Introduction

Holmium laser enucleation of the prostate (HoLEP) was initially described in 1998 [1]. HoLEP has proven to be a minimally invasive, size-independent method for the treatment of benign prostatic obstruction (BPO) with excellent long-term results [2, 3]. Based on HoLEP, alternative techniques for anatomic endoscopic enucleation of the prostate (AEEP) using different energy sources have been described [4]. The surgical management of BPO by AEEP is hindered by an increasing use of chronic oral anticoagulant (AC) and/or antiplatelet (AP) therapy for primary and secondary prevention of cardiovascular diseases [5,6,7]. Perioperative management of AC/AP therapy is a matter of debate: only sparse data exist for AEEP in patients on AC/AP therapy [8]. This review focuses on the literature regarding all AEEP techniques, to assess the safety, efficacy and durability of these procedures in patients on AC/AP therapy, and to further elucidate their potential advantages and limitations.

Materials and methods

Data collection was based on a PubMed search of papers published in the English language from 1998 until September 2020 assessing the impact of intraoperative AC/AP therapy on patients undergoing AEEP for BPO. All retrospective and prospective cohort studies, and randomized controlled trials (RCT) were assessed for possible inclusion (Table 1). Two authors (CN, BB) independently screened all articles.

Table 1 Search terms, inclusion and exclusion criteria of the review
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HoLEP

The first HoLEP series with patients on AC/AP therapy was published in 2002 [9]. Nineteen patients were on oral AC therapy: none of the patients required blood transfusions, and 2 (10.5%) patients developed clot retention, which was managed conservatively. However, neither baseline nor follow-up characteristics of these 19 patients on AC therapy were presented or compared to those of the patients not taking AC therapy. Since then, several HoLEP studies on patients taking AC/AP drugs have been published [10,11,12,13,14,15,16,17,18,19,20,21,22,23] (Table 2). Most of the studies presented perioperative data [11, 12, 17,18,19,20, 22, 24] not exceeding 6-month follow-up [13, 14, 22], except four series with a longer follow-up [9, 10, 15, 20]. While AP therapy was continued [11,12,13,14,15,16,17, 19,20,21,22,23,24], AC therapy was bridged with low molecular weight heparin (LMWH) (Table 2). Only three studies evaluated HoLEP in patients under continuous AC therapy [9, 10, 12]. Highest transfusion rates were found in patients with LMWH bridging or under continuous AC therapy (up to 15%), while transfusion rates under AP therapy did not exceed 3% (Table 2). Postoperative clot retention occurred in 12.5% of the patients maximum, while reintervention rates (RR) were reported in 3.7% of the cases maximum. The feasibility and safety of HoLEP in patients on AC/AP therapy were shown in patients with prostate sizes up to 105.8 ml [9,10,11,12,13,14,15,16,17,18,19,20,21,22,23]. However, a comparison of these studies is hindered by non-reporting of complication rates (CR) and bleeding-related CR (Table 2).

Table 2 Holmium laser enucleation of the prostate (HoLEP) in anticoagulated patients (n = 1966 patients on AC/AP therapy)
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AEEP

The definition “AEEP” was introduced by the EAU Guidelines in 2016 to group all surgical procedures used to perform an anatomical enucleation of the prostate, in spite of the energy source employed [3]. Since then, AEEP have been used in literature reviews for standardization purposes [4, 24, 25]. Although 45% of the HoLEP and 60% of the GreenLEP cases were on AP/AC therapy, bleeding complications were low. 4% of the patients in each group had postoperative hematuria, requiring blood transfusions in 4% of the HoLEP and in 1% of the GreenLEP patients. The Clavien 3b CR was 5% and 3% after HoLEP and GreenLEP, respectively. The 3-month readmission rate did not differ between the groups (9% vs. 4%) [14] (Tables 2/3).

ThuVEP

ThuVEP was described by Bach et al. in 2009 [26]. Hauser et al. presented the first ThuVEP series of 39 patients treated whilst on AC/AP therapy and/or with bleeding disorders. One patient (2.6%) received a blood transfusion. Two patients (5.1%) developed postoperative bladder tamponade, and 5 patients (12.8%) were re-operated due to postoperative bleeding. It remains unclear whether AEEP or a vaporesection procedure was performed [27] (Table 3).

Table 3 Different techniques for anatomic endoscopic enucleation of the prostate (AEEP) in anticoagulated patients
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Netsch et al. evaluated the safety of ThuVEP on 56 patients with high cardiopulmonary risk who were on AC/AP therapy at the time of surgery. Four patients needed blood transfusions (7.1%) and four patients (7.1%) required immediate re-operation. They also provided the first 24-month follow-up in high-risk patients, showing a significant relief of obstructive symptoms with a PSA-reduction of 81.04% during follow-up [5] (Table 3).

The same study group performed a retrospective matched-paired analysis on 26 patients on AC/AP therapy treated with ThuVEP. One patient each required either a blood transfusion or immediate re-operation due to bleeding or had postoperative clot retention. Urodynamic parameters were significantly improved at 6-month follow-up. One patient was re-treated for residual prostatic tissue [28] (Table 3).

Bach et al. prospectively analyzed 2648 patients from four urological departments who underwent TURP, GreenLight Vaporisation, or ThuVEP. 237 patients treated with ThuVEP were on AC/AP treatment. The transfusion rate was 5.5% for prostates < 40 ml, 0.9% for prostates between 40 and 80 ml and 14.9% for prostates > 80 ml. This paper was the first to present large “real life”, multicentric, routine data from patients on AP/AC therapy who underwent ThuVEP. Bach stated that the learning curve and the influence of high-risk patients on perioperative bleeding and transfusion rates seem to be underestimated in RCT [29] (Table 3).

Castellani et al. retrospectively analyzed 88 patients treated with ThuVEP between 2015 and 2019 on AP/AC therapy. Clot retention (2.2%), blood transfusions (2.2%), reintervention (4.5%) and intensive care unit treatment (2.2%) were the most important complications. PSA drop and urodynamic improvements at 12-month follow-up were comparable to previous ThuVEP series. No differences in CR and functional outcomes after ThuVEP were found, regardless of AP regimens. Patients on LMWH also demonstrated comparable results [30] (Table 3).

ThuLEP

ThuLEP was described in 2010 by Herrmann and colleagues [31]. Castellani et al. retrospectively evaluated 412 patients who underwent en-bloc ThuLEP [32]: 46 patients were on AC/AP therapy at time of surgery. The Clavien I (9.2%), II (2.7%), III (1.2%), and IV (0.7%) CR was very low. Urodynamic parameters were significantly improved at 1-year follow-up. Vartak et al. reported a series of 109 high-risk patients who were treated with ThuLEP. Of these 109 patients, 19 were treated whilst on aspirin and 3 under the combination of aspirin and clopidogrel. Perioperative data were, however, not reported [33] (Table 3).

DiLEP

DiLEP was introduced by Buisan et al. using a 980-nm diode-pulsed laser at 100-W [34]. In most DiLEP papers, the 980-nm diode laser is utilized for DiLEP, showing significant RR compared to other lasers [35].

Zhang and co-workers published a RCT comparing DiLEP (1470-nm diode laser) with plasmakinetic resection of the prostate [36]. They also published a retrospective study comparing DiLEP (1470 nm diode laser) on 49 patients under AP/AC therapy with 95 patients not taking AP/AC therapy. No differences in terms of bleeding complications and perioperative data were reported. CR in patients on AP/AC therapy were: transfusions (2%), secondary bleeding (4.1%), clot retention (4.1%). No re-intervention was necessary in this high-risk group during follow-up. At 12-month follow-up, urodynamic parameters had improved significantly and were not different between the two groups [37] (Table 3).

GreenLEP

The first abstract on 180-W XPS GreenLEP was presented at the EAU 2010 [38]. The first paper was published in 2014 [39, 40] followed by a description of the surgical steps [41].

Misrai et al. presented a series of 60 consecutive GreenLEP surgeries, 31 of which were performed on patients under AP/AC therapy. Intraoperative conversion rate to TURP was 16.6%. Hematuria occurred in 5% of the patients. Transfusion rate was 1.6% and RR was 3.3%. At 6-month follow-up, urodynamic parameters had significantly improved. PSA-reduction was 67% [42]. In another study, 99 out of 204 patient were on AP/AC therapy. Overall CR was low: Clavien I, II, IIIa and IIIb CR were 5.4%, 10.8%, 0.98%, and 3.4%, respectively. Transfusion rate was 0.5%. Urodynamic parameters as well as PSA were significantly improved at 6-month follow-up [43] (Table 3).

PVEP

PVEP, using the 180-W XPS GreenLight laser, is less radical than GreenLEP due to its vapoenucleation. A RCT comparing PVEP with HoLEP was published in 2015 [44]. Of the 53 patients in the PVEP arm, 53% were on AP/AC therapy or had bleeding disorders at the time of surgery. A higher intraoperative conversion to TURP was found (24.5% vs. 4%) compared to HoLEP. Postoperative hematuria, blood transfusions, immediate reoperation due to bleeding were reported in 3.7%, 1.8% and 1.8% of the patients. The 1-year RR was 5.7%, which was not significantly different compared to HoLEP (4%). Micturition parameters after PVEP were non-inferior to HoLEP at 12-months, but the PSA drop was significantly lower after PVEP compared to HoLEP (45.9 vs. 82.6%) (Table 3).

BipolEP or PkEP

Since the first published RCT comparing HoLEP with PkEP in 2006 [45], a plethora of different acronyms describing BipolEP has been published [4, 18]. El-Shaer and colleagues published a retrospective analysis of 91 patients on AC/AP therapy who underwent plasmakinetic enucleation and resection of the prostate. The rate of blood transfusions, clot retention, and secondary hemorrhage was 2.2% each. At 6-month follow-up, micturition had improved significantly. PSA drop was only 47%, which indicated that removal of the adenomatous tissue was inferior with PkEP [46]. Boeri et al. compared HoLEP and BipolEP in patients on AP/AC therapy. In the BipolEP group, 15 patients were on AC and 24 on AP therapy. No significant differences between the study arms with regard to bleeding complications and 2-month IPSS were found. The transfusion rate was 2.8%. The Clavien I, II, and III CR was 4.2%, 13.3%, and 0.7%, respectively [18].

Other AEEP techniques

The principles of AEEP were first published in the 1980ies utilizing monopolar energy for MEP [47, 48]. Other AEEP techniques were: ELEP [49,50,51], ThuFLEP [52], and MoLEP [53,54,55]. However, no studies analyzing the impact of AC/AP therapy on perioperative MEP, ELEP, ThuFLEP or MoLEP outcomes have been published so far.

Conclusions

The main issues with most AEEP studies are that almost all of them have a retrospective study design or originate from a single center. Therefore, outcomes are almost exclusively based on procedures performed by expert hands.

In most of the studies, AP/AC therapy was not distinguished. This is a particular weakness for the analysis since in clinical routine aspirin is often not interrupted, whereas, phenprocoumon and new oral anticoagulants are bridged with LMWH. Although data show fewer bleeding-related complications in patients under AP therapy, compared to those under AC therapy and LMWH, these complications only count for prostate glands between 50 and 110 ml. Patients taking both AP and AC therapy are associated with increased bleeding complications.

However, all of the studies show that AEEP is feasible in patients under AC/AP therapy and that functional results do not differ from those of patients not taking AC/AP therapy.