Management of Patients With Upper Urinary Tract Transitional Cell Carcinoma

Jay D Raman; Douglas S Scherr*

Disclosures

Nat Clin Pract Urol. 2007;4(8):432-443. 

In This Article

Endoscopic Treatment

Endoscopic management of upper-tract TCC is generally recommended for patients with anatomic or functional solitary kidneys, bilateral upper-tract TCC, baseline renal insufficiency, or significant comorbid diseases that preclude abdominal surgery.[25] Select patients with a normal contralateral kidney who have small, low-grade lesions can also be reasonable candidates for conservative management.[26] Endoscopic treatment of the upper urinary tract can be performed via either a retrograde ureteroscopic or percutaneous antegrade approach.

Retrograde ureteroscopy can be used for low-volume ureteral and renal pelvic tumors. Tumors of the intramural and distal ureter are best managed by rigid ureteroscopy, while proximal ureter and renal pelvic lesions require flexible ureteroscopes.[3] The principal advantage of retrograde endoscopy is low morbidity while maintaining urothelial integrity.[3,25,27] This technique is limited, however, by the size of instruments that can be accommodated in the ureter, which in turn limits the size of tumor that can be adequately treated. Some portions of the upper urinary tract, such as the lower pole calyces, are less accessible by a retrograde approach. Furthermore, retrograde ureteroscopy is difficult in patients who have undergone a prior urinary diversion.

The ureteroscopic method requires an initial biopsy of the lesion followed by a debulkment to its base using cold-cup forceps (3 Fr or 5 Fr) or a stone basket (1.9 Fr or 2.4 Fr).[3] Given the thin wall of the proximal ureter and renal pelvis, no attempt should be made to resect these regions deeply. The base of the lesion is subsequently addressed by monopolar electrocautery or laser ablation (neodymium:yttrium-aluminum-garnet [Nd:YAG] or holmium [Ho]:YAG laser).[28] With a tissue penetration of less than 0.5 mm, the Ho:YAG laser is well suited for use in the ureter, allowing for excellent hemostasis with minimal transmural thermal damage. Conversely, the Nd:YAG laser has a deeper penetration (5–6 mm) making it better suited for coagulative necrosis of large lesions, particularly in the renal pelvis.[27]

The principal complications associated with retrograde ureteroscopy are ureteral perforation and postoperative strictures. The incidence of perforation in most series is below 10% and is readily managed by ureteral stenting or percutaneous nephrostomy drainage.[29,30] The reported stricture rate following retrograde management of upper-tract TCC ranges from 4.9% to 13.6%.[29,30,31] Data indicate that a lower incidence of strictures is associated with lesions managed by laser ablation than with electrocoagulation.[32] Most postoperative strictures are successfully managed by endoscopic stenting, laser incision, or balloon dilatation. Finally, all ureteroscopic interventions should be followed with short-term ureteral stenting to prevent postoperative obstructive sequelae.

Although more invasive than retrograde ureteroscopy, the percutaneous antegrade approach is preferred for larger tumors of the renal pelvis and proximal ureter. Antegrade nephroscopy offers better visualization of the renal pelvis while accommodating larger caliber working instruments capable of handling a larger tumor burden. The percutaneous approach also allows for superior access to the lower pole calyces, as well as to renal units with complicated calyceal anatomy. The principal disadvantage of this approach is violation of urothelial integrity with reports of tumor seeding of nonurothelial surfaces around the kidney or in the nephrostomy tract.[33,34] Larger series, however, fail to note such tract recurrences, confirming that this phenomenon is uncommon.[35,36,37]

Following establishment of a percutaneous tract that can accommodate a 30 Fr access sheath, the lesion is initially biopsied and subsequently debulked. Owing to the larger access tract, antegrade techniques permit the use of cold-cup biopsy forceps through a standard nephroscope or a cutting loop from a resectoscope. The base of the lesion is resected and sent separately for staging purposes, and hemostasis is achieved by electrocautery or laser ablation as previously described. The established nephrostomy tract can be maintained, allowing for repeated treatment or administration of topical adjuvant therapy.[3,27]

Beyond tumor tract seeding, complications of percutaneous management of upper-tract TCC are similar to those of percutaneous stone procedures and include bleeding, infection, electrolyte abnormalities, adjacent organ injury, and pleural injury.[3,27]

Multiple studies have confirmed the safety and efficacy of ureteroscopic management of upper-tract TCC. In 1997, Tawfiek and Bagley reported on outcomes of 205 patients summarized from 14 modern series and found a recurrence rate of 33% for 61 renal pelvic tumors and 31% for 144 ureteral tumors.[38] More recent reviews demonstrate similar findings, with recurrence rates ranging from 31% to 65% and disease-free rates of 35% to 86%.[28,30,39,40,41,42,43] The most frequent site of recurrence in these series was the bladder. Tumor recurrence was most dependent upon pathologic grade with recurrence rates of 25% for grade I tumors and almost 50% for higher grade lesions.[29] It is important to note that initial endoscopic management does not predict a worse outcome if disease progression occurs. Boorjian and colleagues reported that ureteroscopic tumor ablation before nephroureterectomy did not adversely affect postoperative disease status.[44]

Percutaneous approaches have promising results when taking into consideration that these lesions are more substantial than those managed by retrograde ureteroscopy. In a literature review of 84 patients, Okada et al. found an overall recurrence rate of 27%, with tumor grade strongly predicting outcomes.[45] More recently, Roupret and colleagues noted a similar recurrence rate of approximately 30%, with 5-year disease specific survival of almost 80%.[46] Furthermore, Lee and colleagues reviewed their 13-year experience with percutaneous management of upper-tract TCC patients and found no significant difference in overall survival compared with those patients who underwent a nephroureterectomy.[47] Regardless of treatment modality, patients with low-grade lesions did well, while those with high-grade tumors were predisposed to tumor recurrence and progression.

Over one-third of patients with endoscopically managed upper-tract TCC will develop tumor recurrence.[27] Adjuvant topical immunotherapy or chemotherapy can be used to reduce recurrence rates. Instillation is performed by infusion through a percutaneous nephrostomy tube, via a retrograde ureteral catheter, or by retrograde reflux from the bladder with an indwelling double-J stent or by surgical creation of ureteral reflux. The goal of therapy is continued exposure of the urothelium to the topical agent while maintaining a low pressure system that is free of infection. Such measures minimize major complications such as sepsis; although granulomatous changes in the kidney and systemic adverse effects relating to bacillus Calmette–Guerin (BCG) infection can occur.[48,49]

The same agents used to treat urothelial carcinoma of the bladder can be used to treat tumors of the upper tracts. The most common agents instilled are BCG or mitomycin-C. Orihuela and colleagues noted that patients treated with BCG via a nephrostomy tube had a significantly lower recurrence rate than patients who did not receive BCG (16.6% vs 80%, respectively).[50] However, a follow-up study from this institution failed to demonstrate a survival advantage.[35] Although the cumulative experience seems encouraging, no individual study has shown statistical improvement regarding survival and recurrence rates.[51,52]

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