Management of Early Stage Upper Tract Urothelial Cancers

135 Management of Early Stage Upper Tract Urothelial Cancers

Harish Madala, Carli Calderone, and Wesley A. Mayer

INTRODUCTION

Surgical management of upper urothelial tract cancers (UTUC) includes both nephron-sparing approaches and radical nephroureterectomy (RNU) with lymph node dissection (LND). Patients with UTUC must first be stratified into low risk and high risk in order to determine the appropriate therapy.

In order to be considered low risk, a tumor must comply with all of the following criteria: unifocal, small (<1 cm), low grade on both cytology and ureteroscopic biopsy, and have no evidence of infiltrative disease on CT urogram. In contrast, any one of the following features of a tumor constitutes high risk: the presence of hydronephrosis, large (>1 cm), high grade by either cytology or ureteroscopic biopsy, multifocal tumors, or UTUC occurring after radical cystectomy for bladder cancer (Table 20.1).

Table 20.1 Risk Stratification

Low risk	High risk*
Unifocal	Multifocal
Size: <1 cm	Size: >1 cm
Low-grade histology on cytology or biopsy	High-grade histology on cytology or biopsy
No evidence of infiltrative disease on CTU	Presence of hydronephrosis
	UTUC occurring after radical cystectomy for bladder cancer

CTU, CT urogram; UTUC, upper tract urothelial cancer.

*Note: If any single high-risk feature is present, tumor is considered to be high risk.

136NEPHRON-SPARING SURGICAL APPROACHES

There are two populations of patients for which nephron-sparing management may be appropriate. Nephron-sparing approaches should be considered in all cases of low-risk disease (1). Candidates must be counseled extensively on the need for stringent follow-up after surgery and be willing and able to comply. Otherwise, more aggressive therapy should be considered.

Nephron-sparing procedures may also be necessary in the case of high-risk disease where the contralateral kidney is compromised, as is the case with chronic kidney disease, or in patients with solitary kidneys. Cases must be evaluated on an individual basis according to the patient’s comorbidities, life expectancy, compliance, and preferences.

Endoscopic laser ablation is appropriate for low-risk tumors (1). This is generally accomplished ureteroscopically; however, percutaneous access may be necessary if tumor is inaccessible from a retrograde approach or due to tumor size. Although the percutaneous approach is being utilized less as ureteroscopic techniques and instrumentation advance, it is still a very important approach for some patients (2).

Segmental ureteral resection is indicated in the case of endoscopic failure to remove low-risk tumors, or for all high-risk tumors of the distal ureter when nephron-sparing management is chosen. When high-risk tumors meet certain criteria, the cancer control and survival has been found to be similar between segmental resection and RNU; these characteristics include unifocal tumors of the distal ureter less than 2 cm and ≤ stage T2 (3). Previous research has found that iliac or lumbar ureteral resection may have a higher failure rate than distal ureteral resection (1). Thus, tumor location may play a key role in determining candidacy for nephron-sparing management of high-risk tumors. Lymphadenectomy can also be performed as a part of segmental ureteral resection, and is indicated on a case-by-case basis in instances of high-grade tumor (3).

Radical Nephroureterectomy

In patients with high-risk disease, or in patients who are not able to meet the surveillance requirements of conservative management, a RNU with excision of the bladder cuff is the 137gold standard of treatment. When comparing laparoscopic versus open techniques for RNU, multiple retrospective studies have generally found them to have comparable oncologic outcomes (4–7). Because open RNU is generally offered to patients who are at the highest risk, a question of selection bias has arisen. Regardless, laparoscopic approaches are being increasingly utilized and are generally accepted to provide adequate cancer control.

Robotic approaches have been introduced over the last decade. Sufficient long-term data are still lacking; however, early and intermediate cancer control has been shown to be on par with that of open and laparoscopic approaches (6). A single randomized controlled trial (RCT) demonstrated similar oncologic outcomes between the two approaches in patients with organ-confined disease, with the robotic group experiencing less blood loss and a shorter length of stay (7).

Lymph Node Dissections

There is an insufficient amount of data about the oncologic implications of performing LNDs in patients with UTUC, and thus the topic remains highly debated. However, it is generally thought to be unnecessary to perform an LND on Ta and T1 disease, as the yield of positive nodes is low. Positive lymph nodes are found in 2.2% of patients with Ta or T1 disease compared to 16% in disease staged T2 or greater (8). For T2 disease and above, surgeons generally follow an LND template rather than strive to obtain a specific number of nodes, which does correlate to improved survival (9).

Adjuvant Therapy

Bacillus Calmette-Guérin (BCG) instillation for early/limited stage UTUC has historically not shown any survival benefit (10). However, it may have some role in renal preservation and improving quality of life, especially in patients with carcinoma in situ (11). There is a risk for sepsis if instilled at high pressures or in a patient with an active urinary tract infection.

High-risk patients may benefit from postoperative intravesical chemotherapy to reduce bladder recurrence (12–15). 138Systemic chemotherapy has not shown benefit in early stage UTUC (16).

Surveillance

Recurrence can be local or distant. Any recurrence in the upper tract or bladder itself is considered local (17). Local recurrence is seen most commonly after nephron-sparing management, and is less common after RNU, where most recurrences are in the form of metastases. As such, follow-up schedules and modalities vary by treatment approach and are discussed as follows.

Post-RNU

Local recurrence is very rare after RNU; however, it is recommended to perform cystoscopy and urine cytology at 3 months after surgery and annually after that for at least 5 years. The risk of distant metastases is related to the features of the tumor. For noninvasive tumors, a CT urogram should be obtained annually for at least 5 years. For invasive tumors, a CT urogram should be obtained every 6 months for the first 2 years, and then annually for a total of at least 5 years.

After Nephron-Sparing Treatment

As previously mentioned, nephron-sparing approaches require much more rigorous follow-up; therefore, patient selection is of utmost importance. CT urogram and urine cytology should be performed at 3 months, 6 months, and then annually for at least 5 years. Special consideration may be given to patients with chronic kidney disease (CKD), who cannot receive contrast needed for a CT urogram. Additionally for high-risk patients, cystoscopy, ureteroscopy, and cytology in situ should be performed at 3 months, 6 months, then every 6 months for 2 years, and then annually for a total of at least 5 years. Recurrence rates decrease over time, so early follow-up is essential in detecting tumors, especially those that may have been understaged (18).

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