Radical Cystectomy and Orthotopic Neobladder with Prostate and Seminal Sparing inyoung Patients with Transitional Cell Carcinoma (TCC) of the Bladder

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1 European Urology Supplements European Urology Supplements 4 (2005) Radical Cystectomy and Orthotopic Neobladder with Prostate and Seminal Sparing inyoung Patients with Transitional Cell Carcinoma (TCC) of the Bladder Maurizio Brausi a,b, *, Mirko Gavioli b, Massimo Viola a, Giuseppe De Luca a, Giancarlo Peracchia a, Giorgio Verrini b, Gian Luca Simonini b a Department of Urology, Estense - St. Agostino Institute, Modena, Italy b Department of Urology, B. Ramazzini Hospital, Carpi, Italy Abstract Introduction and Objectives: Radical cystectomy is considered the standard treatment for patients with invasive TCC of the bladder and for high grade, multifocal tumors refractory to conservative therapy. Preservation of sexual function, continence and fertility are important for surgery acceptance in young patients with this disease. The objectives of this study were to evaluate the results of our seminal and prostate sparing technique on cancer control, continence, potency and fertility in a selected group of young patients with TCC of the bladder. Materials and Methods: From March 2000 to November 2004, 312 radical cystectomies were performed on patients with bladder tumors. Fourteen patients (4.5%) met the eligibility criteria and were included in this study. Two patients were excluded from the group undergoing the seminal and prostate sparing procedure after the initial TUR because of the presence of TCC in the prostatic urethra. Twelve patients therefore had the operation, eleven of whom had superficial, recurrent, high grade tumors refractory to adjuvant immunotherapy (7) or chemotherapy (4) and one had a single invasive tumor. Staging was: T1G2 = 2, T1G3 = 6, Cis = 3, T2G3 = 1. The mean age was 52.5 years. Before surgery and during follow-up the EORTC Q-30 and the IIEF questionnaires were administered. The mean PSA was 1.8 ng/ml. Step 1 of the operation included TUR of the prostate maintaining the capsule intact. A frozen section of the peripheral prostatic chips was analyzed. The open surgical step consisted of a bilateral pelvic lymph node dissection and extraperitoneal radical cystectomy preserving the vas deferens, seminal vesicles and neurovascular bundles. Urinary diversion was performed with a modified Studer procedure in a whale tail shaped fashion (2 loops). The reservoir was anastomosed to the prostatic capsule with an interrupted suture on a 22 Fr catheter. Results: Mortality was 0. The mean operating time was 5.45 hours. The mean hospital stay was 17.3 days. The early post-operative complications were low: one patient had a bowel obstruction requiring reoperation. After a mean follow-up of 16 months no delayed complications were observed. No local or distant recurrences were observed and all the patients were alive. Day time continence was complete and immediate in all the patients (100%). One patient had night-time incontinence which lasted for 2 months. Erectile function was present in all the patients: the mean IIEF score was 23. The QoL measured by the EORTC Q-30 questionnaire returned to normal after 3 9 months. All patients had retrograde ejaculation; the sperm analysis from urine of 3 patients showed a mean of 8 million spermatozoa/ml. Conclusion: Radical cystectomy with seminal and prostatic capsule sparing and orthotopic neobladder is a good option for selected young patients with superficial and single localized invasive TCC of the bladder. Functional results are excellent. A longer follow-up is needed in order to confirm the present data. # 2005 Elsevier B.V. All rights reserved. Keywords: Bladder cancer; Radical cystectomy; Prostate and seminal sparing * Corresponding author. Tel ; Fax: address: brausi@interfree.it (M. Brausi) /$ see front matter # 2005 Elsevier B.V. All rights reserved. doi: /j.eursup

2 62 M. Brausi et al. / European Urology Supplements 4 (2005) Introduction Radical cystectomy continues to be the standard treatment for invasive as well as high grade or recurrent refractory cases of superficial TCC of the bladder. However such surgery usually results in a substantial deterioration in the quality of life (QoL) of the patients because of the negative effects on continence, potency and fertility. This aspect is particularly important for surgery acceptance in young patients. The neuro-anatomical studies and the consequent development of radical cystectomy with orthotopic neobladder with nerve sparing techniques resulted in a clear improvement in the final QoL of patients who underwent such surgery. However even in centers where nerve-sparing cystoprostatectomies are performed almost routinely, the probability of potency is no better than 50% and there is a constant 25% 30% incidence of nocturnal incontinence [1]. Therefore a technique of radical cystectomy and orthotopic bladder substitution preserving the vas deferens, seminal vesicles and part of the prostate has been developed in an attempt to improve the continence rate, potency and to maintain retrograde and possibly antegrade ejaculation [2]. The objectives of our study were to evaluate the results of our seminal and prostate sparing technique on cancer control, continence, potency and fertility in a selected group of young patients with TCC of the bladder. 2. Materials and methods Between March 2000 and November 2004, 312 radical cystectomies for bladder tumors were performed at the Departments of Urology of the Estense Institute of Modena and the B. Ramazzini Hospital in Carpi (Modena). Fourteen patients (4.5%) met the eligibility criteria and were included in the study. Two patients were excluded from the seminal and prostate sparing procedure after the initial TUR because of the presence of transitional cell carcinoma in the prostatic urethra. Twelve patients (3.8%) were operated using the seminal and prostate sparing procedure. Eleven of these patients had clinical recurrent, high grade superficial TCC of the bladder with associated Cis in two patients. All the patients had undergone more than 2 TUR and bladder instillation with chemotherapy (4 patients) or immunotherapy (7 patients). One patient had a single invasive TCC of the bladder after the first TUR. The mean age was 52.5 years (range 36 to 59). The preoperative clinical assessment consisted of a complete physical examination, biochemical analysis with prostate specific antigen (PSA) determination (range ng/ml), chest X-ray, and one or more type of abdomen imaging such as computerized tomography (CT), ultrasonography (US), intravenous urography (IVP) or transrectal ultrasound (7.5 MHz probe). A bone scan was requested in one patient with elevated serum alkaline phosphatase; it was negative. To evaluate the impact of surgery on continence, sexual activity and fertility before surgery, the International Index of Erectile function (IIEF) and the EORTC Q-30 questionnaire were administered in all cases. The first step of the operation included the TUR of the prostate from the bladder neck to the veru montanum leaving the prostatic capsule intact. A frozen section of the urethral epithelium and peripheral prostatic stroma was analyzed. The second step was the open surgery. After a 6 7 cm midline incision an extraperitoneal lymph node dissection was performed including obturator, internal, external and common iliac nodes which were sent for frozen section. When histology was positive the lymphadenectomy was extended as far as the aortic bifurcation. The obliterated umbilical artery and superior vesical artery were identified and clipped at their origin at this time. The vasa deferentia were isolated bilaterally and preserved. The posterior part of the bladder wall was bluntly dissected from the peritoneum which was left intact. The ureters were identified, isolated and transected at their entry to the bladder. Both distal ends were sent for frozen section. Following the vas deferens during the dissection, the correct plane between the posterior bladder wall and seminal vesicles was identified and dissected; the neurovascular bundles, the pelvic fascia and the remaining posterior branches of the hypogastric artery were left intact. A traction on the Foley catheter allows the identification of the prostatovesical junction anteriorly. No attempt was made to ligate the Santorini plexus. The bladder and 3 5 mm of the proximal prostatic capsule were removed. After cystectomy, the seminal vesicles and vas deferens remained exposed with the neurovascular bundles completely intact. The peritoneum was opened and an ileal segment of cm. isolated, detubularized and remodelled with two loops in a whale tail shaped fashion according to a modified Studer procedure. The ureters were implanted at the lateral end of the loops with an interrupted suture on a 6 Fr catheter. The prostate ileal anastomosis was performed with an interrupted suture on a 22 Fr catether (Fig. 1). The urethral catheter was left in place for days. Ureteral catheters were removed 9 10 days after surgery. The follow-up protocol included a control visit every 3 months with complete blood tests, arterial blood gas, PSA, urine culture, cytology, ultrasound of the abdomen, urodynamics, and the IIEF and EORTC Q- 30 questionnaires. These tests were requested every three months for the first year then twice a year for 3 years and annually thereafter. Patients were considered to be completely continent when they did not use any pads during the day or night. Potency was defined as the ability to have and maintain an erection sufficient for intercourse without any pharmacological assistance. Fertility was considered possible when spermatozoa were present in the urine after sexual intercourse or masturbation. 3. Results The mortality rate was 0. The mean operating time was 5.45 hours; the mean blood loss was 350 cc (range 120 to 950 cc). The mean hospital stay was 17.3 days (range 13 to 31). Early post-operative complications were limited. One case of small bowel obstruction required reoperation and the patient was discharged from the hospital after 31 days. After a mean follow-up of 16 months (range 3 to 47) no delayed complications have been observed.

3 M. Brausi et al. / European Urology Supplements 4 (2005) mean follow-up of 16 months no local or distant recurrence has been observed and all the patients were alive Continence results After catheter removal all the patients were continent during the day (100%). One out of 12 patients reported nocturnal incontinence which lasted for 2 months. At the 3-month follow-up visit, all patients were completely continent during the day and night (100%). The 3-month uroflowmetry showed a normal curve profile with a mean flow rate of 26 ml/s (range 24 to 35). Cystometry revealed a mean bladder capacity of 180 ml. which reached 300 ml after 6 months. Postvoiding residual urine was less than 40 cc in all patients Potency results All the patients were potent before surgery with a normal IIEF value. After surgery 11 out of 12 reported an adequate sexual function with normal erections and satisfactory intercourse and their IIEF values were similar to the values declared before surgery. One patient is potent with sildenafil Fertility results All the patients had retrograde ejaculation. In 3 patients, the semen analysis obtained from urine after intercourse or masturbation showed a mean spermatozoa number of 8 million/ml. The quality of life measured with the EORTC Q-30 questionnaire returned to normal in all the patients after 3 9 months. 4. Discussion Fig. 1. (a) Ileal neobladder reconstruction in a whale tail shaped fashion. The ureters are implanted laterally into the loops. (b) The prostatic capsule is anastomosed to the ileal neobladder with an interrupted suture Oncological results The pathological stage of the tumors were: pt1g2 in 2 patients, pt1g3 in 6, multiple Cis in 3. One patient had a single pt2g3 with a positive right perivesical node; he did not receive any adjuvant therapy. After a Radical cystectomy continues to be considered the standard treatment for patients with invasive bladder cancer and for high-risk superficial TCC refractory to local treatments. Standard radical cystectomy consists of regional lymphadenectomy with removal of the bladder, prostate, seminal vesicles and part of the vasa deferentia. However this operation inevitably produces important negative changes in QoL of these patients including problems with continence, sexual activity, fertility and social life. This becomes particularly relevant in young patients who are more and more frequently affected by bladder cancer [3]. Walsh and Donker [4] showed that the pelvic plexus provides innervation to the bladder (vesical plexus), prostate (prostate plexus) and corpora cavernosa (cavernous nerves) and that the injury of the iliac

4 64 M. Brausi et al. / European Urology Supplements 4 (2005) Table 1 Summary of the literature reporting nerve sparing cystectomy and orthotopic neobladder Author (year) No. pts Mean age Surgical technique Mean follow-up (months) Complete continence rate (%) Potency rate (%) 5-year survival recurrence Marshall (1991) [8] Ileo-colic + nerve sparing (intrap) n.r. Turner (1997) [7] Studer + nerve sparing (intrap) 32 D = 94, N = n.r. Thurman (2004) [9] Neobladder + nerve sparing 22 n.r. 17 n.r. Total D: day; N: night. plexus during radical cystoprostatectomy constantly leads to impotence. The first report on cystoprostatectomy with preservation of potency was by Walsh and Mostwin in They concluded that, since the pelvic plexus is located posterior and lateral to the seminal vesicles, sexual function can be preserved by ligating the pedicles to the bladder on the lateral surface of the seminal vesicles [5]. Other authors confirmed these data and also reported an improvement in urinary continence when the nerve-sparing technique was adopted during radical cystoprostatectomy and orthotopic bladder substitution [6,7]. However, considering all the relevant literature, even when nerve-sparing surgery was performed by very experienced surgeons the mean potency rate did not exceed 40% with a nocturnal incontinence rate of 25% (Table 1) [7 9]. In order to improve these results a technique of prostate and seminal sparing during radical cystectomy has been proposed since 1992 by different authors in patients with superficial TCC [2,3,10] or nonurothelial malignancy of the bladder [11]. The technique of prostate sparing varied, including total prostate preservation [9], prostate apical dissection [11], prostate adenomectomy according to Millin [12] or according to Freyer [13] and TUR with prostatic capsule preservation [10,14,15]. The functional results were excellent and are summarized in Tables 2 and 3. The continence rate varied from 90% to 100% and the potency rate was between 79% and 100% depending on the different technique adopted. The vast majority of the patients had retrograde ejaculation, allowing semen retrieval from urine, and were considered fertile. The local and distant recurrence rate varied from 0% to 18% and from 0% to 21% respectively. In our study, after a mean follow-up of 16 months, all the patients were completely continent during the day soon after catheter removal, while one patient had nocturnal incontinence which disappeared two months after surgery. The recurrence rate, local and distant, was 0. Interestingly enough, in two series [10,15] where clinical T2 and T3 TCC of the bladder were included, Table 2 Summary of the literature reporting adenomectomy and orthotopic neobladder Author (year) No. pts Median age Mean follow-up (months) Continence (%) Potency Fertility Recurrence Meinhardt (2003) [13] n.r. D = 95.8, N = (a+r) n.r. Thurman (2004) [9] n.r. Apex = 59, Total = 100 n.r. n.r. Muto (2004) [12] D = 95, N = (a+r) 1.6% (adk) Spitz (1999) [11] (a+r) n.r. D: day; N: night. Table 3 Summary of the literature reporting TUR and orthotopic neobladder Author (year) No. pts Median age Mean follow-up (months) Continence (%) Potency Fertility Recurrence Vallancien (2002) [10] Retr. = 100% L = 18% (3 adk) Colombo (2004) [14] A = 11.1, R = 89.9 n.r. Sèbe (2004) [15] D = 90, N = n. r. L = 0, D = 21% Brausi (2001) D = 100, N = n.r. 0 Total L = 5.2, D = 5.2 D: day; N: night; L: local; D: distant.

5 M. Brausi et al. / European Urology Supplements 4 (2005) the local and distant recurrences were 18% and 21% respectively. This raises the question whether or not the use of nerve sparing techniques in bladder cancer surgery is safe. Pritchett et al. showed that although the nerve-sparing technique during radical cystoprostatectomy could compromise cancer eradication by leaving small perivesical lymph nodes, it did not correlate with clinical outcomes [16]. Moreover, other experience showed that when a nerve sparing technique was adopted for infiltrative bladder tumors the local recurrence rate varied from 4% to 18% and was similar to that of non-sparing surgery [17]. However the 21% of distant metastases reported by Sèbe et al. [15] after prostate sparing cystectomy in patients with clinical T2N0M0 disease means that this issue is still unresolved. An important concern, when using this technique, is the possible risk of urethral/prostatic TCC after adenomectomy or TUR and recurrence. In previous studies the incidence of TCC in the prostatic urethra varied between 12%and 25% [10]. However, according to Iselin et al., involvement of the prostatic urethra in TCC of the bladder should not preclude orthotopic bladder reconstruction after cystoprostatectomy [18]. In our study all the prostatic transitional zone was removedandsentforfrozensectiontoexcludeany TCC.In2of14patientsaTCCofthebladderneck(1) and of the prostatic urethra (1) was detected by pathologists and the patients received a standard cystoprostatectomy with orthotopic neobladder. Vallancien et al. [10] reported 2 recurrences of TCC in the prostatic urethra after prostate sparing surgerywhichweretreatedbyextensivetur.in order to avoid this possible complication, we exclude patients with tumor growth in the prostatic urethra and also patients with tumor growth around the bladder neck. Another concern frequently expressed is the possible development of an adenocarcinoma in the prostatic tissue left after surgery, since these patients are young and have a long life expectancy. Analyzing the literature, it emerged that the only report of this complication was by Vallancien et al. In their series of 100 patients with a mean follow-up of 38 months, adenocarcinoma of the prostatic fossa was diagnosed in 3% of cases during follow-up; all 3 patients received hormone therapy [10]. In order to avoid this risk, we do not recommend this operation to patients with familial prostate carcinoma, patients with PSA >3 ng/ml and we suggest prostate mapping to all our patients even when the digital rectal examination is negative. We think that our excellent oncological and functional results should be attributed not only to the new surgical technique adopted but also to the extremely careful selection of our patients. They were all young, potent, with an active sexual and social life and had superficial TCC or single, small T2 TCC of the bladder. We believe that this type of surgery should be restricted to no more than 5% of patients who present with bladder tumors. 5. Conclusions The technique of radical cystectomy with prostate and seminal sparing can determine excellent oncological and functional results with a continence and potency rate approaching 100%. However the selection of the patients is crucial. We think that only young patients with superficial or small single infiltrative TCC of the bladder, who are sexually active, should be treated with this type of surgery. Additional followup data is needed in order to confirm the results we have observed so far. References [1] Olsson CA. Editorial. Cystectomy for bladder cancer. J Urol 2004;171:1829. [2] Muto G, Moroni M. Seminal sparing cystectomy and ileo-capsuloplasty. Acta Urol Ital 1998;12:12 5. [3] Colombo R, Bertini R, Salonia A, Da Pozzo LF, Montorsi F, Brausi M, 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 5. [4] Walsh PC, Donker PJ. Impotence following radical prostatectomy: insight into etiology and prevention. J Urol 1982;128: [5] Walsh PC, Mostwin JL. Radical prostatectomy and cystoprostatectomy with preservation of potency. Results of a new nerve-sparing technique. Br J Urol 1984;56: [6] Light JK, Scardino PT. Radical cystectomy with preservation of sexual and urinary function. Use of the ileocolonic pouch ( Le Bag ). Urol Clin North Am 1986;13: [7] Turner WH, Danuser H, Moehrle K, Studer UE. The effect of nerve sparing cystectomy technique on postoperative continence after orthotopic bladder substitution. J Urol 1997;158: [8] Marshall FF, Mostwin JL, Radebaugh LC, Walsh PC, Brendler CB. Ileocolic neobladder post cystectomy: continence and potency. J Urol 1991;145: [9] Thurman S, Bukkapatnam R, Fishman M, Seigne JD, Salup R, Lockhart G. Erectile function following prostate-sparing radical cystectomy for invasive bladder carcinoma. J Urol 2004;171(4): 177.

6 66 M. Brausi et al. / European Urology Supplements 4 (2005) [10] Vallancien G, Abou El Fettouh H, Cathelineau X, Baumert H, Fromont G, Guilloneau B. Cystectomy with prostate sparing for bladder cancer in 100 patients: 10-year experience. J Urol 2002;168: [11] Spitz A, Stein JP, Lieskovsky G, Skinner DG. 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: [12] Muto G, Bardari F, D Urso L, Giona C. Seminal sparing cystectomy and ileocapsuloplasty: long-term follow-up results. J Urol 2004;172: [13] Meinhardt W, Horenblas S. Sexuality preserving cystectomy and neobladder (SPCN): functional results of a neobladder anastomosed to the prostate. Eur Urol 2003;43: [14] Colombo R, Bertini R, Salonia A, Naspro R, Ghezzi M, Mazzoccoli B, et al. Overall clinical outcomes after nerve and seminal sparing radical cystectomy for the treatment of organ confined bladder cancer. J Urol 2004;171: [15] Sèbe P, Lebret T, Molinie V, Herve JM, Yonneau L, Mignot L, et al. Prostatic capsule and seminal sparing cystectomy for bladder carcinoma: initial results for selected patients. Eur Urol 2004;595(3):151. [16] Pritchett TR, Schiff WM, Klatt E, Lieskovsky G, Skinner DG. The potency-sparing radical cystectomy: does it compromise the completeness of the cancer resection? J Urol 1988;140: [17] Brendler CB, Steinberg GD, Marshall FF, Mostwin JL, Walsh PC. Local recurrence and survival following nerve-sparing radical cystoprostatectomy. J Urol 1990;144: [18] Iselin CE, Robertson CN, Webster GD, Vieweg J, Paulson DF. Does prostate transitional cell carcinoma preclude orthotopic bladder reconstruction after radical cystoprostatectomy for bladder cancer? J Urol 1997;158: