Editorial comment on "Effects of tumor size and location on survival in upper tract urothelial carcinoma after nephroureterectomy".

Upper tract urothelial carcinoma (UTUC) is a rare cancer and accounts for 5% of all urothelial cancers. Because of its rarity, much less is known about this cancer, as compared to urothelial cancers of bladder. Joshi et al.[1] report a retrospective analysis of 8284 patients of UTUC undergoing nephroureterectomy. They evaluated the role of tumor size and location on 5-year overall survival of these patients. Data from the National Cancer Database was collected, and effect of factors such as T stage, pN stage, grade, tumor size, and tumor site (renal pelvis versus ureter) on overall survival was assessed. On multivariate analysis, the authors found that for tumor size <3.5 cm versus ≥3.5 cm, the 5-year overall survival was 45.9% and 58.5%, respectively. Tumor location was not found to make any difference in survival. We congratulate the authors for presenting results from one of the largest series of this rare malignancy. This study provides a wealth of information and raises a few questions.

UTUC is an aggressive cancer and is notorious for both recurrence and progression. Invasion at diagnosis is seen in only 15%–20% of bladder cancers but in 60% of UTUC.[2] Knowledge of factors predicting aggressiveness of this disease can help improve management. Even though neoadjuvant chemotherapy is known to improve survival, it is grossly underutilized with <2% patients receiving neoadjuvant chemotherapy as per SEER database.[3] The current study highlights the importance of tumor size and possibly suggests considering this parameter in selecting patients for neoadjuvant chemotherapy before they undergo nephroureterectomy. Tumor size is an easily assessable parameter preoperatively, and results of this study would help better prognosticate patients with UTUC.

The authors have acknowledged the limitations of this study and many of them stem from the lack of certain data points in the original database used for conducting the study. Lack of information about bladder cuff excision and lymphadenectomy are the most prominent. Bladder cuff excision is the tricky part of this surgery and various techniques such as endoscopic, transvesical, and extravesical have been described. Lack of bladder cuff excision has an impact on recurrence pattern and survival.[4] Including bladder cuff management in multivariate analysis in the current study would have been extremely informative. The role and template of lymphadenectomy in UTUC are still controversial, and it may have an impact on survival.[5] Unfortunately, detailed information about lymphadenectomy is also missing in the current study. It would have been interesting to see if size or location of tumor could predict the involvement of lymph nodes. Similar to its impact in bladder cancer, utilization of neoaduvant chemotherapy may have influenced survival, thereby acting as a potential confounder in the current analysis.

We are also inclined to believe that as opposed to overall survival, cancer-specific survival would have been a more appropriate primary endpoint in this study since a majority of patients in this cohort are in the senior age group, where a number of comorbidities can have an impact on the overall survival.

Having said that, and despite these limitations, this study is important in view of the sheer strength of its numbers. It represents an important starting point to delve deeper into the mystery surrounding the optimal prognostication and management of this elusive disease.