Preoperative urine sediment chromosomal instability level predicts urothelial cancer prognosis

Urothelial carcinomas (UCs) are often characterized by frequent recurrences after surgery, making UC one of the costliest cancers. Chromosomal instability (CIN) has been proven to be a hallmark of UCs and is related to the prognosis of many cancer types. In this study, we evaluated CIN of urine sediments as a prognostic indicator for UCs.

Patients with UC were prospectively recruited. Preoperative urine samples were collected for whole genome sequencing and urine cytology tests. Patients underwent standard-of-care treatment and were followed up until disease relapse or study ended. Concordance and accuracy of CIN alone or in combination with cytology in predicting disease relapse were assessed. The value of CIN combined with European Organization for Research and Treatment of Cancer (EORTC) model were also analyzed.

A total of 137 patients with UCs were included in this study. Median follow-up was 44.2 months and 41.61% patients suffered from cancer relapse. Patients with CIN-high indicated higher relapse rate, and this distinction was significant for patients underwent transurethral resection of bladder tumor (57.89% vs. 34.29%, P = 0.016). Combination of cytology and CIN result could further classified patients into subgroups with distinct relapse risks. Meanwhile, the combination of CIN and EORTC model significantly improved the prediction accuracy compared with EORTC alone (Harrel's C-index: 0.71 vs. 0.65).

CIN level of preoperative urine exfoliated cells had robust prognostic value for bladder cancer patients underwent TURBT. The prognostic model by combining CIN and EORTC may help in stratifying patients to optimize follow-up regimen.