Abstract
Purpose:
To evaluate outcomes of post-holmium laser enucleation of the prostate (HoLEP) robot-assisted radical prostatectomy (RARP).
Patients and Methods:
Using an institutional database, we identified 11 HoLEP patients who subsequently underwent RARP. These were matched 1:2 to RARP patients without a previous transurethral surgical procedure. Variables matched were age, pre-RARP prostate-specific antigen level, and biopsy Gleason score. Urinary continence and sexual function were evaluated by physician questioning, American Urological Association symptom score, and Sexual Health in Men (SHIM) scores. Descriptive statistics were used to compare cohorts.
Results:
RARP pathologic outcomes were similar between cases and controls. Twenty-seven percent of previous HoLEP patients reached strict urinary continence (leak free, pad free) at last follow-up compared with 64% of matched controls (P=0.071). The average (range) SHIM score at last follow-up was 2.6 (1–5) for previous HoLEP patients compared with 13.9 (5–20) (P<0.001). The posterior bladder neck and apical dissections were significantly more challenging in the setting of previous HoLEP and necessitated a low threshold for wider resection to minimize positive surgical margins.
Conclusions:
Post-HoLEP RARP is challenging but preliminarily appears safe and feasible when performed by an experienced robotic surgeon. Patients should be counseled regarding expectations of urinary continence and sexual function in this setting.
Introduction
B
Radical retropubic prostatectomy (RRP) after previous TURP is challenging with varying levels of success. 8 –13 Outcomes of open RRP after HoLEP have been reported to be similar to those of open RRP after TURP. 14 In the era of robot-assisted radical prostatectomy (RARP), we aimed to assess surgical feasibility and early oncologic and functional outcomes of RARP in men who had previously undergone HoLEP. We compared our results with a matched group of men who underwent RARP without a previous transurethral surgical procedure.
Patients and Methods
Patients and procedures
Between 1998 and 2013, 1545 patients underwent HoLEP using previously described techniques. 15 The majority (>90%) of HoLEPs were performed by a single surgeon (JEL). The HoLEP specimen was then submitted for pathologic analysis by dedicated genitourinary pathologists.
One hundred and three patients had prostate cancer identified on HoLEP. Eleven of these patients underwent RARP at our institution. Seven had benign pathology on HoLEP while four had low-risk prostate cancer and subsequently underwent treatment. A 1:2 matched cohort was obtained from an institutional database of patients who had not undergone transurethral surgical procedures. Variables matched between groups included biopsy Gleason score, pre-RARP prostate-specific antigen (PSA) level (within 2 ng/mL), age (within 2 years), and date of RARP (within 2 years). All patients were evaluated preoperatively with medical history and physical examination. Patients with previous HoLEP had baseline scoring of subjective symptoms using validated questionnaires including American Urological Association (AUA) symptom score and Sexual Health Inventory for Men (SHIM). 16,17
RARP was performed (MOK and RSB) in standard fashion. 18,19 Nerve sparing (unilateral or bilateral) was performed in 60% of patients at the surgeon's discretion based on preoperative pathologic information, preexisting erectile function, and surgical tissue planes. Lymph node dissection was performed in 82% of patients and included removal of obturator and external iliac lymph nodes.
After RARP, patients were typically followed at 6 weeks, 3, 6, 9, and 12 months. Patients were asked to fill out validated questionnaires at each office appointment. Patients receiving nerve-sparing surgical procedures were immediately placed on daily low-dose tadalafil postoperatively for 3 months and transitioned to a higher dose if needed and offered a vacuum erectile device if unhappy with recovery of potency.
Outcomes and variables
The primary outcomes of interest were RARP pathology, urinary continence, and sexual function. Variables from the HoLEP included age, PSA level, resection volume, enucleation time, and PSA nadir. RARP variables included demographics, intraoperative, oncologic, and functional recovery. PSA velocity was tabulated. 20 Strict definition of urinary continence was leak free and pad free at most recent follow-up. Loose definition of continence was no pad use or a single security pad that was usually dry. Patients were defined as potent if able to achieve an erection, including with the aid of phosphodiesterase-5 inhibitors or vacuum-assisted devices. Urinary continence and sexual function were evaluated using physician questioning, AUA symptom scores, and SHIMs.
Statistical analysis
Descriptive statistics were performed using the Fisher exact test for categoric variables. Normally distributed continuous variables were evaluated using the Student t test and nonnormally distributed variables by the Mann-Whitney test. Institutional Review Board approval was obtained. All statistical analyses were performed using Stata version 13.0 (Stata Corp. LP, College Station, TX) and P values <0.05 were considered statistically significant.
Results
Patient characteristics at HoLEP are shown in Table 1. Characteristics of these patients and their matched controls at the time of RARP are presented in Table 2. The cases and controls were adequately matched for preoperative variables. Four of 11 (36%) patients had prostate cancer diagnosed at the time of HoLEP (all Gleason 6) and elected surveillance initially. Ten of the 11 (91%) underwent transrectal ultrasonography biopsy during surveillance after HoLEP before RARP. Eight of the biopsies were initiated secondary to concerning PSA kinetics and two were secondary to a palpable nodule during digital rectal examinatioon. One patient with cancer on HoLEP elected for prostatectomy 14 months later without repeated biopsy. Individual HoLEP and RARP patient data are provided in Supplementary Tables 1 and 2 (supplementary data are available online at
Pre-HoLEP PSA was not available for one patient.
HoLEP=holmium laser enucleation of the prostate; SD=standard deviation; RARP=robot-assisted radical prostatectomy; PSA=prostate-specific antigen.
Clinical stage and biopsy Gleason score are not available for one previous HoLEP patient.
Using loose continence definition.
BMI=body mass index.
Perioperative findings are demonstrated in Table 3. Operative time was longer (217 vs 165 minutes; P=0.005) and blood loss higher (209 vs 131 mL; P=0.012) in the previous HoLEP cohort. Patients without previous transurethral surgical procedures had higher baseline potency and underwent bilateral nerve-sparing procedures more frequently (Table 3). At the time of radical prostatectomy, gland size was larger in the HoLEP-naïve cohort, although this was not statistically significant (56 vs 43 g; P=0.206). One previous HoLEP patient was hospitalized for 2 days, but all other radical prostatectomy patients went home on postoperative day 1. There were no perioperative complications recorded during RARP. On initial postoperative cystography, one previous HoLEP patient had a small anastomotic leak that resolved with an additional week of Foley catheter drainage.
Gleason not determined because of one previous HoLEP from single preoperative androgen deprivation therapy.
Only patients with preoperative potency.
IQR=interquartile range; AUA SS=American Urological Association Symptom Score; SHIM=Sexual Health Inventory for Men.
Pathologic data are available in Table 3. Pathologic Gleason score and positive margin rates were similar between groups. The initial two patients in the previous HoLEP group had positive surgical margins at the time of RARP, and all subsequent previous HoLEP patients had negative margins, including two with pT3 disease. Locations of the two positive surgical margins were at the left posterior and apical regions. The incidence of pT3 disease was higher among controls (45% vs 18%, P=0.249), although this did not reach statistical significance. No patient in either cohort had Gleason 8 or 9 disease. One patient in the control cohort had a single positive lymph node.
Recent AUA symptom scores and SHIM scores are listed in Table 3. Among patients potent before RARP, 54% of the control cohort compared with 25% of the previous HoLEP cohort maintained potency at last follow-up (P=0.576). There was no significant difference in the proportion of patients who were continent with zero to one small (security) pad per day between the previous HoLEP (67%) and HoLEP-naive (86%) cohorts (P=0.320). In using a strict criteria for continence (leak free, pad free), a statistically significant difference between groups was approached but not detected with three (27%) previous HoLEP patients compared with 14 (64%) control patients being fully continent (P=0.071). The median time to continence, however, was significantly longer among previous HoLEP patients (6 months vs 12 months, P=0.041). An anastomotic stricture or bladder neck contracture had not developed in any patient at last follow-up. One patient in each group was part of an instititutional randomized control trial involving concurrent placement of a sling during RARP. The urinary function outcomes were not impacted by placement of the sling.
Discussion
HoLEP is an established endoscopic approach in the management of BPH. Prostate cancer detected on HoLEP is typically low grade and can be managed with surveillance. 7,21 A small percentage of HoLEP patients will be immediately diagnosed with intermediate- or high-risk disease while others will have a diagnosis of clinically significant prostate cancer during follow-up. Many of these patients will be considered for radical prostatectomy. In the presented study, we evaluated early outcomes in this unique cohort of patients.
Several reports suggest that radical prostatectomy is effective after TURP or open prostatectomy, albeit with poorer recovery of urinary control and potency. 8 –13 Although no data currently exist for post-HoLEP RARP, Suardi and associates 14 did report on the feasibility of open RRP after HoLEP. They found the procedure challenging but feasible and reported satisfactory oncologic and functional outcomes when compared with patients who had undergone previous TURP or simple prostatectomy. Operative time, hospitalization, and complications were similar between cohorts. Of note, Suardi and associates 14 did not compare HoLEP-naïve patients undergoing open radical prostatectomy with their post-HoLEP radical prostatectomy patients. We similarly report that post-HoLEP radical prostatectomy is feasible but clearly more difficult compared with our HoLEP-naïve controls.
In our series, operative time and estimated blood loss were longer, while hospitalization and catheter indwelling times remained similar. Although our initial two patients had positive surgical margins, the subsequent nine, including our patients found to have pT3 disease, had negative margins. This suggests that there may be a learning curve associated with the operation, even for surgeons who have performed higher volumes of traditional RARP, as was the case in our study. Fortunately, we observed no major perioperative complications or anastomotic strictures with early follow-up. Surgical experience and skill set likely contributed to early favorable outcomes in this initial cohort of patients. 8
Given the small number of previous HoLEP patients who had a diagnosis of prostate cancer or in whom prostate cancer developed in follow-up, it is difficult to determine the importance of PSA kinetics in predicting the presence of disease. Patients with cancer detected on HoLEP had higher PSA values compared with patients with benign pathology in whom prostate cancer developed during follow-up. This observation has similarly been described in previous published reports. 21 It should be noted that patients without an initial diagnosis of prostate cancer had higher PSA nadirs after HoLEP compared with the T1a/T1b group. This supports previous recommendations that patients who do not nadir below 1 after HoLEP should carry a low threshold for biopsy or repeated biopsy if their PSA level continues to rise because this may herald occult prostate cancer. 7
Interestingly, PSA velocity did not differentiate between groups, which might reflect the small numbers we present. No significant differences with regard to Gleason score, the presence of pT3 disease, or nodal involvement were demonstrated in patients with early or delayed detection of prostate cancer after HoLEP. Early oncologic results are encouraging but longer follow-up is needed to fully predict the effectiveness of RARP after HoLEP and the role that PSA kinetics may play in predicting both surgical candidacy and outcomes.
The impact of RARP on continence after HoLEP is difficult to evaluate because previous transurethral surgical patients have varying levels of baseline continence. In addition, timing of the second operation may impact interpretation of results because patients may still be recovering from their HoLEP when receiving a “second hit” with RARP. Interestingly, Suardi and associates 14 found that continence recovery was not affected in patients undergoing open RRP after previous prostate surgery, whether it was HoLEP, TURP, or simple prostatectomy. They also found that patients had satisfactory continence outcomes using standardized questionnaires.
In our study, fewer patients in the previous HoLEP group were continent before and after RARP, although this did not reach statistical significance, likely because of the small sample size. Only 27% of previous HoLEP patients achieved a leak-free, pad-free state, and time to achieving continence was longer in this group. Clearly, in our experience, radical prostatectomy after previous HoLEP negatively impacted recovery of continence. Damage may be an additive effect secondary to intrinsic injury to the sphincter and bladder neck during HoLEP followed by manipulation of the pelvic floor, periurethral, and bladder anatomy during RARP. Patients requesting RARP after previous HoLEP should therefore be counseled to anticipate a slower recovery of continence and poorer overall continence using either the loose (67%) or strict (27%) criteria definition of urinary control.
Similar to continence, functional recovery of erections in the previous HoLEP cohort is difficult to assess, because potency tends to be lower at baseline in these patients. Studies have demonstrated that performing adequate nerve sparing in previous transurethral surgery patients is challenging and that the presence of preserved nerves does not necessarily correlate with the recovery of erections. 8,11,13,14 We found that despite performing some type of nerve sparing in six of the previous HoLEP patients, only a single patient reported adequate erections at last follow-up. Entering the intrafascial nerve plane in this group was difficult and, even when identified, was frequently difficult to dissect away from the prostate capsule. Rather than subject the patient to unwarranted positive margins, we tended to dissect further away from the prostate compared with our standard intrafascial nerve sparing in our HoLEP-naïve patients. Although this may have impacted initial results, clearly lower expectations regarding postoperative potency should be anticipated.
Surgeons performing RARP after previous HoLEP should be aware of unique technical nuances of the operation. One of the most consistent challenges is identification of the posterior bladder neck. As demonstrated in Figure 1A, long-standing BPH can displace the ureteral orifices laterally and sometimes asymmetrically depending on prostate growth and the presence of a median lobe. In addition, laser effects of HoLEP can distort the bladder neck and obscure the demarcation between posterior bladder neck, trigone, and prostate. These anatomic changes are demonstrated in Figure 1B. We recommend taking additional time to identify the ureteral orifices and giving methylene blue or indigo carmine when needed to appropriately delineate the anatomy before division of the posterior bladder neck. We did not find that the posterior Montsouris approach provided added benefit in identifying anatomic landmarks or discerning this dissection plane. 22

(
Challenges also exist during apical dissection because the previous HoLEP has often eliminated the majority of anterior tissue, leaving a very thin capsule and potentially subjecting the surgeon to inadvertent capsule entry when entering through the dorsal venous complex (Figure 1C, arrow 1). We recommend a more distal, anterior dissection arc to avoid iatrogenic violation of the gland in these cases (Figure 1C, arrow 2). Fortunately, the seminal vesicle and posterior rectal dissection was similar to our HoLEP-naïve cohort and did not pose additional challenges during RARP.
This study has important clinical implications. First, post-HoLEP RARP should be performed by experienced robotic surgeons because the surgeon will be faced with numerous anatomic challenges. Patients should be counseled to anticipate longer operative times, slower return of continence, and significant worsening of potency, even when nerve sparing is performed. Despite these risks, patients undergoing post-HoLEP RARP can expect low complication risks and encouraging oncologic outcomes, similar to HoLEP-naïve patients undergoing the same operation.
Several limitations should be noted. Our cohort is small with limited follow-up. This study was retrospective and many patients who underwent RARP after HoLEP had preexisting potency and continence impairment making postoperative functional recovery difficult to interpret. Follow-up visits occurred in 3-months interval; therefore, continence may have been achieved sooner than documented. Patients underwent RARP at various time points after undergoing a HoLEP, so the impact of periprostatic inflammation from the primary intervention was difficult to assess. Despite these limitations, this represents the first study describing feasibility and early oncologic and functional outcomes of RARP after previous HoLEP.
Conclusions
RARP is feasible and safe after HoLEP with encouraging oncologic results. Surgeons will be faced with technical challenges unique to this patient cohort. Strict leak-free, pad-free continence rates are low and time to continence is clearly impacted by previous HoLEP. Neurovascular bundle preservation is difficult, and postoperative erectile function may be compromised. Longer follow-up is needed to fully assess our initial early outcomes.
Footnotes
Acknowledgment
The authors would like to recognize the work of Sharon Teal, the medical illustrator who produced the images for this project.
Author Disclosure Statement
James E. Lingeman is a consultant and meeting participant/lecturer for Lumenis; and a consultant, investor, meeting participant/lecturer, and scientific study trial for Boston Scientific. Michael O. Koch is an investigator for Sonocare. No competing financial interests exist for the remaining authors.
Abbreviations Used
References
Supplementary Material
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