# Chromosomal instability as a predictive biomarker for recurrence risk following transurethral resection of NMIBC

## TL;DR

This study shows that chromosomal instability in bladder cancer tumors can predict the risk of cancer recurrence after surgery, especially within 2 to 5 years.

## Contribution

The study demonstrates that chromosomal instability (CIN) is a novel independent predictor of bladder cancer recurrence after transurethral resection.

## Key findings

- High CIN is significantly associated with tumor recurrence and worse prognosis (median RFS: 22 months vs. unreached in low-CIN group).
- CIN values show good predictive performance for recurrence between the 2nd and 5th years post-surgery.
- Single-chromosome copy number abnormalities are linked to worse outcomes (median RFS: 16–23 months).

## Abstract

To investigate chromosomal instability (CIN) in tumor tissues from transurethral resection of bladder tumor (TURBT) and evaluate its feasibility as a molecular biomarker for prognostic stratification in non-muscle-invasive bladder cancer (NMIBC).

In this retrospective single-center cohort study, DNA was extracted from formalin-fixed paraffin-embedded (FFPE) samples of 50 BC patients using the Qiagen nucleic acid extraction kit. The recurrence defined in this study refers to cystoscopically visible recurrence confirmed by biopsy or surgical pathology. All patients underwent follow-up until January 2025 in strict accordance with the protocol established by the EAU guidelines for NMIBC. Low-coverage whole-genome sequencing (LC-WGS) was performed to analyze CIN in bladder tumors. Time-dependent Receiver Operating Characteristic (ROC) analysis was performed to evaluate the predictive efficacy of CIN values for post-TURBT outcomes. Survival analysis was conducted using the Kaplan-Meier method (log-rank test), and associations between variables and recurrence-free survival (RFS) were assessed via Cox proportional hazards models.

Recurrent bladder cancer patients exhibited significant copy number alterations (CNAs) differences in 67 gene segments versus non-recurrent patients. Time-dependent ROC analysis demonstrates that CIN values exhibit good predictive performance between the 2nd and 5th years. High CIN was significantly associated with tumor recurrence, higher tumor grade, with high-CIN patients exhibiting poorer prognosis (median RFS: 22 months vs. unreached in the low-CIN group, p = 0.009). Multivariate analysis confirmed high CIN as an independent predictor of recurrence (HR = 5.22, 95% CI: 1.52-17.93, P = 0.009). Patients with single-chromosome copy number abnormalities also showed worse outcomes (median RFS: 16–23 months) compared to those without such abnormalities. No significant difference in RFS was detected between Ta and T1 stages (P = 0.577).

High CIN exhibits a correlation with bladder tumor recurrence, higher tumor grade. High CIN or the presence of specific chromosomal abnormalities are indicative of an adverse prognosis. CIN may serve as a prognostic biomarker for predicting recurrence following TURBT, particularly between the 2nd and 5th years post-surgery.