values to non-nominal data which is a conceptual error. This does not in any way mean that lower urinary tract symptoms in patients with BPH are not important but that these scores should only be considered in a qualitative sense. Some authors [6] [13] [19] have however reported correlation between the IPSS and ultrasound measures. We found weak correlation with low maximum flowrate (<10 mL/s) when quality of life, obstructive symptoms score and total IPSS were taken into consideration.
Bassem et al. [4] noted no correlation between the IPSS and objective measures, including the maximum flow rate. The international prostate symptom score should therefore be used with caution in evaluating patients with BPH. We found no correlation between the prostate volume and the maximum flow rate. However, we found little correlation between the intravesical prostatic protrusion and the maximum flow rate. This suggests that the intravesical prostatic protrusion is superior to the prostate volume in the evaluation of voiding dysfunction.
Increasing from mild to moderate IPSS score and from no IPP to IPP grade I both showed a significant increase in the probability of a patient having an abnormal maximum flow rate with odds ratios of 4.4 and 8 respectively. However, after adjusting for confounders with multivariate analysis, only the presence of IPP showed a statistically significant increase in the odds of a patient having an abnormally low maximum flow rate with odds ratio of 5.26 and p-value of 0.03. Open Journal of Urology This confirms that the intravesical prostatic protrusion is superior to the prostate volume in predicting voiding dysfunction. Lieber et al. [24], Aganovic et al. [20], and Shin et al. [25], have all shown the value of the intravesical prostatic protrusion in the prediction of voiding dysfunction.
However, the odds ratio of having a low Qmax decreased as IPP grade increased. This was a surprising finding. This may bring to mind questions on aspects other than the degree of protrusion such as the base of the protrusion which was observed to be wider in some patients than others. This has not been described in literature.
However, the study has some limitations due to the fact that firstly, it was carried out with a small sample size and thus the results may not reflect the general population. Secondly, it is a cross sectional study that makes it impossible to determine a cause-effect relationship between the variables analysed.

Conclusion
The measure of intravesical prostatic protrusion is superior to the prostate volume in the assessment of maximum flow rate and thus the follow up of patients with BPH. This measure which is non-invasive, easy to measure, easily accessible, and cost effective may be a useful tool in predicting voiding dysfunction and acute urinary retention. Patients to be sent for uroflowmetry can therefore be selected based on this to reduce the cost.

Ethical Clearance
Study was approved by the institutional ethical review board

Conflicts of Interest
The authors declare no competing financial or personal interests.