Individualized Seminal Vesicle Sparing Cystoprostatectomy Combined With Ileal Orthotopic Bladder Substitution Achieves Good Functional Results

Individualized Seminal Vesicle Sparing Cystoprostatectomy Combined With Ileal Orthotopic Bladder Substitution Achieves Good Functional Results Chin Hu Ong, Martin Schmitt, George N. Thalmann and Urs E. Studer* From the Department of Urology, University Hospital of Bern, Bern, Switzerland

Purpose: We review the functional and oncologic outcomes of seminal vesicle and prostate capsule sparing cystectomy combined with ileal orthotopic bladder substitution. Materials and Methods: Between May 2003 to April 2009 a select group of 31 patients (median age 61 years, range 30 to 77) underwent seminal vesicle sparing cystoprostatectomy for transitional cell carcinoma of the bladder. Preoperatively all 31 patients were continent, and 23 (74%) were potent and sexually active. Of these patients 17 (55%) underwent unilateral and 14 (45%) underwent bilateral seminal vesicle sparing cystoprostatectomy. Pathological disease stage was pTa/ pT1 in 15 patients (48%), pT2 in 9 (29%), pT3 in 2 (7%) and pT2– 4 pN1 in 5 (16%). Urinary continence and potency outcomes were assessed with validated questionnaires. All patients were followed for local tumor recurrence and distant metastasis. Results: Median followup was 18 months (range 3 to 63). At 6 months 25 of the 30 evaluable patients (83%) had daytime continence and 13 of 30 (43%) had nighttime continence. At last followup (median 18 months) 27 of 29 evaluable patients (93%) had daytime continence and 19 of 29 (66%) had nighttime continence. In terms of postoperative potency 15 of 19 evaluable patients (79%) remained potent, 9 with oral medications. There was pelvic recurrence in 1 patient (3%), distant metastases developed in 4 (13%) and 1 (3%) died of metastatic transitional cell carcinoma. Conclusions: Individualized seminal vesicle and nerve sparing cystoprostatectomy resulted in a high probability of preserving potency, at least with oral medication, without putting patients at undue risk.

Abbreviations and Acronyms CIS ⫽ carcinoma in situ ED ⫽ erectile dysfunction NVB ⫽ neurovascular bundle RC ⫽ radical cystectomy TCC ⫽ transitional cell carcinoma Submitted for publication July 21, 2009. * Correspondence: Department of Urology, University Hospital of Bern, Inselspital, 3010 Bern, Switzerland (telephone: ⫹41 31 6323641; FAX: ⫹41 31 6322180; e-mail: urology.berne@ insel.ch).

See Editorial on page 1278.

Key Words: urinary bladder neoplasms, cystectomy, seminal vesicles, urinary continence, erectile dysfunction PROSTATE and seminal vesicle sparing cystectomy has been reported to improve functional results because there is less risk of damaging the autonomic nerves and the sphincter area.1,2 However, there are concerns regarding oncological radicality because of possible urothelial cancer in the prostatic ducts, prostate cancer etc. In this study we review 31 cases of RC with preserva0022-5347/10/1834-1337/0 THE JOURNAL OF UROLOGY® © 2010 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION

tion of seminal vesicle(s) and neurovascular bundle combined with ileal orthotopic bladder substitution to assess the preliminary functional and oncological outcomes.

PATIENTS AND METHODS During the 6 years between May 2003 and April 2009 a total of 218 patients in our department underwent RC combined with

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orthotopic ileal bladder substitution. Of these patients 31 (14.2%) had sparing of 1 or both of the seminal vesicles and the prostate capsule adjacent to the NVB during cystoprostatectomy. All 31 patients (median age 61 years, range 30 to 77) had histologically proven high grade TCC diagnosed on transurethral resection biopsies. In addition to the usual indications for RC these patients met several inclusion criteria for seminal vesicle sparing cystectomy such as organ confined bladder tumor stage T2 or less based on preoperative assessment, bladder tumor located away from the bladder posterior wall and trigone, negative tumor histology on paracollicular prostatic urethral biopsies and/or staged transurethral resection of the prostate, and strongly expressed desire to preserve potency and/or continence. All patients underwent preoperative clinical assessment including a thorough history, physical examination, digital rectal examination, routine blood tests, urinalysis, chest x-ray, and computerized tomography of the abdomen and pelvis. Rigid cystoscopy and transurethral biopsies of the prostatic urethra at the paracollicular region were performed in all patients. All patients had assessment of preoperative erectile function and continence using validated questionnaires of the International Index of Erectile Function 153 and of Bristol’s lower urinary tract symptoms.4 On preoperative clinical staging 5 patients (16%) had recurrent stage cTa disease, 11 (36%) had stage cT1 disease with or without CIS and 14 (45%) had stage cT2 disease with or without CIS. One patient (3%) had stage cT1 disease with previously diagnosed, radiologically positive pelvic lymph nodes that had responded completely to neoadjuvant chemotherapy. Based on the American Society of Anesthesiologists classification 2 cases were Class I, 20 were Class II and 9 were Class III.

Surgical Technique All operations were performed with the patients under general anesthesia in the supine 30-degree Trendelenburg position with a lower midline incision. Bilateral pelvic lymph node dissection was performed using a standard template as previously described.5 After pelvic lymph node dissection the skeletonized superior and inferior vesical arteries were ligated and divided where they branched off from the internal iliac arteries. The endopelvic fascia was sharply incised medial to the tendinous arc up to the bladder neck. The deep Santorini’s plexus was then bunched with a curved Babcock clamp and ligated over the apical prostate and bladder neck, exposing the lateral aspects of the prostate. The ureters were then transected approximately 4 cm cephalad to the bladder. A sharp transverse incision of the peritoneum was made approximately 4 cm ventral to the rectovesical pouch. Seminal vesicle(s) were then identified, and a plane of dissection was developed bluntly between the seminal vesicle(s) and the dorsal bladder wall when dividing the dorsomedial pedicle. Care was taken to keep dissection ventrolateral to the seminal vesicle(s) and, thus, away from the pelvic plexus, which is located lateral and dorsal to the seminal vesicle. Dissection then proceeded caudally toward the angle of the vesicoprostatic

junction (fig. 1). A lateral incision of the prostatic capsule ventral to the NVB was next made running from the base to the apex, and the prostatic parenchyma was then dissected off the posterior capsule. The prostatic apex was approached directly along the lateral aspect of the prostatic capsule toward the membranous urethra, which was developed out of the donut-shaped prostatic apex. The urethra was transected sharply at the level of the distal verumontanum and the bladder was removed en bloc together with the prostatic parenchyma. Finally the dorsal prostatic capsule between the NVBs and any visible remnant of prostatic tissues attached to the prostatic capsule covering the NVBs was removed until only the capsule of the prostate adjacent to the NVB was left in situ. Whenever feasible, attempts were made to preserve both seminal vesicles with the adjacent NVB. However, in patients in whom the tumor was proximal to the seminal vesicle on 1 side only the contralateral seminal vesicle was preserved. Finally we reconstructed an orthotopic ileal low pressure bladder substitute combined with an afferent isoperistaltic tubular segment as previously described, and anastomosed it directly to the urethral stump, with care to avoid a funnel-shaped outlet.6

Followup After discharge home the patients came for followup visits at least every 3 months for the first 12 months, and every 6 months thereafter until 5 years. Apart from the usual followup examinations the patients were also asked to complete the validated International Index of Erectile Function 15 and Bristol questionnaires to evaluate the functional outcomes of erection and continence.3,4 We defined potency as ability to achieve erection for completion of sexual intercourse. We defined postoperative continence as completely dry with or without occasional loss of a few drops of urine. The patients were instructed to maintain nighttime continence by having an alarm clock to timevoid at least once at night. For patients who were incon-

Figure 1. Plane of dissection ventral to seminal vesicle and sequence of dissection with emphasis on 3 important steps of 1) dissection of plane anterior to seminal vesicle, 2) resection close to vesicoprostatic angle and 3) incision of lateral prostatic capsule to cleave it together with NVB.

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tinent postoperatively the amount of leakage was measured by the average volume of daytime and nighttime urine loss in 24 hours. This amount was quantified based on patient estimates of volume loss, ie loss of less than a tablespoon (less than 10 ml) of urine, loss of up to half a yogurt cup (less than 100 ml) or loss of more than half a yogurt cup (more than 100 ml). Computerized tomography of the pelvis for surveillance was performed 6 and 12 months after surgery. Excretory urography was performed biennially and urethral lavage cytology was performed at 6-month intervals.

100% 80%

83%

43%

All procedures were performed successfully without any major intraoperative complications (see table). A total of 17 patients (55%) underwent unilateral seminal vesicle sparing cystectomy. In 4 of these 17 patients nerve sparing was attempted on the contralateral side as well. Bilateral seminal vesicle sparing cystoprostatectomy was performed in 14 patients (45%). Median duration of surgery was 7 hours (range 5.5 to 8.5). Median surgical blood loss was 700 ml (range 300 to 1,500) and none of the patients required perioperative blood transfusion. Median postoperative catheterization was 12 days (range 10 to 30) and median length of hospital stay was 17 days (range 15 to 25). Postoperative morbidity was present in 8 of the 31 patients (26%). There was no perioperative mortality and none of the patients were lost to followup. Histology On final histology approximately half of the 31 patients (48%) had pTa/T1 with or without CIS disease, a third (36%) had pT2–3 with or without CIS and 5 (16%) had pT2– 4 with node positive pN1 disease. No patient had urothelial cancer in the prostate but 1 had CIS at the margin of the urethra, which was managed vigilantly with no progression. Incidental prostate adenocarcinoma was found in 13 of the 31 patients (42%). Of these patients 5 had Patient characteristics and results Median ng/ml preop serum prostate specific antigen (range) No. seminal vesicle sparing (%): Unilat Bilat No. nerve sparing (%): Unilat Bilat No. complications (%): Urinary sepsis Acidosis requiring readmission Lymphocele Postop urinary retention Prolonged ileus Ureteroileal stricture (at 6 mos)

1.0 (0.3–10.0) 17 14

(55) (45)

13 18

(41) (59)

3 2 1 1 1 1

(10) (6) (3) (3) (3) (3)

93%

66%

Continent Loss of < 10 ml/day Loss of 10 -100 ml/day Loss of > 100 ml/day

60% 17%

40%

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24%

20% 0%

14% 3%

13%

7%

10%

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Night

Continence at 6 months post-op.

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Continence at median of 18 months

Figure 2. Day and nighttime continence results at 6 months after surgery and at last followup (median of 18 months).

Gleason score 5 disease, 7 had Gleason score 6 and 1 had Gleason score 7. Of the 13 patients 2 (both Gleason score 6) had margins positive for prostate adenocarcinoma. Neither patient received any adjuvant treatment for the prostate adenocarcinoma. At the last followup none of the 13 patients with incidental prostate adenocarcinoma showed any biochemical or radiological evidence of progression. Continence Outcomes All patients were continent preoperatively. At 6 months 30 patients had evaluable continence results. For daytime continence 25 patients (83%) were continent, 4 (14%) had occasional urine loss less than 10 ml and 1 (3%) had occasional urine loss of more than 100 ml (fig. 2). In terms of nighttime continence 13 patients (43%) were continent, 5 (17%) had occasional urine loss less than 10 ml, 8 (27%) had occasional urine loss of 10 to 100 ml and 4 (13%) had occasional urine loss of more than 100 ml. At the last followup visit (median of 18 months) 29 patients had evaluable continence results. For daytime continence 27 patients (93%) were continent and 2 (7%) had occasional urine loss of less than 10 ml. For nighttime continence 19 patients (66%) were continent, 7 (24%) had occasional urine loss less than 10 ml and 3 (10%) had occasional urine loss of 10 to 100 ml. Potency Outcomes Of the 31 patients 23 (74%) reported that they were potent before surgery. Of those who did not consider themselves potent 3 had preexisting ED and 6 were no longer sexually active. These patients were excluded from further analysis. Of the 23 preoperatively potent patients 19 were available for postoperative evaluation because 3 were still recovering and were not ready for evaluation, and 1 was no longer sexually active after surgery because his partner had died. Thus, only 19 of the 31 patients (61%) could be evaluated for potency outcomes.

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Based on the questionnaires 15 of the 19 patients (79%) remained potent after surgery, albeit 9 required oral medical therapy (ie phosphodiesterase-5 inhibitors) to assist with erections. Of the 19 patients 3 (16%) with postoperative ED did not respond to oral medical therapy but had good clinical response to intracavernous injection of 10 ␮g prostaglandin E1. However, all 3 patients refused regular use of prostaglandin E1 injection due to pain. Of the 19 patients 1 (5%) did not regain potency despite oral or intracavernous therapy (fig. 3). Oncological Outcomes During the relatively short followup local recurrence at the pelvic floor developed in 1 patient (3%) at 26 months. This patient had a negative margin resection for TCC with pT1N0 stage disease. He also subsequently had metastasis in the liver. Of the 31 patients metastatic TCC developed in 5 (16%) at various sites including the lungs, liver and bones. There were 2 deaths, 1 from metastatic TCC and another from metastatic adenocarcinoma of unknown origin (histologically not prostatic origin). Thus, the number of disease specific deaths was 1 of 31 patients (3%).

DISCUSSION In 1999 Spitz et al first reported a series of 4 patients with nonurothelial bladder cancer who underwent cystectomy with preservation of the vas deferens, seminal vesicles and posterior prostate with excellent fertility and sexual function outcomes.7 This series was followed by reports from Colombo8 and Vallancien1 et al, who described a 2-stage seminal sparing and prostate sparing cystectomy. Then Muto9 and Terrone10 et al introduced a single-stage

100% 80% 60% 40%

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28% 17%

20%

5%

0%

n=5 Potent

n=9 Potent with medication

n=3 Potent with Prostaglandin 10 µg but too painful for regular use

n=1 ED

Figure 3. Potency results after median followup of 14 months

technique combining cystectomy with adenoma enucleation. The seminal vesicle sparing cystoprostatectomy described here, unlike the other approaches mentioned, which aim to preserve the prostate and/or fertility, attempts to spare the autonomic nerves only. It entails removal of almost the entire prostate with only partial sparing of the posterior prostatic capsule. Thus, we believe this constitutes a minimal compromise of oncologic principles, even in the event of unexpected limited invasion of TCC into the prostate. The dissection comprises the 3 essential steps of 1) dissection ventral to the seminal vesicle, 2) preservation of nerve tissues at the vesicoprostatic angle, and 3) incision and cleavage of the dorsolateral prostatic fascia to avoid damage to the NVB (fig. 1). Prostate cancer is found in 30% of 50-year-old men and in 70% of 80-year-old men at autopsy.11 In a review by Stein et al incidental prostate cancer was found in 27% to 46% of men undergoing RC.2 In the present study incidental prostate cancer was found in 42% of patients. All of the prostate cancers we found were of low and intermediate grade Gleason scores. It is unknown if these incidental cancers are of clinical significance, but to date there has been no evidence of progression in any of these patients. In a detailed review of the functional outcomes of orthotopic neobladder in 2,238 patients, daytime continence was reported to be 87% and nighttime continence 72%.12 Stein et al showed that most prostate sparing cystectomies produce higher daytime (greater than 90%) than nighttime continence rates (greater than 80%).2 However, it is arguable that the higher continence rates in patients undergoing prostate sparing cystectomy compared to those undergoing conventional RC are due in part to the significantly younger age of the patients, and to variations in the definitions of continence and followup across study groups. The continence rates achieved with our seminal vesicle sparing cystectomy are more modest, with a daytime continence rate of 93% and a nighttime rate of 66% after a median followup of 18 months. We did not expect our continence results to equal those of most prostate sparing cystectomy series. The median age of our patients was 61 years compared to less than 60 years in most prostate sparing series.2 Our technique involves dissection of the prostatic apex and, thus, has more potential for damage to the striated urethral sphincter and its innervations. Our definition of continence is more rigorous (ie minimally incontinent patients had only occasional loss of small volumes of urine). Finally our median followup was relatively short at only 18 months and undoubtedly the continence rate will continue to improve with time as previously shown.6

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Even with nerve sparing cystoprostatectomy the potency rate is at best only 64%.13 Thus, one of the greatest advantages of prostate sparing cystectomy is the preservation of sexual function. In the 2 largest series to date Muto9 and Vallancien1 et al reported potency rates of 95% and 82%, respectively. Our results show that in patients with evaluable sexual function 15 of 19 (79%) remained potent and were able to resume a sexually active life, albeit 9 of the 15 (60%) required oral medication (phosphodiesterase-5 inhibitors) to assist with erections. One of the more contentious issues associated with prostate sparing cystectomy is the reported higher rates of distant failure. Botto et al reported local recurrence in 3% and widespread metastases in 18% of patients after a mean followup of 26 months.14 In our series 1 patient (3%) had pelvic recurrence combined with liver metastases and 5 (16%) had metastatic disease. These rates do not appear to be particularly high since 52% of the pa-

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tients had stage pT2 disease or higher on final histology. In fact 3 of the 5 patients who had distant failure had pT3 and/or node positive disease, and were at high risk for dissemination. Nevertheless, given the short median followup of 18 months it is hard to draw any conclusions regarding long-term cancer control.

CONCLUSIONS The trend toward increasing use of RC for early nonmuscle invasive bladder TCC may signal an emerging role for more conservative organ sparing techniques. Individualized seminal vesicle sparing cystoprostatectomy combined with attempted nerve sparing resulted in the preservation of potency in 79% of our patients, with some requiring oral medication. The preliminary results on continence and oncological outcomes are at least as good as those of conventional RC.

REFERENCES 1. Vallancien G, Abou El Fettouh H, Cathelineau X et al: Cystectomy with prostate sparing for bladder cancer in 100 patients: 10-year experience. J Urol 2002; 168: 2413. 2. Stein JP, Hautmann RE, Penson D et al: Prostatesparing cystectomy: a review of the oncologic and functional outcomes. Contraindicated in patients with bladder cancer. Urol Oncol 2009; 27: 466. 3. Rosen RC, Riley A, Wagner G et al: The international index of erectile function (IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology 1997; 49: 822. 4. Schatzl G, Temml C, Schmidbauer J et al: Crosssectional study of nocturia in both sexes: analysis of a voluntary health screening project. Urology 2000; 56: 71. 5. Mills RD, Turner WH, Fleischmann A et al: Pelvic lymph node metastases from bladder cancer: out-

come in 83 patients after radical cystectomy and pelvic lymphadenectomy. J Urol 2001; 166: 19. 6. Studer UE, Burkhard FC, Schumacher M et al: Twenty years experience with an ileal orthotopic low pressure bladder substitute–lessons to be learned. J Urol 2006; 176: 161. 7. Spitz A, Stein JP, Lieskovsky G et al: Orthotopic urinary diversion with preservation of erectile and ejaculatory function in men requiring radical cystectomy for nonurothelial malignancy: a new technique. J Urol 1999; 161: 1761. 8. Colombo R, Bertini R, Salonia A et al: Nerve and seminal sparing radical cystectomy with orthotopic urinary diversion for select patients with superficial bladder cancer: an innovative surgical approach. J Urol 2001; 165: 51. 9. Muto G, Bardari F, D’Urso L et al: Seminal sparing cystectomy and ileocapsuloplasty: long-term followup results. J Urol 2004; 172: 76.

10. Terrone C, Porpiglia F, Cracco C et al: Supraampullar cystectomy and neobladder. Eur Urol 2006; 50: 1223. 11. Scardino PT, Weaver R and Hudson MA: Early detection of prostate cancer. Hum Pathol 1992; 23: 211. 12. Steers WD: Orthotopic neobladder: functional outcomes. World J Urol 2000; 18: 330 –7. 13. Brendler CB, Steinberg GD, Marshall FF et al: Local recurrence and survival following nervesparing radical cystoprostatectomy. J Urol 1990; 144: 1137. 14. Botto H, Sebe P, Molinie V et al: Prostatic capsule- and seminal-sparing cystectomy for bladder carcinoma: initial results for selected patients. BJU Int 2004; 94: 1021.

EDITORIAL COMMENT The issue of prostate capsule and seminal vesicle sparing during radical cystectomy and orthotopic neobladder urinary diversion for the treatment of bladder cancer is timely and controversial. The subject is polarizing and evokes strong opinions in supporters and detractors (references 1, 2 and 8 in article).1 Maintenance of oncological safety and simultaneous reduction of surgically related morbidity, particularly with regard to continence, erectile function and preservation of fertility, are the obvious goals of the surgical modifications. In the current series the authors report their experience with the modified technique in a highly

select, contemporary group of 31 patients. The presentation is clear and balanced. The conclusions that the overall disease control of the bladder cancer and of incidental prostate cancer was good are justified. However, it is worthwhile to highlight several critical details that the authors acknowledge. The need to attempt to exclude involvement of urothelial cancer into the prostate urethral mucosa, glands or stroma by measures such as initial transurethral resection as was performed is important. However, 48% of the patients in this series had pTa or pT1 bladder cancer and, thus, were at low risk for

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prostatic extension of the bladder cancer. In addition, 1 patient (3%) experienced pelvic relapse. Although the authors explain that this patient also had early hepatic metastases and, thus, represented hematogenous spread, nonetheless the prevalence of local pelvic relapse is low in patients with low volume local disease. One must retain a healthy concern regarding whether the surgical modifications resulted in any greater risk of pelvic spillage and relapse than was inherent to this aggressive tumor and, if so, whether pelvic relapse increased the risk or even caused the subsequent hematogenous metastases. Obviously one cannot know which came first, but the concern is real. The prevalence of incidental prostate cancer was 42% and is in keeping with many other reports on radical cystectomy for bladder cancer in this age group. Although none of the patients yet has experienced prostate cancer recurrence, there were 2 with positive margins. All would agree that achieving a negative surgical margin is an important goal for primary surgical treatment of prostate cancer. Interestingly the authors did not find an improve-

ment in urinary continence in these selected patients compared to their overall large experience with orthotopic neobladder following standard, complete radical cystoprostatectomy. The authors did not experience any increase in outlet obstruction of the neobladder as has been reported by others after similar surgical modifications. In conclusion, the authors are correct that the results were functionally good and oncologically safe overall in these carefully selected patients. However, for all these reasons it seems the best use of prostate capsule and seminal vesicle sparing during radical cystectomy would be restricted to the highly unusual example of a young male with bladder cancer who wishes maximal effort at preservation of fertility and erectile function. For nearly all other patients the standard technique seems to be safer with regard to disease control, and it offers virtually comparable functional results. Arthur I. Sagalowsky Department of Urology University of Texas Southwestern Medical Center Dallas, Texas

REFERENCE 1. Hautmann RE and Stein JP: Neobladder with prostatic capsule and seminal-sparing cystectomy for bladder cancer: a step in the wrong direction. Urol Clin North Am 2005; 32: 177.