The incidence of VH is rising due to the increased recognition and improved reporting by pathologists.3 VH is an established prognostic factor in urothelial bladder cancer that has been associated with more aggressive disease, more advanced stage at presentation, and worse survival outcomes.4 Nevertheless, less is known regarding the prognostic impact of VH in UTUC patients.5
In this multicenter study, using the Robotic surgery for Upper tract Urothelial cancer Study (ROBUUST) database, we investigated the impact of VH on oncologic outcomes of UTUC patients treated with minimally-invasive radical nephroureterectomy. A total of 687 patients with a median (IQR) age of 71 (64-78) years were included. VH was found in 10% of patients, of which the most common type was squamous (5%), followed by micropapillary (1.5%) and sarcomatoid (1.3%). The presence of VH was significantly associated with higher grade and clinical T stage at diagnosis, as well as higher rates of positive margins, lymphovascular invasion, and adjuvant chemotherapy use. In a median follow-up of 16 months, the incidence of urothelial recurrence, metastasis, and mortality was 27%, 15%, and 12%, respectively. On multivariable Cox regression analysis, controlling for relevant confounders, VH was an independent risk factor for metastasis (HR 2, p = 0.004) but not for urothelial recurrence (HR 0.94, p = 0.8) or death (HR 1.5, p = 0.2).
Figure: Forest plots demonstrating multivariable analysis for (A) urothelial recurrence, (B) metastasis, and (C) mortality risk.
In summary, our findings reflect the presence of more aggressive clinicopathological features associated with VH that resulted in a higher need for adjuvant chemotherapy in this group of patients. In addition, we showed that the presence of VH is an independent risk factor for metastasis following surgery. Nevertheless, overall survival rates and the risk of urothelial recurrence in the bladder or the contralateral upper tract do not seem to be affected by VH. Despite the limitations of our study (e.g., retrospective nature, variations in treatment patterns as well as consistency of data collection and pathology review in each center), we believe that data from our contemporary cohort can be generalizable in today’s treatment paradigm.
Written by: Alireza Ghoreifi, MD, Antoin Douglawi, MD, & Hooman Djaladat, MD
Institute of Urology, Norris Cancer Center, University of Southern California, Los Angeles, CA, USA.
References:
- Coleman JA, Clark PE, Bixler BR, et al. Diagnosis and Management of Non-Metastatic Upper Tract Urothelial Carcinoma: AUA/SUO Guideline. J Urol. 2023; 209:1071-1081.
- Nogueira LM, Yip W, Assel MJ, et al. Survival Impact of Variant Histology Diagnosis in Upper Tract Urothelial Carcinoma. J Urol. 2022; 208:813-820.
- Lobo N, Shariat SF, Guo CC, et al. What Is the Significance of Variant Histology in Urothelial Carcinoma? Eur Urol Focus. 2020; 6:653-663.
- Mori K, Abufaraj M, Mostafaei H, et al. A Systematic Review and Meta-Analysis of Variant Histology in Urothelial Carcinoma of the Bladder Treated with Radical Cystectomy. J Urol. 2020; 204:1129-1140.
- Deuker M, Martin T, Stolzenbach F, et al. Bladder Cancer: A Comparison Between Non-urothelial Variant Histology and Urothelial Carcinoma Across All Stages and Treatment Modalities. Clin Genitourin Cancer. 2021; 19:60-68.e1.