In our study, we analyze the National Cancer Database to evaluate the effect that subtype histology, tumor location, and management strategy may have on mortality rates in this population. We redemonstrate poorer survival rates compared to urothelial carcinoma, corroborate the general efficacy of surgical management in lengthening survival, and further suggest that systemic therapy modalities may be tailored to both the variant’s subtype and the tumor’s location within the upper tract.
We conducted a retrospective analysis of the National Cancer Database, which encompasses 1,563 patients from 2005 to 2016 with variant histology malignancies of the upper tract. We confirmed that VH is diagnosed more often at higher stages, presents more frequently with metastases, and confers higher mortality risk. We identified that squamous differentiation was by far the most common variant, with less common variants consisting of adenocarcinoma, neuroendocrine, micropapillary, and sarcomatous pathologies. Our multivariable analysis revealed that for all variants taken together, surgical management was associated with improved survival compared to urothelial carcinoma, whereas chemotherapy showed improved survival only for tumors in the renal pelvis. When broken down by variant subtype, surgery remained beneficial for most variant subtypes in both locations, whereas chemotherapy conferred a survival benefit in renal pelvis adenocarcinomas and ureteral neuroendocrine tumors. Other modalities of systemic therapy such as radiotherapy or immunotherapy did not demonstrate improved mortality for any individual subtype.
Most research in systemic therapy for urinary tract VH has predominantly focused on lower tract malignancies, but recent case series have begun to examine the impact of chemotherapy on VH of the upper tract, extrapolating from regimens for similar cancers.3-5 Furthermore, several reviews of larger patient cohorts have proposed that the response of upper tract VH to various immunotherapy regimens are no more efficacious than in patients with urothelial carcinoma.6,7 However, understandably due to smaller sample size, these studies group all forms of VH together, despite each subtype expressing unique pathology. Our work suggests that as future studies further evaluate systemic therapy for upper tract VH, there may be utility in employing a framework that distinguishes between variant subtype and tumor location.
Written by: Eric Song, Medical Student, Saint Louis University School of Medicine, St. Louis, MO
References:
- Deuker M, Stolzenbach LF, Colla Ruvolo C, Nocera L, Tian Z, Roos FC, et al. Upper urinary tract tumors: variant histology versus urothelial carcinoma. Clin Genitourin Cancer 2021;19(2):117–24.
- Zamboni S, Foerster B, Abufaraj M, Seisen T, Roupret M, Colin P, et al. Incidence and survival outcomes in patients with upper urinary tract urothelial carcinoma diagnosed with variant histology and treated with nephroureterectomy. BJU Int 2019;124(5):738–45.
- Hensley PJ, Bhalodi AA, Gupta S. Primary upper urinary tract small cell carcinoma: a case series and literature review. J Endourol Case Rep 2017;3(1):165–8.
- Galsky MD, Iasonos A, Mironov S, Scattergood J, Donat SM, Bochner BH, et al. Prospective trial of ifosfamide, paclitaxel, and cisplatin in patients with advanced non-transitional cell carcinoma of the urothelial tract. Urology 2007;69(2):255–9.
- McGregor BA, Campbell MT, Xie W, Farah S, Bilen MA, Schmidt AL, et al. Results of a multicenter, phase 2 study of nivolumab and ipilimumab for patients with advanced rare genitourinary malignancies. Cancer 2021;127(6):840–9.
- McGregor BA, Sonpavde GP. Rare genitourinary malignancies: current status and future directions of immunotherapy. Eur Urol Focus 2020;6(1):14–6.
- Minato A, Furubayashi N, Harada M, Negishi T, Sakamoto N, Song Y, et al. Efficacy of Pembrolizumab in Patients with Variant Urothelial Carcinoma: A Multicenter Retrospective Study. Clin Genitourin Cancer 2022;20(5):499.e1-499.e8.