Should prostatectomy be performed in patients with bladder calculi concomitant benign prostatic obstruction who have not received medical treatment?

doi:10.21203/rs.3.rs-1760902/v1

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Should prostatectomy be performed in patients with bladder calculi concomitant benign prostatic obstruction who have not received medical treatment?

https://doi.org/10.21203/rs.3.rs-1760902/v1

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posted 17 Jun, 2022

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Background: The historical dogma that bladder calculi comprise the main indication for prostatic surgery has recently been questioned. In this study, we aimed to predict which patients should undergo simultaneous prostate and bladder calculi surgery or only bladder calculi removal by evaluating preoperative risk factors.

Methods: One-hundred seventeen men with bladder stones and concomitant benign prostatic obstruction (BPO) who had not received medical treatment before were included in the study. In the first step, only the bladder calculi of the patients were removed and medical treatment for BPO was given. The patients who benefited from medical treatment during the follow-up were defined as Group 1, and the patients who required prostate surgery for any indication were Group 2. Risk factors for prostate surgery requirements were determined by comparing preoperative characteristics between the two groups with a logistic regression model.

Results: In the follow-up of 117 patients with bladder stones removed and medical treatment initiated, 49 (41.9%) patients were found to have prostate surgery indications. The indication in 33 of 49 (67.3%) patients was medical treatment failure. Presence of intravesical prostatic protrusion (IPP) and post-voiding high residual urine volume was found to be preoperative risk factor for the requirement of future prostate surgery (Odds ratio: 2.071, 95% CI: 1.05-4.05, P=0.034, odds ratio:1.013, 95% CI:1.007-1.019, P <0.001).

Conclusion: In patients who have not received medical treatment for BPO before, bladder calculi developing secondary to BPO do not always constitute an indication for prostate surgery.

bladder calculi

benign prostate hyperplasia

intravesical prostatic protrusion

medical therapy

prostate surgery

Bladder calculi constitute only 5% of all urinary tract stones [1]. This incidence is much higher in developing countries [2]. Bladder calculi are classified as a migrant, primary idiopathic and secondary. Secondary stones usually occur as a result of benign prostatic obstruction (BPO) in elderly men [3]. Bladder calculi and concomitant BPO is a common clinical condition in urology practice and bladder calculi incidence is 3–8% in patients with BPO [4, 5].

Advances in medical treatment have reduced the need for surgery due to BPO in recent years [6]. However, surgical management of BPO is still an option in certain indications. Traditionally, the co-existance of bladder stone and BPO is the main indication for prostate surgery [7]. Nowadays, prostate surgeries performed for BPO are usually transurethral resection of the prostate (TUR-P), open prostatectomy, or holmium laser enucleation of the prostate (HoLEP). Surgical management of BPO has sexual or functional complications. For this reason, some patients may be unwilling to undergo prostate surgery due to adverse effects. Prolonged duration of anesthesia may also be risky for elderly men with comorbidities.

In this study, we aimed to demonstrate whether prostate surgery is an absolute indication by determining preoperative risk factors in patients with bladder calculi and BPO.

After obtaining ethics approval from the local ethics committee (approval no:72/1167), we retrospectively identified the prospectively maintained database records of 558 patients diagnosed with bladder calculi concomitant BPO between 2014 January – 2021 January at two tertial referred center. Patients who underwent simultaneous prostate and bladder stone surgery were excluded from the study. Patients with neurogenic bladder, a history of bladder calculi removal or surgery for BPO, history of renal or ureteral stone, renal impairment, urinary tract dilatation, underactive detrusor, and urethral stricture were excluded from the study. Patients who received previous medical therapy for BPO or, not received medical therapy after calculi removal and who had recurrent urinary retention or indwelling foley catheter were also excluded. Figure 1 shows the flowchart of the study.

A total of 117 patients were included in the study. These patients preferred bladder removal only, although combined surgery was recommended Before bladder calculi removal, patients’ data such as age, Charlson Comorbidity Index (CCI) score, American Society of Anaesthesiologists (ASA) score, International Prostate Symptom Score (IPSS), prostate specific-antigen (PSA), prostate volume, post-voiding residual (PVR) urine volume, uroflowmetry, and cystoscopy findings were recorded as baseline values. IPSS with the quality-of-life (QoL) index, ranging from zero (delighted) to six (terrible), was used as the QoL surrogate indicator. The stone size was calculated by ultrasonography using the maximum diameters of the largest calculi. Transabdomial ultrasonography was performed in all patients to measure the total prostate volume and intravesical prostatic protrusion (IPP). The degree of IPP was classified as grade 1 (≤ 5 mm), grade 2 (> 5–10 mm), and grade 3 (> 10 mm) [8]. All patients were administered alpha-blocker and 5-alpha reductase inhibitors after bladder calculi removal. Patients were reassessed at 1, 6, and 12 months and then annually after surgery by IPSS, uroflowmetry, and PVR urine volume. Deterioration in QoL index and lower urinary tract symptoms, presence of residual urine over 100 ml, an increase in IPSS score were considered as medical treatment failure. During follow-up, patients who benefited from medical treatment after bladder calculi surgery were determined as group 1 (control group), and patients who underwent surgery for BPO due to medical treatment failure or any indication were determined as group 2. Preoperative baseline variables between the two groups and their effects on future prostate surgery were investigated. Patients who had undergone prostate surgery at the time of evaluation were excluded from the further analysis. Transurethral resection of the prostate (TUR-P) or holmium laser prostate enucleation (HoLEP) was performed in all patients as the prostate surgical method. The presence of postoperative residual stone was evaluated according to abdominal ultrasonography as well as viewing with direct vision at the end of the surgical process. Residual stones of 4 mm and below were noted as stone-free.

Statistical analysis

Descriptive statistics of data are given as mean, standard deviation, median, minimum-maximum, frequency, and percentage. Pearson chi-square or Fisher’s exact test were performed for categorical variables. Normality assumptions were checked with the Shapiro-Wilk test. The differences between the two groups were evaluated using the Student’s t-test for normally distributed data or Mann-Whitney U test for non-normally distributed data. Cox regression proportional hazard regression was used to identify independent preoperative factors that could predict the requirements for prostate surgery during follow-up. Statistical analysis was performed using IBM SPSS Statistics for Windows version 22.0 (IBM Corp., Armonk, NY). P < 0.05 was considered statistically significant.

The average age of 117 men included in the study was 63.9 ± 5.0 years (range, 55–77). The mean IPSS of all patients before bladder stone removal was 22.5 ± 4.1. Patients’ preoperative characteristics and follow-up duration after bladder calculi removal are summarized in Table 1. Fifteen (12.8%) bladder stone surgeries were performed by percutaneous cystolithotripsy and 102 (87.2%) by the transurethral cystolithotripsy approach. Stone-free status was achieved in all patients.

Table 1

Comparison of preoperative baseline characteristics according to groups
	Group 1 (n:68)	Group 2 (n:49)	P value
Median (IQR,) age, years	63.5 (10)	63 (5)	0.606^†
Median (IQR), CCI score	4 (2)	4 (2)	0.141^†
Median (IQR), PSA, ng/mL	1.8 (1)	2.1 (0.9)	0.176^†
Median (IQR), preoperative IPSS	22.5 (7)	24 (6)	0.346^†
Median (IQR), prostate volume, mL	52 (15)	54 (20)	0.780^†
Median (IQR), Qmax, mL/s	12 (3)	11 (2.5)	0.035^†
Median (IQR), PVR volume, mL	92 (39)	150 (45)	< 0.001^†
Median (IQR), diameter of largest stone, mm	22.5 (9)	24 (9)	0.004^†
Median (IQR), number of stones	1 (1)	2 (4)	0.132^†
Presence of IPP, n (%)	9 (30)	21(70)	< 0.001^¥
IPP grade
Grade 1, n (%)	3 (50)	3 (50)
Grade 2, n (%)	5 (41.6)	7 (58.4)
Grade 3, n (%)	1 (9)	11 (91)
Median (IQR) time for prostate surgery, months		20 (5)
Median (IQR) duration of follow-up, months	41 (16)	37 (2)	0.501^†
Group 1: only receive medical treatment after bladder calculi removal, Group 2: the need for prostate surgery during the follow-up. IQR: interquartile range, CCI: Charlson Comorbidity Index, PSA: prostate specific antigen, IPSS: International Prostate Sypmtom Score, Qmax: maxium flow rate, PVR: post voiding residual, IPP: Intravesical prostatic protrusion, ^†: Mann Whitney-u test, ^¥: Chi-Sqaure test. Data in bold indicate statistically significant associations.

After bladder calculi removal, all patients received alpha-blocker ± 5 alpha-reductase inhibitors. The mean reduce of IPSS score after bladder calculi removal was 10.2 ± 3.9 points (P˂0.001). Prostate surgery indication occurred in 49 (41.9%) patients at median 20 months (min-max, 14–32) follow-up. The indications for prostate surgery included medical treatment failure in 33 (67.3%) patients, urinary retention in 10 (20.4%), recurrent bladder calculi in 3 (6.1%), recurrent urinary tract infection in 2 (4.1%), and macroscopic hematuria 1(2.1%) after bladder calculi removal. HoLEP was performed for 23 of the 49 patients (46.9%), and TUR-P was performed for the remaining 26 (53.1%).

Cox proportional hazards regression was performed to identify the factors that predicted the failure of bladder calculi removal plus medical therapy. The presence of IPP was found to strongest factors to predict requirement prostate surgery (Odds ratio: 2.071, 95% CI: 1.05–4.05, P = 0.034) (Fig. 2). PVR urine volume was also found to be statistically significant factor(Odds ratio:1.013, 95% CI: 1.007–1.019, P < 0.001). Evaluation of preoperative risk factors to predict prostate surgery indication with the cox regression model is shown in Table 2.

Table 2

Cox proportional hazards regression models for prediction of prostate surgery requirements
	β	S.E.	P value	Exp(B)	95% C.I.for EXP(B)
	β	S.E.	P value	Exp(B)	Lower	Upper
IPSS	0.018	0.041	0.649	1.019	0.941	1.103
Prostate volume, mL	0.013	0.013	0.323	1.013	0.987	1.039
Stone diameter, mm	0.028	0.023	0.217	1.028	0.984	1.075
Number of stones	-0.084	0.066	0.199	0.919	0.808	1.045
Qmax, mL/s	0.010	0.060	0.872	1.010	0.898	1.135
PVR volume, mL	0.013	0.003	< 0.001	1.013	1.007	1.019
IPP presence	0.728	0.343	0.034	2.071	1.057	4.059
Data in bold indicate statistically significant associations. IPSS, International Prostate Sypmtom Score; Qmax, maxium flow rate; PVR, post voiding residual; IPP, Intravesical prostatic protrusion; β, regression coefficient,; SE, standard eror; Exp(B), odds ratio, CI; confidence interval.

The approach accepted for years in cases of bladder calculi developing secondary to BPO is the simultaneous surgical intervention of bladder calculi and prostate. In recent years, this indication has become questionable with the increasing success of medical treatment in patients with BPO [9]. The main finding of our study is that prostate surgery is not an absolute requirement in every patient with concomitant bladder stones and BPO who have not received any medical treatment in the past.

The pathophysiology of bladder stone formation in the presence of BPO is still unclear. Studies in the literature reported that PVR urine and stasis play a major role in stone formation [10, 11]. The 3–8% incidence of bladder stones in patients with BPO and stasis indicates that other factors also play a role in stone formation [4]. Child et al. defined these factors as a history of renal stones, gout, and various metabolic disorders [12]. The normal range of PVR urine volume is considered as 50–100 mL in elderly men [13]. Philippou et al. found that preoperative high PVR urine volume was the only predictive risk factor for medical treatment failure in their prospective study [9]. In our study, the need for prostate surgery was found significantly higher during the follow-up of patients with preoperative high PVR urine volume but the odds ratio was only 1.01.

As a result of the success of medical treatments used in patients with BPO, the need for surgery has decreased. In addition, the success of medical treatment allows patients to avoid complications caused by surgery. A-blockers alone provide 30–40% reduction in IPSS and 25% increase in Qmax [14]. Also, previous studies demonstrated that combination therapy is superior to monotherapy for IPSS and Qmax, and superior to α1-blockers alone in reducing the risk of the need for surgical intervention [15, 6]. So, we preferred the combination therapy. Our series demonstrated similar results, with a 45% reduction in IPSS and 22% increase in Qmax after medical treatment. Surgical indications emerged in 49 out of 117 patients included during follow-up. In other words, 68 of the 117 patients were spared the possible complications of the prostate surgery. 33 of 49 patients (67.3%) had prostate surgery indication of medical treatment failure.

The prostate anatomical structure is an important factor predicting the success of medical treatment. It was shown that the benefit of medical therapy is limited in the presence of IPP [16]. Recent studies demonstrated that IPP is an independent risk factor associated with the presence of bladder calculi in men with BPO [17, 18]. In the cox regression model we constructed in our study, the presence of IPP was the most important factor for prostate surgery requirements during follow-up. There was a 2.07-time increased risk of prostate surgery in the presence of IPP.

Our study has some limitations. The main limitation of our study has retrospective design. This may lead to the possibility of misclassification bias. Second, follow-up period was not long enough. Last, lack of confirmation of BPO with urodynamic findings is another limitation. On the other hand, our population number is higher than other studies in the literature.

This present study demonstrated that prostate surgery may not be an absolute indication in every patient with bladder stones and BPO. In the preoperative features of patients who have not previously received medical treatment for BPO, bladder stone removal alone can be performed if IPP is not present and PVR volume is low. Thus, complications and comorbidity of prostate surgery can be avoided. Prospective randomized studies with long follow-up are needed on this subject.

Statement of ethics: Ethics committee approval was obtained from ************* (approval number: 72/1167). This study was conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from patients who participated in this study.

Author contributions HA Project development, Data collection, Data analysis, Manuscript writing/editing. UÜ Project development, Data collection, Manuscript writing/editing. KK Project development, Data collection, Manuscript writing/editing. EV Project development, Data collection, HE Data analysis, Manuscript writing/editing.

Data availability statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.

Conflict of interest: The authors declare that they have no conflict of interest.

Funding sources: No funding was received by any of the authors for this study

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No competing interests reported.

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posted 17 Jun, 2022

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Should prostatectomy be performed in patients with bladder calculi concomitant benign prostatic obstruction who have not received medical treatment?

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Abstract

Figures

Introduction

Materials And Methods

Statistical analysis

Results

Discussion

Conclusion

Declarations

References

Competing Interests

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