Correspondence *Largo Rosanna Benzi 10, National Institute for Cancer Research, Genoa 16132, Italy

Email paolo.puppo@auro.it

Introduction

The popularity of laparoscopic surgery is increasing within the urological community. The increased skill of surgeons and technical developments have allowed more and more centers to perform major laparoscopic procedures. Various new laparoscopic approaches are being tested for feasibility, cost-benefit analyses and clinical results in comparison to open surgery. While laparoscopic nephrectomy and laparoscopic prostatectomy are widely performed, laparoscopic cystectomy with urinary diversion has just begun to emerge. Open radical cystectomy (ORC) is the standard procedure for the treatment of muscle-invasive bladder cancer. Following the pioneering reports by Parra et al.,¹ Sanchez de Badajoz et al.,² and Puppo et al.,³ however, the use of the laparoscopic procedure has expanded: 239 laparoscopic radical cystectomy (LRC) procedures have been reported in peer-reviewed journals in the past decade (Tables 1,2,3), of which 178 were performed in men and 61 in women.^{4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25} Laparoscopic simple cystectomy was first reported in 1992.³ In early reports of LRC, the accompanying urinary diversion was conducted either extracorporeally or through a limited laparotomy incision. Gill et al.²³ reported the initial experience with LRC and creation of an ileal conduit undertaken completely intracorporeally in two patients. Turk et al.²² reported five cases of LRC with continent urinary diversion by creation of a rectal sigmoid pouch undertaken completely intracorporeally. Gill et al.²¹ later reported two patients with bladder cancer who underwent LRC with an orthotopic ileal neobladder, again with the entire procedure undertaken intracorporeally. Seminal nerve-sparing cystectomy has now been performed laparoscopically,¹⁵ but long-term functional and oncologic data are not yet available. Despite the technical advances that have made laparoscopic techniques possible, therefore, LRC must still be seen as experimental.

Table 1 Patients' characteristics in series of laparoscopic radical cystectomy

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Table 2 Safety and outcomes of laparoscopic radical cystectomy in reported series

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Table 3 Technical features of laparoscopic radical cystectomy in reported series

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The main advantages with LRC that encourage further investigation are reduced blood loss, which leads to improved recovery of patients, and short hospital stays after the procedure. Here we review critically the data available on LRC, and we are able to confirm the advocated advantages of LRC and point out some possible disadvantages compared with ORC.

Does LRC meet the surgical standard established for ORC?

Optimum bladder cancer treatment with ORC has well-defined standards. Mortality and morbidity during and after surgery, surgical margin status, and the number of lymph nodes retrieved are the main indicators of quality. Mortality associated with ORC is lower than 4% in the largest series.^{26, 27, 28, 29, 30} Knap and colleagues²⁶ reported a mortality of 2% among 268 patients who underwent radical cystectomy at a median age of 65 years, from 1992 to 1998. The European Organization for Research and Treatment of Cancer (EORTC)²⁷ published results from 976 patients, which showed mortality of 3.7%. Ghoneim and colleagues²⁸ performed 1,026 radical cystectomies from 1969 to 1990, and noted mortality of 4%, while Stein et al.²⁹ reported 2.5% mortality among 1,054 patients assessed from 1971 to 1997. In those series, ORC morbidity did not exceed 30%^{29, 30, 31} and the surgical re-exploration rate did not exceed 17%.^{26, 29, 30} Overall, approximately 50% of patients presented with tumors of stages pT3–pT4, except within the cohort reported by Ghoneim et al.,²⁸ in which 80% of the tumors were in these stages. Lymph nodes retrieved were positive in approximately 20% of the studies.

Herr and colleagues established standards for radical cystectomy in 2004.³² They reported a series of 1,091 radical cystectomies performed by 16 experienced surgeons in four institutions from 2000 to 2002. Positive surgical margin rates are generally considered acceptable when lower than 10% overall and 15% in pT3 or pT4 tumors. The median number of pelvic lymph nodes retrieved during surgery should be 10–14. The lowest number of procedures per center required to reach this standard was calculated to be 10 per year.⁸

Among 239 patients treated with LRC, only one death has been linked to surgery.²⁴ The number of cases is small, however, and such a low death rate could, therefore, be serendipitous. Age and comorbidities should not have a substantial influence on operative mortality; only 33 (14%) participants in the LRC series were older adults, with American Society of Anesthesiologist scores of 3 or advanced stage bladder cancer.^{10, 11, 14, 19, 24} Furthermore, the procedure is performed only in leading urologic units and by experienced surgeons. Denewer and colleagues,²⁴ who reported the single perioperative death, treated 7 of 10 patients with salvage LRC. Globally, the number of patients with advanced local stages pT3–pT4 or with positive lymph nodes who undergo LRC is lower than those reported in the major series of ORC (50 [24%] of 207 cases versus 17 [8%] of 211 cases).

Only five (2%) LRC cases have had positive surgical margins.^{4, 9, 11, 14} In three cases the prostate was involved by a neoplasm originating in the bladder or by a primary tumor, and in two cases the margins were detected at the bladder pedicle in locally advanced carcinomas. Overall, the very low rate of positive surgical margins—even in advanced local stages—could be due to the magnification during dissection, but is more likely to be a result of patient selection. On the other hand, dissection of the prostate apex or pedicles is technically difficult in cases of cancer infiltration.

Overall, complications related to surgery during LRC have been reported in 35 (15%) cases. This rate is lower than the 30% reported in the major ORC series.^{29, 30, 31} Again, the selection of patients could be a reasonable explanation for this difference. Moreover, complications caused conversion to ORC in only five (2%) cases.^{9, 14} Only five reports on LRC include the number of lymph nodes retrieved, which ranges from 2 to 49;^{4, 7, 12, 14, 19} a median of 13 or 14 nodes, as reported in two series,^{4, 7} is within the range fixed as the standard by Herr et al. for ORC.³²

Blood loss in ORC and LRC is limited and, consequently, transfusions are rarely needed.³¹ Also, the lengths of hospital stay are similar for patients treated with LRC or ORC when performed in experienced urological units.³¹ This finding is easily explained, since the time of discharge is linked primarily to bowel function recovery, removal of indwelling catheter (in orthotopic diversions), and then, to a much lesser extent, to the operative technique and consequent stress.

Only two published series of LRCs include at least 10 procedures per year.^{4, 7} Future studies of this kind of surgery should, therefore, be concentrated in a few centers in order to collect an adequate number of cases per year.

LRC seems to meet the surgical standards of ORC. Morbidity, mortality and positive surgical margin rates are significantly lower with LRC, but could be easily explained by selection bias. Patients who undergo LRC are more likely than those who undergo ORC to have tumors of a lower pathological stage and with lower American Society of Anesthetists scores. On the other hand, blood loss and length of hospital stays seem to be similar and good in both.

Technical features of LRC

LRC procedures are generally performed with five or six ports. Operative times vary according to the level of experience of the surgeon and the type of diversion created. For example, intracorporeal urinary diversion takes much more time than extracorporeal diversion, especially when an orthotopic reservoir is created. The total time of surgery ranges from 180 min to 12 h.

Only nine patients have undergone hand-assisted LRC,^{11, 17} whereas 18 have undergone robot-assisted LRC.^{12, 13, 16} Vascular pedicles were secured by staples in 7 of 18 series. In addition, some papers reported achieving excellent vascular control with the use of harmonic scalpels.^{8, 20} Extreme caution must be taken to avoid tumor spillage during dissection because tumor seeding is common for transitional-cell cancers.

Typically, tumors weigh between 200 g and 400 g and have a corresponding volume, allowing for extraction from a compliant wound of the abdomen, vagina, or anus. An incision in the abdomen is frequently used to pull out the gut to configure the urinary diversion. The length of the incision ranges from 3.5 cm to 15.0 cm,⁹ but it is usually between 5 cm and 7 cm; a Y-shaped incision can be made to facilitate extraction.⁴ A new incision can be made, or an existing port site extended. In hand-assisted LRC, specimens are extracted through the hand port. Since ORC can easily be performed via a 12–15 cm umbilicopubic incision, the advantage of sparing 5–10 cm of incision is questionable.

Vaginal extraction, originally described by Puppo et al.,³ is not always carried out in women, even if access through the anterior vaginal wall facilitates a complete cystectomy and, if necessary, a total urethrectomy. Transvaginal extraction might be used in cases of anterior pelvic exenteration, while in selected cases of sex-organ-sparing cystectomy the specimen can be extracted through the abdominal wound, avoiding the need to open.⁷ At present, only Turk and colleagues²² have extracted tumors transanally. Apparently, this route seemed the most natural during ureterosigmoidostomy.

Thus far, urinary diversion during LRC has been accomplished by cutaneous ureterostomy in 7 (3%) patients, sigmoid ureterostomy in 17 (7%), ileal conduit in 97 (41%) cases, continent ileal pouch in 4 (1.5%), and continent colic pouch in 1 (0.5%). In the other 113 (47%) patients, an orthotopic ileal neobladder procedure was performed. Interestingly, one case of robot-assisted LRC and intracorporeal creation of orthotopic neobladder has been reported.¹⁶ Usually, the orthotopic neobladder is configured and sutured extracorporeally. Some surgeons then anastomize the ureters and the urethra after re-establishing pneumoperitoneum. Only two authors have, however, reported complete intracorporeal ileal neobladder constructions.^{7, 16}

Execution of LRC and orthotopic neobladder procedures is time-consuming and tends to require long learning curves. The procedure takes 380–720 min—much longer than the time required for the open procedure, which is typically only about 180 min. The length of time required is probably the reason why many laparoscopic cystectomies of well-selected patients result in undesirable diversion options, including incontinent cutaneous and anal diversions. The LRC orthotopic diversion rate has been reported as 47% in a population of well-selected patients, 76% among patients with organ-confined disease, and 92% among those without nodal disease; all of these values seem suboptimal. Hautmann, one of the major experts in the field of radical cystectomy and urinary diversion, has reported an overall 58% rate of orthotopic urinary diversion over the past 20 years in a series of 2,289 cystectomies.³³

Oncologic outcomes of LRC

Radical cystectomy is the gold standard for treatment of muscle-invasive and high-risk superficial bladder cancer. The largest single-center series of ORC were performed and published by Ghoneim and colleagues,²⁸ Stein et al,²⁹ and Bassi and co-workers.³⁴ Approximately 80% of patients in the series reported by Ghoneim et al. had stage pT3 or pT4 tumors, and around 50% had these stages of cancer in the two other series. The overall 5-year survival in each series was 48%,²⁸ 66%,²⁹ and 56%,³⁴ respectively, while the rate of positive lymph nodes at pathological examination was approximately 20% in each.

LRC has been reported to have considerably shorter durations of follow-up and lower numbers of patients included with pT3 to pT4 or pN+ bladder cancer than ORC. Furthermore, follow-up data were not reported in nine of the published series.^{9, 11, 12, 13, 18, 20, 22, 23, 24} Four series have a follow-up period of less than 6 months.^{10, 15, 16, 17} Only seven series have five or more patients and durations of follow-up of at least 1 year; the longest follow-up is 44 months.^{4, 6, 7, 8, 14, 19, 25} Altogether, 162 patients were studied, of whom 131 (80%) currently remain alive and free from disease. Of these 162 patients, 153 have pathology reports: 37 (24%) had pT3 or pT4 disease and 12 (8%) had developed nodal metastases. Given the short follow-up durations and the selection of patients with lower stages of disease, the resulting cure rate for LRC seems to be inadequate compared with that for ORC. In the series of Stein et al.²⁹ and Bassi et al.,³⁴ about 80% of patients remained disease free after 2 years of follow-up. In the same series about 50% of patients had pT3–pT4 bladder cancer and 20% had nodal metastases. Yet, only one port-site metastasis has so far been reported, which is a surprisingly low incidence considering that tumor seeding is common for transitional-cell cancer.³⁵

The limited number of patients studied to date does not enable definitive conclusions about the oncologic safety of LRC; therefore, the aforementioned reports of prostate-sparing LRC should be considered as advanced experiments of an already experimental procedure.^{6, 7, 12, 15}

Conclusions

LRC is still an experimental procedure, although the range of indications that are considered treatable with this approach is increasing within centers that prefer laparoscopy. The first 239 cases have demonstrated that LRC is feasible, since associated morbidity and mortality are lower than those reported in the major series of ORC; however, these differences are probably explained by selection bias in the LRC series. Blood loss and length of hospital stays for patients have become similar for both ORC and LRC. In addition, surgical margin rates are surprisingly lower with LRC, even in advanced cases.

Most series in which LRC has been studied have included patients with fewer comorbidities and lower-stage cancers than participants in ORC studies. Also, publications on LRC often do not report the number of lymph nodes retrieved during the procedures; consequently, there is a dearth of that type of information. Some later papers report a median number of nodes excised within the range fixed as standard for ORC.

Overall, most of the information published on LRC is devoted to the description of the operative technique; follow-up data and survival rates are generally lacking. In addition, given the more favorable inclusion criteria for participants in LRC than in ORC studies, the disease-free survival of 80% at follow-up seems to be inferior to that reported by major series of ORC. Obviously, to assess adequately the surgical safety and the extent of cancer control achieved with LRC, studies must be done with more-homogeneous cohorts and with cohorts comprising a broader range of patients, along with longer follow-up periods than those that have been used to date.

LRC is expensive and time-consuming, and surgeons endure a long learning curve to master the technique; therefore, the choice of urinary diversion becomes limited. Meanwhile, advances in ORC techniques have reduced blood loss and duration of surgery. Before LRC can be advocated for integration into clinical practice, the effect of the degree of invasiveness on outcomes needs to be compared for LRC and ORC. The reduction in length of skin incisions by a few centimeters in LRC does not justify an overhaul of established urological surgical practice.

Further reductions in blood loss, consumption of analgesics, and length of hospitalization, might overcome the high cost of LRC instruments, long operating times and the need for dedicated teams of surgeons. So far, however, the main advocated advantages of LRC—low transfusion rate and short hospital stay—are at best similar to those of ORC. Disadvantages of LRC, such as worse oncologic outcomes and the excessive use of nonorthotopic types of diversion, might outweigh these advantages.

References

1. Parra RO et al. (1992) Laparoscopic cystectomy: initial report on a new treatment for retained bladder. J Urol 148: 1140–1144 | PubMed |
2. Sanchez de Badajoz E et al. (1995) Laparoscopic cystectomy and ileal conduit: case report. J Endourol 9: 59–62 | PubMed | ChemPort |
3. Puppo P et al. (1995) Laparoscopically assisted transvaginal radical cystectomy. Eur Urol 27: 80–84 | PubMed |
4. Gerullis H et al. (2007) Laparoscopic cystectomy with extracorporeal-assisted urinary diversion: experience with 34 patients. Eur Urol 51: 193–198 | Article | PubMed |
5. Abreu SC et al. (2006) Laparoscopic-assisted radical cystectomy with U-shaped orthotopic ileal neobladder constructed using nonabsorbable titanium staples. Urology 68: 193–197 | Article | PubMed |
6. Cathelineau X et al. (2005) Laparoscopic assisted radical cystectomy: the montsouris experience after 84 cases. Eur Urol 47: 780–784 | Article | PubMed |
7. Moinzadeh A et al. (2005) Laparoscopic radical cystectomy in the female. J Urol 173: 1912–1917 | Article | PubMed |
8. Simonato A et al. (2005) Laparoscopic radical cystoprostatectomy: our experience in a consecutive series of 10 patients with a 3 years follow-up. Eur Urol 47: 785–792 | Article | PubMed |
9. Basillote JB et al. (2004) Laparoscopic assisted radical cystectomy with ileal neobladder: a comparison with the open approach. J Urol 172: 489–493 | Article | PubMed |
10. Sorcini A and Tuerk I (2004) Laparoscopic radical cystectomy with ileal conduit urinary diversion. Urol Oncol 22: 149–152 | PubMed |
11. Taylor GD et al. (2004) Hand assisted laparoscopic cystectomy with minilaparotomy ileal conduit: series report and comparison with open cystectomy. J Urol 172: 1291–1296 | Article | PubMed |
12. Menon M et al. (2004) Robot-assisted radical cystectomy and urinary diversion in female patients: technique with preservation of the uterus and vagina. J Am Coll Surg 198: 386–393 | Article | PubMed |
13. Menon M et al. (2003) Nerve-sparing robot-assisted radical cystoprostatectomy and urinary diversion. BJU Int 92: 232–236 | Article | PubMed | ChemPort |
14. Hemal AK et al. (2003) Laparoscopic radical cystectomy and ileal conduit reconstruction: preliminary experience. J Endourol 17: 911–916 | Article | PubMed | ChemPort |
15. Guazzoni G et al. (2003) Laparoscopic nerve- and seminal-sparing cystectomy with orthotopic ileal neobladder: the first three cases. Eur Urol 44: 567–572 | Article | PubMed |
16. Beecken WD et al. (2003) Robotic-assisted laparoscopic radical cystectomy and intra-abdominal formation of an orthotopic ileal neobladder. Eur Urol 44: 337–339 | Article | PubMed |
17. Peterson AC et al. (2002) Laparoscopic hand assisted radical cystectomy with ileal conduit urinary diversion. J Urol 168: 2103–2105 | Article | PubMed |
18. Chiu W et al. (2002) Internal bladder retractor for laparoscopic cystectomy in the female patient. J Urol 168: 1479–1481 | Article | PubMed |
19. Gupta NP et al. (2002) Laparoscopic radical cystectomy with intracorporeal ileal conduit diversion: five cases with a 2-year follow-up. BJU Int 90: 391–396 | Article | PubMed |
20. Abdel-Hakim AM et al. (2002) Laparoscopic radical cystectomy with orthotopic neobladder. J Endourol 16: 377–381 | Article | PubMed |
21. Gill IS et al. (2002) Laparoscopic radical cystectomy and continent orthotopic ileal neobladder performed completely intracorporeally: the initial experience. J Urol 168: 13–18 | Article | PubMed |
22. Turk I et al. (2001) Laparoscopic radical cystectomy with continent urinary diversion (rectal sigmoid pouch) performed completely intracorporeally: the initial 5 cases. J Urol 165: 1863–1866 | Article | PubMed | ChemPort |
23. Gill IS et al. (2000) Laparoscopic radical cystoprostatectomy with ileal conduit performed completely intracorporeally: the initial 2 cases. Urology 56: 26–29 | Article | PubMed |
24. Denewer A et al. (1999) Laparoscopic assisted cystectomy and lymphadenectomy for bladder cancer: initial experience. World J Surg 23: 608–611 | Article | PubMed |
25. Puppo P and Ricciotti G (2001) Videoendoscopically assisted transvaginal radical cystectomy. J Endourol 15: 411–413 | Article | PubMed |
26. Knap MM et al. (2004) Early and late treatment-related morbidity following radical cystectomy. Scand J Urol Nephrol 38: 153–160 | PubMed |
27. International collaboration of trialists (1999) Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: a randomised controlled trial. Lancet 354: 533–540 | ISI |
28. Ghoneim MA et al. (1997) Radical cystectomy for carcinoma of the bladder: critical evaluation of the results in 1,026 cases. J Urol 158: 393–399 | Article | PubMed | ChemPort |
29. Stein JP et al. (2001) Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. J Clin Oncol 19: 666–675 | PubMed | ISI | ChemPort |
30. Novotny V et al. (2007) Perioperative complications of radical cystectomy in a contemporary series. Eur Urol 51: 397–401 | Article | PubMed |
31. Frazier HA et al. (1992) Complications of radical cystectomy and urinary diversion: a retrospective review of 675 cases in 2 decades. J Urol 148: 1401–1405 | PubMed |
32. Herr H et al. (2004) Standardization of radical cystectomy and pelvic lymph node dissection for bladder cancer: a collaborative group report. J Urol 171: 1823–1828 | Article | PubMed |
33. Hautmann RE et al. (2006) Long-term results of standard procedures in urology: the ileal neobladder. World J Urol 24: 305–314 | Article | PubMed | ISI |
34. Bassi P et al. (1999) Prognostic factors of outcome after radical cystectomy for bladder cancer: a retrospective study of a homogeneous patient cohort. J Urol 161: 1494–1497 | Article | PubMed | ISI | ChemPort |
35. El-Tabey NA and Shoma AM (2005) Port site metastases after robot-assisted laparoscopic radical cystectomy. Urology 66: 1110 | PubMed |

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Subject areas under which this article appears: Urologic oncology (nonprostatic)