Management Of Upper Tract Transitional Cell Carcinoma Research Articles

UP-01.202 Endoscopic Management of Upper Tract TCC: Long Term Follow-Up

Nephroureterectomy with excision of a bladder cuff used to represent the standard therapy for upper transitional cell carcinoma (TCC). Endoscopic management became a reasonable treatment option in selected cases. This report focuses on the long-term follow-up of patients with endoscopically treated upper TCC to determine the effectivennes of endoscopic therapy.

Voided Urine Fluorescence In Situ Hybridization Testing for Upper Tract Urothelial Carcinoma Surveillance

Fluorescence in situ hybridization is gaining popularity for transitional cell carcinoma screening. We determined the accuracy of fluorescence in situ hybridization for identifying upper tract transitional cell carcinoma. A retrospective review of our upper tract transitional cell carcinoma database from 2005 to 2008 identified 35 patients with upper tract transitional cell carcinoma who submitted voided urine specimens for fluorescence in situ hybridization at commercial laboratory during a routine office visit. Each patient was evaluated endoscopically in the operating room within 3 months of sampling. Suspicious lesions were biopsied and treated. Transitional cell carcinoma in the lower or upper tract was proved by direct visualization, positive biopsy or upper tract cytology read as positive or highly suspicious for malignancy. Of the patients 35 satisfied study inclusion criteria. A total of 67 fluorescence in situ hybridization specimens were submitted. Upper tract transitional cell carcinoma was identified on 51 operative evaluations, of which 23 showed concurrent bladder tumor. For all encounters the sensitivity of fluorescence in situ hybridization was 56% and specificity was 80%. Sensitivity for low and high grade lesions was 68% and 67%, respectively. Only upper tract tumors were noted in 28 patients, in whom there were 2 false-positive and 13 false-negative voided fluorescence in situ hybridization results. In these cases sensitivity was 54% and specificity was 78% compared to the 18% sensitivity and 100% specificity of bladder cytology. Sensitivity for low and high grade upper tract transitional cell carcinoma was 60% and 50%, respectively. Voided fluorescence in situ hybridization has become an adjunct for bladder transitional cell carcinoma surveillance. However, it has limited value for upper tract tumor surveillance.

Oncologic Outcomes for Complete Robot-Assisted Laparoscopic Management of Upper-Tract Transitional Cell Carcinoma

The gold standard for treatment of upper-tract transitional cell carcinoma (TCC) is nephroureterectomy. For distal ureteral TCC, distal ureterectomy with ureteral reimplantation represents a treatment option. Multiple minimally invasive techniques have been introduced with the goal of replicating these open procedures. Currently, there is a paucity of literature for the use of robot-assisted laparoscopic (RAL) management of upper-tract TCC. We evaluated our experience with RAL management of upper-tract TCC. A retrospective chart review was performed on all patients who underwent complete RAL nephroureterectomy or distal ureterectomy with ureteral reimplantation at our institution. Eleven patients with a mean age of 67.4 years underwent RAL nephroureterectomy. Mean operative time was 326 minutes (range 243-470 minutes), estimated blood loss 200 mL (range 100-400 mL), and mean length of hospital stay was 4.7 days. With a mean follow-up of 15.2 months (range 2-31 months), four patients experienced recurrence, and two ultimately died from metastatic disease. Four patients with a mean age of 73.5 years underwent RAL distal ureterectomy with ureteral reimplantation for distal ureteral TCC. Mean operative time was 311 minutes (range 225-446 minutes), estimated blood loss 200 mL (range 100-350 mL), and mean length of hospital stay was 4.7 days. With a mean follow-up of 30.5 months (range 12-48 months), only one patient, whose pathology exhibited carcinoma in situ within periureteral tissue, required adjuvant treatment for recurrent disease. RAL nephroureterectomy and distal ureterectomy with ureteral reimplantation are feasible options for patients with upper-tract TCC with promising short-term oncologic outcomes.

Ureteroscopic Management of Upper-Tract Urothelial Cancer: An Exciting Nephron-Sparing Option or an Unacceptable Risk?

To discuss the merits of the endoscopic management of upper-tract transitional-cell carcinoma (UTTCC). We present original data from our institution over an 8-year period and a review of some of the world literature. A discussion of the overall suitability of this modality for both clinician and patient is presented. A retrospective chart review was performed comprising operative logs, departmental databases, and pathologic registers. These sources were analyzed, and data were collected on all patients who underwent ureteroscopic treatment of UTTCC. Patients with at least 6 months of follow-up were included in the study. Forty-five patients (mean age 65 yrs) were identified who had undergone ureteroscopic treatment for UTTCC with either therapeutic or palliative intent between 1998 and 2006. Of these, 19 procedures were performed electively in patients with normal contralateral kidneys. Those patients with low-volume, low-grade tumors on biopsy and negative results of urinary cytologic evaluation recovered well, with few recurrences. None of this group progressed to radical surgery. Of 12 patients never considered for radical surgery, only 1 died of the disease after a median follow-up of 15 months. Elective ureteroscopic holmium:yttrium-aluminum-garnet laser ablation of UTTCC is a safe and effective treatment for a select group of patients. In our institution, patients with normal functioning contralateral kidneys are considered for endoscopic treatment and follow-up of their disease if disease is found to be of low grade and volume. Inadequacies in the staging of UTTCC mean that this may, in some cases, turn out to be suboptimal management, and therefore we maintain a low threshold for recommending radical surgery. For another group of patients with single kidneys, global renal dysfunction, or severe comorbidity, endoscopic treatment can prove a valuable palliative option even in those persons who have a large tumor bulk or relatively rapid disease recurrence.

Is There a Role for FISH in the Management and Surveillance of Patients with Upper Tract Transitional-Cell Carcinoma?

Fluorescence in-situ hybridization (FISH) assay has been approved by the U.S. Food and Drug Administration for the detection of recurrent transitional-cell carcinoma (TCC) of the bladder and in the initial workup of hematuria. In this study, we retrospectively reviewed our initial 94 FISH specimens taken from patients monitored for upper-tract TCC. Between 2004 and 2007, 43 patients had one or more FISH assays performed as part of the workup and management of upper-tract TCC. Of 94 specimens sent for FISH analysis, 25 voided specimens collected at an outpatient encounter and 40 specimens taken as a bladder wash or selective upper-tract washing under anesthesia were followed by upper-tract endoscopy. The sensitivity and specificity of the FISH assay for detecting urothelial lesions in this population were calculated and compared with cytology specimens from the same sources. Overall sensitivity of FISH in the detection of TCC in this population was 52%, compared with 26% for urinary cytology. Both FISH and cytology showed superior sensitivity for high-grade (79% and 50%, respectively) nu low-grade tumors (41% and 12%, respectively). Selective upper-tract washings were more sensitive and specific for upper-tract TCC than bladder washings or voided specimens. While the sensitivity of FISH for upper-tract TCC parallels its performance in bladder cancer, the preponderance of low-grade, recurrent disease in the population undergoing surveillance and minimally invasive therapy for upper-tract TCC may limit its usefulness in this setting. Until a high-sensitivity marker for low-grade urothelial lesions is developed, the surveillance of upper-tract TCC will continue to require vigilant direct visual inspection.

Endourologic Management of Patients with Upper-Tract Transitional-Cell Carcinoma: Long-Term Follow-up in a Single Center

To evaluate the outcome of endoscopic management of upper-tract transitional-cell carcinoma (TCC). From March 1991 to March 2006, 40 patients with upper-tract TCC were treated by an endoscopic approach as the primary management: 37 (90.2%) by ureteroscopy and by percutaneous techniques or both approaches in 2 cases each (5%). Follow-up was between 5 and 115 months (mean 41.6 months). Most of the patients, 26 (65%), had a normal contralateral kidney, and the indication for conservative management was low tumor grade or tumor size (<2 cm) and patient commitment to a rigorous follow-up protocol. Absolute and relative indications for conservative management such as solitary kidney were met in 14 patients (35%). Treatment consisted of electrocautery only in 15 cases (36.6%), neodymium:YAG or holmium:YAG laser only in 11 (26.8%), and combinations in 15 (36.6%). Most of the patients (74.3%) had an upper-tract recurrence. The renal-preservation rate was 70.7%, and the survival rate was 80%. Conservative treatment is preferred in patients with bilateral disease, a solitary kidney, or co-morbidities that contraindicate major surgery. Patients with low-grade, low-stage disease and normal contralateral kidneys also benefit from this approach provided adequate endoscopic follow-up can be achieved and the surgeon has a low threshold for carrying out ablative surgery.

Office-Based Surveillance Ureteroscopy After Endoscopic Treatment of Transitional Cell Carcinoma: Technique and Clinical Outcome

The reference standard treatment for transitional cell carcinoma (TCC) of the upper tract remains nephroureterectomy. However, with improvements in endoscopic technology and techniques, endoscopic ablation of upper tract TCC has become a reality for highly selected patients. We report our present technique and 16-year experience of office-based ureteroscopy for surveillance of TCC after initial endoscopic ablation. The office and hospital records of all patients undergoing office-based anesthesia-free ureteroscopy were retrospectively reviewed. The patient characteristics, tumor characteristics, ureteroscopic technique and findings, and complications were documented. Ten patients with a mean age of 68.8 years were treated with endoscopic ablation of upper tract TCC. A total of 67 (range 1 to 19 per patient) surveillance ureteroscopies in the office setting were performed. Office ureteroscopy revealed seven upper tract TCC recurrences in 5 patients. A thorough ureteroscopic examination in the operating room of these patients revealed that only 1 patient had more extensive disease than was recognized during the office-based ureteroscopy. All patients tolerated office-based ureteroscopy well, and each procedure was successfully completed with minimal patient discomfort. No acute complications were noted. One patient who experienced multiple recurrences and underwent ablation of extensive ureteral TCC developed a benign ureteral stricture. The results of our study have shown that for the rare patient undergoing endoscopic management of upper tract TCC, office-based anesthesia-free ureteroscopic surveillance is a reasonable management strategy. The technique has been free of complications and appears to be as accurate as surveillance ureteroscopy performed in the operating room.

Endoscopic Management of Upper Tract Urothelial Carcinoma in Patients With a History of Bladder Urothelial Carcinoma

Endoscopic management of renal pelvis and ureteral urothelial carcinoma is gaining acceptance as a conservative treatment modality. Patients with a history of bladder urothelial carcinoma are at high risk for upper tract recurrence. We evaluate the role of endoscopic management of upper tract urothelial carcinoma in patients with a history of primary bladder urothelial carcinoma. We retrospectively reviewed 90 patients with a history of primary bladder urothelial carcinoma who underwent endoscopic treatment of localized upper tract urothelial carcinoma between 1983 and 2004. Median patient age at diagnosis was 73 years (range 50 to 90). A total of 13 (14.4%) patients previously underwent cystectomy. With a median followup of 4.3 years (range 0.1 to 17), 105 upper tract urothelial carcinoma recurrences developed in 55 patients at a mean of 0.6 years (range 22 days to 5.9 years). Of these recurrences 76 were amenable to endoscopic management while 29 required nephroureterectomy. In 38 patients there were 91 bladder recurrences. At last followup 48 patients died, 17 of urothelial carcinoma at a median of 3.4 years (range 1 to 10). Cancer specific survival at 5 years for this cohort was 71.2%. Risk of death from urothelial carcinoma was significantly associated with stage (RR 3.23) and grade (RR 4.05) of upper tract urothelial carcinoma, imperative indication (RR 4.30), and treatment of bladder urothelial carcinoma with cystectomy (RR 3.34). Endoscopic management of upper tract urothelial carcinoma in patients with primary bladder urothelial carcinoma demonstrates a significant local recurrence rate. Furthermore, 5-year cancer specific survival is low. These patients represent a high risk cohort requiring strict ureteroscopic followup after endoscopic management is instituted.

Laparoscopic Nephroureterectomy with Bladder-Cuff Resection: Techniques and Outcomes

Advancements in minimally invasive instrumentation and technique have provided the impetus to performing urologic procedures with reduced perioperative morbidity, shorter hospital stays, and, most importantly, efficacious oncologic results. At multiple centers of excellence, laparoscopic nephroureterectomy (LNU) has evolved into a new standard for the management of upper-tract transitional-cell carcinoma (TCC) that is not amenable to endoscopic resection. An LNU may be performed via a transperitoneal or retroperitoneal approach together with excision of the distal ureter and a bladder cuff. Analysis of present-day studies comparing LNU with open techniques demonstrates equivalent oncologic outcomes. In addition, those patients undergoing LNU fare better than their counterparts having open surgery with respect to hospital stay, analgesic requirements, and convalescence. With multiple options for excision of a cuff of bladder, a consensus has not been established. However, LNU has emerged as the new standard of care for the treatment of upper- tract TCC. Review of the techniques and outcomes of LNU from the minimally invasive urology community are described.

Current Practice Patterns in Urologic Management of Upper-Tract Transitional-Cell Carcinoma

To determine the current practice patterns in the management of upper-tract transitional-cell carcinoma (TCC) among a large group of urologists. A survey was sent to 220 practicing members of the Society of Urologic Oncology (SUO) and the Endourological Society (ES) and members of the American Urological Association who did not belong to either society. The survey consisted of 16 focused questions pertaining to the surveillance and management of upper-tract TCC. The responses were used to create a database, which was then analyzed to determine practice trends. Eighty-four of the urologists responded, for a response rate of 38%. Fourteen responses were excluded because of multiple answers to a given question, so 70 were included in the final analysis. Eighty percent of the respondents were in academic practice. A CT urogram was the favored initial procedure for diagnosis of upper-tract TCC and an intravenous urogram was the next commonest choice (53% and 40%, respectively). Ureterorenoscopy was the surveillance tool of choice (70%) after conservative treatment of upper- tract TCC. Laparoscopic nephroureterectomy was the preferred procedure (73%) for a high-grade, large renal-pelvic TCC. Twenty-one percent of the endourologists recommended ureteroscopic ablation for a high-grade, large distal ureteral tumor. This was in sharp contrast to 77% of the respondents who favored a distal ureterectomy for the same clinical scenario. This study confirms that most urologists treating upper-tract TCC follow the principles reported in the published literature regarding the management of these patients. Further, most urologists, regardless of society affiliations or years in practice, favor minimally invasive techniques for the management of upper-tract TCC. This information may be useful in formulating clear guidelines for the management of this disease.

Endourologic management of upper tract transitional cell carcinoma.

Transitional cell carcinoma (TCC) occurs only rarely in the upper urinary tract and accounts for less than 5% of all cases of urothelial neoplasia. Like TCC of the bladder, however, it often represents a field change disease characterized by multiple recurrences in both time and space, though this tendency towards polychronotopism is generally confined to the ipsilateral renal unit or to the bladder. As a result, the incidence of TCC in the contralateral renal unit is only 3%. This natural history supports the use of nephroureterectomy with resection of a cuff of bladder as the gold standard for the management of upper urinary tract TCC. It in fact attempts to perform more conservative, renal sparing open operations for upper tract TCC that have universally met with high rates of local or ipsilateral recurrence. 4-6 With the advent of sophisticated techniques for the endourologic management of many benign urologic diseases of the upper tracts, there has been growing enthusiasm for the application of these same techniques to the management of upper tract TCC. Recent advances in the fields of retrograde ureteroscopy and percutaneous pyeloscopy include the development of small caliber, actively deflecting fiberoptic telescopes, improved optics, and the development of small caliber adjunctive instruments and laser fibers. These advances have opened the field of upper tract TCC to a variety of innovative approaches, particularly for those patients in whom standard nephroureterectomy may present a prohibitive operative risk or leave the patient functionally anephric. These include patients with upper tract TCC in an anatomically or functionally solitary kidney, those with bilateral disease, or patients with significant chronic renal insufficiency. Endourologic alternatives to open surgery have also been advocated for those patients with significant comorbid disease in whom an open operation would be poorly tolerated. This article will review the endourologic management of upper tract TCC to further help define its role in current urologic practice.

Comparison of Hand Assisted and Standard Laparoscopic Radical Nephroureterectomy for the Management of Localized Transitional Cell Carcinoma

Hand assisted laparoscopy affords the surgeon tactile sensation and blunt dissection, which are currently limited using the standard laparoscopic technique. Therefore, we compared standard and hand assisted laparoscopic radical nephroureterectomy for localized upper tract transitional cell carcinoma. The medical records of 27 patients who underwent standard (11) or hand assisted (16) laparoscopic radical nephroureterectomy between April 1998 and January 2001 were retrospectively reviewed. The parameters of efficacy, efficiency, safety and convalescence were compared. Mean patient age was 64 and 66 years (p = 0.72) in the standard and hand assisted groups, and the mean American Society of Anesthesiologists score was 2.5 and 2.7 (p = 0.64), respectively. All standard and 15 of the 16 hand assisted (94%) procedures were successfully completed via laparoscopy. Total operative time was more than 1 hour shorter for hand assisted than for laparoscopic radical nephroureterectomy (4.9 versus 6.1 hours, p = 0.055). Mean estimated blood loss was similar in the standard and hand assisted groups (190 and 201 ml., p = 0.78). In each group 1 patient required blood transfusion. Mean specimen weight was significantly higher in hand assisted cases (576 versus 335 gm., p = 0.036). Mean time to oral intake was similar in patients who underwent standard and hand assisted laparoscopic radical nephroureterectomy (13 and 20 hours, respectively, p = 0.45). The mean analgesic requirement was also similar (29 and 33 mg. morphine sulfate, respectively, p = 0.83). Mean hospital stay in uncomplicated cases was similar for standard and hand assisted surgery (2.9 and 2.5 days, respectively). Overall hospital stay in the 2 cohorts was also similar (3.3 and 4.5 days, respectively, p = 0.59). Four patients per group experienced postoperative complications. There were no deaths in the standard group but 1 patient (6%) in the hand assisted group died postoperatively. Mean time to partial and complete convalescence in the standard and hand assisted groups was 2.4 and 5.2, and 3.5 and 8.0 weeks, while mean followup was 27.4 and 9.6 months, respectively. Compared with standard laparoscopy hand assisted laparoscopy decreases operative time without significantly altering short-term parameters of convalescence. However, long-term convalescence after hand assisted laparoscopic radical nephroureterectomy is 1 to 3 weeks longer (p = 0.27). Longer followup in the hand assisted cohort is necessary to determine whether there are any differences in the 2 methods in regard to cancer control.

LAPAROSCOPIC RADICAL NEPHROURETERECTOMY FOR UPPER TRACT TRANSITIONAL CELL CARCINOMA: THE CLEVELAND CLINIC EXPERIENCE

We report our single institutional experience with retroperitoneal laparoscopic radical nephroureterectomy in patients with upper tract transitional cell carcinoma and compare results to those achieved by the open technique. A total of 77 patients underwent radical nephroureterectomy for pathologically confirmed upper tract transitional cell carcinoma. Of these patients 42 underwent laparoscopic nephroureterectomy from September 1997 through January 2000 and 35 underwent open surgery. All specimens were extracted intact. Of the laparoscopic group the juxtavesical ureter and bladder cuff were excised by our novel transvesical needlescopic technique in 27 and radical nephrectomy was performed retroperitoneoscopically in all 42. Data were compared retrospectively with 35 patients undergoing open radical nephroureterectomy from February 1991 through December 1999. Laparoscopy was superior in regard to surgical time (3.7 versus 4.7 hours, p = 0.003), blood loss (242 versus 696 cc, p <0. 0001), specimen weight (559 versus 388 gm., p = 0.04), resumption of oral intake (1.6 versus 3.2 days, p = 0.0004), narcotic analgesia requirements (26 versus 228 mg., p <0.0001), hospital stay (2.3 versus 6.6 days, p <0.0001), normal activities (4.7 versus 8.2 weeks, p = 0.002) and convalescence (8 versus 14.1 weeks, p = 0.007). Complications occurred in 5 patients (12%) in the laparoscopic group, including open conversions in 2, and in 10 (29%) in the open group (p = 0.07). Followup was shorter in the laparoscopic group (11.1 versus 34.4 months, p <0.0001). The 2 groups were similar in regard to bladder recurrence (23% versus 37%, p = 0.42), local retroperitoneal or port site recurrence (0% versus 0%) and metastatic disease (8.6% versus 13%, p = 1.00). Mortality occurred in 2 patients (6%) in the laparoscopic group and 9 (30%) in the open group. Cancer specific survival (97% versus 87%) and crude survival (97% versus 94%) were similar between both groups (p = 0.59). In patients with upper tract transitional cell carcinoma who are candidates for radical nephroureterectomy the retroperitoneal laparoscopic approach satisfactorily duplicates established technical principles of traditional open oncological surgery, while significantly decreasing morbidity from this major procedure. Short-term oncological and survival data of the laparoscopic technique are comparable to open surgery. Although long-term followup data are not yet available, it appears that laparoscopic radical nephroureterectomy may supplant open surgery as the standard of care in patients with muscle invasive or high grade upper tract transitional cell carcinoma.

Laparoscopic nephroureterectomy: making management of upper-tract transitional-cell carcinoma entirely minimally invasive.

Endoscopic treatment of upper-tract transitional-cell carcinoma (TCC) is well established. Nevertheless, many patients still required major ablative surgery. We have applied our experience with laparoscopic nephrectomy to the performance of laparoscopic nephroureterectomy in order to make the management of upper-tract TCC entirely minimally invasive. Since 1993, we have performed 22 laparoscopic nephroureterectomies for upper-tract TCC. Initially, we excluded patients with tumors below the pelvic brim, but we now offer a trial of laparoscopy to all patients. We describe the evolution of our technique, which involves resecting the ureteral orifice prior to laparoscopic dissection of the kidney and ureter. We have had to convert three cases to open surgery, one each for bleeding, failure to progress, and unappreciated tumor extent. Operative times averaged 156 minutes, which compares well with contemporary times for open nephroureterectomy. Complication rates, transfusion requirements, and length of stay, although higher than those of laparoscopic nephrectomy, were all reduced in comparison with open nephroureterectomy.