What’s known on the subject? and What does the study add?

Prostate biopsy is the most common diagnostic procedure in urology practice. It is generally an easily applicable and well-tolerated method, but lower urinary tract symptoms (LUTS) has an important place among the increasing complication rates recently. There is no consensus in the literature regarding risk factors and prophylactic measures for biopsy-associated LUTS. Targeted antibiotic prophylaxis is recommended by recent studies and guidelines, especially for patients at risk. In our study, it was seen that targeted prophylaxis had a significant effect on biopsy-associated LUTS, and it could be an important method in preventing LUTS complaints.

Introduction

Prostate cancer is the most prevalent solid organ cancer observed in males, and it is the second most prevalent type of cancer that leads to malignancy-related mortality worldwide (1). The prevalence of prostate cancer increases by 2-3% every year in Europe and the USA (2). Among the reasons for this increase are the widespread use of prostate-specific antigen (PSA) screening tests and the increasing role of multiparametric magnetic resonance imaging applied in the pre-biopsy period (3). Hence, prostate biopsy is the most frequently used diagnostic procedure in urology, and its application number in Europe and the USA is more than two million (4). Most of these applications are performed with a transrectal approach, and although there are new techniques developing today, the most frequently used method is still transrectal ultrasound (TRUS) guided biopsy, which is also the standard procedure for pathological sampling in the diagnosis of prostate cancer (5).

TRUS guided prostate biopsy is a method that is easily applied and well tolerated. However, a significant increase in biopsy-related complications has recently been reported (6). One of the current debates over this issue is related to antibiotic prophylaxis to be applied before the procedure. In studies conducted and American Urological Association guidelines, it has been stated that targeted antibiotic prophylaxis applied because of culture obtained through rectal swab is more successful compared to standard fluoroquinolones prophylaxis or augmented prophylaxis, and that a decrease by 84% in complication rates has been achieved (7).

Lower urinary tract symptoms (LUTS) that develop following prostate biopsy are among the more frequently observed complications compared to infectious complications such as fever and sepsis (8). These complaints usually develop because of a biopsy procedure and causes related to the application procedure such as trauma, edema, inflammation, and infection. The probability of LUTS development following TRUS-guided prostate biopsy is reported to be 40% (9). In the literature, there are studies that were conducted in order to determine risk factors for urination complaints that may develop after TRUS-guided prostate biopsy and in which medical agents that could be applied prophylactically for LUTS were used; however, there is no clear procedure related to this issue (10).

In relevant guidelines, targeted antibiotic prophylaxis is recommended especially in risky patients due to its effect on post-biopsy complications (11). However, the number of prospective randomized trials that examined the effects of this procedure on LUTS is rather limited. Therefore, it was aimed in the present study to examine whether targeted antibiotic prophylaxis has a more significant effect on LUTS compared to fluoroquinolone prophylaxis and to discuss the results obtained considering the literature.

Materials and Methods

In the study, the data of 240 patients who underwent prostate biopsy between January 2021 and January 2023 and were followed up by prospectively recording their information were analyzed. Using GPower 3.1 software, it was calculated that the sample size should be at least n=220 (110+110) for a statistical power of 0.95 at alpha=0.05 level. The study was conducted in line with the principles of the Declaration of Helsinki and was approved by the local ethics committee of Ordu University, Turkiye (approval no: 2021/208, date: 23.09.2021). Written informed consent of the patients included in the study was obtained before the procedure.

TRUS - guided 12-quadrant prostate biopsy was applied to patients who presented to the urology outpatient clinic and who had serum PSA levels of 4 ng/mL and abnormal digital rectal examination findings. The patients were divided into two groups according to pre-planned randomization. While routine ciprofloxacin prophylaxis was applied to one group of patients, the other group was administered antibiotic prophylaxis in line with the antibiogram obtained from the rectal sample, which was previously taken through the rectal swab method. Antibiotic prophylaxis was applied as 1-day prophylaxis, once 2 h prior to the procedure and once at the 12^th hour post-procedure 12^th hour.

The patients’ age, body mass index (BMI), comorbidities, biochemical parameters, serum PSA values, medical treatment for BPO, antibiogram results of the targeted antibiotic prophylaxis group and antibiotic agents used in prophylaxis, number of nocturia, maximum urinary flow rate (Qmax) values, prostate volumes (P.V.), and international prostate symptom scores and detailed points were analyzed.

The International Prostate Symptom Score (IPSS) is a validated and current 7-item questionnaire that inquires about patients’ lower urinary tract complaints. It examines incomplete emptying (urinary retention), need to urinate again in less than 2 h (frequency), intermittent urination (intermittency), inability to hold urination (urgency), decrease in urinary flow rate (weak stream), difficulty in starting urination (straining), and number of nocturia. Also, it is a commonly used questionnaire in diagnosis and follow-up of patients with the addition of quality of life to urinary symptoms.

Patients who were below the age of 40 years, who had life expectancy of less than 10 years, who had undergone rectal or pelvic surgery, who had active urinary system infection, who received pelvic radiotherapy, who were suspected to have neurogenic urination symptoms, whose postvoiding residue amount was more than 150 mL, whose Qmax value was below 15 mL/s and who needed additional treatment for BPO, and who had rectal anomaly or a disease that might affect rectal flora were excluded from the study.

Statistical Analysis

In the analysis of the data obtained because of the study, SPSS 21.0 package software was used. Kolmogorov-Smirnov test was employed in determining whether the data were normally distributed. Nonparametric tests of Mann-Whitney U, Wilcoxon Signed-Ranks test, and mixed pattern ANOVA were used in the analysis of the data. Statistical significance level was set as p<0.05.

Results

In the group that was administered targeted antibiotic prophylaxis, the mean age was found to be 65.6±7.2 years (n=120), while it was determined to be 65.3 65.3±6.4 years (n=120) in the control group. BMI values were calculated as 28.7±3.7 kg/m² and 29.3±4.2 kg/m², respectively (p=0.858). No significant difference was found between the groups in terms of systemic diseases and prevalence rates (Table 1). The mean serum PSA value measured before the procedure was found to be 24.45±6.66 ng/mL in the targeted antibiotic phylaxis group, while it was determined to be 25.41±6.53 ng/mL in the control group, with no significant difference between them (p=0.958). No significant difference was observed between the groups before the procedure in terms of inflammatory parameters of C-reactive protein (p=0.919), sedimentation (p=0.501), fibrinogen (p=0.444) values, blood count results, and biochemical parameters (Table 2).

According to the antibiogram results of the group from which rectal swab was taken, the most frequently growing agents were Escherichia coli in 74 patients (62%), enterobacterial in 22 patients (18%), klebsiella in 14 patients (12%), and pseudomonas in 10 patients (8%). In line with the antibiogram results, antibiotic agents administered the most were ceftriaxone in 44 patients (36.7%), gentamicin in 30 patients (25%), amikacin in 22 patients (18.3%), ceftazidime in 14 patients (11.7%), and ciprofloxacin in 10 patients (8.3%) (Figure 1).

When LUTS prevalence was questioned as yes/no after the biopsy was applied to the patients, 36 patients (30%) in the targeted antibiotic prophylaxis group responded as yes, while 70 patients (58.3%) responded as yes (p=0.002). The number of urinations during the daytime was 4.8±2.1 in the prophylactic group and 4.7±2.3 (p=0.775) in the control group before the procedure, while it was found to be 5.6±2.7 and 7.7±3.5 (p=0.03) respectively on the post-procedure 7^th day and 5.5±2.8 and 6.8±3.7 (p=0.044) respectively in the post-procedure 1^st month.

In the pre-procedure period, while the Qmax value was determined as 18.3±5.1 mL/s in the prophylaxis group, it was measured as 17.4±4.6 mL/s in the control group (p=0.157). The Qmax value was measured as 14.6±3.3 mL/s and 11.7±4.1 mL/s on the post-procedure 7^th day (p<0.001), and it was calculated to be 16.8±4.3 mL/s and 14.9±3,5 mL/s (p=0.013) respectively in the post-procedure 1^st month. The mean P.V. value before the procedure was 50.77±25 mL in the targeted prophylaxis group and 46.47±27 mL in the control group (p=0.511).

In the evaluations made over the patients’ IPSS questionnaire items and their total scores, the feeling of residue after urination before the procedure was found to be 2.08±1.0 in the prophylaxis group and 2.32±1.1 (p=0.055) in the control group, while these values were 2.37±1.3 and 3.10± 1.6 (p=0.009), respectively, on the post-procedure 7^th day and 2.22±1.2 and 2.95±1.5 (p=0.006) respectively in the post-procedure 1^st month. The patients’ need for urination in less than 2 h was determined as 1.78±0.7 in the prophylaxis group and 2.25±0.9 (p=0.004) in the control group, while it was 2.08±0.9 and 2.86±1.3 (p<0.001) respectively on the post-procedure 7^th day and 2.07±0.9 and 2.98±1.7 (p<0.001) respectively in the post-procedure 1^st month. The patients’ intermittent urination complaints before the procedure were found to be 1.88 1.88±0.7 in the prophylactic group and 2.05±0.9 (p=0.69) in the control group, while they were 2.93±1.1 and 3.57±1.5 (p<0.001) respectively on the post-procedure 7^th day and 2.53±1.1 and 3.52±1.5 (p<0.001) respectively in the post-procedure 1^st month. The patients’ complaints regarding difficulty in holding urination before the procedure were found to be 1.82 1.82±0.7 in the prophylaxis group and 2.28±1.1 (p=0.007) in the control group, while they were 2.43±1.2 and 3.13±1.5 (p=0.006) respectively on the post-procedure 7^th day and 2.35±1.1 and 3.08±1.4 (p=0.003) respectively in the post-procedure 1^st month. Decreases in urinary flow rate before the procedure were found to be 1.95 1.95±0.8 and 2.22±1.2 (p=0.139) in the prophylaxis group and the control group, respectively, while they were 2.83 2.83±1.3 and 3.18±1.5 (p=0.175) respectively on the post-procedure 7^th day and 2.73±1.2 and 3.25±1.4 (p=0.039) respectively in the post-procedure 1^st month. Difficulty in starting urination before the procedure was found to be 1.68±0.8 and 2.37±1.1 (p<0.001) in the two groups, respectively, while it was 2.43±1.1 and 3.15±1.4 (p=0.003) on the post-procedure 7^th day and 2.37±1.0 and 3.17±1.4 (p=0.001) in the post-procedure 1^st month. Finally, nocturia complaint before the procedure was found as 3.03±1.5 and 3.08±1.4 (p=0.859) in the groups, respectively, while this value was 3.33±1.5 and 3.85±1.4 (p=0.063) on the post-procedure 7^th day and 3.23±1.5 and 3.88±1.4 (p=0.02) in the post-procedure 1^st month (Table 3).

While the patients’ quality of life (QoL) score before the procedure was 2.4±1.0 in the targeted prophylaxis antibiotic group and 2.7±1.3 (p=0.057) in the control group, it was determined to be 2.8±1.3 and 3.6±.1.6 (p=0.004) respectively on the post-procedure 7^th day and 2.6±1.1 and 3.5±1.6 (p=0.002) respectively in the post-procedure 1^st month.

Discussion

In this study, it was determined that the application of targeted antibiotic prophylaxis before prostate biopsy was significantly effective on LUTS with respect to standard prophylaxis. When IPSS total scores of the patients who underwent prostate biopsy were examined, it was seen that this value was 13.93±4.1 in the prophylaxis group and 16.67±5.6 before the procedure (p=0.03), while their scores were calculated as 18.1±6.1 and 22.9±7.4 respectively on the post-procedure 7^th day, which was a statistically significant difference (p<0.001). The patients’ total scores were calculated as 17.5±5.5 and 22.8±7.5 respectively in the post-procedure 1^st month (p<0.001) (Table 3). When the effective factors on the values in both patient groups were analyzed, it was seen that the increase in the scores of the prophylaxis group determined in the measurements performed at different times was statistically significantly lower according to the mixed pattern ANOVA test compared to the control group (p<0.001). It was determined that targeted antibiotic prophylaxis had a positive effect in terms of preventing LUTS that might develop after prostate biopsy compared to the control group (p=0.001) (Figure 2).

LUTS is among the leading complications that are frequently seen the most following prostate biopsy with rates reaching up to 40% (12). There are various causes of LUTS development after prostate biopsy. Prostatic edema that may develop because of inflammation after the procedure and trauma caused by the biopsy procedure are especially the first ones that come to mind. periprostatic blockage applied during the procedure is effective in the development of LUTS (13). In addition to the inflammation developing in the prostatic tissue, expansion of intestinal microbiota due to transrectal application and gradual spreading of bacteria resistant to prophylactic agents administered routinely in intestinal microbiota today are becoming a serious problem (14). It is thought that other than the septic complications caused by resistant strains, localized infections and inflammatory problems occupy a significant place in biopsy-related urination disorders, and LUTS complaints occur because of bladder outflow resistance along with all these causes (15). For this reason, there are studies in the literature in which various agents such as fluoroquinolones and additionally fosfomycin, cephalosporins, aminoglycosides, ertapenem, trimethoprim, and metronidazole are used alone or in combination. Currently, fluoroquinolones can be used frequently in current randomized controlled trials and were routinely applied to patients in the control group in our study. It has been stated that patients’ complaints regarding LUTS generally continue for one month after transrectal prostate biopsy (16). When the risk factors that could create a sensitivity towards LUTS in patients before the procedure are examined, it has been stated in the literature that prostate volume does not affect post-procedure urination symptoms, that postvoiding residue amount has no effect on IPSS score after the procedure, that the number of cores sampled during the procedure and symptoms do not correlate, and that procedures applied to the transitional zone do not create an additional risk factor for urination symptoms (17,18). It has also been indicated that the presence of LUTS before the procedure is not exacerbate existing symptoms (19). The presence of LUTS is usually considered a factor that causes patients to present to a doctor in early periods. In some studies, it was attempted to use a PSA value between 4 and 10 ng/mL as a predictive value for determining the presence of LUTS. However, it was stated that the presence of LUTS did not have any effect on biopsy results and post-biopsy complications (20). Nevertheless, it has been stated in some studies that biopsy-related LUTS should be considered especially in patient groups with IPSS score above 20 (21). In this study, pre-procedure IPSS scores were determined as 13.9±4.1 in the targeted antibiotic prophylaxis group and 16.6±5.6 in the control group. A higher IPSS score in the control group before the procedure is not considered as an additional risk factor in the literature. When the increases in IPSS scores in both groups are compared, it is seen that the increase in the prophylaxis group was lower compared to the control group, that their biopsy-related LUTS rate was lower, and that targeted biopsy had significant effects on LUTS (p<0.001) (Figure 3).

When IPSS questions are examined in detail in both groups, it is seen that the difference between the two groups resulted especially from the need to urinate in less than two hours and urgency and storage symptoms such as difficulty in holding urination. Although there is no significant difference between the groups in terms of the presence of additional diseases such as diabetes, long-term changes related to chronic diseases can be effective in reducing the differences in scores (22,23). Patients’ awareness levels about changes occurring in the long term also affect the responses given. Regarding the symptoms inquired through the 7 questions in the IPSS questionnaire as yes/no before the procedure in the present study, incomplete emptying was found in 38 patients (31.7%) in the prophylaxis group and in 52 patients (43.3%) in the control group (p=0.190); need to urinate again in less than two hours was determined in 20 patients (16.7%) in the prophylaxis group and in 38 patients (31.7%) in the control group; intermittent urination was found in 58 patients (48.3%) and 74 patients (%61.7), respectively (p=0.145); inability to hold urination and urgency was determined in 38 patients (31.7%) and in 46 patients (38.3%), respectively (p=0.448); decrease in urinary flow rate was found in 70 patients (58.3%) and in 72 patients (60%), respectively (p=0.854); difficulty in starting urination was identified in 47 patients (39.2%) and in 63 patients (52.5%), respectively (p=0.75); and nocturia complaint was determined in 45 patients (37.5%) and in 39 patients (32.5%), respectively (p=0.236). When they were asked verbally, no significant difference was observed between the groups in terms of complaints. In addition, lack of a significant difference between the groups in terms of Qmax values before the procedure and IPSS scores being lower than 20 in both groups before the procedure are important in terms of evaluating the study results. Therefore, when the increases in IPSS scores after the procedure are compared, the significantly higher increase in the IPSS score of the control group shows that targeted antibiotic prophylaxis application could be an effective method in terms of preventing biopsy-related LUTS. Because of infectious complications developing after transrectal prostate biopsy, the frequency of prostate biopsy applications through transperineal methods is increasing. However, LUTS complaints and retention problems are more frequently witnessed in transperineal applications as well (24, 25). When both infection and LUTS-related problems involved in applications through transrectal method and increased LUTS risk in the transperineal method, need for anesthesia, difficulty in performing the procedure, and increased costs thereof are considered, it is thought that targeted antibiotic prophylaxis is increasingly becoming a more effective and significant method (26).

Study Limitations

The study being conducted at a single center and the absence of urodynamic studies regarding LUTS complaints are the limitations of this study. There is a need for multicenter studies with larger samples to evaluate the effects of targeted antibiotic prophylaxis on LUTS complaints.

Conclusion

Although there still exist different opinions on prophylactic antibiotic regimens before prostate biopsy, targeted antibiotic prophylaxis has been recommended by studies and guidelines in recent years. Because of the present study, it was determined that targeted antibiotic prophylaxis had a significant effect on LUTS, which is a common problem frequently seen after prostate biopsy. We believe that applying targeted antibiotic prophylaxis as a routine treatment would be a significant method for preventing LUTS complaints and infectious complications.

Ethics

Ethics Committee Approval: The study was conducted in line with the principles of the Declaration of Helsinki and was approved by the local ethics committee of Ordu University, Turkiye (approval no: 2021/208, date: 23.09.2021).

Informed Consent: Written informed consent of the patients included in the study was obtained before the procedure.

Peer-review: Externally peer-reviewed.

Authorship Contributions

Surgical and Medical Practices: A.Y., E.B., A.Ç., İ.N., Concept: A.Y., E.B., A.Ç., İ.N., Design: A.Y., E.B., İ.N., Data Collection or Processing: A.Y., A.Ç., M.K., N.K., Analysis or Interpretation: E.B., A.Ç., M.K., N.K., Literature Search: A.Y., M.K., N.K., Writing: A.Y.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declare that they have no relevant financial.