Incidence

Several theories exist concerning the pathophysiology of urethral carcinoma following radical cystectomy. Given the field defect nature of urothelial carcinoma, urethral lesions may reflect metachronous occurrences of the primary disease. Such lesions may also represent a true recurrence of disease at the margin of resection or anastomosis in the case of orthotopic diversions. Lastly, these may be previously unrecognized areas of disease in the proximal urethra. Regardless of the true pathophysiology, the incidence of this entity has been reported as ranging from 0% to 18% in several series. A 2002 meta-analysis combined several large series of patients undergoing radical cystectomy and reported a urethral recurrence rate of 8.1% in a pooled cohort of 3165 subjects. A more recent analysis of urethral tumors following radical cystectomy from the University of Southern California reported an incidence of 4.4% in more than 1000 subjects. A preponderance of these subjects underwent some form of continent diversion with a large proportion receiving an orthotopic diversion. A total of 42% of these subjects were diagnosed within 1 year of cystectomy with a median time to diagnosis of 18.5 months.

Risk factors

Several clinic features have been associated with urethral urothelial carcinoma following radical cystectomy, including multifocal disease, carcinoma in situ, upper tract urothelial carcinoma, bladder neck involvement, and involvement of the prostatic urethra. Although most of the aforementioned factors implied various degrees of risk within the literature, the involvement of the prostate had proven to be the most consistent risk factor noted across cystectomy series. Furthermore, the degree of prostatic involvement has been shown to correlate with recurrence of urothelial carcinoma in the retained urethra. In a 1990 series of 30 subjects with urothelial carcinoma of the prostate, there were no recurrences in those with mucosal involvement, there were recurrences in 25% of those with ductal involvement, and a recurrence rate of 67% in subjects with prostatic stromal involvement. In another series of 436 subjects who underwent radical cystectomy, the 5-year urethral recurrence was 6% in subjects without prostatic involvement, 15% in subjects with mucosal involvement of the prostate, and 21% in those with stromal invasion of the prostate gland.

As orthotopic neobladder substitution has become an option for many patients, the issue of recurrent urothelial carcinoma in the functional male urethra has been assessed in several series. Overall, the evidence points toward a protective effect of maintaining a functional urethra via orthotopic neobladder when compared with ileal conduit cutaneous diversion and the resulting dry urethra. The first complete report of this trend is from a 1996 series of 436 subjects and reported a urethral recurrence rate of 2.9% in subjects undergoing orthotopic neobladder substitution compared with 11.1% in those undergoing ileal conduit cutaneous diversion. A more recent series reported a urethral recurrence rate of 0.5% of subjects undergoing orthotopic neobladder compared with 2.1% of those undergoing ileal conduit in a series of 415 subjects undergoing radical cystectomy. Although these overall recurrence rates are lower, the trend toward lower recurrence rate in subjects undergoing orthotopic neobladder is consistently evident. Whether this is caused by patient selection, a systemic effect of continent diversion, excretion of protective substances from the bowel segment used in the diversion, or a protective effect of urine exposure to the retained urethra is unclear.

A cohort of 252 men undergoing orthotopic ileal neobladder was analyzed to determine if preoperative transurethral prostatic urethral biopsy was a predictor of final distal urethral margin status at the time of radical cystectomy. Although this is not a direct predictive model for urethral recurrence following cystectomy, it may affect the patients’ candidacy for orthotopic bladder substitution. Positive transurethral biopsies of the prostatic urethra only correlated with frozen section urethral margin status at the time of cystectomy in 68% of cases. The negative predictive values for transurethral biopsies and intraoperative frozen section were 99.4% and 100%, respectively. Overall, this data does not support the routine use of preoperative transurethral prostatic urethra biopsies to determine fitness for orthotopic neobladder. This point is significant when discussing urethral recurrence following cystectomy because orthotopic neobladder has been associated with lower rates of urothelial carcinoma in the retained urethra.

Risk factors

Several clinic features have been associated with urethral urothelial carcinoma following radical cystectomy, including multifocal disease, carcinoma in situ, upper tract urothelial carcinoma, bladder neck involvement, and involvement of the prostatic urethra. Although most of the aforementioned factors implied various degrees of risk within the literature, the involvement of the prostate had proven to be the most consistent risk factor noted across cystectomy series. Furthermore, the degree of prostatic involvement has been shown to correlate with recurrence of urothelial carcinoma in the retained urethra. In a 1990 series of 30 subjects with urothelial carcinoma of the prostate, there were no recurrences in those with mucosal involvement, there were recurrences in 25% of those with ductal involvement, and a recurrence rate of 67% in subjects with prostatic stromal involvement. In another series of 436 subjects who underwent radical cystectomy, the 5-year urethral recurrence was 6% in subjects without prostatic involvement, 15% in subjects with mucosal involvement of the prostate, and 21% in those with stromal invasion of the prostate gland.

As orthotopic neobladder substitution has become an option for many patients, the issue of recurrent urothelial carcinoma in the functional male urethra has been assessed in several series. Overall, the evidence points toward a protective effect of maintaining a functional urethra via orthotopic neobladder when compared with ileal conduit cutaneous diversion and the resulting dry urethra. The first complete report of this trend is from a 1996 series of 436 subjects and reported a urethral recurrence rate of 2.9% in subjects undergoing orthotopic neobladder substitution compared with 11.1% in those undergoing ileal conduit cutaneous diversion. A more recent series reported a urethral recurrence rate of 0.5% of subjects undergoing orthotopic neobladder compared with 2.1% of those undergoing ileal conduit in a series of 415 subjects undergoing radical cystectomy. Although these overall recurrence rates are lower, the trend toward lower recurrence rate in subjects undergoing orthotopic neobladder is consistently evident. Whether this is caused by patient selection, a systemic effect of continent diversion, excretion of protective substances from the bowel segment used in the diversion, or a protective effect of urine exposure to the retained urethra is unclear.

A cohort of 252 men undergoing orthotopic ileal neobladder was analyzed to determine if preoperative transurethral prostatic urethral biopsy was a predictor of final distal urethral margin status at the time of radical cystectomy. Although this is not a direct predictive model for urethral recurrence following cystectomy, it may affect the patients’ candidacy for orthotopic bladder substitution. Positive transurethral biopsies of the prostatic urethra only correlated with frozen section urethral margin status at the time of cystectomy in 68% of cases. The negative predictive values for transurethral biopsies and intraoperative frozen section were 99.4% and 100%, respectively. Overall, this data does not support the routine use of preoperative transurethral prostatic urethra biopsies to determine fitness for orthotopic neobladder. This point is significant when discussing urethral recurrence following cystectomy because orthotopic neobladder has been associated with lower rates of urothelial carcinoma in the retained urethra.

Surveillance

Screening strategies for patients following radical cystectomy include urethral cytology and endoscopic examination of the urethra. Symptomatic bleeding or urethral discharge are indications for urethroscopy and correlate with the presence of urothelial carcinoma in the retained urethra. Cytology has been shown to be a reliable indicator of urethral urothelial carcinoma in patients who are symptomatic and asymptomatic. In a series of 24 subjects who underwent urethrectomy following cystectomy for urethral urothelial carcinoma, 17 (71%) were asymptomatic but had a positive urethral wash cytology, whereas 7 (29%) were not followed with urethral cytology and presented with symptomatic bleeding. Another earlier series reported similar results. In a group of 47 subjects who underwent radical cystectomy, urethral urothelial carcinoma was diagnosed by screening cytology alone in 35% of these subjects, and 94% of all subjects diagnosed with urethral urothelial carcinoma in this group had a positive urethral cytology. One series also reported a 12.5% false-positive rate for urethral cytology in screening subjects for recurrence following radical cystectomy. These screening practices can be applied to patients with cutaneous diversions and a dry urethra, and those with orthotopic neobladders. However, patients with orthotopic neobladders and urethral urothelial carcinoma may also present simply with a change in voiding habits. This data provides support for periodic cytology obtained by urethral washing as a minimum screening tool, with endoscopic evaluation of the urethra a useful addition particularly in patients who present with symptomatic bleeding or urethral discharge. In the case of these patients, urethrectomy should be strongly considered even in the absence of frank pathology. In the case of gross findings on cystoscopy or palpable disease, cross-sectional imaging should be obtained.