[Abstract] Objective To investigate the risk factors and management of urethral recurrence after total bladder resection for bladder cancer. Methods The clinical data of 278 patients with total bladder resection for bladder cancer were retrospectively analyzed, among which 24 cases had urethral recurrence. The risk factors affecting recurrence were evaluated by using Cox’s multifactorial regression model. The results showed that none of the 6 cases of elective urethrectomy in this group died from tumor; 10 of the 24 cases of urethral recurrence died from metastasis of tumor. Multifactorial analysis showed that prostate involvement, bladder neck involvement, tumor in the triangle, multiple tumors, and carcinoma in situ were risk factors affecting urethral recurrence, with relative risk ratios of 1.573, 1.532, 1.360, 1.337, and 1.213, respectively. Patients with preserved urethra underwent urinary diversion with orthostatic voiding as much as possible.
[Keywords] bladder tumor; cystectomy; urethrectomy; recurrence, urethra
The prognosis of recurrent tumors in the urethra after total cystectomy for migratory cell carcinoma of the bladder is poor. A total of 278 patients with total cystectomy for bladder cancer were admitted to our hospital from January 1978 to May 2001, and the Cox’s multifactor analysis model was used to explore the factors affecting urethral recurrence. It is reported as follows.
Materials and methods
I. Clinical data
There were 278 patients with total cystectomy for bladder cancer, aged 39 to 75 years, with an average of 59.8 years. In 49 female cases, no urethral recurrence occurred; in 229 male cases, 6 cases (2 with carcinoma in situ, 3 with multiple and located in the triangle, and 1 involving the cyst neck and prostate urethra) underwent total cystectomy at the same time. The average age of urethral recurrence was 59.5 years (40-75 years). 5 cases were found to have metastatic cell carcinoma by postoperative cytological examination of urethral flushing fluid, 19 cases were found to have urethral blood spillage, pink or dark red; 8 cases were accompanied by perineal pain, and all were confirmed to have tumor recurrence by urethroscopy. The recurrent tumors in urethra were mostly multiple tumors (13/24), papillary or villous, 0.3~1.1 cm in diameter. 22 cases were located in posterior urethra, 2 cases in anterior urethra, urethral membrane was the most common, followed by urethra of penis and urethral navicular fossa. The recurrence interval ranged from 1 month to 29 months, with a mean of 14.6 months. 5 of the 24 patients underwent posterior urethrectomy, and 1 case still had postoperative urethral overflow and underwent anterior urethrectomy again; 19 patients underwent total urethrectomy.
II. Statistical methods
Statistical indicators: for 223 male patients, 13 indicators were counted, including age, smoking index, number of tumors (single and multiple), morphology, site, size, pathological grading, tumor stage, whether in situ cancer, presence of lymph node metastasis, prostate involvement, cystic neck involvement, and postoperative biological treatment.
Quantification of indicators.
(1) The actual observed values were used for the measurement indicators.
(2) Rank indicators were quantified in rank order.
(3) The two-phase classification count indicators were transformed using (0, 1).
(4) The count indicators of multiphase classification were quantified in their order according to the proportional hypothesis test chart.
Single-factor analysis method: Kruskal-Wallis method.
Multi-factor analysis method: Cox’s proportional risk model. Risk function formula: h(t)=h(t0). exp(β1×1+β2×2+…+βixi). All data were entered into Foxpro 6.0 to create a database, and statistical analysis was performed using SPSS 8.0.
Results
Six patients who underwent simultaneous total urethrotomy were followed up from 6 months to 3 years, five were alive, no tumor recurrence or metastasis was detected, and one died of other diseases.
Twenty-four patients with urethral reissue urethrectomy were followed up from 11 months to 10 years, 10 died of tumor recurrence and metastasis, and 3 died of other diseases.
Univariate analysis associated with recurrence showed that nine factors: multiple tumors, tumors in the delta, tumor size, pathologic grade, tumor stage, carcinoma in situ, lymph node metastasis, prostate involvement, and bladder neck involvement were factors affecting recurrence.
Multi-factor analysis of Cox’s model related to recurrence: the nine variables that were significant in univariate analysis were introduced into Cox’s proportional risk model for multi-factor analysis, and multiple tumors, tumors in the triangular region, carcinoma in situ, prostate involvement, and bladder neck involvement were the main factors influencing recurrence in the urinary tract. (Table 1).
Discussion
The chance of urethral recurrence after total cystectomy and extra-urethral diversion for bladder cancer is 3.5-17%
[ 1], and the prognosis is poor. The most important symptom of urethral recurrence is urethral blood spillage, which can be detected early by routine postoperative urethroscopy and cytological examination of urethral irrigation fluid. There is a consensus on the indications and procedures for total cystectomy, but it is controversial whether urethrotomy should be performed at the same time as total cystectomy.
［Zabbo et al.
[3], concluded that the decision to perform concomitant urethrectomy should be based on the risk factors for bladder cancer.
In recent years, studies have shown that urethral diversion with orthostatic voiding can better protect renal function and significantly improve patients’ quality of life, and the postoperative urethral recurrence rate is only 2.9%, which is lower than that of other urethral diversions (11.1%) [4, 5], which may be related to the continuous flushing of urine and the protective factors secreted by the intestinal mucosa of the surrogate bladder [6], which rarely occurs after surgery in patients with bladder cancer who are not undergoing total cystectomy This is also evidenced by urethral tumors. Therefore, prophylactic urethrotomy is unwise and selective urethrotomy should be performed.
Recurrence of bladder cancer is related to tumor grade, number, p53, VEGF and other factors [7] and is a reflection of the multicentric growth of metastatic cell carcinoma in time and space. Our data showed that urethral recurrence after total cystectomy for bladder cancer is closely related to local factors,the risk of urethral recurrence is highest after prostate involvement, followed by bladder neck involvement and tumor in the triangular region.Hardeman et al [6] reported that the rate of urethral recurrence was as high as 37% after prostate involvement, while the recurrence rate was only 4% after excluding prostate involvement. It has also been reported that prostatic stromal involvement has a higher risk of recurrence than prostatic ductal and prostatic part urethral involvement, up to 64%. In female patients, bladder neck involvement is the predominant high risk factor [8]. Multiple tumors and carcinoma in situ often suggest active tumor cell growth and a relatively low risk of urethral recurrence, suggesting that the molecular biological mechanisms of the tumor itself are different in the risk of urethral recurrence and bladder recurrence.
In view of the close relationship between urethral recurrence and local residual, implantation and infiltration of tumor cells after total cystectomy for bladder cancer, for patients who intend to preserve the urethra, preoperative cystoscopy should be performed together with urethroscopy to pay attention to the prostate and urethra of the prostate, and pathological biopsy should be performed if necessary to exclude prostate involvement. If the tumor is found, the urethra should not be preserved; the operation should be performed gently to avoid transection of the tumor, and tumor-free surgery should be performed to prevent tumor implantation in the posterior urethra. After posterior urethral resection, the anterior urethra still has the possibility of recurrence, and there is one case in our group.
Postoperative follow-up should not be neglected. Postoperative urethroscopy and cytological examination of urethral flushing fluid should be routinely performed every three months for two years, and every six months thereafter. There are cases of urethral recurrence 16 years after total cystectomy and continuous lifelong follow-up review is necessary. Most of the recurrences detected by review are early non-invasive tumors and have a better prognosis after surgical treatment.
Based on the assessment of the risk of urethral recurrence, we believe that the indications for prophylactic urethrectomy in patients with total cystectomy for bladder cancer are.
(1) Preoperative examination proving concurrent prostatic urethral involvement or anterior urethral involvement.
(2) Multiple tumors, tumors in the triangle, carcinoma in situ, or bladder neck involvement.
(3) Intraoperative urethral margin cryopathology confirmed the presence of tumor remnants.
(4) Postoperative pathology confirmed prostate involvement. Patients with urethra-preserving bladder cancer should undergo urinary diversion with orthostatic voiding as much as possible.
Urethrectomy should be performed immediately if
(1) Follow-up review (urethroscopy or cytology of urethral flushing fluid) reveals tumor recurrence or malignant cells.
(2) The patient presents with urethral overflow.