A systematic review and meta-analysis of oncological and renal function outcomes obtained after segmental ureterectomy versus radical nephroureterectomy for upper tract urothelial carcinoma: Beyond the Abstract

While radical nephroureterectomy (RNU) has traditionally served as the gold standard treatment for upper tract urothelial carcinoma (UTUC), post-operative decline in renal function remains a concern.  Aside from the increased mortality risk directly related to the development or exacerbation of chronic kidney disease (CKD), declines in renal function may also decrease eligibility for platinum-based chemotherapy regimens, thereby potentially affecting survival outcomes further.  As a result, considerable interest has been generated in determining methods to mitigate declines in renal function while managing UTUC.

In a subset of patients, renal-sparing approaches may be a feasible option to avoid radical excision of the kidney, including partial ureterectomy (PU) and endoscopic management.  Recent data emerging from our institution demonstrated equivalent long-term oncologic efficacy between PU and RNU,1 with similar impact on post-operative renal function outcomes.2  To address these findings further, we recently published a systematic review and meta-analysis of comparative studies reporting both oncological and renal function outcomes of PU versus RNU for UTUC (http://www.urotoday.com/recent-abstracts/urologic-oncology/upper-tract-tumors/91059-a-systematic-review-and-meta-analysis-of-oncological-and-renal-function-outcomes-obtained-after-segmental-ureterectomy-versus-radical-nephroureterectomy-for-upper-tract-urothelial-carcinoma.html).3  In this paper, we incorporated a total of 11 retrospective studies including 3,963 patients with UTUC (25% PU, 75% RNU) and found that oncologic outcomes were rather similar between the two approaches, yet renal function preservation was superior in the PU group.  In light of this, there remains a discrepancy between the incidence of ureteral tumors amenable to PU and the actuarial utilization of PU, which is estimated at only 10%, suggesting that PU may be underutilized. 

Undoubtedly, not all patients with UTUC are eligible to undergo PU based on tumor characteristics and hence require RNU.  In these patients, identifying pre-operative risk factors predictive for post-operative declines in renal function may be helpful in facilitating pre-operative counseling of patients and in characterizing the appropriate timing of chemotherapy administration, which as of yet remains unknown.  That is, identifying predictors for and degree of renal function loss following RNU may help determine which patients would be eligible for upfront surgery followed by adjuvant chemotherapy versus those who would be more likely to derive benefit from pre-operative chemotherapy due to decreased likelihood of chemotherapy eligibility following surgery.  In the adjuvant setting, retrospective series appear to demonstrate benefits for both overall and cancer-specific survival, yet prospective data is still pending.  In the neoadjuvant setting, we continue to await the results of prospective trials currently recruiting (NCT01261728, NCT02412670).

In our institutional study, we identified that patients with pre-operative hydronephrosis tend to experience less decline in renal function than those without hydronephrosis (http://www.urotoday.com/recent-abstracts/urologic-oncology/renal-cancer/90824-preoperative-hydronephrosis-is-associated-with-less-decline-in-renal-function-after-radical-nephroureterectomy-for-upper-tract-urothelial-carcinoma.html).4  The potential implications for timing of chemotherapy administration are particularly relevant in this group of patients, given the oncologic association of hydronephrosis with more advanced disease characteristics and worse prognostic outcome.5  It is plausible that patients with renal obstruction related to tumor experience some degree of ipsilateral renal compromise pre-operatively.  As a result, the contralateral kidney may be accounting for the majority of the renal function, and removal of the less functional kidney may be less detrimental.  While we did not confirm this in our study with pre-operative renal scintigraphy or quantitative measures of renal cortical thickness, such information would certainly provide useful functional and anatomic information in evaluating our hypothesis.

Indeed, when managing patients with UTUC, nephron-sparing surgical approaches in the appropriate clinical setting warrant consideration in the interest of maximizing post-operative renal function without compromising oncologic outcomes.  As we await the results of prospective studies to shed light on the benefits of chemotherapy administration in the neoadjuvant and adjuvant settings, attention to risk factors predisposing patients to post-RNU declines in renal function may help guide a skillful multimodal approach to therapy while maximizing options.

Written by: Nirmish Singla, M.D.Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX


1. Bagrodia, A., Kuehhas, F. E., Gayed, B. A. et al.: Comparative analysis of oncologic outcomes of partial ureterectomy vs radical nephroureterectomy in upper tract urothelial carcinoma. Urology, 81: 972, 2013

2. Singla, N., Gayed, B. A., Bagrodia, A. et al.: Multi-institutional analysis of renal function outcomes following radical nephroureterectomy and partial ureterectomy for upper tract urothelial carcinoma. Urol Oncol, 33: 268 e1, 2015

3. Fang, D., Seisen, T., Yang, K. et al.: A systematic review and meta-analysis of oncological and renal function outcomes obtained after segmental ureterectomy versus radical nephroureterectomy for upper tract urothelial carcinoma. Eur J Surg Oncol, 42: 1625, 2016

4. Singla, N., Hutchinson, R., Haddad, A. et al.: Preoperative hydronephrosis is associated with less decline in renal function after radical nephroureterectomy for upper tract urothelial carcinoma. Can J Urol, 23: 8334, 2016

5. Chung, P. H., Krabbe, L. M., Darwish, O. M. et al.: Degree of hydronephrosis predicts adverse pathological features and worse oncologic outcomes in patients with high-grade urothelial carcinoma of the upper urinary tract. Urol Oncol, 32: 981, 2014

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