European Urology

2.1. Historical background

The first simple laparoscopic cystectomy for pyocystis was performed by Parra et al in 1992 [5]. In 1995 de Badajoz et al published the first study on LRC for muscle-invasive bladder cancer, wherein the ileal conduit urinary diversion was performed extracorporeally [6]. In 1995 Puppo et al described five cases of a combined laparoscopic and transvaginal anterior pelvic exenteration for bladder cancer: One bilateral cutaneous ureterostomy and four ileal conduits were performed through a minilaparotomy; the surgical specimen was withdrawn en bloc transvaginally [7]. In 2001 Turk et al described a completely intracorporeal LRC with a continent urinary diversion (rectal sigmoid pouch) [8]. A completely intracorporeal reconstruction of the entire LRC and urinary diversion procedure was reported by Gill et al, who also performed the first purely laparoscopic ileal conduit urinary diversion surgery and the first purely laparoscopic orthotopic Studer neobladder reconstruction surgery in 2000 and 2002, respectively [9], and [10].

2.2. Indications and contraindications

LRC is typically offered to patients with organ-confined, nonbulky bladder cancer as determined by preoperative clinical and radiographic findings. Presence of bulky lymphadenopathy, locally advanced disease, uncorrected coagulopathy, and morbid obesity are contraindications for LRC. Prior abdominal surgery, radiotherapy, or neoadjuvant chemotherapy may be relative contraindications for LRC and need to be assessed on a case-by-case basis. Assessment is important because these factors can significantly increase the degree of technical challenge.

2.3. Laparoscopic technique

The LRC technique is now approaching standardization, duplicating the established ORC technique. The ureters are dissected from the bladder base up to a point proximal to the common iliac arteries bilaterally and transected distally. In the male, the dissection is started in the cul-de-sac between the rectum posteriorly and the prostate, the seminal vesicles, and the bladder anteriorly. Bilateral vascular pedicles are controlled with sequential firings of the articulating endoscopic gastrointestinal anastomosis (GIA) stapler (Ethicon Endosurgery, Cincinnati, OH, USA) or using a Ligasure system (Valleylab, Boulder, CO, USA; Fig. 1). This postero-lateral dissection is carried out distally up to the midprostate. The urachus is divided high (Fig. 2); the anterior surface of the bladder is mobilized; the endopelvic fascia is incised bilaterally, and the dorsal vein is secured with a stitch or a staple (Fig. 3). If necessary, the technique of nerve sparing is used, which is similar to that used in laparoscopic radical prostatectomy (LRP). To avoid spillage of urine, the urethra is closed before transection. Once the urethra is transected and the dissection is completed, the specimen is immediately entrapped in an Endocatch-II bag (United States Surgical Corp, Norwalk, CT, USA). Tissue samples from the distal ureteral margin and urethral stump margin were sent for frozen-section biopsy [11]. In the female, either a conventional anterior exenteration or a uterus-sparing and vaginal-sparing LRC can be performed [12]. After completion of cystectomy, bilateral extended lymph-node dissection is performed toward the aortic bifurcation, based on the open template: laterally, genitofemoral nerve; medially, perivesical tissue; posteriorly, obturator nerve; distally, node of Cloquet, and proximally, aortic bifurcation and presacral tissue [14]. Some authors start with the extended pelvic lymph-node dissection before performing the LRC [15]. The LRC technique of urinary diversion replicates the ORC procedure with completely intracorporeal bowel work, bilateral uretero-ileal anastomosis, and urethro-neobladder anastomosis. The presently preferred, extracorporeal technique employs a 5–7 cm periumbilical midline minilaparotomy to extract the specimen and to perform the bowel work and the ureteroileal anastomosis. In patients undergoing orthotopic neobladder reconstruction, the urethro-neobladder anastomosis is executed laparoscopically after re-establishing the pneumoperitoneum.

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Fig. 1 Exposure and hemostasis of the vascular pedicles.

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Fig. 2 Division of the urachus.

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Fig. 3 Endopelvic fascia is incised bilaterally, before securing the dorsal vein.

3.1. Operative outcomes and complications

The selected literature confirm the technical feasibility and low perioperative morbidity of LRC. In our initial 37 patients undergoing LRCs and extracorporeal urinary diversions (18 ileal conduit diversions, 19 orthotopic neobladder reconstructions), the mean operating time was 6.3 h and the mean blood loss was 378 ml. One patient (3%) required a blood transfusion; postoperative time before first oral intake was 3 d, and postoperative time before ambulation was 2.4 d (Table 1). Four patients (11%) presented with major complications that required re-operation: urinary extravasation requiring open revision of the uretero-ileal anastomoses (n = 1) and a small bowel obstruction requiring open adhesiolysis (n = 3) [16]. Gerullis et al reported their experience with 34 patients undergoing LRC and extracorporeal urinary diversion: the mean operating time was 244 min, the mean blood loss was 325 ml, and the blood transfusion rate was 5.9% [17]. No perioperative mortality occurred. Poor bowel function was observed in three cases (8.8%). Five patients (14.7%) presented with unilateral obstruction of the upper urinary tract between postoperative week 2 and week 5, without flank pain and creatinine increase, raising concerns regarding anastomosis stricture.

Cathelineau et al reported their results of 84 laparoscopic assisted prostatocystectomies or cystectomies to remove transitional cell carcinomas of the bladder [18]. The median operating time was 280 min, and the mean blood loss was 550 ml, with a blood transfusion rate of 5%. There were no conversions to an open technique. Complications occurred at a rate of 8%: one pulmonary embolism, two urinary fistulas, three hematomas, and one pyelonephritis. All the surgical margins were free of tumor invasion.

Simonato et al reported that analgesic requirements were limited to the first postoperative night in 10 consecutive patients [19]. Patients were ambulant between postoperative day 1 and day 3, and bowel activity returned between postoperative day 2 and day 4.

4.1. Laparoscopic assisted versus open radical cystectomy

In a recent study, we retrospectively compared our recent, consecutive 50 LRCs (38 men, 12 women) with extracorporeal urinary diversion (13 ileal conduit diversions, 12 orthotopic neobladder reconstructions) with a contemporary cohort of 50 case-matched patients undergoing ORC (34 men, 16 women). There were no significant differences between the LRC and ORC groups with respect to mean patient age (66 vs 67; p = 0.61), body mass index (BMI; 27 vs 26; p = 0.50), comorbidities, history of prior abdominal surgery, and operative indications. Tumors were organ confined (≤pT2N0), nonorgan confined (pT3-4N0), and lymph-node positive (pT_anyN+) in 66%, 28%, and 6% of the LRC patients, respectively, and in 62%, 20%, and 18% of the ORC patients, respectively, with no significant differences between the groups (p = 0.15). Compared to ORC, LRC with extracorporeal urinary diversion was associated with reduced blood loss, decreased ileus, and somewhat shorter hospital stay, without significant differences in operating time and postoperative complications (Table 2) [20].

Basillote et al compared 11 men who underwent ORC to 13 men who underwent LRC with ileal neobladder reconstruction performed extracorporeally [29]. This study showed that the laparoscopic approach was associated with decreased postoperative analgesic use (parenteral morphine: LRC [61 mg] vs ORC [144 mg]; p = 0.042), more rapid postoperative return to oral intake (LRC [2.8 d] vs ORC [5 d]; p = 0.004), shorter hospital stay (LRC [5.1 d] vs ORC [8.4 d]; p = 0.0004), and earlier resumption of light work (LRC [11 d] vs ORC [19 d]; p = 0.0001). Operating time was not significantly increased with LRC, and complication rate was similar between the two groups. The authors concluded that LRC contributes to decreased postoperative pain and quicker recovery than ORC, with complication rates similar to those of ORC.

Propiglia et al, through a prospective comparative study, compared 20 LRCs to 20 ORCs [21]. The LRC group had less analgesic consumption and a more rapid postoperative return to oral intake (p < 0.05). No significant statistical difference was observed between the two groups with respect to intraoperative and postoperative parameters. The authors concluded that LRC contributed to reduced analgesic consumption and allowed early recovery of peristalsis with more rapid return to oral nutrition.

4.2. Purely laparoscopic urinary diversion versus laparoscopic assisted urinary diversion

We compared our initial 17 patients who underwent LRC with completely intracorporeal construction of the urinary diversion (purely laparoscopic), with 37 subsequent patients undergoing LRC with extracorporeal construction of the urinary diversion (laparoscopic assisted). Data presented in Table 1 suggest that the laparoscopic assisted urinary diversion technique provides statistically significant decreases in operating time, blood loss, transfusion rate, and more rapid postoperative return to oral intake and ambulation. Minor complications were higher in the purely laparoscopic urinary diversion group, mainly related to prolonged ileus. Major complications requiring re-operation occurred in 29% of patients in the purely laparoscopic urinary diversion group and 11% in the laparoscopic assisted urinary diversion group (p = 0.08). The majority of these complications were related to the intracorporeal bowel work and uretero-ileal anastomosis. Complications after hospital discharge were not statistically different when comparing the two techniques [16].

4.3. Nerve-sparing cystectomy

Indications for nerve-sparing cystectomy are limited to select young patients with organ-confined, low-volume, extratrigonal disease who are keen to maintain their sexual potency.

The preservation of sexual function after nerve-sparing radical cystoprostatectomy has rarely been analyzed. Guazzoni et al reported on three patients with laparoscopic nerve-sparing and seminal-sparing cystectomies [24]. All surgical margins were negative. Postoperatively, all three patients resumed normal continence within one month; two patients had normal erections, and one patient required oral sildenafil citrate. Lane et al described the technique of energy-free nerve-sparing LRC with transrectal Doppler ultrasound guidance and reported early outcomes in five select patients with bladder cancer [25]. All patients were free of recurrence at a median follow-up period of 30 mo. At 12 mo, nocturnal continence and daytime continence were preserved in 100% and 75% of patients, respectively. Sexual function was preserved in the female patient and in two of the four male patients. Menon et al described a technique of nerve-sparing, robotic assisted radical cystoprostatectomy [26]. However, their published results on these 14 men lacked potency data.

4.4. Organ-sparing cystectomy in women

Moinzadeh et al reported on an organ-sparing technique of female LRC with preservation of the fallopian tubes, ovaries, uterus, and vagina [12]. Game et al reported on 13 women with neurogenic vesical dysfunction who had an LRC which spared the uterus, fallopian tubes, ovaries, and vagina [13]. Mean duration of the operation was 325 ± 36 min and mean blood loss was 323.1 ± 246.3 ml. Before surgery, 77% of the women were sexually active: 80% of them were sexually active 4 mo after the surgery.

For female patients, data concerning the effect of radical cystectomy on sexual function are sparse. Menon et al described the preservation of the uterus and vagina in three women who underwent RRC [27]. Functional and oncological outcomes were not presented.

4.5. Laparoscopic prostate-sparing radical cystectomy

Prostate-sparing LRC technique has been described as having promising continence and erectile function results in select young patients for whom preservation of sexual potency and urinary continence are important [28]. Dissection was performed between the seminal vesicles posteriorly and the bladder anteriorly. The bladder neck, along with 1-cm rim of prostate base, was incised. The prostatic adenoma can be resected preoperatively using transurethral resection of the prostate, or intraoperatively using laparoscopic techniques. Arroyo et al reported on 25 patients in this series with a mean operating time of 285 min and a mean blood loss of 640 ml. However, this technique is controversial, and long-term oncological outcomes remain unavailable but are necessary to confirm whether it is safe to propose this surgery for the treatment of young patients with organ-confined malignancies, invasive malignancies, or high-risk superficial bladder malignancies.

4.6. Hand-assisted laparoscopic radical cystectomy

Hand-assisted LRC decreases the advantages of a minimally invasive technique like those reported with pure LRC. It can decrease the learning curve when switching from ORC to LRC. Taylor et al compared eight ORCs to eight hand-assisted LRCs [30]. Hand-assisted LRC appears to have less postoperative analgesic requirements and facilitates earlier postoperative return of bowel function; further, patients enjoy a shorter hospital stay compared to ORC. Mean blood loss tends to be less in the hand-assisted LRC group (637 vs 957; p = 0.23), but this did not reach statistical significance. We feel that the presence of the operator's hand may compromise exposure in the limited pelvic surgical space because most surgeons performing LRC have experience with LRP. The expertise gleaned from the former may carry over to pure LRC, thereby negating the need for hand-assisted LRC.

4.7. Robotic assisted radical cystectomy

Although the initial clinical publications focused on laparoscopic surgical techniques, recent reports have described the use of robotic assistance [36], [37], and [38]. The perceived advantage of this RRC technique compared to the purely laparoscopic technique is the decreased learning curve for surgeons without prior experience in laparoscopic surgery. The RRC may facilitate intracorporeal suturing of the uretero-ileal anastomosis, the neobladder anastomosis, and the urethro-neobladder anastomosis. However, Balaji et al reported on the feasibility of RRC with intracorporeal construction of ileal conduit in three patients, although each case took more than 10 h [31]. Menon et al clearly demonstrated that operating time can be reduced with extracorporeal reconstruction of the urinary diversion [26], and [27] (Table 3). Advantages and oncological outcomes of RRC in a larger series of patients remain unknown.

4.8. Oncological outcomes

While many early studies established the technical feasibility and encouraging perioperative results of LRC, oncological outcomes to define the place of the laparoscopic approach for bladder malignancy are awaited. Hrouda et al reviewed nine papers on LRC [39]. Among a total of 102 patients described in these nine papers, there were no instances of positive surgical margins or inadvertent incisions of the bladder. Simonato et al reported on 10 patients with a mean follow-up period of 26 mo (range: 16–36 mo). Five patients were alive without any evidence of disease; four patients had died of metastatic disease, and one had died of unrelated causes. No patients had developed local recurrence of metastasis [19]. Deger et al reported on LRCs in 20 patients [40]. At a median follow-up period of 2.7 yr, no patient had developed local recurrence of metastasis; three had developed distant metastases—two of whom died of metastatic disease.

Although reports on oncological outcomes are limited, Haber and Gill [41] reported on oncological data from follow-up periods ≤5 yr in 37 patients with pathological tumor stage distribution comparable with most contemporary open series. Two patients had focal positive surgical margins. At a mean follow-up period of 31 mo (1 mo–5.5 yr), there were no local or port-site recurrences. Metastases were noted in 5.4% of patients, and the estimated overall survival rate and cancer-specific survival rate after 5 yr were 63% and 92%, respectively. More recently, we have extended our analysis and reported on intermediate-term follow-ups of 76 more patients (56 men, 20 women), with a mean age of 66.5 yr (range: 26–87 yr), who underwent LRC and urinary diversion for invasive or high-risk superficial bladder cancer. In 65 patients (85.5%), extended pelvic lymphadenectomy was performed. The majority of tumors (n = 71, 93%) were transitional cell carcinomas, two (3%) were adenocarcinomas, and three (4%) were squamous cell carcinomas [48]. Most lesions were of high grade: grade 3 (n = 59; 78%), grade 2 (n = 16; 20%), and grade 1 (n = 1; 2%), and nine (11.8%) patients had concomitant carcinomas in situ. Pathological staging yielded the following results: pT1N0 (n = 9; 12%), pT2N0 (n = 41; 54%), pT3N0 (n = 14; 18%), and pTanyN+ (n = 12; 16%). The median number of excised lymph nodes for patients with extended lymph-node dissection was 17 (range: 10–24). Two (2.6%) patients had positive surgical margins. Follow-up data were available for 67 patients (88.1%), and 10 patients (13.1%) completed a 5-yr follow-up. The mean follow-up period was 25 mo (range: 1–83 mo). At the last follow-up, 54 patients (71%) were alive without evidence of disease, and 13 (29%) were dead: 3 (23%) of metastasis and 10 (77%) of unrelated causes. Three patients (3.9%) had no follow-up. Overall survival rate and cancer-specific survival rate at 2 yr were 84.2% and 94.5%, respectively [20].

Recent reports emphasize the potential benefits of an extended pelvic lymph-node dissection with a radical cystectomy for transitional cell carcinoma and the importance of greater numbers of lymph nodes being examined in improving survival rates [32]. In a report of 22 patients undergoing LRC, Finelli et al described the technical feasibility of an extended, pelvic lymph-node dissection laparoscopically to enhance node yields [14]. The initial 11 patients who underwent a limited dissection were compared with the subsequent 11 consecutive patients who had an extended lymphadenectomy. With a limited lymphadenectomy, the median number of lymph nodes retrieved was 3 (range: 1–15) versus 21 (range: 6–30) for the extended template (p = 0.001). The median node yield of the extended laparoscopic lymphadenectomy is commensurate with current open oncological recommendations, which suggest that at least 10–15 lymph nodes need to be removed for histopathological examination [23], [42], and [43]. In a different LRC study, the mean number of lymph nodes retrieved was 15.5 (range: 2–49) [17], [19], [21], and [40]. A large series of ORC with extended lymphadenectomy had a mean number of lymph nodes retrieved of 36.5 (1–99) [22], and [23].

The risk of port-site metastasis is an important issue when approaching bladder cancer laparoscopically. No published reports of port-site metastasis with LRC are available, although an anecdotal report exists of port-site recurrence after an RRC [44].

4.9. Future perspectives

An International Registry for LRC has been organized with the aim of standardizing the operative technique, postoperative data collection, and meticulous long-term follow-up. Each select center had performed at least 10 LRCs. The registry involves 13 centers with published experience in LRC. A total of 572 patients are included at this writing. The mean age is 65 yr, with a mean BMI of 26. Extirpative procedures mainly included cystoprostatectomy (72%) and female anterior pelvic exenteration (13%). The most common types of urinary diversion techniques included orthotopic neobladder reconstruction (53%) and ileal conduit diversion (35%). The reconstructive part of the procedure was performed extracorporeally in 89% and intracorporeally in 11%. Mean blood loss was 556 ml (range: 30–5000 ml). Mean operating time was 6.2 h (range: 1.6–13.8 h). Mean length of hospital stay was 13 d (range: 3–90 d). Complications occurred intraoperatively in 33 patients (7%) and postoperatively in 139 patients (28%). Nine (2%) positive surgical margins were reported. The mean number of lymph nodes retrieved was 13 (range: 0–36); 80 patients (16%) had nodal involvement. Mean follow-up period in 474 patients (96%) was 18 mo (range: 0.5–72 mo). Overall survival rate and cancer-specific survival rate were 65% and 80%, respectively. Local recurrences were noted in 27 patients (5%); systemic recurrences were recorded in 39 patients (8%), and no port-site recurrences were noted. However, oncological outcomes are encouraging, but preliminary, and need long-term assessment [45].

The feasibility and the efficiency of the extirpative component of LRC are well established. However, laparoscopic reconstruction remains challenging, time-consuming, and associated with major complications. Currently, an orthotopic ileal neobladder reconstruction represents the most physiological bladder substitute after radical cystectomy for cancer and has been used extensively in men and women [33], [34], and [35].

Completely intracorporeal urinary diversion should be approached with caution until more experience is gained or until endoscopic absorbable staplers, which could decrease the technical difficulty associated with laparoscopic reconstruction, become widely available. In the future, novel bladder substitutes such as tissue engineering [46] and ureteral augmentation [47] may decrease the technical difficulty associated with laparoscopic reconstruction.