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Impact of Ureteroscopy Prior to Nephroureterectomy for Upper Tracturothelial Carcinoma on Oncologic Outcomes- Beyond the Abstract

Upper tract urothelial cell carcinoma (UTUC) is challenging to diagnose, stage, and manage. Historically, radical nephroureterectomy (NU) was performed for clinical suspicion of UTUC based primarily on imaging, with or without positive cytology. In the modern era, after the development of modern endoscopy techniques, many urologists will perform ureteroscopy (URS) prior to NU with diagnostic or therapeutic intent. The concern with this procedure is that it can disturb the tumor microenvironment and increase pyelovenous pressure with reports in the literature of disease progression following URS (1-4). Although these reports are anecdotal, it has led some urologists to advocate against upper tract instrumentation prior to NU. To address this concern, we compared the oncologic outcomes of patients with UTUC and no history of bladder cancer treated at our institution who were managed with and without URS prior to NU.

The results of our study show that patients undergoing URS prior to definitive NU are at higher risk of developing intravesical tumor recurrence (IR) (HR 2.58; 95% CI 1.47, 4.54; p = 0.001), however, there is no increased risk of death (HR 0.73; 95% CI 0.44, 1.21; p=0.2) or distant metastasis (HR 0.90; 95% CI 0.47, 1.73; p=0.8). The mechanism underlying this phenomenon is not well understood. One possible explanation may be that viable upper tract tumor cells slough off during URS, drift downstream and reimplant in bladder mucosa. Another explanation may be that patients with distal ureteral tumors, a site that is associated with increased risk of IR, are more likely to undergo URS prior to NU.

There are conflicting data in the literature regarding the association between URS and IR after NU. Similar to our findings, a recent study by Luo et al. found that patients undergoing URS prior to definitive NU had an increased risk of IR compared to those who had not undergone prior URS (HR 1.44, p=0.05) (5). In contrast, however, a study by Ishikawa et al. found no association between URS and IR at 2 years followup (6). Moreover, they found that the only factor that predisposes one to IR is a distal location of primary ureteral tumor.

Recent clinical trials have studied the utility of administering adjuvant intravesical chemotherapy after NU in preventing intravesical recurrence. A recent meta analysis of the pooled data of these clinical trials found that peri-operative administration of intravesical chemotherapy reduced the likelihood of a IR with an odds ratio of 0.45 (7). It is unclear if this finding is applicable to the post-URS setting . It may be a worthwhile endeavor to prospectively study the use of adjuvant intravesical chemotherapy after URS.

We also observed that time to death from disease after recurrence at any site was longer in patients undergoing URS prior to NU. This is likely explained by a higher proportion of recurrences in the URS group being intravesical, which are commonly detected at an early state when tumors are superficial and effectively controlled with local treatment. Additionally, we did not find any evidence to suggest that URS prior to NU is associated with a higher rate of metastasis or a higher overall mortality rate. These findings contrast with previous anecdotal reports of URS leading to poor outcomes for UTUC patients.

In summation, URS has a role in diagnostic and therapeutic management prior to definitive extirpation of UTUC and based on our study, we did not find evidence that URS prior to NU adversely impacts patient survival. Patients are at higher risk for IR after NU when they have undergone prior diagnostic URS; however, recurrence in these patients is not associated with mortality. Currently, there are conflicting data in literature assessing the association between URS and risk of intravesical recurrence, with most studies, like ours, consisting of small cohorts and adjusting for different covariates. A multi-institutional study would clarify whether a significant association between URS and IR still exists once more measured covariates are adjusted for. Results from such a study could aid treating physicians when deciding whether the benefits of pre−NU URS, including more accurate staging and possible endoscopic ablation, outweigh the increased risk of post−NU IR.

Written by: 
Michael Chevinsky, MD Division of Urology, Department of Surgery, Barnes Jewish Hospital, St. Louis, MO
Alexander Sankin, MD MS Department of Urology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY

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References:

1. Grasso M, McCue P, Bagley DH. Multiple urothelial recurrences of renal cell carcinoma after initial diagnostic ureteroscopy. The Journal of urology.1992;147(5):1358-60.

2. Kulp DA, Bagley DH. Does flexible ureteropyeloscopy promote local recurrence of transitional cell carcinoma? Journal of endourology / Endourological Society.1994;8(2):111-3.

3. Lim DJ, Shattuck MC, Cook WA. Pyelovenous lymphatic migration of transitional cell carcinoma following flexible ureterorenoscopy. The Journal of urology. 1993;149(1):109-11.

4. Tomera KM, Leary FJ, Zincke H. Pyeloscopy in urothelial tumors. The Journal of Urology. 1982;127(6):1088-9.

5. Luo HL, Kang CH, Chen YT, et al. Diagnostic ureteroscopy independently correlates with intravesical recurrence after nephroureterectomy for upper urinary tract urothelial carcinoma. Annals of surgical oncology. 2013;20(9):3121-6.

6. Ishikawa S, Abe T, Shinohara N, et al. Impact of diagnostic ureteroscopy on intravesical recurrence and survival in patients with urothelial carcinoma of the upper urinary tract. The Journal of urology. 2010;184(3):883-7.

7. Wu P, Zhu G, Wei D, et al. Prophylactic intravesical chemotherapy decreases bladder tumor recurrence after nephroureterectomy for primary upper tract urothelial carcinoma: a systemic review and meta-analysis. J BUON. 2015;20(5):1229-38.