Better timing for HoLEP: a retrospective analysis of patients treated with HoLEP over a 10-year period with a 1-year follow-up

Abstract

The aim of this study was to explore the optimal timing of holmium laser enucleation of the prostate (HoLEP) in patients presenting benign prostatic hyperplasia (BPH) with lower urinary tract symptoms (LUTS). A retrospective analysis was conducted based on the perioperative and postoperative outcome data of 1212 patients who underwent HoLEP in Shanghai Ninth People’s Hospital (Shanghai, China) between January 2009 and December 2018. According to the preoperative International Prostate Symptom Score (IPSS), all patients whom we analyzed were divided into Group A (IPSS of 8–18) and Group B (IPSS of 19–35). Peri- and postoperative outcome data were obtained during the 1-year follow-up. IPSS changes were the main postoperative outcomes. The postoperative IPSS, quality of life, peak urinary flow rate, postvoid residual, and overactive bladder symptom score (OABSS) improved significantly. The IPSS improved further in the group with severe LUTS symptoms, but the postoperative IPSS was still higher than that in the moderate LUTS group. OABSSs showing moderate and severe cases after follow-up were more frequent in Group B (9.1%) than in Group A (5.2%) (P < 0.05). There were no significant intergroup differences in the intraoperative American Society of Anesthesiologists or hospitalization expense scores, and the medication costs, as well as the total costs, were significantly higher in Group B. In this retrospective study, HoLEP was an effective treatment for symptomatic BPH. For patients with LUTS, earlier surgery in patients with moderate severity may result in a marginally better 12-month IPSS than that in men with severe symptoms.

INTRODUCTION

Benign prostatic hyperplasia (BPH) is common in aging males, and its prevalence increases with age.1,2 According to the latest guidelines, treatment options for patients with moderate (i.e., International Prostate Symptom Score [IPSS] of 8–18) and severe (i.e., IPSS of 19–35) symptoms of BPH include watchful waiting/lifestyle modification, as well as medical, minimally invasive, or surgical therapies. Pharmacotherapy is considered the first choice of treatment for lower urinary tract symptoms (LUTS) caused by BPH.3,4 Conservative treatment could significantly reduce LUTS5 and effectively postpone or even avoid surgical intervention. Many patients choose surgery only after conservative treatment fails.6,7 However, at least one in every five patients with LUTS will eventually need surgery.8 Although the mechanism is not yet well known, overactive bladder (OAB) symptoms are highly prevalent in patients with BPH and are bothersome to these individuals.9 For patients with severe LUTS, symptoms of outlet obstruction are clearly resolved after holmium laser enucleation of the prostate (HoLEP); however, a nonnegligible proportion of patients report some degree of transitory urgency and urge urinary incontinence.10 Therefore, it is critical to determine the optimal surgical timing for patients with LUTS. HoLEP is currently recommended as an alternative to transurethral resection of the prostate (TURP) or open prostatectomy (OP) in men with moderate to severe LUTS if performed by a HoLEP-trained surgeon.11,12 HoLEP has been performed since 2008 in Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine (Shanghai, China). As one of the first centers in China to perform HoLEP, Shanghai Ninth People’s Hospital has been working to improve and promote HoLEP in China for more than 10 years.13 This study , which compared the surgical risk, economic expenditures, and postoperative urinary function of LUTS patients, summarized 10 years of cases treated in Shanghai Ninth People’s Hospital, and we hope to provide a theoretical basis for the timing of HoLEP treatment by analyzing data from a large sample over a long period.

PATIENTS AND METHODS

Patients’ data

This study was approved by the ethics review board of Shanghai Ninth People’s Hospital (approval No. SH9H-2020-T217-1), and written informed consent was obtained from the patients during hospitalization.

A total of 1212 patients with LUTS underwent HoLEP in Shanghai Ninth People’s Hospital between January 2009 and December 2018 were included. All patients were diagnosed at Shanghai Ninth People’s Hospital and their initial outpatient data were recorded, including IPSS, quality of life (QoL), the maximum flow rate (Qmax), postvoid residual (PVR), and overactive bladder symptom score (OABSS).

Patients included in this retrospective study met these criteria: (1) age at surgery of 50–90 years; and (2) treatment with HoLEP and completion of at least 1 year of follow-up at Shanghai Ninth People’s Hospital. Patients with prostate carcinoma, bladder calculi, neurogenic bladder dysfunction, bladder cancer, history of previous prostate surgery, urethral stricture, or coagulopathy were excluded from this analysis.

Methods

All patients were divided into two groups according to their preoperative IPSS: Group A (IPSS of 8–18) and Group B (IPSS of 19–35). We collated the patients’ baseline characteristics including urological history, presence of concurrent diseases, previous drug therapy, prostate volume on the transrectal ultrasound, PVR volume, IPSS, QoL score, and Qmax.13 To assess urinary function, we evaluated the IPSS, QoL score, Qmax, PVR, and OABSS at the end of postoperative 1 month and 12 months. In addition, to assess the early postoperative changes in LUTS, all patients were followed up by telephone at 3 months postoperatively. Intraoperative safety was evaluated using the American Society of Anesthesiologists (ASA) score.

The total medical expenditures were estimated by adding up the hospitalization expenses (including outpatient treatment expenses and hospital stay expenses) and medication expenses preoperatively and 1 year postoperatively. The hospitalization expenses were tallied based on patient case documentation during the hospital stay. Patients’ outpatient records provided information on the cost of outpatient treatment such as indwelling catheterization and prostate puncture. The total medication expenditure was calculated by adding up the cost of medication after diagnosis until hospital admission and postoperative discharge for the treatment of postoperative complications. Each medication expenditure was calculated by multiplying the drug unit’s official sales price with the regular medication time (in month) according to the medical records. Assessments consisted of IPSS as the primary outcome, while OABSS, QoL score, ASA score, and total medication expense were the secondary outcomes.

All surgeries were performed by the chief physician of Shanghai Ninth People’s Hospital, and a holmium laser (enucleation power, 2.0 J × 40 Hz; Rikeren, Shanghai, China, or Lumenis, Tel Aviv, Israel) was used for enucleation. The tunnel technique was used to perform the enucleation. First, a continuous-flow cystoscope was inserted to observe the prostate, urethra and bladder, and identify the verumontanum which is one of the most important landmarks for enucleation. Second, using a holmium laser, a short horizontal incision was made around the 6 o’clock position in front of the verumontanum deep to the surgical capsule of the prostate. Next, the prostate surgical capsule was exposed from the incision to the bladder neck under the median lobe. When the operation is close to the bladder neck, it was ensured that the mucosa and the muscle were protected to facilitate efficient urinary control. Third, enucleation of the left lobe began at the incision near the verumontanum to 12 o’clock in an anticlockwise direction at the level of the surgical capsule and then the other lateral lobe was enucleated similarly.14 Transurethral morcellation was performed through a 26-Fr nephroscope (Storz, Tuttlingen, Germany) using a mechanical morcellator (VersaCut, Tel Aviv, Israel). The patients underwent general anesthesia and were placed in the lithotomy position during surgery. An irrigating catheter was inserted after surgery. Bladder irrigation was used as necessary until the hematuria resolved.13

Statistical analyses

Statistical software SPSS version 26.0 (SPSS Inc., Chicago, IL, USA) was used for the data analysis. The results are presented as mean ± standard deviation (s.d.). Intergroup equality was analyzed using Student’s t test, and the Chi-square test was used to calculate categorical data. Statistical significance was set at P < 0.05.

RESULTS

From January 2009 to December 2018, 1835 patients underwent HoLEP in Shanghai Ninth People’s Hospital, meeting the inclusion criteria. Among them, 192 had bladder stones, 81 had a postoperative diagnosis of prostate cancer, 324 had combined urethral stricture, and 42 had neurogenic bladder, including three with combined prostate cancer and bladder stones, 25 with combined bladder stones and urethral stricture, and 16 with combined urethral stricture and neurogenic bladder dysfunction. A total of 39 patients had a previous prostatic urethral history, including three with combined bladder stones, four with combined urethral stricture, and two with combined urethral stricture and neurogenic bladder dysfunction. A total of 623 patients were excluded from the study. We included 1212 patients in this analysis: 191 patients in Group A and 1021 patients in Group B. There was no significant intergroup difference in baseline characteristics (Table 1).

Table 1.

Characteristics of patients

Parameter	Group A (n=191)	Group B (n=1021)	P
Age (year)	70.9±8.3	71.0±8.5	0.81
Prostate volume (ml)	62.68±25.39	66.42±22.85	0.08
ASA score	2.24±0.66	2.31±0.78	0.22
Medication cost (kUSD)	0.61±0.21	1.17±0.42	<0.001
Hospitalization expense (kUSD)	3.34±0.43	3.38±0.38	0.25
Overall cost (kUSD)	3.96±0.47	4.55±0.55	<0.001

Data were presented in the form of mean±s.d. P represents the comparison between Group A (IPSS of 8–18) and Group B (IPSS of 19–35). ASA: American Society of Anesthesiologists; kUSD: thousand-United States dollar; s.d.: standard deviation; IPSS: International Prostate Symptom Score

There was also no significant intergroup difference in ASA score or hospitalization expense. However, the medication costs were significantly increased in cases with a higher preoperative IPSS. The total cost (mean ± s.d.) of Group B patients (thousand-United States dollar [kUSD] 4.55 ± 0.55) was also higher than that of Group A patients (kUSD 3.96 ± 0.47) (P < 0.05; Table 1).

Group A and Group B both achieved clinically similarly low IPSS (Qmax and PVR) at 12 months, and in both the voiding and the storage domains (Table 2 and 3). However, patients with severe preoperative LUTS barely reached a “symptom-free” status like their counterparts. Preoperative IPSS storage and IPSS voiding were both significantly higher of patients in Group B than those in Group A. Postoperatively, the mean IPSS voiding was significantly reduced and tended to be similar between groups. Storage symptoms (OABSS) appear to be clinically more persistent in a small group of patients even after HoLEP. In addition, retrospective data suggest that storage symptoms can be more persistent in a small group of patients (Table 2).

Table 2.

Changes in International Prostate Symptom Score

Parameter	Timeline	Group A (n=191)	Group B (n=1021)	P
IPSS	Preoperative	13.93±2.73	23.64±3.74	<0.001
	1 month postoperative	5.98±2.34	7.17±2.86	<0.001
	3 months postoperative	6.04±2.49	6.58±3.09	0.02
	12 months postoperative	4.98±1.76	5.61±2.80	0.003
IPSS-storage	Preoperative	6.08±3.69	9.07±2.57	<0.001
	1 month postoperative	3.34±2.07	4.17±2.57	<0.001
	3 months postoperative	2.48±1.91	3.20±2.34	<0.001
	12 months postoperative	2.04±1.70	2.42±1.96	0.01
IPSS-voiding	Preoperative	7.85±3.99	14.56±3.53	<0.001
	1 month postoperative	2.64±2.64	3.14±3.17	0.04
	3 months postoperative	3.55±2.64	3.51±3.09	0.85
	12 months postoperative	2.94±2.02	3.32±2.87	0.08

Data were presented as mean±s.d. P represents the comparison between Group A (IPSS of 8–18) and Group B (IPSS of 19–35). IPSS: International Prostate Symptom Score; s.d.: standard deviation

There was no intergroup difference in Qmax. The postoperative PVR was statistically higher in Group B than that in Group A (P < 0.05; Table 3); at the end of 12 months, ten patients in Group A (n = 191) had moderate-to-severe OAB symptoms versus 93 patients in Group B (n = 1021). OABSS >5 after 12 months of follow-up was more common among moderate and severe cases in Group B (9.1%) than in Group A (5.2%) (P < 0.05).

Table 3.

Changes in subjective and objective parameters

Parameter	Timeline	Group A (n=191)	Group B (n=1021)	P
PSA (ng ml−1)	Preoperative	2.38±3.15	2.28±2.59	0.64
	1 month postoperative	1.83±2.80	1.50±2.30	0.08
	12 months postoperative	1.34±2.64	1.13±2.24	0.24
QoL score	Preoperative	3.72±1.17	4.17±1.03	<0.001
	1 month postoperative	2.56±1.15	2.56±1.01	0.97
	12 month postoperative	1.05±1.04	1.05±0.73	0.96
Qmax (ml s−1)	Preoperative	8.94±3.54	8.35±3.59	0.04
	1 month postoperative	21.77±3.62	21.63±3.66	0.61
	12 months postoperative	21.43±3.65	21.88±3.37	0.09
OABSS	Preoperative	4.10±1.92	6.67±2.10	<0.001
	1 month postoperative	2.46±1.79	3.25±2.29	<0.001
	12 months postoperative	1.99±1.58	2.83±2.05	<0.001
PVR (ml)	Preoperative	130.33±52.17	125.55±57.55	0.29
	1 month postoperative	23.94±7.87	25.25±7.96	0.04
	12 months postoperative	21.27±8.04	22.82±8.17	0.02

Data were presented as mean±s.d. P represents the comparison between Group A (IPSS of 8–18) and Group B (IPSS of 19–35). IPSS: International Prostate Symptom Score; QoL: quality of life; Qmax: the maximum flow rate; OABSS: overactive bladder symptom score; PVR: postvoided residual; PSA: prostate-specific antigen; s.d.: standard deviation

Complications were reported within 12 months (Table 4). Transient urine leakage (TUL) was defined as persistent urine leakage for more than 24 h but less than 3 months after catheter removal. Fifteen patients in Group A versus 94 in Group B required medical treatment for TUL (P = 0.54). In Group B, 27 patients had persistent urinary incontinence (>3 months; P < 0.05); of these, seven cases lasted until the end of the 1-year follow-up (P = 0.53).

Table 4.

Adverse events after surgery

Adverse events	Group A, n (%)	Group B, n (%)	P
Blood transfusion	1 (0.5)	7 (0.7)	1.00
Recatheterization	2 (1.0)	15 (1.5)	0.90
Urethral stricture	3 (1.6)	19 (1.9)	1.00
Transient urine leakage	15 (7.9)	94 (9.2)	0.54
Urinary incontinence at 3rd month	0 (0)	27 (2.6)	0.04
Urinary incontinence at 12th month	0 (0)	7 (0.7)	0.53

P was calculated by the Chi-square test. P represents the comparison between Group A (IPSS of 8–18) and Group B (IPSS of 19–35). IPSS: International Prostate Symptom Score

DISCUSSION

BPH is not a life-threatening disease, but it requires continuous care. Many patients with severe symptoms and IPSS of 18–35 rejected surgery and chose conservative treatment. Factors affecting surgical intention include age, economic expenditure, chronic comorbidities, etc.15 Through this study, Shanghai Ninth People’s Hospital aimed to explore the possibility of early surgery for LUTS.

There was no significant difference in age between Group A and Group B. Patients with different IPSS may have had the same age at surgery for the following reasons. First, BPH is a senile disease; patients do not expect it to improve with treatment as they consider the deterioration of urinary symptoms to be a product of aging.15,16 Younger patients (IPSS of 8–18) do not have a strong desire for surgery or even medical attention. According to recent research, many patients under 65 years of age tend to seek treatment for BPE through social networks15 rather than following their doctor’s advice. Meanwhile, because of the risk of surgery, some elderly patients (IPSS of 19–35) are not surgical candidates. In addition, many studies have indicated that there is no correlation between prostate size and IPSS.

There was no statistically significant intergroup difference in ASA scores. Since BPH is a chronic disease, its surgical risks are more stringent, and some patients (IPSS of 19–35) lose the opportunity to undergo surgery. The true cost of treatment and intervention for BPH includes direct costs (drugs, procedures, imaging, and office visits), indirect costs (lost earnings), and intangible costs (pain and suffering).17 This study focused on direct costs by analyzing the economic costs of BPH by different IPSS. It should be acknowledged that although BPH is commonly thought as a disease found in older men, the costs of its treatment begin to accrue in men in their 40s.17 For the patients in Group B (IPSS of 19–35), who had a longer disease course than those in Group A (IPSS of 8–18), the medication expenses were significantly higher. It is reasonable to infer that the economic costs of BPH treatment will increase with the postponement of HoLEP. For most patients, medications were discontinued after 1 year postoperatively, so this study defined total medical expenditures as that postdiagnostic and through 1 year postoperative. This has some limitations because the follow-up period was only 1 year, and the medical pathway could not be predicted for patients with long-term urinary incontinence. In addition, for patients undergoing secondary surgery for prostate enlargement, the data are inaccurate.

Urinary function improved significantly after HoLEP, and this trend could last throughout the follow-up period. HoLEP is an extremely durable and effective treatment for patients with LUTS due to BPH.18 Our results show that although patients with severe preoperative LUTS had a more significant improvement in symptoms after HoLEP, they never reached a “symptom-free” status like their counterparts with moderate LUTS. The Group B had higher preoperative IPSS storage, which may indicate bladder dysfunction and a higher postoperative IPSS storage. We did not identify these same changes in IPSS voiding.

In terms of bladder function evaluations, since this was a retrospective study, we could not obtain certain invasive examination data, such as bladder detrusor function. Therefore, we used the OABSS combined with PVR and Qmax to evaluate postoperative voiding function in our patients. Many studies have revealed that the OABSS is a reliable evaluation index to evaluate bladder function in patients.19–22 The Chinese OABSS was developed and validated as a reliable instrument for assessing patients with OAB.23 Since Qmax and PVR are important indicators for postoperative uroflowmetry testing and noninvasive bladder function testing, we added them to assist in the interpretation of bladder function.

There was no significant intergroup difference in the improvement of QoL score and Qmax at the end of follow-up. Patients in Group B had the same QoL score as those in Group A possibly because of the more significant improvement in postoperative urinary function. A previous study suggested that a higher Qmax could be a predictor of poor postoperative outcomes for patients with LUTS and may contribute to more storage rather than voiding symptoms.24 For the patients in Group B, the postoperative Qmax returned to the same level as that in Group A; however, the PVR levels of Group B was worse than that of the control group. The improvement in the OABSS of Group A was better than that of Group B. OABSS improvements in moderate and severe cases (OABSS >5) after 12 months of follow-up occurred more frequently in Group B than in Group A. An association between OAB and bladder outlet obstruction (BOO) secondary to BPH is presumed.25 For males, OAB symptoms may develop secondary to BOO.26,27 The early surgical removal of BOO can reduce the risk of postoperative OAB. Mirone et al.28 has indicated that long-term BOO promotes bladder dysfunction and may lead to irreversible bladder damage, which manifests as poor contractility and detrusor overactivity.28 Maybe earlier treatment for patients with moderate LUTS, rather than awaiting further aggravation of severe symptoms, could be a good choice for patients with LUTS.

The current study had certain limitations that must be acknowledged. First, it did not include the costs of outpatient visits for LUTS, inpatient nonsurgical treatments, and postoperative complications in other centers.12,29 Second, BPH is a long-term disease that many patients live with for more than 10 years or 20 years, and 1 year of postoperative follow-up time may not be able to include clinical data of patients undergoing a secondary surgery30 or lifetime conservative treatment.31 Third, as this was a retrospective analysis, we could not include data that have not been followed up previously, for example, sexual complications (ejaculatory/erectile dysfunction), which patients with earlier surgery might suffer from earlier on. Fourth, many patients postponed surgery due to long-term drug treatment but then lost surgical candidacy due to advanced age or other aging-related diseases and, therefore, might have required long-term indwelling catheters. These patients and those who had not undergone surgery and whose condition was well-controlled by medication were not included in this study due to the length of the follow-up period. Hence, prospective studies with larger cohorts are needed to confirm our findings.

CONCLUSIONS

HoLEP is an effective treatment for symptomatic BPH. For patients with an IPSS of 8–35, early surgery may result in a positive prognosis and improve urinary function. The risk of moderate and severe OAB syndrome increases with an increase in preoperative IPSS.

AUTHOR CONTRIBUTIONS

YCT carried out the data analyses and drafted the manuscript. ZWW helped carry out the statistical analysis and draft the manuscript. CL participated in its design and coordination. MG and QC helped revise the manuscript. YBC and ZW conceived of the study, participated in its design, and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.

COMPETING INTERESTS

All authors declare no competing interests.