Evaluation of the non-invasive indicators in predicting detrusor underactivity in individuals with small-volume prostatic hyperplasia and lower urinary tract symptoms

1. Introduction

Benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) are prevalent and globally impact the life quality of elderly males [1]. LUTS arise from factors including BPH, neurogenic bladder, bladder outlet obstruction (BOO), overactive bladder (OAB), and detrusor underactivity (DU) [2]. There is a reduction in the strength or duration of detrusor contractions in DU which results in the prolonged bladder emptying [3]. DU is challenging for the healthcare professionals and affected individuals. Presently, the pharmacological interventions are lacking in managing DU [4]. Parasympathomimetics in combination with alpha-adrenoreceptors antagonists are the common pharmacotherapies of DU, however their therapeutic impacts are limited. Potential pharmacological targets for treating DU may involve bombesin receptors, prostaglandins, adenosine triphosphate (ATP), nitric oxide (NO), calcitonin gene related peptide (CGRP), substance P (SP), nerve growth factor (NGF) and agrin-dependent pathways [5]. However, the successful treatment approaches for DU are lacking.

It is clinically imperative to precisely diagnose DU. Kim et al. [5] observed that DU pathophysiology might encompass abnormal tissue inflammation, fibrosis, denervation and apoptosis of bladder muscle tissue [6]. Vascular endothelial injury is a risk factor contributing to the development of arteriosclerosis and hypertension. Inadequate blood supply to the pelvic tissues can occur in pelvic vascular injury to result in the localized tissue fibrosis and potentially necrosis. This vascular impairment can be an underlying factor in DU occurrence [7]. Inflammation can harm the structural integrity of vascular endothelium which may impair the vascular endothelium and subsequent local tissue ischemia. This, in turn, exacerbates the organs dysfunction [8].

DU is diagnosed by the urodynamic studies, however widely accepted diagnostic criteria are lacking. Several approaches contribute to the diagnosis, wherein most assess the detrusor contraction strength, although this is one aspect of urination [9]. The projected isovolumetric pressure (PIP) determination is based on Schafer’s nomogram which assesses the detrusor pressure during bladder isovolumetric contraction. PIP formula is PIP = Pdet@Qmax + 5Qmax for men, and the PIP between 100 and 150 is the normal contractility range [10]. DU is found in 48% of men with over 70 years age compared to 9–28% in men under 50 years. In Korea, the DU prevalence is 40.2% in men with LUTS of above 65 years age. DU prevalence is recorded as 23% in an Australian study [10, 11]. The prevalence and clinical significance of DU in elderly population remains unknown because of no standard measurement techniques or quantitative diagnostic criteria. It is important to note that this examination is invasive and can cause discomfort and pain for certain patients. Herein, the objective is to utilize easily measurable serum hematological parameters or other indicators for enhancing the diagnostic precision of DU in male patients with BPH and LUTS who are unwilling or unable to undergo urodynamic examinations.

2. Methods

3. Results

A total of 196 BPH/LUTS patients were included for the urodynamic assessment where 93 were diagnosed with DU and 103 had no DU. The average age of patients’ cohort was 69.0 ± 7.3 years, wherein 70 (35.7%) individuals had hypertension and 25 (12.8%) had diabetes. Additionally, 32 (16.3%) patients had a history of cardiovascular disease while 24 (12.2%) of bladder stone. Besides, 78 (39.8%) patients had hyperlipidemic status, and 54 (27.6%) had smoking habits. Thirteen (6.6%) patients required clean intermittent catheterization (CIC). No significant differences were observed between the groups pertaining to BMI, testosterone, prostate volume, hypertension, diabetes, cardiovascular disease, bladder stone, hyperlipidemic states, smoking habits, CIC, NLR, PNI, SII, LMR or SIRI. The patients in DU group had higher age and lower PSA compared to those without DU. The baseline clinical characteristics of the cohort had been presented in Table 1. The multivariate analysis revealed that the age had an odds ratio (OR) equal to 1.06, 95% confidence interval (CI) 1.02–1.11, p = 0.004. The value of 1.06 was not that big compared to 1, but it was too strong to affirm that the age was an independent factor. Furthermore, high PSA level was a protective factor (OR 0.81, 95% CI 0.72–0.92, p = 0.001) (Table 2). As shown in Fig. 1, ROC curve for age yielded an Area Under Curve (AUC) value of 0.71. The optimal age cutoff was calculated as 66.5 years with sensitivity of 0.72 and specificity of 0.46. ROC curve for PSA yielded an AUC value of 0.37 which indicated poor discrimination. The optimal age cutoff was calculated as 2.90 ng/mL with sensitivity of 0.30 and specificity of 0.49. It was poorly discriminated according to its accuracy performance.

Fig. 1.ROC curves for the DU prediction. ROC: receiver operating characteristic; AUC: area under the curve; PSA: prostate-specific antigen; PLR: platelets to lymphocyte ratio; LMR: lymphocyte to monocyte ratio; SII: systemic immune inflammation index; SIRI: systemic inflammation response index; PNI: prognostic nutritional index; NLR: neutrophil to lymphocyte ratio.

4. Discussion

According to ICS, the underactive bladder (UAB) had a slow urinary stream, hesitancy and straining to void, with or without the feeling of incomplete bladder emptying, sometimes with storage symptoms. DU referred to the low detrusor pressure or short detrusor contraction time in combination with low urine flow rate, resulting in prolonged bladder emptying and/or failure to achieve complete bladder emptying in normal time span as measured via the urodynamic assessment. DU thus referred to the urodynamic finding of impaired bladder contraction, whereas UAB was defined as the combination of associated symptoms [15, 16]. The gold standard for diagnosing DU in clinical practice remained the urodynamic examination despite the associated risks of hematuria and urinary tract infection. No effective non-invasive index could be discovered to enhance DU diagnosis accuracy. The timely identification of DU was a challenge in the clinical management of BPH/LUTS patients. This study represented a convenient approach in investigating the prognostic significance of inflammation in BPH/LUTS patients with small PV. The objective was to identify potential independent factors for accurately predicting the DU presence. In this small-scale study, it was discovered that PSA could forecast the DU presence but with poor discrimination. Only a few pre-selected factors tested in complete blood count did not reflect that inflammation markers were not important in relation to DU. In future studies, the patient CRP, cytokines and other markers would be incorporated for examination. Based on multivariate analysis, the age and PSA were emerged as independent predictors of DU diagnosis through urodynamic studies in the patients of low PV (<50 mL). Among this subgroup of patients, the older individuals and those with lower PSA levels faced higher DU risk. DU was a prevalent condition associated with LUTS. DU etiology remained poorly understood despite its high prevalence. Additional investigations were thus imperative to explore the key risk factors contributing to DU presence [14]. Reem et al. [16] compiled the risk factors associated with DU. The study identified DU predictors including age, congenital factors, neurogenic factors and BOO. Furthermore, it highlighted that individuals with diabetes were at elevated risk of developing DU [16]. However, in this study, no significant association was observed between the diabetes and risk of developing DU. Luo et al. [6] posited that PV as a predictor could enhance the precision of diagnosing DU with optimal cutoff of 46 mL. However, in this study, the patients of low PV did not exhibit statistically significant difference in PV upon comparing DU group to the control. The data could not be compared to this study as the population herein differed—our patients were older with lower PV and PSA values. Contrary to the findings of their study, this work suggested that PSA could be regarded as a predictor having independent influence on DU occurrence. This study revealed that PSA had a role in DU diagnosis. Moreover, the non-DU group exhibited elevated PSA levels compared to those of DU. A positive correlation was observed between the levels of inflammation in prostate and PSA concentration in the bloodstream. An increase in prostate inflammation was associated with higher PSA values. Therefore, the etiology of LUTS in individuals without DU was associated with prostate inflammation. LUTS in DU group was linked to the bladder detrusor dysfunction, although with insufficient evidence. There might be an inverse relationship between inflammation and DU occurrence. Several studies had established a strong correlation between age and detrusor contractility, however the disagreement remained in the academic community. Ameda et al. [17] demonstrated no correlation between maximum detrusor pressure and age in LUTS patients. Conversely, Kullmann et al. [18] argued that detrusor contractility was weakened as age increased. In this research, ROC curve analysis revealed that 66.5 years age had the highest Youden index value. Kim et al. [7] developed a DU rat model by inducing chronic bladder ischemia through arterial damage. This model provided evidence that vascular endothelial damage was a contributor to DU [19]. Inflammation had detrimental effects on the vascular endothelium. It was thus hypothesized that the presence of inflammatory markers in bloodstream might be associated with chronic bladder ischemia which contributed to the DU presence. Previous works had investigated the correlation between inflammatory markers including NLR, PLR, SII, SIRI and PNI, and the incidence and prognosis of various tumor types [20, 21]. These indicators reflected the extent of systemic inflammation in the organism.

Shortcomings of this study included the limited number of participants and incomplete incorporation of inflammation markers. Increasing the sample size and including the healthy individuals would make the results more authentic. Besides, it would be meaningful to include investigations of inflammatory markers such as C-reactive protein (CRP) and cytokines. The hematological markers chosen for this study were over-simplified and did not provide comprehensive representation of patient’s condition. The objectives of this study were evident, and the obtained results were practical.

5. Conclusions

The diagnosis and underlying causes of DU remain unclear. The utilization of invasive diagnostic techniques in clinical settings may lead to adverse complications for patients. Our investigations have identified the age and PSA as the indicators for predicting DU presence in low PV patients. The inflammation factors can serve as the predictors to enhance DU diagnostic accuracy. Their absence in our findings can be attributed to the limited sample size. Therefore, further research is necessary to explore the association between inflammation and the risk of DU occurrence.

Availability of data and materials

All data during this research process are included in this published article.

Author contributions

YYW, JQ and ZPW—protocol development, manuscript writing. YDH and SW—data analysis. All authors read and approved the final manuscript.

Ethics approval and consent to participate

This study along with the associated procedures was conducted according to the World Medical Association Declaration of Helsinki, and the Guidelines for International Council on Harmonization and Good Practice (ICH-GCP). Protocol review, study coordination, data management, and safety monitoring were carried out through the hospital’s Clinical Research Unit. The trial was approved from the Ethics Committee of Xinhua Hospital, Shanghai Jiao Tong University School of Medicine (Ethics No. XHEC-C-2021-106-1). All the patients signed an informed consent form prior to any examination.

Acknowledgment

We would like to thank Jiatong Zhou for the work in the revision of this article.

Funding

This study was supported by National Nature Science Foundation of China (81970657), Medical and Health Project of Zhejiang Province (2023KY075), Chinese Medicine Science and Technology Plan of Zhejiang Province (2023ZL301), and Zhejiang Cancer Hospital Science Fund for Young Scholars (2917).

Conflict of interest

The authors declare no conflict of interest.