Endoscopy: Safe option in select upper tract transitional cell carcinomas?

Cancun, Mexico-The gold-standard treatment for upper tract transitional cell carcinoma is, without question, nephroureterectomy. However, with continuing advances in endoscopic equipment (ie, smaller scopes, digital technology, improved biopsy and fulguration equipment) combined with the increasing dissemination of ureteroscopic skills, upper tract TCC is increasingly being evaluated and treated endoscopically.

A number of studies presented at the World Congress of Endourology here focused on medium- to long-term outcomes of endoscopic management of upper tract TCC. Overall, endoscopic treatment was shown to be efficacious, but follow-up research in one study raises doubts about its long-term safety.

Michael Wines, MD, presented data from a study led by Michael Nomikos, MD, and colleagues at the Scottish Lithotriptor Center, Western General Hospital of Edinburgh, Scotland.

Of 23 patients who had low-grade disease, only 11 of their cohort had absolute indications for endoscopic management: 6 had comorbidities; 5 had solitary kidneys. Treatments included ureteroscopic laser ablation, electrofulguration, and percutaneous electrofulguration.

Thirty of the 41 patients (74.3%) developed recurrence of disease, Dr. Nomikos and colleagues reported. However, only 12 patients (29%) underwent nephroureterectomy during follow-up. Nephroureterectomy was associated with early recurrence and/or high-grade disease. Of those who underwent laparoscopic nephroureterectomy, the average time to operation was 38 months, thereby providing the majority of these patients with both renal units for a substantial period of time.

Disease-specific and overall survival were 100% and 80%, respectively, with a renal preservation rate of 71%.

"In select patients, low-grade TCC of the upper tract can be managed endoscopically. However, [endoscopic management] needs to have strict selection criteria, requires strict follow-up, and we must define when to go on to nephroureterectomy," Dr. Wines advised.

"One select group is the elderly population, where the mortality of undertaking a nephroureterectomy has significant risks."

Risk of recurrence?

While multiple groups looked at the oncologic outcomes of endoscopic management of upper tract TCC, researchers at New York University assessed the risk of upper tract manipulation leading to subsequent bladder recurrence. The group, led by Ojas Shah, MD, was designed to examine patients treated for upper tract TCC to determine whether performing endoscopy before definitive treatment increases the risk of subsequent tumor recurrence in the bladder.

"All previous studies on this subject have shown no increase in bladder recurrence, and this is the current dogma. As a result, many, if not most, urologists now routinely perform ureteroscopy before definitive treatment," explained Mark Perlmutter, MD, a resident in Dr. Shah's group who presented the research. "However, at our institution, we've noticed that many people who had undergone endoscopy beforehand are developing recurrences, so we wanted to revisit the subject."

The NYU team reviewed all patients treated and followed for upper tract TCC between 1998 and 2007 at their institution who were without concurrent bladder pathology or who later underwent cystectomy.

Forty-seven patients (mean age, 68.2 years) met inclusion criteria. Of these 47, 35 patients (74%) underwent endoscopic manipulation prior to treatment of upper tract TCC and 12 were evaluated with imaging and cytology alone. No significant differences were reported with respect to patient age, sex, history of bladder tumor, or grade of disease. Sixty-two percent of the upper tract TCC tumors were high-grade lesions on pathology.

Nine months after definitive treatment, 51% of those who had undergone endoscopic manipulation developed recurrence in the bladder, and of those who recurred, 92% of bladder recurrences had the same pathologic grade as the initial upper tract lesion, Dr. Perlmutter reported. Review of the baseline characteristics of those who did and did not undergo endoscopic manipulation found no differences, except 31.4% of those in the endoscopy group had a history of previous or concurrent bladder tumors compared with 8.3% of those who had imaging and cystoscopy.

At a median 14 months follow-up, overall, 60% of those who underwent endoscopic manipulation and 25% of those who did not had recurrent cancer of the bladder (p=.0383). Among those with primary upper tract TCC, bladder recurrence occurred in nearly 70% of the endoscopic manipulation cohort versus less than 30% of those who did not receive endoscopic treatment (p=.035).

That statistically significant increase persisted among those with primary upper tract TCC (ie, no previous or concurrent disease), thus negating the only baseline difference between the two groups. Further, endoscopic manipulation in those with high-grade lesions on pathology was associated with a three-fold likelihood of recurrence in those who underwent ureteroscopy with biopsy or ablation (p=.0153).

However, endoscopic manipulation did not appear to affect time to recurrence: Subset analysis found no significant difference among those who did and did not undergo the procedure, even among those with primary upper tract TCC and those with high-grade disease.

"These data are important because they suggest that our current practice of routinely performing diagnostic ureteroscopy in patients with suspected upper tract TCC is increasing the risk of a bladder recurrence in many of these people," Dr. Perlmutter concluded. "As a result, we now recommend that ureteroscopy only be performed before definitive treatment for upper tract TCC when there is potential for complete treatment endoscopically, when there is a need for nephron sparing, when radiographic findings are indeterminate, or when there is positive urine cytology with normal imaging and normal cystoscopy."