, and the Upper TractUrothelial Carcinoma Collaboration BACKGROUND: The literature on upper tract urothelial carcinoma (UTUC) has been limited to small, single center studies. A large series of patients treated with radical nephroureterectomy for UTUC were studied,

Study Type – Prognosis (retrospective cohort)
Level of Evidence 2b What’s known on the subject? and What does the study add? Upper‐tract urothelial carcinoma (UTUC) is a relatively uncommon urological malignancy with survival and outcomes data largely determined from single‐centre series which can be limited by relatively small case numbers. Through review of a large population based cohort, this study provides valuable information regarding epidemiological and survival patterns for over 13,000 patients with UTUC diagnosed over the past three decades. OBJECTIVE • To evaluate epidemiological and survival patterns of upper‐tract urothelial carcinoma (UTUC) over the past 30 years through a review of a large, population‐based database. PATIENTS AND METHODS • Data from the Surveillance, Epidemiology and End Results (SEER) database from 1973 to 2005 were reviewed in 10‐year increments to evaluate disease trends. • Univariate and multivariate survival analyses identified prognostic variables for outcomes. RESULTS • In total, 13 800 SEER‐registered cases of UTUC were included. The overall incidence of UTUC increased from 1.88 to 2.06 cases per 100 000 person‐years during the period studied, with an associated increase in ureteral disease (0.69 to 0.91) and a decrease in renal pelvic cancers (1.19 to 1.15). • The proportion of in situ tumours increased from 7.2% to 31.0% (P < 0.001), whereas local tumours declined from 50.4% to 23.6% (P < 0.001). • There was no change in the proportion of patients presenting with distant disease. • In multivariate analysis, increasing patient age (P < 0.001), male gender (P < 0.001), black non‐Hispanic race (P < 0.001), bilateral UTUC (P= 0.001) and regional/distant disease (P < 0.001) were all associated with poorer survival outcomes. CONCLUSIONS • The incidence of UTUC has slowly risen over the past 30 years. • Increased use of bladder cancer surveillance regimens and improved abdominal cross‐sectional imaging may contribute to the observed stage migration towards more in situ lesions. • Although pathological disease characteristics impact cancer outcomes, certain sociodemographic factors also appear to portend worse prognosis.

The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we perform an integrative multi-omics analysis of patients diagnosed with NMIBC (n = 834). Transcriptomic analysis identifies four classes (1, 2a, 2b and 3) reflecting tumor biology and disease aggressiveness. Both transcriptome-based subtyping and the level of chromosomal instability provide independent prognostic value beyond established prognostic clinicopathological parameters. High chromosomal instability, p53-pathway disruption and APOBEC-related mutations are significantly associated with transcriptomic class 2a and poor outcome. RNA-derived immune cell infiltration is associated with chromosomally unstable tumors and enriched in class 2b. Spatial proteomics analysis confirms the higher infiltration of class 2b tumors and demonstrates an association between higher immune cell infiltration and lower recurrence rates. Finally, the independent prognostic value of the transcriptomic classes is documented in 1228 validation samples using a single sample classification tool. The classifier provides a framework for biomarker discovery and for optimizing treatment and surveillance in next-generation clinical trials.

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