Stesura Seveso 353Archivio Italiano di Urologia e Andrologia 2020; 92, 4 ORIGINAL PAPER No conflict of interest declared. DOI: 10.4081/aiua.2020.4.353 How urologists deal with chronic prostatitis? The preliminary results of a Mediterranean survey Konstantinos Stamatiou 1, Vittorio Magri 2, Gianpaolo Perletti 3, Evangelia Samara 1, Georgios Christopoulos 1, Alberto Trinchieri 4 1 Urology Department, Tzaneion Hospital, Piraeus, Greece; 2 Urology Secondary Care Clinic, ASST-Nord, Milan, Italy; 3 Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy; Faculty of Medicine and Medical Sciences, Ghent University, Ghent, Belgium; 4 Manzoni Hospital, Lecco, Italy. being characterized by symptoms of pelvic, genital and suprapubic pain, often associated with lower urinary tract symptoms (LUTS) and sexual dysfunction. It is an easy to suspect, hard to prove condition. In fact, evalua- tion and diagnosis of chronic prostatitis (CP) can be con- fusing and challenging. Although the Meares-Stamey (MS) 4-glass test is the standard method of assessing inflammation and the presence of bacteria in the prostate, it is time consuming and not accurate enough to give a clear diagnosis of bacterial prostatitis. For this reason, it was not universally employed by urologists. However, it is not known to which extent is infrequent- ly used by Greek urologists and which diagnostic tests they perform in affected patients alternatively to the MS test. In order to examine Greek healthcare professionals' preferences for diagnostic investigation and testing for CP, we performed a questionnaire survey. Responses were compared with the ones given by Italian counter- parts in an attempt to assess similarities or differences in the diagnostic approaches to chronic prostatitis syn- dromes in Southern European Mediterranean countries. MATERIALS AND METHODS We translated the original Italian questionnaire presented by Magri and Montanari in Milan on 26 October 2018 and validated its Greek version (1). This 5-item questionnaire explores practice characteristics, attitudes, and diagnostic strategies for the management of chronic prostatitis in Italy. After its validation, the questionnaire was uploaded in the internet and Greek healthcare professionals were invited by mail to respond, in an attempt to investigate current diagnostic practices for CP in Greece. Responses were compared with those collected by our Italian research part- ners, reflecting the diagnostic habits of Italian urologists, as presented in the study of Magri et al. (1). The aim of this study was to assess similarities and differences in clini- cians’ attitudes regarding the diagnostic assessment of CP. The local research ethics committee approved the study. RESULTS Seventy-seven Greek urologists were surveyed. Responders diagnose chronic prostatitis in a substantial Objectives: We performed a questionnaire survey to investigate various issues in the diagnosis of chronic prostatitis (CP) performed by Greek urolo- gists and to assess some aspects of prostatitis workup in Greece. Replies were compared with those of Italian clinical research partners in an attempt to clarify the CP diagnostic approaches in Southern European Mediterranean countries. Methods: We translated the original Italian questionnaire pre- sented by Magri and Montanari in the frame of a urological congress held in Milan on October 26th, 2018. Τhis 5-item questionnaire explores clinical practice characteristics, atti- tudes, and diagnostic strategies for the management of chronic prostatitis (Chronic Bacterial Prostatitis or Chronic Prostatitis/Chronic Pelvic Pain Syndrome, according to NIH cri- teria). After its validation the questionnaire was uploaded in the internet and Greek healthcare professionals were invited by mail to respond. Responses were compared with those of Italian urologists, in order to determine similarities and differences in attitudes between clinicians regarding the diagnostic assess- ment of CP. Results: There is a wide variation in participants' preferences for diagnostic methods, laboratory tests and clinical examina- tions both in Italy and in Greece. In both countries many diag- nostic tests performed in affected patients are only geared to exclude other treatable conditions (e.g., benign prostatic hyper- plasia, bladder cancer), but more suitable methods and tests for the assessment of CP are less frequently used. Conclusions: Urologists' choices for the diagnostic workup of CP, show a wide international or intra-national variability between Greece and Italy. Although several diagnostic tests are available to differentiate and categorize the types of CP, a large number of urologists use less suitable methods and tests. This fact reflects both the lack of consensual vision in the liter- ature and the difficulties encountered on a daily basis by the physicians. Under the light of this evidence, the need of studies establishing consensual guidelines for the optimal diagnosis of CP is becoming imperative. KEY WORDS: Chronic prostatitis; Prostate; Infection; Stamey-Meyers. Submitted 25 February 2020; Accepted 10 March 2020 INTRODUCTION The term "chronic prostatitis" indicates syndromes which show different aetiologies and variable clinical features Summary Archivio Italiano di Urologia e Andrologia 2020; 92, 4 K. Stamatiou, V. Magri, G. Perletti, E. Samara, G. Christopoulos, A. Trinchieri. 354 number of men each year (the median number of patients per specialist per month is 11 patients). Almost 72% percent of the Greek professionals use in their clin- ical practice the classification of "chronic prostatitis" pro- posed by the National Institutes of Health (NIH), which identifies two major CP conditions: Chronic Bacterial Prostatitis (CBP) and Chronic (abacterial) Prostatitis/ Chronic Pelvic Pain Syndrome (CP/CPPS). There is a wide variation in participants' preferences for diagnostic meth- ods, laboratory tests and clinical examinations both in Italy and in Greece. In both countries many diagnostic tests performed in affected patients are geared toward excluding other treatable conditions (e.g., benign prosta- tic hyperplasia, bladder cancer) however more suitable methods and tests for the assessment of CP are less fre- quently used. A comparison between Italian and Greek survey is presented in the Tables 1-4. DISCUSSION CP is a common situation affecting relatively young men. Its exact frequency is not known. As reported by Krieger et al., men in the United States with CP account for 2-5 million ambulatory physician visits per year including 8% of all appointments with a urologist. Magri and Montanari reported a frequency of 23 patients per urolo- gist per month on average (1). Similarly to our study, Swiss urologists see a median of 10 patients per month (4). The abovementioned variations could be attributed to differences in health care policies, patients’ preference and urologists’ experience. Notably, the average age of responders to our questionnaire was significantly lower than that of the Italian study. This fact explains the lower median number of patients per Greek specialist and it may also explain the difference in the use of the NIH classification of "prostatitis" in the clinical practice between Greek and Italian specialists (62.7 vs 31.2%). This is likely due to the fact that, compared to older col- leagues, the compliance of younger urologists with clin- ical practice guidelines is higher. However, this might not be the case since a limited use of the NIH classifica- tion system was also reported in the UK (33%) (5) and in France (35%) (6). Large deficits in familiarity with and knowledge of CP, along with a significant uniformity in the medical approach to this condition may explain the above findings (7). As a matter of fact, most urologists acknowledge that chronic prostatitis is the most frustrating and difficult clinical problem to deal within urology (8). This happens likely because the etiopathology of prostatitis is uncer- tain, several diseases of the urogenital system share com- mon symptoms, the diagnostic work-up of prostatitis is not completely standardized, the microbiological diag- nosis is partly inadequate and there are restrictions in the prescription of some clinical and laboratory tests in sev- eral countries. As shown in Table 1, the preferred diagnostic methods (89.6 and 84.4% of Greek and 98.12% and 96.62% of Italian urologists) are medical history and physical exam- ination alone or combined with the IPSS questionnaire. The greatest part of them (37.6 and 41%) do not use questionnaires routinely. In general, diagnosing CP can Table 1. Comparison of preferences of diagnostic methods. Preferred diagnostic methods Italy Greece Answer choices % % Medical history 98.12 89.6 Clinical examination (DRE) 96.62 84.4 IPSS questionnaire 51.13 40.2 NIH-CPSI questionnaire 17.29 19.4 SHIM questionnaire (modified IIEF questionnaire) 16.17 10.3 IIEF questionnaire 7.89 1.29 PEDT questionnaire 6.39 1.29 UPOINT questionnaire 1.88 5.19 Other questionnaires 0.00 0.00 Total respondents 266 77 Table 3. Comparison of preferences of clinical tests. Preferred clinical tests Italy Greece Answer choices % % Uroflometry 72.18 81.8 Abdominal ultrasound 62.78 92.20 Transrectal ultrasound 45.11 10.30 Scrotal ultrasound 12.78 6.49 Urodynamics 2.63 3.88 Urethocystoscopy 3.01 2.59 Urethrocystography 2.63 0.00 Other diagnostic tests 20.68 10.3 No diagnostic test 0.00 2.59 Total respondents 266 77 Table 4. Comparison of preferences of microbiological tests. Preferred microbiological tests Italy Greece Answer choices % % Gram+ 83.08 85.6 Gram- 86.84 100 Fungi 56.77 20.7 Sexually transmitted microbes 77.82 79.4 Table 2. Comparison of preferences of laboratory tests. Preferred laboratory tests Italy Greece Answer choices % % PSA 81.20 57.1 Midstream urine test 72.18 49.3 Urethral swab 39.10 2.59 Urethral swab after prostate massage 13.91 1.20 Meares & Stamey test 20.30 11.6 Meares & Stamey test with count of the number of leukocytes in VB2 and VB3/EPS 16.92 1.20 Nickels’ ‘’two glass test’’ 6.39 11.6 Semen culture 67.29 74.0 Semen culture with count of the number of leukocytes in ejaculate 24.81 2.69 Urine cytology 9.02 0.00 Spermiogram 13.16 1.20 Total respondents 266 77 355Archivio Italiano di Urologia e Andrologia 2020; 92, 4 Mediterranean urologist and chronic prostatitis be difficult, as the patient history and examination modalities may be quite diverse. In fact, most patients claim genitourinary pain or discomfort, though newly presented sexual dysfunction and new onset of urinary symptoms are also common. Less usual presentations include recurrent febrile infections of the urinary tract and the genital system and asymptomatic elevation of serum PSA levels (9). The physical examination is usual- ly normal. Digital rectal examination findings suggestive of CP (painful and or edematous hardened and tender prostate) may be found in half of the cases (10). Other abnormalities that can be found during examination of the prostate, such as calculi and nodules, may impact management decisions. Symptom assessment by the NIH-CPSI is rarely used in both Greece and Italy (17.29 and 19.4% of respondents, respectively). An even lower number (12%) was report- ed by Zbrun et al. (4). Actually, the NIH-CPSI was devel- oped to assess symptoms and quality of life in men with CP/CPPS and has demonstrated good reliability and validity (11). It has been long used as the primary out- come variable in multiple trials and studies, though its role as a diagnostic tool is debatable (12). On the other hand, the questions in the NIH-CPSI provide a universal clinical assessment of CP, both in terms of initial evalua- tion and during therapeutic monitoring (13). Notably, UK guidelines recommend the NIH-CPSI and similar diagnostic tools such as the International Prostate Symptom Score (IPSS), the Urinary, Psychosocial, Organ- specific, Infection, Neurological, and Tenderness (UPOINT) algorithm, the International Index of Erectile Function (IIEF-5) and/or the Sexual Health Inventory for Men (SHIM) scales to assess initial symptom severity and evaluate patient-tailored phenotypic differences (Level 3 recommendation) (14). They also suggest psychosocial screening with Patient Health Questionnaire-9 (PHQ-9) and/or Generalised Anxiety Disorder-7 (GAD-7) Scales as well (Level 5 recommendation) (11). Even though the Meares and Stamey (MS) “4-glass” test is the gold standard test for the CP diagnosis, few Italian and Greek responders perform it alone (20.3% and 11.6% respectively) or in combination with leukocyte counts (16.92% and 1.2% respectively). Time and geographical trends in the use of this test may exist, since the number of Italian CP patients not subjected to the MS test was greater in the past 15 years (15). Sixty-six per cent of the Canadian practitioners’ and 80% of the US counterparts never or rarely perform the MS test in making a diagnosis of prostatitis (16, 17). In contrast, 61% of the British and 51% of the Dutch urologists are reported to be using the test (5, 18). Kiyota et al. found that only 1.5% of Japanese urologists diagnose CP using the MS test, while almost 45% adopt the the “2-glass” pre- and post-massage test (19). A similar number was reported by Swiss urologists (4). The “2-glass” test is rarely used in both Italy and Greece (6.39 and 11.39% respectively). On the other hand, in our study, semen culture, combined or not with leukocyte counts, was by far the most popular test (76.59 and 92.1% for Greek and Italian responders respectively) and is known to be the second most used diagnostic test by Dutch urol- ogists (18). According to Yang et al., the simple culture of expressed prostatic secretion (EPS) is the most commonly (43.4%) performed test for the diagnosis of CP in China (20). To our knowledge, current EAU guidelines suggest semen culture not to be routinely part of the diagnostic assessment of CP. Regarding microbiology tests, both Italian and Greek responders’ preferences include both Gram-negative and Gram-positive organisms. Some clinicians and microbi- ologists debate the role of Gram-positive other than Enterococci (21). Currently, Gram-positive bacteria tend to be the most frequent isolates in EPS and VB3 speci- mens from CP patients, with coagulase-negative staphy- lococcal species being the most prevalent isolates in Greece (22). In agreement with our findings, most urologist worldwide do not count the number of leukocytes in VB2 or VB3/EPS to differentiate between inflammatory and non-inflamma- tory chronic prostatitis/chronic pelvic pain syndrome. The proportion of urologists following this practice vary signif- icantly worldwide (4, 17, 19). Reasons explaining these differences are practically unknown. Ku et al., suggest that the personal beliefs and professional characteristics of physicians are the most determinant factors with respect to the urologists’ preferences and routine performance or non-performance of culture tests (23). Kiyota et al. found that more than half of Japanese urologists felt pessimistic about dealing with CP (19). Although many urologists think that chronic non-bacterial prostatitis/chronic pelvic pain syndrome is not an infectious disease, they prescribe antibiotics even when no white blood cells are detected in prostate-specific specimens (4, 23). As shown in our study, a variety of diagnostic tests are performed in patients with a suspected diagnosis of CP, in order to exclude other treatable conditions (e.g., benign prostatic hyperplasia, bladder cancer). These include imaging, endoscopy, urodynamics and PSA testing. None of them is specifically recommended in the evaluation of patients with prostatitis. However, ultrasonography and uroflowmetry are non-invasive, low cost tests for a rapid study of the anatomy of the urinary system and for a gen- eral estimation of the urinary function; hence they could be adopted in CP diagnostic work up (24). CONCLUSIONS Urologists' preferences for diagnostic investigation and testing for CP show considerable worldwide diversity. 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Correspondence Konstantinos Stamatiou, MD stamatiouk@gmail.com Evangelia Samara, MD Georgios Christopoulos, MD Urology Dpt, Tzaneion Hospital 2 Salepoula str, 18536 Piraeus (Greece) Vittorio Magri, MD Urology Secondary Care Clinic, ASST-Nord, Milan (Italy) Gianpaolo Perletti, PhD Department of Biotechnology and Life Sciences, University of Insubria, Varese (Italy) Alberto Trinchieri, MD Manzoni Hospital, Lecco (Italy)