Primary transitional cell carcinoma in vesical diverticula

ELSEVIER PRIMARY TRANSITIONAL CELL CARCINOMA IN VESICAL DIVERTICULA JACK BANIEL AND TALI VISHNA ABSTRACT Objectives. To evaluate the treatment and prognosis of primary tumors in bladder diverticula. Methods. The cases of 61 1 patients treated for bladder tumors at a single medical center were retrospectively reviewed. Results. Eight patients had primary intradiverticular transitional cell carcinoma. Five patients had Stage Ta tumor, and 3 had Stage Tl tumor. Most patients were treated by local resection and adjuvant intravesical chemotherapy. All patients with initial Ta disease are disease free at the time of this writing. One patient with Tl disease died, 1 patient’s disease recurred several times, and 1 patient showed positive cytology without apparent disease. Conclusions. Superficial intradiverticular tumors may be treated conservatively. Routine cystoscopy for patients with a bladder diverticulum is warranted for early diagnosis of possible intradiverticular tumor. UROLOGY 50: 697-699, 1997. 0 1997, Elsevier Science Inc. All rights reserved. eoplasms arising in a vesical diverticulum are of special interest because they present a complex disease treatment problem. The incidence of neoplasms in vesical diverticula varies from 0.8% to 10%.l12 The first report of a neoplasm occurring in a diverticulum was described in 1896.3 As in other bladder tumors, diverticular neoplasms are most prevalent in men above the age of 40 years.4 The relatively scarce documentation of this disease published in the literature suggests an overall poor prognosis.2,5 It is postulated that the thin diverticular wall, which contains only a small amount of smooth muscle (if any), facilitates early invasion.2 We review our experience in the treatment of 8 patients with neoplasms occurring within bladder diverticula. N MATERIAL AND METHODS Six hundred eleven cases of superficial bladder cancer treated between 1978 and 1995 were retrospectively reviewed. All patients were followed up at the outpatient clinic at Rabin Medical Center, Beilinson campus, Petach Tikva, Israel. Of these patients, 9 men also had a vesical diverticulum, and in From the Department of Urology, Rabin Medical Center (Beilinson campus), Petach Tikva, Israel Reprint requests: Jack Buniel, M.D., Urology Section, Rabin Medical Center, Beilinson Campus, Petach Tikvu 49100, Israel Submitted: February 18, 1997, accepted (with revisions): May 13,1997 0 1997, ELSEVIER SCIENCE ALL RIGHTS RFSFRVFII 8 patients, the primary neoplasm occurred in a diverticulum. The clinical course, diagnosis, treatment, and prognosis were also reviewed. The patient’s ages ranged from 45 to 80 years, with an average age of 68.6 years. Follow-up ranged from 7 months to 17 years, with a median of 5 years. RESULTS The presenting symptom of all but 1 patient was gross hematuria. The remaining patient presented with dysuria. Intravenous urography (IVU) was performed in 6 of the patients before surgery and did not reveal any filling defect in the bladder. Cystoscopy was performed in all 8 patients. In 7 patients, a tumor was seen inside a diverticulum. In 1 patient, a second cystoscopy was diagnostic and revealed a tumor. The pathologic diagnosis in all patients was transitional cell carcinoma (TCC). Four patients had poorly differentiated carcinomas (grade III), 2 had grade II carcinomas, and the remaining 2 had grade I carcinomas. Five patients had Stage Ta tumor and 3 patients had Stage Tl tumor (Table I). Treatment is outlined in Table I. Open diverticulectomy was performed on 5 patients, and transurethral resection of the bladder tumor (TURBT) was performed on 3 patients. Of the 5 patients who underwent diverticulectomy, 2 were treated postoperatively with bacille Calmette-GuCrin (BCG) instillations, 1 with thiotepa instillations, 1 with postoperative irradiation, and 1 was followed up INC. 0090-4295/97/$17.00 PII soogo-4295(97)oo319-1 697 TABLE Patient 1 2 3 4 5 6 7 8 Grade I. Stage I I II II III III III III Ta Ta Ta Ta Ta Tl Tl Tl KEY: AWD = alive with disease; KG tumor. = bacille Calmette-GuCrin; Patient management Initial Follow-up M-1 Management TURBT + BCG Diverticulectomy + thiotepa Diverticulectomy + radiation TURBT + BCG Partial cystectomy + BCG Partial cystectomy + BCG TURBT + BCC Diverticulectomy (2000 rad) COMMENT Vesical tumors occurring in diverticula pose a difficult treatment problem because of their generally poor prognosis.4,6-8 This poor prognosis is mainly a result of difficulty in diagnosis and early invasion. It is difficult to diagnose a tumor in a diverticulum.7 In our study, IVU was not diagnostically successful in 6 patients. Even cystoscopy failed to reveal the existence of a tumor in 1 of the 8 patients. The second and more important reason for poor prognosis is believed to result from the anatomy of the diverticulum. Bladder diverticula are pseu- Status NED NED NED NED NED DOD NED? AWD 5 11 17 0.6 5.5 1.8 2 5.5 DOD = dead of disease; NED = no evidence of disease; TLJRBT = transurethral without postoperative treatment. All 3 patients who underwent TURBT received adjuvant intravesical BCG instillations. The survival data are outlined in Table I. Four patients are disease-free 5 or more years beyond diagnosis. One patient is disease free after 7 months of follow-up, and 1 patient has died. All patients with Stage Ta disease are alive. Three patients had TlG3 disease. One patient died of disease. He was treated by diverticulectomy and postoperative BCG intravesical instillation. Sixteen months after initial diagnosis, he had occurrence of pulmonary metastasis and died. Another patient with TlG3 disease was managed by TURBT and BCG instillations. He was diseasefree for 2 years, and at the time of this writing has no positive cytology with no apparent disease. Another patient with initial TlG3 disease is under follow-up for 5.5 years; he had several recurrences, the first occurring 4 years after initial diagnosis. His disease recurred in a ureter and nephroureterectomy was performed. Histology revealed a poorly differentiated tumor with muscular involvement. Currently he is receiving adjuvant chemotherapy. Five patients were staged as Ta. Four patients have follow-up of more than 5 years and are disease-free. One patient who was recently treated is without evidence of disease for 7 months. 698 and follow-up resection of the bladder dodiverticula; they appear in areas deficient in muscle fibers and are composed of mucosa and serosa alone. The lack of muscle fibers in a diverticulum may allow the tumor to invade earlier and more easily than in a normal thick muscle containing bladder wall. 2,9-11This also raises the question of accurate staging. Because muscle is absent or deficient, should invasion of the lamina propria (Tl) be synonymous in this case with Stage T2/T3 disease in normal bladder? In this study, only 3 of 8 patients (37.5%) had a potentially invasive tumor, and were defined as having Stage Tl disease. In other studies, the majority of patients presented with high stage tumor. Faysal and Freiha6 found nine (69.2%) invasive and only four (30.8%) noninvasive tumors arising in a diverticule. Lowe et a1.7 described 5 cases of tumors in diverticula, all of which were invasive. At present, lack of sufficient data on this topic precludes the creation of a special staging system for diverticular tumors. The tendency is to treat Tl tumors more aggressively. Garzotto et al.” presented a highly aggressive management plan in which 8 patients were treated by diverticulectomy and a combination of chemotherapy and radiotherapy. Their study did not specify initial stage and cannot be compared to the above. Because cancer of the bladder occurs predominantly in men, most of the patients with tumor in a diverticulum are men2,4,6,10,11 who are over the age of 40 years.6”o In this study, all patients were men, and the average age was 68.6 years. The histology of the cancer in this study, as in many others, was transitional cell carcinoma.6,7,10 The survival rate of patients in this study, unlike other reports, is relatively high (2-year survival rate of 87.5%; S-year survival rate of 71.4%). Lowe et a1.7 described 6 cases of tumors in diverticula. Only 1 of the 6 patients survived after 2 years. Faysel and Freiha6 described 12 cases of tumors within a diverticulum with results better than Lowe’s (2-year survival rate of 58.3%), but no paUROLOGY 50 (51, 1997 tients survived after 5 years (9 of 9 had died); tumor recurrence was reported in 91.7% of the patients. Montague and Boltuch” described a fair prognosis but with limited follow-up; 90% of their patients survived after 2 years. In Montague’s study, management of patients did not differ markedly from other series, and only 1 of 10 patients had had a total cystectomy. These authors claim that the low mortality rate was due to early detection. In their study, 40% of the patients were diagnosed with Stage Ta disease. In this study, 62.5% of the tumors were noninvasive, which may be the reason for the low mortality rate observed. Even where aggressive management was implemented, as in the study by Garzotto et u1.,12 survival was 50%, with a median of 3.2 years. It may be assumed that for Ta tumors, conservative treatment may suffice. Early detection of tumors may result from better imaging studies or from more frequent cystoscopies. In our study, 6 patients had IVU, and none were diagnosed with tumor. Cystoscopy, on the other hand, failed to detect the tumor only once. Cystoscopy is very important in the detection of tumors in diverticula.’ Some studies6a12,13 claimed that aggressive treatment improves the prognosis of patients with carcinoma in a diverticulum. In this study, even though most of the patients were treated conservatively, the outcome was fair. The incidence of neoplasms in bladders with a diverticulum is higher than the incidence of neoplasms within a normal bladder, ranging from 0.8% to lOoA When there is a diverticulum and neoplasm in the same bladder, most of the neoplasms will be located within the diverticulum.2,14 In our study, we found 9 patients who had both a bladder tumor and a diverticulum. Only in 1 patient did the tumor appear outside of the diverticulum. The coexistence of neoplasms and diverticula can be explained by stagnation of urine within the diverticulum, allowing local carcinogens to act on the walls of the diverticulum. Urine promotes chronic irritation and inflammation, and all factors together act as promoters of carcinogenesis.2,4z9 Diverticula increase the risk of neoplasm of the bladder, and a neoplasm inside a diverticulum has a poor prognosis unless diagnosed early; thus, we recommend routine cystoscopy for any patient who appears to have a diverticulum.*~1° Patients UROLOGY 50 is), M7 with outflow obstruction are prone to develop vesical diverticula and thus comprise a group at risk for the occurrence of an intradiverticular lesion. Intravenous urography or other radiographic studies may not be sufficient for timely detection of diverticular tumors. When dealing with invasive bladder diverticular tumors (Tl), disease management should probably be aggressive (radical cystectomy versus diverticulectomy plus adjuvant intravesical treatment), although the paucity of cases precludes clear recommendation of cystectomy versus local resection.4’12’14 We conclude that early detection is the key to improving the overall survival rate of patients presenting with this disease, and that the punishment should fit the crime-the treatment should be aggressive only if the tumor is invasive. REFERENCES 1. Lawrence WW (Ed): Current Surgical Diagnosis and Treatment, 10th ed. Englewood Cliffs, New Jersey, PrenticeHall, 1994, pp 952-954. 2. Melekos MD, Asbach HW, and Barbalias GA: Vesical diverticula: etiology, diagnosis, tumorgenesis and treatment. Analysis of 74 cases. Urology 30: 453-457, 1987. 3. Targett JH: Diverticula of the bladder, associated with vesical growths. Trans Path Sot London 47: 155, 1896. 4. 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