The clinical value of holmium laser enucleation of the prostate in octogenarians

With holmium laser enucleation of the prostate (HoLEP) a size‐independent method for surgical treatment of lower urinary tract symptoms (LUTS) secondary to benign prostatic obstruction (BPO) has been introduced. HoLEP offers durable long‐term results with reduced perioperative morbidity. As the risk of disease progression increases with age, the main goals, when offering surgery to an elderly population, are reducing perioperative morbidity and preserving quality of life (QoL). We therefore analyzed the impact of age on outcomes and perioperative morbidity in patients undergoing HoLEP for LUTS at our tertiary referral center.


| INTRODUCTION
Transurethral resection of the prostate (TURP) has been considered as the surgical standard treatment for lower urinary tract symptoms (LUTS) secondary to benign prostatic obstruction (BPO). In 1996, holmium laser enucleation of the prostate (HoLEP) was introduced by Gilling et al and has since become one of the most scrutinized forms of surgical intervention for BPO. 1,2 When comparing HoLEP to TURP, HoLEP has been accepted as at least equal in efficacy and even superior regarding perioperative morbidity. [3][4][5] HoLEP is independent of prostate size, and its effectiveness in relief of LUTS is comparable to open prostatectomy (OP) with less blood loss, shorter catheterization time and hospital stay. 6,7 As the benefits associated with HoLEP seem durable in long-term follow-up, it has even been considered the "new gold standard" for surgical intervention in LUTS secondary to BPO. 4,8 The risk of progression of LUTS increases with age. During the last century, life expectancy in Western civilizations has been steadily increasing. By 2040, one in four Americans will be over the age of 65, most likely leading to a higher incidence of LUTS secondary to BPO. 9,10 When offering surgical treatment to patients, the risk of developing complications is related to patients' health status, which generally worsens with age. 11 The main goals when offering surgery to an elderly population are reducing perioperative morbidity and mortality and preserving quality of life (QoL).
We therefore analyzed the impact of age stratification on outcomes and perioperative morbidity and mortality of patients undergoing HoLEP for LUTS/BPO. We especially focused on feasibility of HoLEP in the oldest patient cohort (>80 years of age) and aimed to analyze safety and efficacy.  Table 1 displays the demographic parameters of patient groups 1, 2, and 3. In total, 487 patients underwent HoLEP for LUTS secondary to BPO.
The median weights of resected tissue were significantly different in group 1 vs group 3 with 55 g (IQR 40-77.8) and 78 g (IQR 55-105), respectively (P < .02), with no difference for group 2 with 62.5 g (IQR 42-87.5, P = .182). There was no statistically significant difference in the overall median hemoglobin drop between the three groups (P = .505).

| Perioperative complications
In total, 20 (20/487, 4.1%) patients of the entire cohort experienced at least one perioperative complication. In groups 1, 2, and 3, five (2.4%), ten (6.0%), and five (4.3%) patients, respectively, had at least one perioperative complication. There was no significant difference between all three groups (P = .176). The groups did not differ in the severity of their perioperative complications described by the Clavien-Dindo score in Table 3

| Antiplatelet medication
As antiplatelet medication is very common in the aging population, we summarized the use of time-released Aspirin (acetylsalicylic acid 100 mg, Leverkusen, Germany), clopidogrel (P2Y12 inhibitors), new oral anticoagulants (NOAC; apixaban, rivaroxaban; factor Xa inhibitors), and warfarin stratified by age group (

| DISCUSSION
Bothersome LUTS affect considerably QoL in the elderly male population. LUTS secondary to BPO is age dependent and present in at least 40% of 50-to 60-year-old men and in about 80% of 80-year-old men.
More than half of those affected will become symptomatic. 12,16 As demographic changes will lead to a more aged population in Western countries, incidence of advanced-age LUTS will rise. Although many centers have shown that HoLEP for LUTS/BPO is feasible, the influence of age on functional outcomes and perioperative morbidity and mortality is of great importance in an ever-aging population. 4 In our high-volume tertiary referral center, we analyzed patients' age at time of HoLEP and their respective perioperative complications und postoperative outcomes. It is accepted that HoLEP is associated with high functional efficacy, low perioperative morbidity, and even lower mortality compared with TURP or OP. 4,6,8 Frail older patients often present with various comorbidities, such as anemia. 19 Our patient cohorts are highly comparable. They only significantly differed in preoperative hemoglobin value and score ≥III in the oldest patient cohort. Recently, Steinmeyer et al could show that anemia is present in a striking 20.83% of patients above the age of 80, while frailty depicted by the score is well documented in an elderly population with various comorbidities. 10,19,20 However, there was no need for perioperative blood transfusion. This corresponds well to the data gathered on the perioperative safety profile of performing HoLEP in octogenarians by Mmeje et al. 21 Also, postoperative drop in hemoglobin value showed no statistically significant difference between all age groups in our study population.
All patients in our study cohort showed significant improvement in functional outcomes after HoLEP. Patients in group 1 had the greatest improvement in postoperative IPSS and Q max ( Table 2). Although the association between a patient's geriatric status and functional outcome after minimally invasive prostate resection remains controversial, the prevalence of detrusor underactivity increases with age and is thereby contrasted in a decline of bladder outlet obstruction and therefor may explain the less pronounced effect on the older patient cohorts. [22][23][24] Patients aged 80 years and over had the highest absolute and relative amount of prostate tissue removed ( The limitations to our study surely include its retrospective design. We did not include patients undergoing other laser treatment options or TURP for LUTS/BPO in our study. There also was a smaller proportion of patients in our ≥80-years-of-age group than in the other groups, which naturally limits the power of our analysis. Being a tertiary referral center brings with it the problem of following up the patient at home, preventing the complete collection of data for more cases. A longer follow-up is required for complete appraisal of functional outcomes and the safety profile. However, we could show that there are no limitations to using HoLEP in an elderly patient cohort with exceptionally low morbidity and nonexistent perioperative mortality. When offering HoLEP as a treatment option in LUTS/BPO, one should consider offering it at even an earlier stage of the disease as younger patients may profit from increased functional results.

| CONCLUSION
In light of increasing life expectancy in Western nations, we sought to evaluate the impact of age on perioperative morbidity and mortality as well as functional outcomes in elderly patients undergoing HoLEP for LUTS/BPO. HoLEP provides a favorable safety profile even in the oldest patient cohort (≥80 years). Therefore, HoLEP for LUTS/BPO can be offered as viable treatment option even in oldest patients.

ACKNOWLEDGMENT
Open access funding enabled and organized by Projekt DEAL.

AUTHOR CONTRIBUTIONS
Alexander Tamalunas: project development, data collection and analysis, manuscript writing. Thilo Westhofen: data collection and management, data analysis. Melanie Schott: data collection and management, data analysis. Patrick Keller: data collection and management, data analysis. Michael Atzler: data collection and management.
Christian G. Stief: project development. Giuseppe Magistro: project development, data collection and analysis, manuscript writing.

CONFLICT OF INTEREST
The authors have not received any financial grants and declare that they have no industrial links or affiliations.

STATEMENT OF ETHICS
All human subjects provided written informed consent with guarantees of confidentiality. In lieu of an ethical review board, the authors state that this article does not contain any studies with human participants performed by any of the authors. Our research was carried out in accordance with the Declaration of Helsinki of the World Medical Association, and informed consent was obtained from all patients. All data were collected and analyzed anonymously.

DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request. ORCID