Prognostic Value of Gene Methylation and Clinical Factors in Non-Muscle-Invasive Upper Tract Urothelial Carcinoma After Radical Nephroureterectomy.

INTRODUCTION

To systematically analyze the outcomes and prognostic value of gene methylation and clinical parameters in non-muscle-invasive upper tract urothelial carcinoma (NMIUTUC) after radical nephroureterectomy (RNU).

PATIENTS AND METHODS

The methylation status of 10 selected genes and clinical parameters of 192 NMIUTUC patients who received RNU and postoperative intravesical mitomycin were assessed. Univariate and multivariate Cox regression models were performed to evaluate the prognostic factors of cancer-specific mortality and intravesical recurrence.

RESULTS

For 192 NMIUTUC patients, 1-, 3-, and 5-year cancer-specific survival (CSS)/bladder recurrence-free survival (BRFS) rates were 98.4%/86.4%, 90.6%/74.6%, and 86.9%/62.4%, respectively. After the multivariate analysis, the methylation of ABCC6 (hazard ratio [HR], 3.46, P = .005), GDF15 (HR, 2.03, P = .002), multiple tumors (HR, 2.11, P = .049), impaired renal function (HR, 3.09, P = .004), and open RNU (HR, 2.14, P = .047) were independently associated with cancer-specific mortality, whereas the methylation of GDF15 (HR, 0.55, P = .022), RASSF1A (HR, 0.31, P = .006), multiple tumors (HR, 2.11, P = .002), and concomitant ipsilateral hydronephrosis (HR, 1.87, P = .022) were independently associated with intravesical recurrence after RNU. The c index of the multivariate model to predict cancer-specific mortality and intravesical recurrence was 0.81 and 0.78, respectively.

CONCLUSION

As an early stage disease, NMIUTUC has better postoperative survival and later intravesical recurrence than upper tract urothelial carcinoma; however, the intravesical recurrence rate is not decreased. The nomogram can be used to accurately predict the oncologic outcomes of NMIUTUC patients and can be used to guide clinical decision making.