Villeda-Sandoval CI; Herrera-Cáceres JO; Ruiz-Hernández JA; Castillo-de-León J; Castillejos-Molina RA; Rodriguez-Covarrubias F

Research Article

Austin J Urol. 2014;1(2): 5.

The Significance of Histological Chronic Prostatitis in Transrectal Prostate Biopsy

Villeda-Sandoval CI, Herrera-Cáceres JO, Ruiz-Hernández JA, Castillo-de-León J, Castillejos-Molina RA and Rodriguez-Covarrubias F*

Department of Urology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico

*Corresponding author: Rodriguez-Covarrubias F, Department of Urology, Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”. Vasco de Quiroga 15, Col. Sección XVI, Tlalpan 14000, Mexico City, Mexico

Received: June 21, 2014; Accepted: July 28, 2014; Published: Aug 04, 2014

Abstract

Purpose: The histological finding of chronic prostatitis (CP) has been linked to higher levels of prostatic specific antigen (PSA), prostate cancer (PCa) and lower urinary tract symptoms. However, its clinical meaning is still uncertain. We performed a retrospective analysis to determine the role of CP and its relationship to the diagnosis of PCa.

Methods: Patients undergoing prostate biopsy from January 2008 to June 2013 were selected from our database. Those with the histological finding of CP were the focus of this analysis. They were categorized depending on the presence or absence of this feature. We determined the association between CP and PCa diagnosis using univariate and multivariate analyses. Statistical significance was stated as p<0.05.

Results: 540 patients were selected. The mean age was 65 ± 7.51 years and median PSA of 7.49 ng/ml. Two groups were defined: 1) 331 patients with chronic prostatitis and 2) 209 without chronic prostatitis. No statistical differences were found between groups regarding age, PSA, IPSS score, prophylactic antibiotic use, comorbidities, alpha-blocker or 5-α-reductase inhibitor therapy, transurethral catheter at biopsy or infectious complications. Significant differences were found for previous hospitalizations, number of previous biopsies, suspicious digital prostate exam, number of cores taken, prostate volume, cancer diagnosis, percentage of positive cores and Gleason score >=7. A multivariate analysis model showed “protective” effect between CP and diagnosis of PCa (HR 0.17, p= <0.01).

Conclusion: Our results suggest that the histological finding of CP is inversely related to PCa diagnosis.

Keywords: Chronic Prostatitis; Prostate Biopsy; Prostate Cancer; Mexico

Abbreviations

ASAP: Atypical Small Acinar Proliferation; CP: Chronic Prostatitis; LUTS: Lower Urinary Tract Symptoms; NIH: National Institutes of Health; PSA: Prostate Specific Antigen; PCa: Prostate Cancer; BPH: Benign Prostatic Hyperplasia; TRPB: Trans-Rectal Prostate Biopsy; DRE: Digital Rectal Exam; MetS: Metabolic Syndrome

Introduction

From a clinical point of view, chronic prostatitis (CP) refers to a condition characterized by pelvic pain and lower urinary tract symptoms (LUTS). When confirmed histologically it is characterized by inflammatory infiltrates within prostate tissue [1]. According to the National Institutes of Health (NIH), prostatitis can be classified as type I: acute-bacterial prostatitis, type II: chronic-bacterial prostatitis, type III: chronic prostatitis/chronic pelvic pain syndrome and type IV: asymptomatic [2]. The latter presents only, as histological diagnosis without symptoms. CP has been linked to nonspecific elevation of prostate specific antigen (PSA) [3], development of prostate cancer (PCa) [4] and progression of benign prostatic hyperplasia (BPH) [5]. A transrectal prostate biopsy (TRPB) is the most common method to obtain prostatic tissue [6]. Although pelvic pain and prostatic enlargement are not indications for this procedure, it has been found that less than 5% of biopsies show significant evidence of inflammation (10 or more leukocytes per high-power field) [7]. However, the diagnosis of CP is found more often than expected in TRPB performed to rule out PCa.

The aim of our study was to assess the association of histologically confirmed CP detected in TRPB advocated to PCa diagnosis and to determine the potential role of this finding.

Material and Methods

A retrospective analysis of our institutional database of TRPB performed from January 2008 to June 2013 was performed. The procedure technique and antibiotic prophylaxis used at our Institution have been previously reported [8,9]. Only patients with complete medical records were included. Information was obtained from clinical charts including perioperative variables, histopathological reports, and follow-up data. Patients were categorized according to the presence or absence of CP on histological reports. CP was defined as “CP type IV” according to the NIH classification of prostatitis syndromes (asymptomatic inflammatory prostatitis). A comparison between groups was made to identify clinical and pathological differences. Student’s t-test for independent groups was used for continuous variables and Chi square and Mann-Whitney U tests were used for nonparametric variables. A multivariable model was created to analyze the impact of CP on the detection of PCa. A p<0.05 was determined as significant. Statistical analysis was made with the aid of SPSS® v. 17.0 (IBM®, New York) program.

Results

A total of 540 patients were included with a mean age of 65 ± 7.51 years. Median PSA was 7. 49 ng/ml. Indications for TRPB were high PSA in 63%, suspicious digital rectal exam (DRE) in 36.2%, atypical small acinar proliferation (ASAP) in 1 patient and active surveillance in another patient. Two groups were integrated: 1) 331 patients with chronic prostatitis (61.3%) and 2) 209 patients without chronic prostatitis (38.7%). Of these, 172 (31.8%) had PCa and 368 (68.2%) did not. Of the 331 patients with CP, 51 (15.4%) had simultaneous PCa. On the other hand, of the 209 without CP, 121 (57.9%) had a PCa report in pathology.

Clinical characteristics are described in Table 1. There were no differences except for previous hospital admissions (p=0.01) and number of previous biopsies (p=0.03) Features concerning indications for TRPB and histological information are summarized in Table 2 & 3, respectively. We found differences regarding suspicious DRE (p<0.01), number of biopsy cores (p<0.01), prostatic volume (p=0.04), positive core percentage (p<0.01) and Gleason score ≥7 (p<0.01). PCa was diagnosed in 57.9% and 15.4% of patients without and with CP, respectively (Table 3; p<0.01).

Table 1: Clinical variables.



  
    Variable 
    Units 
    Without Chronic    Prostatitis 
      n=209 
    With Chronic Prostatitis 
      n=331 
    p Value 
  
  
    Age (mean ± SD) 
    Years
    65.7 ± 7.8
    65.8 ± 7.4
    0.94
  
  
    PSA (median) 
    ng/dL
    7.43
    8.9
    0.52
  
  
    IPSS (mean ± SD) 
    Total
    7.8 ± 6.0
    8.6 ± 5.5
    0.38
  
  
    Diabetes mellitus 
    Yes
      No
      Unknown
    62
      144
      3
    103
      224
      4
    0.73
  
  
    Hypertension 
    Yes
      No
      Unknown
    101
      105
      3
    172
      155
      4
    0.71
  
  
    Dyslipidemia 
    Yes
      No
      Unknown
    82
      124
      3
    115
      212
      4
    0.28
  
  
    Previous/active smoking 
    Yes
      No
      Unknown
    111
      95
      3
    153
      175
      3
    0.10
  
  
    LUTS therapy (alpha-blockers) 
       
    Yes
      No
      Unknown
    129
      77
      3
    223
      104
      4
    0.19
  
  
    LUTS therapy 
      (5-ARI) 
    Yes
      No
      Unknown
    10
      196
      3
    20
      307
      4
    0.54
  
  
    Transurethral catheter at    prostate biopsy 
    Yes
      No
      Unknown
    13
      193
      3
    24
      304
      3
    0.66
  
  
    Hospitalization 1 month    before prostate biopsy 
    Yes
      No
      Unknown
    20
      186
      3
    14
      314
      3
    0.01
  
  
    Previous biopsies number 
    None
      One or more
      Unknown
    168
      38
      3
    242
      85
      4
    0.04



Table 1:  Clinical variables.

Table 2: Procedure characteristics.



  
    Variable 
     
    Without Chronic    Prostatitis 
      n=209 
    With Chronic Prostatitis 
      n=331 
    p Value 
  
  
    Antibiotic prophylaxis 
    Piperacillin/
      tazobactam
      Others
      Unknown
    194
       
      12
      3
    310
       
      17
      4
    0.76
  
  
    Number of cores taken    (mean±SD) 
    Total
    13.9 ± 3.5
    15 ± 3.6
    <0.01
  
  
    DRE suspicious of    malignancy 
    Yes
      No
      Unknown
    90
      112
      7
    99
      221
      11
    0.02
  
  
    Prostatic volume    (mean±SD) 
    cm³
    48.2 ± 31.6
    53.7 ± 27.3
    0.04
  
  
    Early infectious    complications* 
    Yes
      No
      Unknown
    12
      196
      1
    14
      317
      0
    0.41



Table 2:  Procedure characteristics.

Table 3: Histological findings.



  
    Variable 
     
    Without Chronic    Prostatitis 
      n=209 
    With Chronic Prostatitis 
      n=331 
    p Value 
  
  
    PCa diagnosis 
    Yes
      No
    121
      88
    51
      280
    <0.01
  
  
    Gleason score ≥ 7 
    <7
      ≥7
      Unknown
    86
      33
      2
    41
      9
      1
    0.18
  
  
    Atrophy 
    Yes
      No
    65
      144
    218
      113
    <0.01
  
  
    Hyperplasia 
    Yes
      No
    119
      90
    276
      5
    <0.01
  
  
    PIN/ASAP 
    Yes
      No
    15
      194
    10
      321
    0.16



Table 3:  Histological findings.

Table 4 shows multivariate analysis performed with CP, DRE, and number of cores retrieved, prostate volume, age and PSA to determine their association with diagnosis of PCa. Only age, PSA and CP remained independent predictors of PCa. Interestingly, the presence of CP had a protective effect on PCa diagnosis (HR 0.17; 95%CI [0.10–0.29]; p<0.01).

Table 4: Multivariable regression analysis. Dependent variable: cancer diagnosis.



  
    Variable 
    HR 
    95% CI 
    p Value 
  
  
    Presence of chronic prostatitis 
    0.17
    0.10-0.29
    <0.01
  
  
    Digital prostate exam 
    1.43
    0.80-2.53
    0.23
  
  
    Number of cores taken 
    0.98
    0.90-1.06
    0.59
  
  
    Prostatic volume >50    cc 
    0.58
    0.43-1.00
    0.05
  
  
    Age 
    1.04
    1.00-1.08
    0.04
  
  
    PSA 
    1.02
    1.00-1.03
    0.03



Table 4:  Multivariable regression analysis. Dependent variable: cancer diagnosis.

Discussion

Although the influence of inflammation on prostatic architecture is not well understood, different factors have been proposed as potential causes of this association, such as urinary reflux, dietary factors, estrogen or direct infections [10]. Several pro-inflammatory cytokines such as IL-15 [11], IL-18 with T-leukocyte infiltrate [12], TGF-beta [13], IFN-λ [14] and IL-8 [15] have been found to be elevated in biopsies of patients with BPH. However, no study has shown a statistically significant correlation. Some authors have proposed that treating the inflammatory processes may have a preventive role for BPH development. Di Silverio et al. [16] found that the combination of rofecoxib plus finasteride provided better short-term benefit for reducing clinical symptoms of BPH than finasteride alone.

In our series, the histological finding of CP showed a “protective” association with the diagnosis of PCa despite both groups had no statistically significant difference regarding PSA levels (Table 1). Moreover, although group 2 patients were more prone to have suspicious DRE, they had lower frequency of PCa diagnosis. De Nunzio et al. [17] conducted a review of the National Library of Medicine database from 2000 to 2012; they found that patients with chronic inflammation in prostate biopsies developed an increase of prostatic tissue and modification of prostatic architecture due to prostatic dynamic inflammatory mechanisms. Although different hypotheses relating metabolic syndrome (MetS) and BPH development were proposed, they failed to find any specific evidence to support this association. Conversely, another study found an association between MetS and architectural changes in prostatic tissue [18].

Recently, a meta-analysis [5] including 3 different databases between 2005 and 2012 found that the release of cytokines from stromal prostatic tissue could promote neo-vascularization with the subsequent development of prostatic hyperplasia. This study found a clear association between chronic prostatic inflammation, BPH development, and increasing LUTS severity. Furthermore, chronic inflammation might be a predictor of poor response to medical therapy in patients with BPH.

We also found that patients with histological chronic prostatitis had a lower frequency of PCa. This may be related with a higher frequency of prostatic hyperplasia and higher prostate size, both well-known factors associated with lower incidence of PCa. Our results contrast with recent studies suggesting an association between chronic prostatitis and pre-malignant changes in prostatic epithelium [19] and higher incidence of PCa.

Van Vuuren et al. [4] described that patients with CP had an increased frequency of urinary retention. In the present study, this relationship was not suggested because the prevalence of transurethral catheter was not affected by the presence of CP.

The reduce (Reduction by Dutasteride of prostate Cancer Events) trial [20] found that 77.6% of participants had prostatic inflammation at biopsy and a positive association between inflammation and prostate volume. In the MTOPS (Medical Therapy of Prostatic Symptom) trial, patients with acute or chronic prostatitis symptoms had larger prostates and higher PSA levels with higher progression of LUTS [21].

The interaction between inflammation and PSA levels was evaluated as well. In our series, no significant difference was found. However, previous studies have suggested that prostate inflammation plays a role in PSA elevation in PCa patients with no detectable clinical signs. Opposite results were proposed in a series of 518 patients in whom no significant difference in total to free PSA ratio was found among those with chronic prostate inflammation [22].

Previous hospitalizations are related to a higher frequency of histological chronic prostatitis. This is a novel association supporting a role for exogenous stimulus in relation to prostate inflammation. This leads to the assumption that invasive procedures in patients could increase local inflammation of the prostate. We also found that CP might be an independent factor against PCa diagnosis. This strong association is interesting, although the design of the present series does not allow us to make further conclusions. Our investigation has some limitations, including its retrospective design, which decreases the accuracy of data. Second, biopsies lacked a standardized grading for inflammatory infiltrate; and third, we used histopathological reports instead of a revision of histological slides, representing potential bias. Finally, the associations found cannot be interpreted as a cause-effect association; thus, further investigation is required to determine the impact of chronic histopathological prostatitis on the development of malignancy [23].

Perhaps, more than a protective association of CP against PCa, the former is a differential diagnosis that should be taken in consideration. Currently, type IV Prostatitis (Asymptomatic Inflammatory Prostatitis) has negligible significance. In this analysis, we found that mean PSA values were higher among patients with CP compared to patients without CP who underwent TRPB. Furthermore, an abnormal DRE was more frequent in patients without CP, suggesting that indication for biopsy in patients with CP is frequently based solely on PSA values. In addition, patients with CP had more subsequent biopsies (with a negative result for PCa), which may be explained by persistently elevated PSA in the absence of cancer.

With the previous considerations, we believe that the decision to perform a second biopsy looking for cancer in patients with CP in the first TRPB should be taken in a more conservative fashion compared to patients without CP. In conclusion, histological CP could be associated to other pathological findings in TRPB. In our series it had a “protective” association to PCa diagnosis; however the presence of CP is not related to the presence of PCa.

Disclosure

Dr. Villeda-Sandoval has nothing to disclosure.

Dr. Herrera-Cáceres has nothing to disclosure.

Dr. Ruiz-Hernández has nothing to disclosure.

Dr. Castillo-de-León has nothing to disclosure.

Dr. Castillejos-Molina reports personal fees from Lilly and GSK, outside the submitted work.

Dr. Rodriguez-Covarrubias reports personal fees from GSK and Ferring Pharmaceuticals, outside the submitted work.

Acknowledgement

Villeda-Sandoval C. participated in the design, data analysis and writing of the paper.

Herrera-Caceres JO participated in the design, acquisition of data and writing of the paper.

Ruiz-Hernandez JA participated in the acquisition of data and writing the paper.

Castillo-De-León J participated in the acquisition of data.

Castillejos-Molina R participated in the design and writing of the paper.

Rodríguez-Covarrubias F participated in the design, supervision and writing of the paper.

References

Download PDF

Citation: Villeda-Sandoval CI, Herrera-Cáceres JO, Ruiz-Hernández JA, Castillo-de-León J, Castillejos-Molina RA and Rodriguez-Covarrubias F. The Significance of Histological Chronic Prostatitis in Transrectal Prostate Biopsy. Austin J Urol. 2014;1(2): 5. ISSN:2472-3606

Instruction for Authors

Submit Your Article