Positive Pre-cystectomy Biopsies of the Prostatic Urethra or Bladder Neck Do Not Necessarily Preclude Orthotopic Bladder Substitution.

PURPOSE: We investigated the influence of positive pre-cystectomy biopsies of the prostatic urethra in males and the bladder neck in females on urethral recurrence, cancer specific and overall survival, and functional outcomes after orthotopic bladder substitution. MATERIALS AND METHODS: We retrospectively analyzed the records of 803 consecutive patients, including 703 males and 100 females, who underwent orthotopic bladder substitution as well as pre-cystectomy biopsy of the prostatic urethra in males and the bladder neck in females, at our institution between April 1986 and December 2017. RESULTS: Pre-cystectomy biopsies were negative in 755 of the 803 patients (94%) (group 1) and positive in 48 (6%) (group 2). Biopsies in group 2 revealed carcinoma in situ in 35 of the 48 cases (73%), pTaG1/G2 in 5 (10%) and pTaG3/pT1G3 in 8 (17%). Median followup was 64 months (IQR 21-128). At a median followup of 56 months (IQR 18-127) urethral recurrence developed in 45 of the 803 patients (5.6%), including 30 of the 755 (4%) in group 1 and 15 of the 48 (31.3%) in group 2 (p <0.001). Only 10 of the 45 patients (22%) with urethral recurrence required salvage urethrectomy while locally conservative treatment was successful in 27 (60%). Of the remaining 8 patients 6 of 45 (13%) underwent synchronous palliative chemotherapy and 2 of 45 (4%) refused treatment. Multivariate regression analysis revealed a higher risk of urethral recurrence if patients had positive pre-cystectomy biopsies (group 2 HR 6.49, 95% CI 3.33-12.62, p <0.001) or received neoadjuvant or adjuvant chemotherapy (HR 3.05, 95% CI 1.66-5.59, p <0.001). Cancer specific and overall survival as well as functional outcomes were similar in the 2 groups. CONCLUSIONS: Positive pre-cystectomy biopsies prior to orthotopic bladder substitution increased the urethral recurrence rate but did not lower cancer specific or overall survival. Most urethral recurrences were managed successfully by local treatment. Orthotopic bladder substitution is an option in highly selected patients with positive, noninvasive pre-cystectomy biopsies, provided that they undergo regular followup including urethral cytology.

Urethral recurrence after cystectomy: current preventative measures, diagnosis and management.

To summarise the current literature on the diagnosis and management of urethral recurrence (UR) after radical cystectomy (RC), as UR after RC is rare but associated with high mortality. With the recently increased use of orthotopic bladder substitution and the questionable benefit of prophylactic urethrectomy, identification of patients at high risk of UR, management of the remnant urethra, and treatment of UR become critical questions. A review of the PubMed database from 1980 to 2014 was performed to identify studies evaluating recurrent urothelial cancer of the urethra after RC. The search terms used included 'urethral recurrence', 'cystectomy' or 'cystoprostatectomy'. Selected studies provided information on the type of urinary diversion performed, the incidence of UR, and the time to UR. Incidence of UR after RC ranges from 1% to 8% with most recurrences occurring within the first 2 years after surgery. Increased risk of UR is associated with involvement of the prostate, tumour multifocality, bladder neck involvement, and cutaneous diversion. The median overall survival after UR ranges from 6 to 54 months and the 5-year disease-specific survival after UR is reported to be between zero and 83%. UR remains a relatively rare event. Current literature suggests that urethral wash cytology may be useful in patients with intermediate- to high-risk of recurrence to enable early detection of non-invasive disease, which may be amenable to conservative therapy before urethrectomy.

[Management of the male urethra before and after cystectomy: from the prophylactic urethrectomy to the intraoperative frozen section biopsy of the urethral margin]. / Actitud con la uretra antes y durante la cistectomía en el varón: de la uretrectomía profiláctica a la biopsia por congelación del margen uretral.

CONTEXT: Decision making regarding the urethra before and after radical cystectomy due to urothelial carcinoma has always been controversial. OBJECTIVE: To analyze the changes produced in the management of the urethra from the beginning of the cystectomy up to the present moment. EVIDENCE ACQUISITION: Analysis of original articles and reviews obtained through a search in PubMed, related with the risk factors of urethral recurrence (UR) and with the management of the urethra in patients subjected to radical cystectomy. EVIDENCE SYNTHESIS: At first, many authors recommended urethrectomy simultaneously with cystectomy. The identification of risk factors of the bladder tumor related with the appearance of UR limited the indication of prophylactic urethrectomy in patients with multifocal disease and with prostate tumor involvement. The development of orthotopic bladder substitutes (OBS) complicated the situation. The involvement the prostatic urethral tumor was maintained as the principal risk factor for UR, which then gave importance to its pre-cystectomy staging. Series of OBS observed a lower incidence of UR regarding patients with skin derivations, even in cases with prostatic urethral involvement. Prostatic urethral involvement stopped being a contraindication for OBS when the frozen section biopsy of the urethral margin was negative. CONCLUSIONS: Currently, most authors agree that the intraoperative frozen section biopsy of the urethral margin will determine whether an OBS or urethrectomy should be performed. In spite of this, we have very few series in which this approach has been systematically used and with sufficient follow-up.

The risk factor for urethral recurrence after radical cystectomy in patients with transitional cell carcinoma of the bladder.

PURPOSE: We evaluated the incidence and risk factors for urethral recurrence following radical cystectomy and urinary diversion in transitional cell carcinoma. PATIENTS AND METHODS: A retrospective review was performed of the 412 consecutive patients who underwent radical cystectomy and urinary diversion for transitional cell carcinoma of the bladder between 1986 and 2004. A total of 294 patients were enrolled in this study. We investigated the impact of various clinical and pathological features on urethral recurrence by univariate and multivariate analysis. RESULTS: Urethral recurrence developed in 13 patients (4.4%) and the 5-year urethral recurrence-free probability was 94.9%. On univariate analysis, positive urethral margin, prostatic stromal invasion, and prostatic urethral involvement had a significant influence on urethral recurrence (p < 0.05). The other clinical and pathological features were not significantly associated with urethral recurrence (p > 0.05). A multivariate Cox proportional hazard model revealed that a positive urethral margin (hazards ratio (HR) = 18.33, p < 0.001), prostatic urethral involvement (HR = 7.95, p < 0.001), and prostatic stromal invasion (HR = 5.80, p = 0.018) were independent risk factors for urethral recurrence. CONCLUSION: A positive urethral margin is considered an absolute indication for prophylactic urethrectomy. In addition, more careful patient selection is necessary for orthotopic urinary diversion in patients with prostatic urethral involvement and prostatic stromal invasion.

Urethrectomy following cystectomy for bladder cancer in men: practice patterns and impact on survival.

PURPOSE: The benefit of urethrectomy in patients with bladder cancer who are undergoing cystectomy is controversial. We describe the frequency of urethrectomy by bladder cancer stage and identify clinical characteristics that predict urethrectomy. We also investigated whether urethrectomy offers any additional independent survival benefit. MATERIALS AND METHODS: A total of 2,401 men who underwent radical cystoprostatectomy between 1991 and 2002 were identified in the Surveillance, Epidemiology and End Results-Medicare database. A multivariate logistic regression model was used to analyze factors driving urethrectomy. We then analyzed the records of 195 men who underwent urethrectomy to find predictors of that procedure as salvage for urethral recurrence vs concurrently with cystoprostatectomy or as a staged procedure. Using multivariate Cox regression analysis we analyzed whether urethrectomy had an independent effect on disease specific survival. RESULTS: The only significant predictor of urethrectomy was stage. Patients at a teaching hospital were more likely to undergo salvage urethrectomy for recurrence vs immediate urethrectomy compared to those at urban nonteaching hospitals. Patient age, race, number of comorbidities and tumor stage were significant independent predictors of survival. Survival in men who underwent urethrectomy concurrently with cystoprostatectomy was higher than in those who did not undergo urethrectomy but not statistically significant (HR = 0.775, 95% CI 0.592-1.014, p = 0.0632). CONCLUSIONS: Disease stage is related to urethrectomy performance. Age, race, stage and comorbidities were independent predictors of overall survival in patients with bladder cancer undergoing cystectomy. Urethrectomy did not confer a significant independent survival benefit.

Immediate versus staged urethrectomy in patients at high risk of urethral recurrence: is there a benefit to either approach?

OBJECTIVES: To compare treatment-related outcomes of immediate and staged urethrectomy in patients at high risk of urethral recurrence. METHODS: We retrospectively identified 76 male patients with cystectomy for transitional cell carcinoma of the bladder who had undergone urethrectomy in the absence of established urethral recurrence. Concomitant cystoprostatectomy and urethrectomy was performed in 57 patients and staged urethrectomy in 19 patients. The criteria for staged urethrectomy were the presence of a positive urethral margin or established transitional cell carcinoma of the urethra in the cystectomy specimen. The mean interval from cystectomy to staged urethrectomy was 4.7 months (range 1.4 to 14). RESULTS: The most common pathologic finding of the urethrectomy specimens was prostatic duct involvement (31.6%) in the immediate urethrectomy group and Stage pT0 in the delayed urethrectomy group (73.7%). No statistically significant difference in disease-specific survival was noted between the immediate and staged groups (P = 0.14). Similarly, no difference was noted in postoperative complication rates or total operative blood loss (P = 0.77 and P = 0.64, respectively). However, a slight benefit for immediate urethrectomy was noted in the total duration of hospitalization (P = 0.01). The presence of local or distant recurrence was a predictor of disease-specific survival (P = 0.02 and P = 0.02, respectively). CONCLUSIONS: Immediate and staged urethrectomy appear to be similar in surgical morbidity and disease-specific survival. A benefit was noted for the immediate group in the total duration of hospitalization. The development of local or distant recurrence was a predictor of poor survival.

Short- and long-term issues regarding urethral management in male radical-cystectomy patients.

PURPOSE OF REVIEW: Radical cystectomy remains the gold-standard therapy for invasive bladder cancer. Management of the urethra before, during, and after cystectomy, however, is still not standardized. Herein, the rationale for different management algorithms is given. RECENT FINDINGS: The literature remains inconsistent regarding the best diagnostic and therapeutic management of the urethra before and during cystectomy as well as afterwards. The risk of urethral recurrence may in fact be lower after orthotopic urinary diversion, but the evidence for this and other recommendations comes from retrospective series. Urethral recurrence, although uncommon, continues to have a poor prognosis, and the optimal follow-up regimen is unclear. The importance of lifelong follow-up is unquestioned. SUMMARY: Risk factors for urethral involvement/recurrence can be determined before, during, and after radical cystectomy. The best way to diagnose and predict who will recur, however, is still unknown, as is the optimal follow-up regimen and treatment for the remnant urethra. The type of urinary diversion may in fact influence disease recurrence, as it also affects possible therapy for patients with recurrence.

Lack of effects of sodium 2-mercaptoethane sulfonate (mesna) on Ochratoxin A induced renal tumorigenicity following life-time oral administration of Ochratoxin A in DA and Lewis rats.

Sodium 2-mercaptoethane sulfonate (Mesna) reacts with urotoxic metabolites of oxazaphosphorine drugs (e.g. cyclophosphamide or ifosfamide) and has been used clinically to protect against damage induced by these aggressive anti-neoplastic drugs in the kidney and lower urinary and genital tracts. Ochratoxin A (OTA) is a potent nephrotoxin in several species. In order to elucidate whether mesna has curative or preventive effects on OTA-induced renal damage or renal tumor development, we administered OTA and/or mesna to both DA and Lewis rats for their life-time and examined kidney, urethra and urinary bladder histologically. OTA induced sex- and strain-specific renal tumors. However, there was no evidence of any effect of mesna on the incidence and distribution of any type of tumor or non-neoplastic finding in the kidney in either strain or treated group. In this study, we have confirmed that mesna treatment did not show any curative or preventive effects on either OTA-induced kidney damage or renal tumor development in two different strains that have distinct metabolic characteristics.

Urethral recurrence after radical radiotherapy for bladder cancer.

PURPOSE: Following cystectomy for bladder cancer, orthotopic reconstruction may result in a decreased risk of urethral recurrence compared to cutaneous diversion. We evaluate the rate of urethral recurrence after radical external beam radiotherapy. MATERIALS AND METHODS: We reviewed the records of 214 men who had received radical radiotherapy at a single center from 1990 to 1995. Patients treated with chemotherapy were excluded from study. RESULTS: A total of 214 men (median age 69 years, range 39 to 86) underwent radical radiotherapy for cure. Tumor stages were T1 in 7%, T2 in 41%, T3 in 42% and T4a in 10% of the patients. Median followup was 32 months (range 1 month to 8.4 years) and 5-year survival rate was 30%. Urethral recurrence developed in 7 (3.2%) cases and was detected within 18 months (median 10 months, range 3 months to 5 years) of followup in 5. In 2 of these 7 cases recurrence developed in the prostatic urethra, and when these 2 cases were excluded from analysis the recurrence rate decreased to 2.3%. A total of 64 men completed 5-year followup, with a 4.7% rate of urethral recurrence (3.1% excluding prostatic urethral recurrence). Multifocal disease, bladder neck involvement, prostatic disease and cis were possible risk factors for urethral recurrence. CONCLUSIONS: The risk of urethral recurrence after radical radiotherapy for transitional cell carcinoma of the bladder is comparable with that reported after orthotopic reconstruction. It is not possible to exclude completely that men at higher risk were offered cystectomy, but the data are consistent with the suggestion that continued contact with urine may be protective.

Prepubic urethrectomy with urethral stripping.

PURPOSE: Prepubic urethrectomy is a simple, safe alternative to perineal urethrectomy. The lithotomy position can be avoided and, thus, operative time and risk of deep venous thrombosis are decreased. We developed a simple modification because of difficulty in dissecting the bulbous urethra. MATERIALS AND METHODS: From 1996 through 1998 prepubic urethrectomy was performed using a modified procedure in 21 patients with invasive bladder carcinoma undergoing radical cystectomy and supravesical diversion. After periurethral mobilization the urethra was cannulated with an 18F catheter, sutured distal and stripped free. RESULTS: Operative time decreased to 20 to 30 minutes with no significant postoperative complications. CONCLUSIONS: Our modification of prepubic urethrectomy is safe, fast and easy.

Transitional cell carcinoma of the urethra in men after radical cystectomy for bladder cancer. Is prophylactic urethrectomy indicated?

A retrospective study of the incidence and clinical course of transitional cell carcinoma of the urethra is reported. Of 110 consecutive male patients who underwent cystectomy during a 9-year period, 9 had or developed a urethral tumour. Five patients undergoing radical cystectomy had known or suspected urethral involvement which was confirmed at urethrectomy. All 5 had deeply invasive (T3 or T4) transitional cell carcinomas of the bladder and subsequently died of metastatic disease. Four patients underwent urethrectomy because of signs or symptoms of urethral recurrence at an average interval of 2.5 years after cystectomy. There were two deaths in this group, neither of which appeared to be due to urethral recurrence. Six additional patients had undergone prophylactic urethrectomy because of prostatic urethral involvement or diffuse carcinoma in situ in the cystectomy specimen, and none had identifiable tumour in the anterior urethra. The residual urethra is a potential focus for recurrent tumour and this necessitates careful follow-up with serial cytology, but the low incidence of urethral recurrence (3.5% in this series) does not appear to warrant routine urethrectomy at the time of cystectomy.

Selective urethrectomy following cystoprostatectomy for bladder cancer.

The poor prognosis in patients who have symptomatic urethral carcinoma after cystoprostatectomy has prompted some investigators to recommend prophylactic urethrectomy. However, this approach subjects the majority of these patients (up to 90 per cent) to an operation for a disease that they might never have and precludes some innovative urinary diversion techniques. From June 1976 to July 1985 we performed 75 cystoprostatectomies for bladder cancer in men. Three patients underwent simultaneous urethrectomy because of tumor in the urethra. Of the remaining 72 patients who were followed by urethral wash cytology studies every 6 months 7 (10 per cent) had positive cytology studies during followup and underwent urethrectomy. Subsequent histological examination showed carcinoma in situ in all 7 specimens. To date 6 of the 7 patients are free of disease. One patient died 18 months after urethrectomy without evidence of transitional cell carcinoma. We have had no false positive urethral wash cytology studies and no patient has had local recurrence in the absence of a positive cytology study.

Risk of local urethral recurrence after radical cystectomy for bladder cancer.

Radical cystectomy and urinary diversion were performed on 349 patients with transitional cell cancer of the bladder. Followup for 4 to 13 years revealed that 91 and 83 per cent of the patients were free of urethral recurrence 5 and 10 years after cystectomy, respectively. Statistical elimination of urethral recurrences did not improve the over-all survival rate significantly. It appears that supplementation of cystectomy with simultaneous urethrectomy may not be justified if the urethra is not involved by the cancer.

Management of the urethra in men undergoing radical cystectomy for bladder cancer.

The records of 119 men who had undergone radical cystectomy for cancer of the bladder were reviewed for involvement of the urethra at the time of cystectomy and for later recurrence of urethral tumor. Urethral recurrences contributed significantly to the over-all pelvic recurrence rate and were associated with a uniformly poor prognosis. Prophylactic urethrectomy is indicated when pathologic examination reveals multifocal tumors, concurrent upper tract tumors, diffuse carcinoma in situ, involvement of the trigone or prostatic urethra, or positive urethral margin on frozen section. Those patients not undergoing urethrectomy should be followed with periodic urethral wash cytology.