# Endourologic Management of Upper Tract Transitional Cell Carcinoma following Cystectomy and Urinary Diversion

Authors: Jeffrey John Tomaszewski; Marc Christopher Smaldone; Michael Cecil Ost
Journal: Advances in Urology
 (2009)

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## Abstract

Traditionally, nephroureterectomy is the gold standard therapy for upper tract recurrence of transitional cell carcinoma (TCC) following cystectomy and urinary diversion. With advances in endoscopic equipment and improvements in technique, conservative endourologic management via a retrograde or antegrade approach is technically feasible with acceptable outcomes in patients with bilateral disease, solitary renal units, chronic renal insufficiency, or significant medical comorbidities. Contemporary studies have expanded the utility of these techniques to include low-grade, low-volume disease in patients with a normal contralateral kidney. The aim of this report is to review the current outcomes of conservative management for upper tract disease and discuss its application and relevance in patients following cystectomy with lower urinary tract reconstruction.


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## Body

## 1. Introduction

Upper tract transitional cell carcinoma (UTTCC)
represents 5% of all urothelial cancers [1]. Due to the proposed field defect associated
with these lesions, removal of the entire urothelium on the ipsilateral side
offers the best chance of surgical cure. For this reason, the traditional and
gold standard treatment for UTTCC has been radical nephroureterectomy [2].
However, minimally invasive endoscopic techniques have been developed to treat
patients with bilateral upper tract disease, poor candidates for radical
surgery, and those with solitary renal units. In more recent times, even healthy patients with low-grade, noninvasive tumors have been managed endoscopically, with the understanding that some may require radical nephroureterectomy if UTTCC should recur or progress.The incidence of
upper tract recurrence following radical cystectomy is low (3–5%), but there is
an increased incidence of upper tract recurrence in patients undergoing
cystectomy with a prior history of superficial bladder disease [3].
Treatment of upper tract recurrence following lower urinary tract
reconstruction is challenging, but with recent technological advances, both
ureteroscopic and percutaneous techniques have been utilized for surveillance
and management in these complex patients. We review the literature in order to
summarize and define the advantages and disadvantages of ureteroscopic and percutaneous
management of upper tract TCC following urinary diversion.


## 2. Discussion

Upper tract
transitional cell carcinoma (UTTCC) is relatively uncommon, accounting for
approximately 5% of all urothelial tumors and 10% of all renal tumors or
approximately 3000 cases per year in the United States [4, 5]. The incidence of upper tract recurrence following
radical cystectomy for urothelial cancer ranges from 2% to 6% [3, 6–11],
with the majority of recurrence in the first 3 years [3]. Additionally,
Tran et al. [3] demonstrated that the risk of upper
tract recurrence does not change with time, emphasizing the critical importance
of continued surveillance for UTTCC following cystectomy. Patients with associated carcinoma in situ of
the bladder or prostatic urethra, recurrent high risk superficial cancer of the
bladder, and tumor multifocality are at higher risk of ureteral involvement at
the time of cystectomy [3, 12–17]. In the subgroup with ureteral
involvement at the time of cystectomy, tumor recurrence in the upper tract was
noted in 16–17% [3, 16], with the authors concluding that these patients require vigorous follow up with
urine cytology and upper tract surveillance imaging.Treatment of upper
tract recurrence following cystectomy remains a clinical dilemma. Due to
improvements in fiberoptic technology and refinement of endoscopic techniques,
conservative management of UTTCC has evolved into a viable treatment
alternative with similar efficacy to that of radical therapy in select patients
with noninvasive and low-grade disease. Indications for ureteroscopic and/or percutaneous
endoscopic management include patients with a solitary kidney, bilateral
disease, renal insufficiency, or patients who would require dialysis after
nephroureterectomy [18–20].
However, in recent series, minimally invasive procedures have increasingly been
utilized in patients with a normal contralateral kidney [21–23].
These studies have concluded that patients who have solitary, small
(<1.5 cm), low-grade, and completely resectable tumors are candidates for
endoscopic management if they are willing to accept lifelong surveillance for
recurrence [21, 24].Surveillance
should be lifelong and tailored to the patient's tumor grade and stage. Our
institution's surveillance protocol includes urine cytology every three months,
and upper tract imaging (computed tomography urogram, intravenous pyelogram, or
retrograde pyelogram) every six months for the first two years, then yearly
thereafter [20, 25, 26]. Contemporary surveillance protocols for
upper tract disease include surveillance ureteroscopy at frequent defined
intervals [26, 27].
In patient's with lower urinary tract reconstruction, this may not be feasible
and needs to be tailored to each individual patient. Management of recurrent
upper tract TCC is comparable to that of primary upper tract TCC and must be
adapted to the tumor characteristics and patient; nephroureterectomy is usually
recommended for recurrences that have evidence of grade and stage progression.A drawback of
endoscopy in the management of pelvicaliceal lesions is its low sensitivity for
the detection of invasive lesions and thus its low reliability in staging [25, 26, 28].
The correlation between grade and stage of upper tract tumors has previously
been demonstrated, thus many rely primarily on the grade of the endoscopic
biopsy specimen for pathologic assessment [26, 29]. Abnormal upper tract urinary cytology results
have been shown to predict tumor recurrence and correlate with pathologic tumor
grade and stage [26, 28, 30].Surgical resection
of a UTTCC following cystectomy and continent or incontinent urinary diversion
presents a unique challenge. Although such a recurrence portends an overall
poor prognosis, a maximal effort must be made to resect localized disease. Endoscopic management of upper tract
abnormalities in patients following urinary diversion is complicated by difficult
retrograde access to the upper collecting system [31]. Although technically
challenging, endoscopic retrograde, percutaneous antegrade or combined
antegrade, and retrograde approaches have been described [31, 32] and can be utilized in the evaluation
and treatment of upper tract urothelial cancer recurrence.


## 3. Retrograde Ureteroscopic Access

The ureteroscopic approach is typically the
least invasive surgical treatment option for UTTCC. It is also the most
thorough procedure for surveying the entire collecting system for posttreatment
surveillance. Advantages include limited morbidity in the setting of an
outpatient procedure and the potential oncologic benefit of a closed system [31]. The most challenging aspect
of ureteroscopic management following both continent and incontinent lower
urinary tract reconstruction is obtaining retrograde access to the ureter.In cases following
continent diversion, the neobladder can be accessed via the urethra using rigid
or flexible ureteroscopy [33]. In cases of incontinent
urinary diversion, a flexible cystoscope can be passed through the stoma into
the reservoir. Mucous and debris is often encountered on initial inspection and
must be copiously irrigated to improve visualization [31]. A cystogram or loopogram
under fluoroscopic guidance can be performed to help delineating the afferent
limb and the ureteral anastomosis. Administration of methylene blue or indigo carmine may aid in the identification
of the ureteral anastamoses. Upon identification, the ureteral orifices can be
cannulated with guidewires or open-ended ureteral access catheters. The use of
contrast to clearly delineate anatomic landmarks can also facilitate a combined
antegrade/retrograde approach in select mid-ureteral tumors that may require
dual access for complete resection. In select cases ureteral access sheaths can
help to facilitate repeated passes of the ureteroscope and tumor
basketing. In addition, the use of an
access sheath decreases irrigation pressure [34] and may theoretically reduce
the possibility of pyelolymphatic backflow and tumor dissemination. Baskets or
biopsy forceps can be used for tumor debulking and biopsy, and electrocautery or laser fibers can be used to
ablate tumor and control hemorrhage [33]. Disadvantages include
potential staging errors, inability to treat large lesions in a single setting,
and difficulty in accessing lower pole lesions [35].Although minimally
invasive treatment methods were originally developed for patients that could
not undergo open surgery, the ureteroscopic approach to UTTCC has been shown to
be an efficacious first-line treatment to address UTTCC of low stage and grade [35]. Ureteroscopy provides
adequate access for biopsy under direct vision, and mechanical, ablative, or
laser removal of papillary lesions anywhere along the upper tract urothelium.
Chen and Bagley [36] treated 23 patients with
UTTCC; 8 remained disease-free, and 15 had recurrences treated at a mean follow
up of 35 months, with 100% disease-specific survival. Keeley et al. [26] and Martínez-Piñeiro et al. [19] reported tumor-free rates of
76% and 71%, respectively, among patients with low-grade UTTCC. Due to its
efficacy, safety, and minimal morbidity, the ureteroscopic approach is a very
attractive treatment alternative for low-grade urothelial carcinoma [33].Nelson et al. [31] reported their experience
with retrograde ureteroscopy for the management of 13 renal units in 8 patients
following continent neobladder diversion. Indications for evaluation included upper
tract filling defect, positive cytology, or renal calculi. The ureter and renal
pelvis were successfully accessed and visualized in 76%, and they were unable
to access the ureteral orifices in three remaining patients. While
demonstrating that retrograde access is technically feasible in this patient
population, attempting to access the collecting system retrograde in
reconstructed patients may have severe consequences. Care must be taken to
avoid damaging the continence mechanism, perforating the reservoir, or
disrupting the ureteral-enteric anastomoses. In our practice, primary ureteroscopic
therapy is considered for upper tract evaluation in patients with lower urinary
tract reconstruction for small filling defects on upper tract imaging or
positive cytology, with the intention of treating small lesions during the
initial setting. All patients are counseled that access or treatment failure is
a distinct possibility, and that further antegrade or more definitive open or
laparoscopic surgical procedures may be warranted. Complications specific to
ureteroscopic tumor treatment include extraluminal spillage or propagation of
neoplasm, ureteral perforation, and ureteral stricture formation [22].
The reported stricture rate following ureteroscopic management of upper tract
TCC has ranged from 5% to 14% [19, 26, 37].
When a ureteral stricture forms following endoscopic management of upper tract
TCC, it is imperative to perform a biopsy of the region to rule out malignant
disease [36].


## 4. Percutaneous Access

The evolution of lower
urinary tract reconstruction has resulted in a growing number of patients in
need of complex upper tract management. Although technically feasible,
evaluation and treatment of upper tract abnormalities are complicated by
difficult retrograde access to the upper collecting system due to unusual
anatomy and lack of anatomic landmarks [31]. The difficulty of accessing
both refluxing and nonrefluxing ureterointestinal anastamoses restricts the use
of the size and type of endoscopic equipment necessary for complete resection
of UTTCC which is challenging from a retrograde approach under ideal
circumstances. Although more invasive, a percutaneous approach avoids these
difficulties through direct access and offers a high success rate with minimal
morbidity [32].The method of obtaining percutaneous access is similar to what has been described
for percutaneous nephrolithotomy. Under fluoroscopic guidance, a direct
puncture of the involved calyx or an upper pole or central calyx puncture for
renal pelvis, lower pole, or ureteral tumors is recommended [38]. Following tract dilation, a
30Fr access sheath is placed, and rigid or flexible nephroscopy may be
performed. Once the offending lesion is visualized, frozen section pathology
examination is recommended to rule out a high-grade lesion. The ideal resection
modality depends on tumor size and type, but monopolar and bipolar cautery,
laser, rollerball electrode, and electrovaporization techniques have been
described. The entire tumor should be ablated and the base fulgurated or
resected. Flexible nephroscopy should be
carried out to ensure that all areas of the kidney are clear of tumor. A
nephrostomy tube should be left in place for external drainage to preserve
access and to facilitate adjuvant chemotherapy. In select cases, a second look
nephroscopy on postoperative day 1-2 to ensure
complete resection is recommended. In
the case of continent cutaneous diversion, percutaneous access into the pouch
under direct vision with a 10 mm trocar has also been described [39]. Historically utilized in
cases of large urinary diversion calculi, this technique requires cystoscopy
through the continent stoma to achieve percutaneous access under direct vision
which has the potential for damage to the continence mechanism as well as the
development of stomal stenosis and has only theoretical implications for access
to the upper tract.Smith et al. reported
the first large series of percutaneous resections of UTTCC in a solitary kidney [40]. The oncologic efficacy of
percutaneous resection has most often been measured in terms of disease
recurrence, which has been shown to correlate with tumor grade [20, 41–43].
In review of several large series, recurrence rates for grade 1 (5–20%) [23, 41–44] and grade 2 diseases (6–33%) [23, 41–45] have been reported as significantly lower than recurrence rates for grade 3
disease (31–60%) [23, 41–43]. In addition, tumor grade has been shown to
have prognostic significance, and death from low-grade UTTCC is rare [45]. It is important to note that
prognosis for high-grade and high-stage UTTCCs is poor regardless of treatment
modality. In a series of 25 patients
undergoing percutaneous resection of grade 3 disease, Liatsikos et al. reported
a 56% recurrence rate and 64% disease-specific survival [43] which is comparable to series examining ureteroscopic resection and radical
therapy.The major advantages of the percutaneous approach in patients following urinary diversion
are that it allows
direct access and the use of larger endoscopes, improving visualization. Both
rigid and flexible endoscopes can be passed through the percutaneous tract,
facilitating inspection of the entire calyceal system. The use of larger
instruments facilitates the resection of large lesions, and makes tumor removal
more efficient. The availability of larger instruments, including
resectoscopes, grasping/biopsy forceps, and laser fibers, minimizes resection
time allowing complete resection of large tumors in a single setting that would
be difficult ureteroscopically [38]. Direct antegrade access also facilitates
access to lower pole calyceal tumors. Ureteroscopic access and visualization of
the lower pole are limited by the loss of deflection caused by instrument
passage through the working channel [22].
The additional benefits of repeat nephroscopy for additional resection and the
delivery of adjuvant therapy are facilitated by a percutaneous approach. This is of particular advantage in patients
with large (>1 cm) tumor burden, solitary kidney, poor renal function, or
significant comorbidites that would preclude open or laparoscopic nephroureterectomy.
Bleeding due to the vascularity of the kidney and proximity to the hilum [46]
and antegrade tract seeding [47] are complications of percutaneous
treatment that despite infrequently being reported are still of significant
concern. In comparison to the retrograde approach, percutaneous resection of
upper tract TCC is more invasive and is associated with higher complication
rates. Major complications of percutaneous resection include perforation,
nephrostomy tract seeding, and bleeding. The incidence of blood loss varies among investigators and depends
greatly on the size and extent of the treated lesion as well as ease of access,
but transfusion rates up to 37% have been reported [43].


## 5. Adjuvant Therapy

A beneficial role
for topical adjuvant therapy following the resection of UTTCC has not been
proven in randomized trials. While retrograde instillation of agents into the
collecting system has been described [35, 48],
percutaneous resection with simultaneous nephrostomy tube placement facilitates
antegrade instillation, maximizing chemotherapeutic agent contact with the
urothelium. A disadvantage of retrograde catheterization, particularly in
patients with continent urinary diversion, is that cystoscopy with
ureteral catheter placement must be performed prior to each instillation.Currently, there
is no consensus as to which technique is more effective. In an initial study
comparing outcomes in patients receiving postresection BCG with those who did
not, Jabbour and Smith reported a significantly lower recurrence rate in patients
with grade 1 tumors who received adjuvant BCG. There was no benefit for
patients with grade 2 and grade 3 disease [38]. Rastinehad et al. [49] reported a 25% decreased
likelihood of progression at 65 months follow up among 24 renal units with low-grade
UTTCC undergoing BCG instillation. Despite the lack of evidence from randomized
trials, the potential benefits and relative safety of adjuvant therapy provide
an attractive alternative in patients with grade 2 and grade 3 disease in a solitary
renal unit, patients with chronic renal insufficiency, or patients that are
poor surgical candidates.


## 6. Conclusions

Nephroureterectomy
is the gold standard treatment modality for high-grade and large-burden upper
tract TCC recurrence following cystectomy and urinary diversion. However, with technical advances in
equipment and increasing facility with endoscopic techniques, a minimally
invasive approach is feasible in select patients. In the setting of a solitary
kidney, chronic renal insufficiency, or significant comorbidity, preservation
of renal function and prevention of recurrence are paramount. Reports of
percutaneous tract seeding and recurrence due to pyelovenous backflow are
uncommon but are a significant concern with each modality of conservative
therapy. When choosing a surgical approach in a patient following lower urinary
tract reconstruction, the ease of access, preservation of renal function, and
oncologic efficacy must all be taken into consideration. Although technically
possible, accessing the lower tract from a retrograde approach can be difficult
and the capability for complete resection is limited for larger or lower pole
lesions. Although more invasive, a percutaneous approach offers direct access
with increased visualization, improved resection capability, and acceptable
morbidity rates. Experience with ureteroscopic and percutaneous techniques enables
full access to the reconstructed urinary tract and adds to the armamentarium of
therapeutic options in the management of upper tract recurrence following
cystectomy and urinary diversion.



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