Histological prostatitis and its influence on benign prostatic hyperplasia: a systematic review and meta-analysis

Abstract

Background

Inflammation is considered one of the potential etiological factors in the development and progression of benign prostatic hyperplasia (BPH). However, whether inflammation plays a critical role in the onset or progression of BPH remains controversial. Therefore, we conducted this systematic review and meta-analysis to comprehensively evaluate the impact of histological prostatitis on BPH.

Methods

We systematically searched cohort and cross-sectional studies published up to April 2025 in PubMed, the Cochrane Library, Embase, and Web of Science. The quality of the included cohort studies was assessed using the Newcastle-Ottawa Scale (NOS), and cross-sectional studies was evaluated with the Joanna Briggs Institute (JBI) checklist. Data were extracted on prostate volume (PV), International Prostate Symptom Score (IPSS), prostate-specific antigen (PSA), maximum urinary flow rate (Qmax), and residual urine volume (RUV). The effect sizes were pooled using the weighted mean difference (WMD) with corresponding 95% confidence intervals (CIs).

Results

A total of 11 studies were included, comprising 6 cohort studies and 5 cross-sectional studies, with a combined sample of 3,135 patients. In cross-sectional studies, compared with patients with BPH alone, those with BPH combined with histological prostatitis had an increase of 1.50 ng/mL in PSA level (95% CI: 0.09 to 2.91; I²=91%; P<0.05), an increase of 3.92 points in IPSS score (95% CI: 2.20 to 5.64; I²=28%; P<0.00001), and an increase of 13.78 mL in PV (95% CI: 10.00 to 17.56; I²=0%; P<0.00001). Qmax decreased by 1.56 mL/s (95% CI: −3.44 to 0.32; I²=80%; P=0.10), with no statistically significant difference. In cohort studies, compared with patients with BPH alone, those with BPH combined with histological prostatitis showed an increase of 1.19 ng/mL in PSA level (95% CI: 0.37 to 2.02; I²=28%; P<0.05), an increase of 10.24 mL in PV (95% CI: 0.79 to 19.69; I²=89%; P<0.05), and a decrease of 2.42 mL/s in Qmax (95% CI: −3.44 to −1.40; I²=65%; P<0.00001). Changes in IPSS (95% CI: −1.33 to 6.22; I²=97%; P=0.20) and RUV (95% CI: −1.66 to 18.07; I²=39%; P=0.10) were not statistically significant.

Conclusions

Histological prostatitis may play a promoting role in the progression of BPH. Compared to patients with BPH alone, those with coexisting histological prostatitis exhibited higher PSA levels, higher IPSS, larger PV, and lower Qmax. Therefore, the clinical significance of histological prostatitis should not be overlooked, and it ought to be considered as an important factor in the clinical management of urological patients. Future large-scale prospective studies are warranted to clarify its role in the pathogenesis of BPH.

Highlight box.

Key findings

• Histological prostatitis is associated with increased prostate-specific antigen (PSA), prostate volume (PV), International Prostate Symptom Score (IPSS), residual urine volume (RUV), and decreased Qmax in benign prostatic hyperplasia (BPH) patients, suggesting it may promote BPH progression.

What is known and what is new?

• Inflammation has been suspected as a contributing factor in BPH, but evidence has been inconsistent.

• This meta-analysis provides quantitative evidence linking histological prostatitis to multiple clinical and functional changes in BPH patients.

What is the implication, and what should change now?

• Histological prostatitis significantly influences BPH characteristics and progression.

• Inflammation should be considered in the clinical evaluation and management of BPH. Anti-inflammatory strategies may merit further investigation.

Introduction

Benign prostatic hyperplasia (BPH) is a common chronic and progressive urological disorder among elderly men, typically occurring in individuals over the age of 40 years. With the aging of the population, the prevalence of BPH continues to rise: approximately 20% in men over 40 years, 60–70% in men over 60 years, 80% in men over 70 years, and as high as 90% in men aged 90 years and above (1). Anatomical changes in the urethra caused by BPH can result in elevated bladder pressure, leading to lower urinary tract symptoms (LUTS). Storage symptoms mainly include urinary frequency, urgency, nocturia, and urge incontinence; voiding symptoms involve hesitancy, weak stream, and intermittency; and post-voiding symptoms include incomplete emptying and post-micturition dribbling (2). These symptoms significantly impair patients’ quality of life.

Although the molecular mechanisms underlying the abnormal proliferation of epithelial and stromal cells in the prostate remain unclear, current evidence suggests that BPH is associated with multiple factors, including hormonal dysregulation, chronic inflammation, dysregulation of growth factors, and an imbalance between cell proliferation and apoptosis. Histological prostatitis is defined as a pathological diagnosis based on the identification of inflammatory cell infiltration in prostate tissue samples under microscopic examination. Compared with diagnostic methods based on clinical symptoms, this approach allows for a direct visualization of the distribution of inflammatory cells and the structural alterations of the tissue, offering higher specificity and sensitivity. In recent years, inflammation has received increasing attention as a potential etiological factor in BPH (3-6). One study involving cytological and immunohistochemical analysis of 283 BPH patients found that 81% had T lymphocyte markers (CD3), 52% had B lymphocyte markers (CD20), and 82% had macrophage markers (CD163) (7). Additionally, the study demonstrated that patients with higher-grade prostatic inflammation had significantly larger prostate volumes (PVs) and higher International Prostate Symptom Scores (IPSS) than those with lower-grade inflammation. Another retrospective study of 196 BPH patients who underwent transurethral resection of the prostate (TURP) found that those with coexisting histological prostatitis had a higher incidence of acute urinary retention (AUR), larger PV, and more severe LUTS. However, no significant differences were observed in IPSS, residual urine volume (RUV), or maximum urinary flow rate (Qmax) between the two groups (8).

Our study aimed to provide an updated overview of the impact of histological prostatitis on BPH by evaluating current clinical research data, thereby offering more accurate insights into the uncertainties surrounding this potential risk factor. The study was registered with PROSPERO (Registration ID: CRD420251014985). We present this article in accordance with the PRISMA and MOOSE reporting checklists (available at https://tau.amegroups.com/article/view/10.21037/tau-2025-421/rc) (9).

Methods

Search strategy

We systematically searched the PubMed (Table S1), Cochrane Library (Table S2), Embase (Table S3), and Web of Science (Table S4) databases for cohort and cross-sectional studies investigating the association between histological prostatitis and BPH, from database inception to April 2025. A comprehensive search strategy combining Medical Subject Headings (MeSH) and free-text terms was employed. Search terms included “Prostatic Hyperplasia”, “Inflammation”, “Cohort Studies”, “Cross-Sectional Studies”, and their related synonyms. In addition, we manually screened the reference lists of included studies and searched relevant clinical trial registries to identify potentially eligible studies. Only human studies published in English were included.

Study selection

The screening process was conducted in two stages: initial screening of titles and abstracts to eliminate studies that were clearly ineligible, followed by full-text evaluation for eligibility. Two researchers independently performed the screening, and any disagreements were resolved through discussion with a third reviewer. The inclusion criteria were as follows: (I) study design was a cohort or cross-sectional study published in English; (II) participants were diagnosed with BPH by histopathological examination, with or without histological prostatitis (histological prostatitis is diagnosed and graded histopathologically based on the number or density of inflammatory cells, the extent or distribution of inflammatory cell infiltration, and the anatomical location of the inflammation), regardless of nationality or ethnicity; (III) the study reported at least one of the following outcome measures: PV, IPSS, prostate-specific antigen (PSA), Qmax, or RUV. Studies were excluded if they were duplicate publications or had a sample size of fewer than 10 participants.

Data extraction

For the studies ultimately included, two reviewers independently extracted data using a standardized data extraction form. The extracted data mainly included the following information: first author, publication date, study period, study design, PV, IPSS, PSA, Qmax, and RUV.

Level of evidence and quality assessment

The quality of cohort studies was assessed using the Newcastle-Ottawa Scale (NOS) (10), while cross-sectional studies were evaluated using the Joanna Briggs Institute (JBI) checklist (11) . The quality assessment was independently performed by two reviewers, and any disagreements were resolved through discussion with a third reviewer.

Statistical analysis

Meta-analyses of the included cohort and cross-sectional studies were performed separately using RevMan 5.4.1 software. According to the methods proposed by Wan and Luo et al. (12,13), data reported as medians and interquartile ranges (IQRs) were converted into means ± standard deviations (means ± SD) to facilitate comparability and pooled analysis across studies (as the sample sizes were relatively large and the data were approximately normally distributed, the accuracy of the conversion was considered high).The weighted mean difference (WMD) and its 95% confidence interval (95% CI) were used to pool effect estimates. A P value <0.05 was considered statistically significant.

Given the potential heterogeneity among the included studies in terms of design and population characteristics, a random-effects model was applied for all pooled analyses to enhance generalizability. Heterogeneity was assessed using the I² statistic, with I² values of 25–50% indicating moderate heterogeneity, 50–75% substantial heterogeneity, and >75% considerable heterogeneity. Sensitivity analysis was conducted using Stata 14.0 software by sequentially excluding individual studies (leave-one-out method). Due to the limited number of included studies, subgroup analyses to explore potential sources of heterogeneity could not be conducted, and the Begg’s test could not be reliably performed to assess publication bias.

Results

Search result

A total of 433 relevant studies were identified through database searches and citation searching, of which 85 were duplicates. After screening the titles, abstracts, and full texts of the remaining 348 studies, 11 studies met the inclusion criteria. The study selection process followed the PRISMA guidelines and is illustrated in Figure 1.

Figure 1.

Flow diagram of the literature search process based on PRISMA guidelines.

Study characteristics

A total of 11 studies were included in this systematic review, comprising 5 cross-sectional studies and 6 cohort studies, with a combined total of 3,135 patients. The basic characteristics of the included studies are summarized in Table 1. Among them, 8 studies evaluated the effect of histological prostatitis on PSA levels (8,14-19,22); 8 studies reported changes in IPSS (8,14-18,21,23); and 8 studies assessed changes in PV (8,14-18,20,22). In addition, 4 studies evaluated Qmax (8,14,15,23), and another 3 studies reported post-void RUV (8,18,22). A total of nine studies obtained prostate tissue samples through TURP (8,14-20,22), one study obtained specimens via suprapubic prostatectomy (SPP) (20), and two studies used samples collected via transurethral plasmakinetic resection of the prostate (TUPKRP) (21,23). In all included studies, histological prostatitis was diagnosed based on histopathological assessment of inflammatory cell infiltration, and the degree of prostatic inflammation was graded accordingly. However, the grading criteria varied across studies, as summarized in Table 1.

Table 1. Main characteristics of the included studies.

Study	Design	Country	Sample collection method	Grade of inflammation	Sample size	RUV (mL)	Qmax (mL/s)	PV (mL)	IPSS	PSA (ng/mL)
Jiang 2015 (14)	Cross-sectional studies	China	TURP	Mild-inflammatory, moderate-inflammatory and severe-inflammatory	BPH with HP 45	220±40.8	5.40±1.10	66.90±14.50	25.80±5.70	5.10±1.30
					BPH without HP 15	157.5±21.1	7.80±1.20	54.40±18.70	23.70±4.50	3.10±1.20
Kim 2013 (15)	Cross-sectional studies	Korea	TURP	Classified into three grades (Grade I, II, and III) based on severity	BPH with HP 181	–	9.20±4.87	49.20±23.80	23.17±6.72	4.93±6.27
					BPH without HP 44	–	9.66±4.69	36.00±11.40	19.14±7.30	3.22±5.91
Cao 2017 (16)	Cross-sectional studies	China	TURP	Classified into three grades (Grade I, II, and III) based on severity	BPH with HP 110	–	–	50.76±20.61	21.15±5.34	4.91±3.56
Inamura 2018 (17)	Cohort studies	Japan	TURP	Mild-inflammatory, moderate-inflammatory and severe-inflammatory	BPH without HP 10	–	–	32.23±16.55	15.89±3.56	2.36±2.06
					BPH with HP 177	101.1±110.8	9.00±4.20	57.80±30.60	19.10±8.30	5.09±4.28
					BPH without HP 2	90±0.0	7.60±0.00	32.50±12.10	16.00±0.00	1.75±1.80
Hu 2015 (18)	Cohort studies	China	TURP	Mild-inflammatory, moderate-inflammatory and severe-inflammatory	BPH with HP 55	62.94±36.77	–	66.61±30.91	24.25±3.06	4.56±4.64
					BPH without HP 51	60.38±41.58	–	49.34±31.43	25.31±3.14	4.34±4.50
Di Silverio 2003 (19)	Cross-sectional studies	Italy	TURP	Mild-inflammatory, moderate-inflammatory and severe-inflammatory	BPH with HP 721	–	–	–	–	5.20±3.10
					BPH without HP 743	–	–	–	–	5.10±2.80
Wu 2011 (20)	Cross-sectional studies	China	TURP or SPP	–	BPH with HP 60	–	–	62.70±26.60	–	–
					BPH without HP 34	–	–	49.20±22.90	–	–
Li 2022 (8)	Cohort studies	China	TURP	Classified into three grades (Grade I, II, and III) based on severity	BPH with HP 154	78.73±95.16	9.23±3.25	61.19±23.84	23.94±2.54	6.36±5.33
					BPH without HP 42	56.86±29.81	11.05±2.91	52.28±11.66	21.86±3.63	5.52±4.14
Wang 2013 (21)	Cohort studies	China	TUPKRP	–	BPH with HP 40	–	–	–	20.50±7.12	–
					BPH without HP 40	–	–	–	18.65±5.72	–
Cakir 2018 (22)	Cohort studies	Turkey	TURP	Mild-inflammatory, moderate-inflammatory and severe-inflammatory	BPH with HP 154	69.27±48.12	–	57.10±6.80	–	3.80±4.40
					BPH without HP 274	64.21±42.70	–	57.50±11.30	–	2.50±1.80
					BPH with HP 113	–	5.33±2.46	–	23.57±3.44	–
Zhang 2020 (23)	Cohort studies	China	TUPKRP	Mild-inflammatory, moderate-inflammatory and severe-inflammatory	BPH without HP 70	–	8.20±2.10	–	16.75±3.92	–

BPH, benign prostatic hyperplasia; HP, histological prostatitis; IPSS, International Prostate Symptom Score; PSA, prostate specific antigen; PV, prostate volume; Qmax, maximum urinary flow rate; RUV, residual urine volume; SPP, suprapubic prostatectomy; TURP, transurethral resection of the prostate; TUPKRP, Transurethral Plasmakinetic Resection of the Prostate.

Quality assessment

The quality of the six included cohort studies was assessed using the NOS (Table 2), with total scores ranging from 6 to 9. Among them, five studies scored ≥7 and were rated as high quality, while one study scored 6 and was considered of moderate quality. The five included cross-sectional studies were assessed using the JBI critical appraisal tool (Table 3). Among these, three studies had “yes” responses for most items, indicating no significant risk of bias and were rated as high quality. The remaining two studies had some items rated as “no” or “unclear”; however, the overall risk of bias was deemed acceptable, and these studies were rated as moderate quality.

Table 2. Quality assessment of cohort studies.

Study	Selection					Comparability		Outcome			Overall NOS scores
	Is the case definition adequate?	Representativeness of the cases	Selection of controls	Definition of controls		Comparability of cases and controls on the basis of the design or analysis		Ascertainment of exposure	Same method of ascertainment for cases and controls	Non-response rate
Inamura 2018 (17)	★	★	★	★		★		★	★	★	8
Hu 2015 (18)	★	★	★	★		★		★	★	–	7
Li 2022 (8)	★	★	★	★		★★		★	★	–	8
Wang 2013 (21)	★	★	★	★		★		★	–	–	6
Cakir 2018 (22)	★	★	★	★		★★		★	★	–	8
Zhang 2020 (23)	★	★	★	★		★★		★	★	★	9

“★” indicates “yes”. NOS, Newcastle-Ottawa Scale.

Table 3. Quality assessment of Cross-sectional study.

Study	Were the criteria for inclusion in the sample clearly defined?	Were the study subjects and the setting described in detail?	Was the exposure measured in a valid and reliable way?	Were objective, standard criteria used for measurement of the condition?	Were confounding factors identified?	Were strategies to deal with confounding factors stated?	Were the outcomes measured in a valid and reliable way?	Was appropriate statistical analysis used?	Overall appraisal
Jiang 2015 (14)	No	Yes	Yes	Yes	Yes	No	Yes	Unclear	Include
Kim 2013 (15)	Yes	Yes	Yes	Yes	No	No	Yes	Yes	Include
Cao 2017 (16)	Yes	Yes	Yes	Yes	Yes	No	Yes	Yes	Include
Di Silverio 2003 (19)	Yes	Yes	Yes	Yes	Yes	No	Yes	Yes	Include
Wu 2011 (20)	Yes	Yes	Yes	Yes	Yes	No	Yes	Yes	Include

Meta-analysis

PSA

A total of four cross-sectional studies (14-16,19), including 1,869 patients, reported differences in PSA levels between patients with BPH and those with BPH combined with histological prostatitis. The meta-analysis showed that patients with BPH and histological prostatitis had significantly higher PSA levels than those with BPH alone, with a mean difference of 1.50 ng/mL (95% CI: 0.09 to 2.91; P<0.05; Figure 2A). Substantial heterogeneity was observed (I²=91%; P<0.00001). In addition, four cohort studies (8,17,18,22), involving 909 patients, also reported differences in PSA levels between the same two groups. The meta-analysis revealed that PSA levels were, on average, 1.19 ng/mL higher in patients with BPH and histological prostatitis compared to those with BPH alone (95% CI: 0.37 to 2.02; P<0.05; Figure 2B). No substantial heterogeneity was observed (I²=28%; P=0.24).

Figure 2.

Forest plots of the difference in PSA levels between patients with BPH and those with BPH combined with HP. (A) Cross-sectional studies; (B) cohort studies. BPH, benign prostatic hyperplasia; CI, confidence interval; HP, histological prostatitis; IV, inverse variance; PSA, prostate-specific antigen; SD, standard deviation.

IPSS

Three cross-sectional studies (14-16), including a total of 405 patients, reported differences in IPSS between patients with BPH and those with BPH combined with histological prostatitis. The meta-analysis showed that patients with BPH and histological prostatitis had significantly higher IPSS scores compared to those with BPH alone, with a mean difference of 3.92 points (95% CI: 2.20 to 5.64; P<0.00001; Figure 3A). No substantial heterogeneity was observed (I²=28%; P=0.25). In addition, four cohort studies (8,17,21,23), involving a total of 565 patients, also reported differences in IPSS scores between the two groups. The meta-analysis revealed that patients with BPH and histological prostatitis had IPSS scores 2.44 points higher on average than those with BPH alone, but the difference was not statistically significant (95% CI: −1.33 to 6.22; P=0.20; Figure 3B). Substantial heterogeneity was observed (I²=97%, P<0.00001).

Figure 3.

Forest plots of the difference in IPSS between patients with BPH and those with BPH combined with HP. (A) Cross-sectional studies; (B) cohort studies. BPH, benign prostatic hyperplasia; CI, confidence interval; HP, histological prostatitis; IPSS, International Prostate Symptom Score; IV, inverse variance; SD, standard deviation.

PV

A total of four cross-sectional studies (14-16,20), involving 499 patients, reported differences in PV between patients with BPH and those with BPH combined with histological prostatitis. The meta-analysis showed that the PV in patients with BPH and histological prostatitis was, on average, 13.78 mL greater than in those with BPH alone (95% CI: 10.00 to 17.56; P<0.00001; Figure 4A). No substantial heterogeneity was observed (I²=0%, P=0.84). Another four cohort studies (8,17,18,22), including 909 patients, also reported similar differences. The meta-analysis revealed that the PV in patients with BPH and histological prostatitis was, on average, 10.24 mL larger than in patients with BPH alone (95% CI: 0.79 to 19.69; P<0.05; Figure 4B). Substantial heterogeneity was observed (I²=89%, P<0.00001).

Figure 4.

Forest plots of the difference in PV between patients with BPH and those with BPH combined with HP. (A) Cross-sectional studies; (B) cohort studies. BPH, benign prostatic hyperplasia; CI, confidence interval; HP, histological prostatitis; IV, inverse variance; PV, prostate volume; SD, standard deviation.

Qmax

A total of two cross-sectional studies (14,15), including 285 patients, reported differences in Qmax between patients with BPH and those with BPH combined with histological prostatitis. The meta-analysis showed that Qmax was, on average, 1.56 mL/s lower in patients with histological prostatitis compared to those with BPH alone, but the difference was not statistically significant (95% CI: −3.44 to 0.32; P=0.10; Figure 5A). Substantial heterogeneity was observed (I²=80%; P=0.03). Additionally, two cohort studies (8,23), including 379 patients, also reported differences in Qmax. The meta-analysis showed that Qmax was, on average, 2.42 mL/s lower in patients with BPH and histological prostatitis than in those with BPH alone (95% CI: −3.44 to −1.40; P<0.00001; Figure 5B). Substantial heterogeneity was observed (I²=65%, P=0.09).

Figure 5.

Forest plots of the difference in Qmax between patients with BPH and those with BPH combined with HP. (A) Cross-sectional studies; (B) cohort studies. BPH, benign prostatic hyperplasia; CI, confidence interval; HP, histological prostatitis; IV, inverse variance; Qmax, maximum urinary flow rate; SD, standard deviation.

RUV

A total of three cohort studies (8,18,22) involving 730 patients reported differences in postvoid RUV between patients with BPH and those with BPH combined with histological prostatitis. The meta-analysis showed that RUV was on average 8.20 mL higher in BPH patients with histological prostatitis compared to those with BPH alone, but the difference was not statistically significant (95% CI: −1.66 to 18.07, P=0.10; Figure 6). No substantial heterogeneity was observed (I²=39%; P=0.19).

Figure 6.

Forest plot of the difference in RUV between patients with BPH and those with BPH combined with HP (cohort studies). BPH, benign prostatic hyperplasia; CI, confidence interval; HP, histological prostatitis; IV, inverse variance; RUV, residual urine volume; SD, standard deviation.

Sensitive analysis

For meta-analyses with high heterogeneity (I²>50%), sensitivity analysis was conducted using a leave-one-out method. The results showed that exclusion of any single study did not significantly alter the 95% confidence interval of the pooled effect size, indicating good robustness of the findings (Figure 7).

Figure 7.

The results of the sensitivity analysis of the included studies. (A) Cross-sectional studies on PSA; (B) cohort studies on IPSS; (C) cohort studies on PV. CI, confidence interval; IPSS, International Prostate Symptom Score; PSA, prostate-specific antigen; PV, prostate volume.

Discussion

Our findings suggest that histological prostatitis may aggravate BPH. Compared with patients with BPH alone, those with BPH combined with histological prostatitis exhibited significantly higher levels of PSA, higher IPSS, larger PV, and lower Qmax.

In recent years, an increasing number of studies have investigated the association between prostatitis and BPH (6,24-27). However, meta-analyses in this field remain limited. A systematic review and meta-analysis published in 2020 reported a correlation between prostatitis and BPH, which indicates that prostatitis may substantially increase the risk of developing BPH (28).

Although the pathogenesis of BPH remains unclear in certain aspects, the pivotal role of prostatitis in its development and progression has garnered increasing attention. Numerous studies have demonstrated that inflammatory cytokines within prostatic tissue play a significant role in the pathophysiology of BPH (5,24,29-31). However, the specific impact of prostatitis on clinical parameters in BPH patients, such as PV, IPSS, PSA, Qmax, and RUV, has not been systematically investigated. Therefore, further research is needed to clarify the influence of prostatitis on clinical symptoms and relevant diagnostic findings in patients with BPH.

This study included both cross-sectional and cohort studies investigating the relationship between BPH and histological prostatitis, with a specific focus on the association between histological prostatitis and BPH, which distinguishes it from previous research. A meta-analysis conducted in 2020 did not classify prostatitis subtypes and included patients with acute bacterial prostatitis, chronic bacterial prostatitis, chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), and asymptomatic prostatitis. Given the different pathophysiological mechanisms of these subtypes (32), their impact on BPH may vary. The authors of that study also acknowledged that this heterogeneity could affect the results.

In contrast, our study included only patients with clearly diagnosed histological prostatitis, including five published cross-sectional studies and six cohort studies. The 2020 study, by comparison, included only one case-control study (33) and one cohort study (34), resulting in limited statistical power and reduced reliability of its conclusions. Our meta-analysis, with a greater number of included studies, demonstrated higher statistical power and more stable pooled effect estimates, thus providing more convincing evidence.

Furthermore, the 2020 study explored only the correlation between prostatitis and BPH, without further evaluating the effects of prostatitis on specific clinical parameters such as IPSS, PSA, and Qmax. In our study, we systematically assessed the impact of histological prostatitis on multiple clinical indicators in patients with BPH, including PV, IPSS, PSA, Qmax, and RUV.

Although not all BPH patients present with significant prostate enlargement, PV remains a critical parameter that warrants attention (1). IPSS is the most commonly used and widely accepted tool for evaluating LUTS in BPH patients. It reflects both storage and voiding symptoms, as well as the impact on quality of life, and is also used to assess symptom severity (35). Moreover, PSA levels are positively correlated with the number of BPH cells (36), making the evaluation of histological prostatitis’s influence on PSA clinically meaningful. Qmax is useful in determining the presence of urethral narrowing or obstruction, while RUV reflects the degree of urinary obstruction; increased RUV is closely associated with the progression of obstruction (37). Together, these parameters offer a comprehensive assessment of BPH severity.

This meta-analysis primarily focused on clinical parameters in patients with BPH and did not extensively investigate inflammatory cytokines or related signaling pathways. Nevertheless, accumulating evidence suggests that the occurrence and progression of BPH may be closely associated with inflammation, involving inflammatory cytokines such as IL-8, IL-2, IL-15, IL-17, and IL-6, as well as key signaling pathways including transforming growth factor-beta (TGF-beta) and NF-κB (5,24-27). For instance, some studies reported that IL-8 levels may be associated with an increased risk of acute urinary retention in BPH patients (38). Therefore, future research should further explore the impact of inflammatory cytokines and related signaling pathways on clinical parameters such as PSA, PV, Qmax, and IPSS, to more comprehensively elucidate the role of inflammation in the development and progression of BPH. Clinically, for patients who respond poorly to α-adrenergic blockers or 5α-reductase inhibitors and present with elevated PSA, high IPSS, reduced Qmax, or increased RUV, assessment of histological prostatitis may be considered as part of the BPH diagnostic and management process, which could help achieve more precise disease stratification and individualized treatment.

This study has several limitations. First, some results exhibited statistical heterogeneity, which may be attributed to the following factors: (I) differences in study populations: The included studies involved participants from various countries and regions, whose genetic backgrounds, lifestyles, and dietary habits differed. These factors may influence the degree of prostatic inflammation and the progression of BPH, thereby affecting the results. (II) Differences in age distribution: as the included studies were observational in design (cross-sectional and cohort studies), there were no strict age inclusion criteria. Given that age can affect the occurrence of prostatic inflammation and BPH progression, variations in age distribution across studies may increase heterogeneity in the pooled analysis. (III) Differences in histological grading criteria: currently, there is no standardized histological grading system for prostatitis. All included studies diagnosed histological prostatitis based on the presence of inflammatory cells, but the specific grading methods varied. Therefore, subgroup analyses according to the severity of inflammation could not be performed. (IV) Differences in prostate tissue acquisition methods: Among the included studies, most obtained prostate tissue via TURP, one study used SPP, and two studies used TUPKRP. TURP specimens were often fragmented, and mechanical and monopolar electrocautery-induced thermal damage was more pronounced, which may affect the morphology of inflammatory cells and the integrity of glandular structures. In contrast, SPP specimens were more intact, with less mechanical and thermal damage, allowing better preservation of histological details. TUPKRP specimens exhibited mechanical and thermal damage levels intermediate between TURP and SPP. Overall, although different surgical approaches may have some impact on the observation of prostatic inflammatory cells and glandular structures, this effect is relatively limited. (V) Differences in study types and sample size distribution: for example, in cohort studies, differences in IPSS and RUV were not statistically significant, whereas in cross-sectional studies, they were significant. In contrast, Qmax differences were significant in cohort studies but not in cross-sectional studies. This discrepancy may be related to the inherent characteristics of the study designs. In addition, the numbers of included cross-sectional and cohort studies differed, resulting in differences in total sample sizes between the two study types, which may have led to variations in statistical power and consequently produced different results. Second, due to the limited number of included studies, Egger’s test and funnel plots could not be performed to assess publication bias, so the presence of such bias cannot be excluded. Third, only studies published in English were included. While this approach may help ensure the quality of the studies and the accuracy of data interpretation, and may reduce heterogeneity to some extent, it may also exclude relevant non-English studies, potentially introducing language bias.

Conclusions

In summary, this meta-analysis systematically evaluated the impact of histological prostatitis on BPH. The results showed that, compared with patients with BPH alone, those with coexisting histological prostatitis exhibited higher PSA levels, more severe IPSS scores, larger PV, and lower Qmax. These findings suggest that inflammation may play an important role in the development and progression of BPH. In clinical practice, the influence of inflammatory factors should be fully considered when assessing BPH patients, and potential anti-inflammatory interventions may be explored in addition to conventional treatment strategies to improve patient outcomes. However, all studies included in this analysis were observational, and the potential influence of confounding factors has not been fully eliminated, so the conclusions should be interpreted with caution. Future research with larger sample sizes and prospective designs is needed to further elucidate the role of inflammation in BPH and to explore inflammatory cytokines or signaling pathways as potential therapeutic targets. Histological prostatitis may be an important factor in the development and progression of BPH, and incorporating its assessment into BPH risk and disease evaluation could provide new insights for precise disease stratification and individualized treatment in clinical practice.

Supplementary

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Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.