The goal of radical prostatectomy (RP) by any approach is the eradication of cancer while, whenever possible, preserving pelvic organ function [1]. Actually, both laparoscopic (LRP) and robot-assisted radical prostatectomy (RARP) represents well-established alternatives to open surgery as they can reduce hospital stay and blood loss [2, 3]. Incidental prostate cancer is found in 3%-16% of transurethral resection of the prostate (TUR-P) specimens [4]. It has been reported that nerve-sparing radical prostatectomy (nsRP) after previous prostate surgery can be challenging [4-8]. A recent meta-analysis suggested that RARP is feasible but challenging after TUR-P and it significantly increases the difficulty of operation and compromises surgical, functional, and oncological outcomes [6]. Many studies on erectile dysfunction (ED) following nerve-sparing RRP have been published, revealing widely disparate potency rates (30-86%) among various groups in different studies [9]. This variation in potency rates may be due to patient selection, surgeon and hospital volume, and the proportion of nerve-sparing procedures. The aim of our study was to investigate the effect of laparoscopic bilateral nerve-sparing radical prostatectomy after TUR-P (nsLRPT) on surgical and functional outcomes in patients previously diagnosed with incidental prostate cancer.

Study design

This was a retrospective, single-surgeon study of 125 consecutive patients who underwent extraperitoneal laparoscopic bilateral nerve-sparing radical prostatectomies (nsLRPT) for incidental prostate cancer diagnosed after TUR-P. All patients were informed of the procedures and provided written informed consent. Our surgical technique has been described previously [2]. Briefly, after dissection of the bladder neck (Figure 1), the periprostatic fascia including the neurovascular bundles is mobilized and dissection is performed posteriorly behind the bladder neck, and the seminal vesicles and the ductus deferens are identified and dissected. The Denonvilliers' fascia was stripped from the prostatic capsule, and the prostatic pedicles were clipped and dissected (Figure 2A & B). No coagulation or ultrasonic dissector was used during this step. Inclusion criteria were as follows: PSA < 10, Gleason ≤ 7, and only two positive cores from a minimum of 12 biopsies. Surgical and functional outcomes were compared. Postoperatively, all patients were treated with tadalafil 20 mg (on demand) and a vacuum constriction device for a consecutive period of 12 months. No patient underwent nerve-sparing LRP within the first 4 months after TUR-P to reduce periprostatic inflammation due to the first intervention. All surgical procedures were performed by one surgeon (F.G.) who had completed at least 70 nsLRPTs and at least 500 laparoscopic radical prostatectomies before the beginning of the study, thus reducing the learning curve effect. Data are expressed as mean ± standard deviation (SD), and statistical significance was accepted at P < 0.05. Statistical analysis was performed using SigmaPlot^® software version 13.0 (SPSS Inc., Chicago, IL, USA) and Graphpad Prism 5 (Graphpad Software, CA, USA). Fisher's exact test was applied to evaluate statistical differences between groups in pathological stages. Changes in sexual function scores over time were analyzed by repeated measures two-way analysis of variance.

Main outcome measures

The primary outcome parameters were defined as any change in sexual function as measured by the IIEF-5 at 12 months postoperatively compared to baseline, as well as changes in IIEF-5 domain and total scores over time. The IIEF-5 questionnaire has been given to patients preoperatively and at each follow-up visit (3 months, 6 months, 1 year). All questionnaires were completed independently. The secondary outcome measure of the study was to evaluate the efficacy and clinical performance of nsLRPT in patients with incidental prostate cancer.
Preoperatively, all patients were evaluated with a general medical history, sexual history, physical examination, 24-hour pad count (number of sanitary pads used in 24 hours), video urodynamics, and cystoscopy. Urinary continence and erectile function at follow-up were evaluated using the International Prostate Symptom Score (IPSS), the International Consultation of Incontinence Questionnaire-Urinary Incontinence (ICIQ-UI) short-form instrument. All patients reporting no need for pads were defined as continent. All patients with an IIEF-5 > 17 were defined as potent.

In recent years, mini-invasive RP has been suggested as a safe and effective treatment for prostate cancer in specialized centers [10-16]. Nevertheless, a Cochrane review comparing either RARP or LRP vs. open RP, which included two RCTs, found no significant differences between the comparisons for oncological, urinary, and sexual function outcomes, although RARP and LRP both resulted in statistically significant improvements in duration of hospital stay and blood transfusion rates compared with open RP [17]. Therefore, one surgical approach cannot be recommended over the other and is mostly based on surgeon preference and experience.
Performed by any of the surgical approaches, previous TUR-P may impose technical difficulties for the surgical teams, especially during dissection of the bladder neck. Moreover, previous infections of the prostate and seminal vesicles and perforation of the prostate capsule during TUR-P with extravasation of irrigation fluid might result in peri-prostatic fibrosis and distortion of the surgical plains, making dissection difficult. With better visualization of the anatomy and a relatively bloodless field, LRPT has the potential to provide good functional outcomes with equal oncologic effectiveness [18]. Although Jaffe et al. [19] reported that patients with a history of transurethral prostate resection who undergo laparoscopic radical prostatectomy have worse outcomes with respect to operative time, length of stay, positive margin rate and overall complication rate, other reports indicated that radical prostatectomy may be performed safely with an acceptable morbidity rate following TUR-P, although postoperative urinary incontinence and erectile dysfunction are more frequent as compared to primary cases [20-23]. Colombo et al. [7] reported on 109 patients who underwent RRP for prostate cancer, after surgical intervention for BPH. In 88 of these 109 patients the previous intervention was TUR-P. Patients were matched in pairs according to PSA level, age, and clinical stage. The peri- and post-operative morbidity was moderately increased in comparing with naïve patients, but functional results were assessed in only 48.8% of patients. In that study, complete urinary control was achieved in 86%, and adequate erectile function in 12% at 1 year follow-up after RRP.
Performing nerve-sparing radical prostatectomy in patients who previously had surgery for urinary obstruction can present some unexpected difficulties, requiring better surgical skills [6, 8]. In 2008, Suardi et al. [8] reported their experience with 15 consecutive patients who underwent nsRRPT after holmium laser enucleation of the prostate (HoLEP) and after TUR-P, with encouraging results. All operations were successfully performed without major complications. It has been postulated that nsLRPT resulted in a higher rate of positive margins. For an objective evaluation of the positive margin rate, three aspects have to be considered. The first is the technique of histopathologic examination, because pathologic evaluation of the prostate can influence the detection of positive margins. The second aspect is the stratification of positive margin rates according to pathologic stage. The third aspect is case selection (with or without adjuvant therapy) [15]. In many reports in the literature [7, 8, 20-23], there was no significant difference in the rate of positive margins associated with open or laparoscopic RP after TUR-P, as also found in our study (2.7% and 5.2% in the laparoscopic and open groups, respectively).
The quality of life is strongly affected by urinary incontinence. It has been shown that the incidence of postoperative incontinence depends on the experience of the urologist, patient age (increased frequency after 70 years), and the operative technique (i.e., nerve-sparing or not) [24, 25]. Laparoscopic surgery may offer an improved identification of anatomic landmarks such as striated muscles and neurovascular bundles, resulting in less damage to the striated sphincter. Moreover Stolzenburg et al. [14] proved better results on early continence by preserving the puboprostatic ligament during nsLRP. The main question associated with a RP after TUR-P is represented by its safety concerning the postoperative continence and potency rates. Again, the study group of the University Vita-Salute San Raffaele, Milan [8] reported an interesting continence rate in all patients who underwent nsRRPT after HoLEP and TUR-P. At 6 months after the procedure, 93.3% of all patients were continent and 53.3% of patients after HoLEP and 40% of patients after TUR-P reported satisfactory sexual intercourse with the use of PED5 inhibitors.
In our study, all procedures were performed without major complications. An earlier return to continence was observed in 43.8% of patients. Nevertheless, complete continence was reported at 12 months in 98.4% of patients who underwent surgery. Regarding sexual potency, the outcomes resulted to be promising, with 52% and 78.4% of all patients reporting the ability to engage in sexual intercourse at 6 and 12 months after surgery, respectively. However, these results should be evaluated considering the use of PED5 inhibitors and vacuum constriction device for a consecutive period of 12 months. Although our results can be interpreted as promising, nsLRPT remains a challenging procedure that requires extensive surgical experience and should be performed in high-volume centers. Future prospective studies comparing mini-invasive RP after TUR-P with alternative therapies including HIFU or radiotherapy are needed to identify the best treatment for incidental prostate cancer after TUR-P.

nsLRPT represents a feasible mini-invasive approach to the treatment of prostate cancer also for patients with prior prostate resection. Given the technical difficulties associated with this procedure, LRPT should be performed by experienced surgeons in high-volume centers, in order to improve postoperative oncologic and functional outcomes with regard to urinary continence and sexual potency.

Financial support and sponsorship

None.

Conflicts of interest

Francesco Greco is a member of the editorial board of Uro-Technology. The authors declare that they have no conflicts and were not involved in the journal's review or decision regarding this manuscript.

Ethical statement

This study was approved by the Institute Research Medical Ethics Committee of Centro Salute Uomo. All patients were informed of the procedures and provided written informed consent.