The relationship among bladder emptying, incident acute urinary retention and all-causes mortality in men having lower urinary tract symptoms

YUEN K1, CHAN C1, TEOH J1, YEE C1, CHIU K1, LIU A1, YIP S1, TAM H2, WONG H1, WONG H1, CHAN Y1, MAK S1, LI K1, LO K1, WONG C1, LEUNG K1, HOU S1, NG C1, NG C1, LI S3, KWOK S4, SAE LO K3

Research Type

Clinical

Abstract Category

Male Lower Urinary Tract Symptoms (LUTS) / Voiding Dysfunction

Abstract 218
Male Lower Urinary Tract Symptoms 1
Scientific Podium Short Oral Session 11
Wednesday 4th September 2019
16:52 - 17:00
Hall K
Male Bladder Outlet Obstruction Benign Prostatic Hyperplasia (BPH) Nocturia Prospective Study
1.SH Ho Urology Centre, Department of Surgery, The Chinese University of Hong Kong, 2.SH Ho Urology Centre, The Chinese University of Hong Kong, 3.Prince of Wales Hospital, The Chinese University of Hong Kong, 4.Princes of Wales Hospital, The Chinese University of Hong Kong
Presenter
K

Kar Kei Steffi Yuen

Links

Abstract

Hypothesis / aims of study
Previous retrospective study suggested that men having undergone transurethral prostate surgery for treating acute urinary retention (AUR) have higher all-causes mortality compared to men of the same age structure in the general population [1]. 
This prospective study is conducted to
1) describe the incidence of AUR in a longitudinal cohort of consecutive men with initial lower urinary tract symptoms (LUTS) presented to the general urology clinic;
2) determine if similar association exists between the men who develop AUR within the study period and all-causes mortality; 
3)  determine if there is/are any parameter(s) of the lower urinary tract function to predict the incident AUR  and/or all-cause mortality
Study design, materials and methods
A cohort of 974 men (mean age 66.7; range 35–93; SD:10.15) with LUTS presented to the general urology clinic is prospectively followed.       At the clinic, they fill out International Prostate Symptoms Score (IPSS) questionnaires,  undergo uroflowmetry, have their post-void residual (PVR) checked by the bladder scan.     Arthropometric measurements,   baseline haemodynamics,  blood tests,   prostate volume measurement by transrectal ultrasound are performed.      History of diabetes mellitus (DM),  hypertension (HT), ischaemic heart disease (IHD), stroke (CVA), and peripheral vascular diseases (PVD) are taken.     The men will receive therapy (medical/surgical) for their LUTS if clinically indicated,  after evaluation by the urologists and be followed regularly afterward.         The occurrence of any AUR and information about any mortality across the study period are retrieved from the electronic medical record stored in a central territory-wide computer database.    
Parametric t-test / Kruskall-Wallis test for comparing continuous data, and Chi-square / Fisher-Exact tests for comparing categorical variables are performed, where appropriate.     The incidence rate of AUR and the overall all-cause mortality is expressed in terms of rate / 1000 person-years (py).      ROC analysis is performed to identity the cut-off values of the continuous parameter(s) that can be used to predict the occurrence of AUR / deaths, followed by the survival analysis using Kaplan-Meier point estimator method to evaluate its ability to differentiate men being at risk to develop AUR and/or all-causes mortality from the others in the same cohort. 
Categorical variables, dichotomized continuous variables will be analysed by multivariate Cox-regression hazard proportional analysis using stepwise backward LR method to determine the independent factor(s) rendering the men to develop AUR and/or to die within the study period.     Statistical analysis is performed using IBM SPSS-V.24 statistical package.       Statistical significance is taken when p<0.05.        The study is approved by the ethics and research committee.
Results
Of the 974 men, 12 men were excluded for analysis due to the presence of prostate cancer or missing data.       The remaining 962 men are stratified into groups according to their status of AUR and mortality within the study period for comparison.        Baseline characteristics, occurrence of AUR, need of prostate surgery for LUTS/AUR,  mortality status, time spanning from the first visit to the day of prostate surgery, length of follow up, all-causes mortality rate and age-specific rate of AUR are tabulated in the table attached. 
Incident AUR increases with age {Rate ratio (RR) >80yo/60-70yo = 2.50; 95%CI: 1.34-4.55, whereas RR >80yo/<60yo = 2.86; 95%CI: 1.40-5.87}.            Subjects who develop AUR within the study period also have higher overall all-causes mortality (Rate ratio : 2.20  95%CI: 1.22- 3.78) in the cohort. 
Men being able to survive and/or evade AUR across the study statistically differ from their contrasting subjects by their age, weight, systolic blood pressure, pulse pressure, medical background, LUTS quantification by IPSS, episodes of nocturia (>=3 per night), parameters of uroflowmetry, prostate size and glomerular filtration rate by Modification of Diet in Renal Disease (e-GFR MDRD).         Of note, the difference is most drastic in the volume of voided urine at baseline uroflowmetry (its magnitude differed by 40-50%).        ROC analysis showed that its value of the area under curve (AUC) to predict AUR and all-causes mortality are  0.671 (95%CI: 0.622-0.720) (p < 0.001) and 0.704 ( 95% CI: 0.649-0.760) (p<0.001) respectively.       Cut-off values of 125 ml, 175 ml, and 250 ml of voided volume are taken respectively for survival analysis to assess their ability to predict future AUR and/or all-causes mortality.       The K-M analyses are depicted in the figure attached.         Cut-off value of 250 ml is taken as <5% of men acquiring such a characteristic will develop AUR in ~ 5 years (Log-rank p=0.002).
Cox regression proportional hazard analysis showed that only age>67 (B= -0.474, SE= 0.212, Wald statistics= 5.014, p=0.025) and volume of voided urine <250ml ( B= -1.390, SE=0.286, Wald statistics= 23.658, p<0.001) are the independent variables determining AUR, whereas for all-causes mortality, their values for B, SE, Wald statistics and p-values are: -1.234, 0.269, 21.102, <0.001 for age >67y.o. ;  -0.913, 0.284,10.331, 0.001 for voided volume <250ml and -0.448, 0.239, 3.505, 0.061 for DM, respectively.
Interpretation of results
The age-specific AUR rates and the baseline variables predicting AUR of our cohort are similar to those reported  elsewhere [2] [3] except for the variable of volume of voided urine at baseline uroflowmetry during which the men are strongly encouraged to have a very full bladder before passing their urine to the flowmeter.           This act of bladder emptying may more easily tryout the maximal limits of the storage bladder function (linked to vascular health) and its voiding function (bladder contractility +/- bladder outlet obstruction).            Following that, it may unmask the failing lower urinary tract associated with the diseased status and any health insufficiency.           The volume of voided urine is cut-off at 250 ml to characterize those being able to survive and evade AUR across the study period. 
In our cohort, co-morbid medical background pre-determines impending all-cause mortality but not risk of developing AUR.                Otherwise, these two outcomes of interest share the same kinds of factors of the LUTS severity, degree of nocturia and uroflowmetry parameters.             In contrast, men more inclined to develop AUR and men more at risk of all-causes mortality differ markedly on their prostate size in our prospective cohort.            Indeed, those who died within the study period possessed the smallest average size of the prostates, which can only be reliably measured by transrectal ultrasound.         This indicates that more attention should be paid to the systemic factors that may account for the impaired bladder emptying in men whose prostates are not very enlarged. 
Of note, those who received prostate surgery during the study were operated significantly latter than those without, implicating  the need of revising the current treatment algorithm for male LUTS in regard to the merit of more early surgical intervention.              Nonetheless, nocturia, volume of voided urine at baseline uroflowmetry and prostate size are the three key parameters that are easily available when patients first present to the urology clinic.       The risk of future AUR/all-causes mortality are important in guiding the therapy at the early stage of the treatment algorithm for male-LUTS.
Concluding message
Our age-specific rate of incident AUR is similar to the others reported earlier but AUR is associated with higher all-causes mortality.           Both of them are worsened with the increasing age of the men yet  with the diminished volume of voided urine at baseline uroflowmetery.         The cut-off value is 250 ml based on its differentiating capability.         Nocturia>=3 per night has the potential to serve as the other common denominator.           In contrast, these two related but different outcomes can be discriminated by the markedly different prostate size measured by transrectal ultrasound.
Figure 1 Figure showing the probability of the men, across the study period, to evade acute urinary retention (A) in men <= 67 y.o ; (B) in men > 67y.o. and to survive all-cause mortality (C) in men <= 67 y.o. and (D) in men > 67 y.o.
Figure 2 Table showing baseline characteristics, number of acute urinary retention (AUR), number of prostate surgery, time to surgery, number of deaths, follow up time, all-cause mortality rate and age specific incidence rate of AUR in person-years (py)
References
  1. Teoh JY, Chan CK, Wang MH, Leung CH, Chan ES, Chiu PK, Yee CH, Wong HM, Hou SS, Ng CF ; Asian J Androl 2019 Jan 1, doi: 10 10.4103/aja.aja_101_18 [ Epub ahead of print ]
  2. Verhamme KMC, Dieleman JP, Wijk MAM et al., Eur Urol 2005, 47: 494 - 498
  3. Roehrborn CG, BJU Int 2006 97 Suppl 2: 7 – 11 ; discussion 21 – 22
Disclosures
<span class="text-strong">Funding</span> Research grant from Division of Urology, Departmen of Surgery, The Chinese University of Hong Kong <span class="text-strong">Clinical Trial</span> No <span class="text-strong">Subjects</span> Human <span class="text-strong">Ethics Committee</span> Ethics Committee of New Territories East Cluster <span class="text-strong">Helsinki</span> Yes <span class="text-strong">Informed Consent</span> No