Establishing cM0 (i+) stage criteria in localized renal cell carcinoma based on postoperative circulating tumor cells monitoring.

Background: The diagnostic criteria for cM0 (i+) stage proposed by American Joint Committee on Cancer (AJCC) in renal cell carcinoma (RCC) still remains unclear. The present study aimed to establish and validate the criteria of cM0 (i+) stage based on postoperative circulating tumor cells (CTCs) monitoring in patients with localized renal cell carcinoma (LRCC).

Materials And Methods: This study enrolled 204 patients with LRCC who received partial or radical nephrectomy from January 2015 to November 2021. Cases were randomly divided into test set and validation set. The correlation between clinicopathological features and CTCs counts were analyzed and prognostic variables were determined by Lasso regression. Receiver operating characteristic curve of the prognosis-related CTCs terms were plotted to determine their optimal cut-off value to establish the criteria of cM0 (i+) stage. Its clinical prognostic significance was explored by Kaplan-Meier analysis and Log-rank test. The above analysis was conducted by SPSS26.0 software and R Studio software. P < 0.05 was considered to be statistically significant.

Results: A total of 204 patients were analyzed in this study.There were no significant differences in variables between the validation and test sets (P>0.05). Total CTCs, mesenchymal CTCs (MCTCs), and CTCs showing a progressive trend were selected as the diagnostic basis for the cM0 (i+) stage through correlation analysis and Lasso regression. The cM0 (i+) stage identified patients meeting the following criteria simultaneously: (1) total CTCs ≥ 6; (2) MCTCs ≥ 1; and (3) a demonstrated trend of progression in either total CTCs or MCTCs. In the validation group, Kaplan-Meier analysis showed that patients with cM0 (i+) stage had significantly shorter progression-free survival than the control group(P<0.05). The results of multivariate Cox regression analysis also showed cM0 (i+) was an independent risk factor for postoperative progression of LRCC patients [12.448 (1.874-82.666) P < 0.05]. Its 1-3 years' prediction discrimination is better than that of UISS score and SSIGN score, which was also verified in the validation set.

Conclusion: The study proposed a diagnostic criterion for M0 (i+) stage in LRCC based on postoperative CTCs monitoring. It was identified as an independent risk factor for postoperative progression and demonstrated potential advantages over the UISS and SSIGN scores in internal validation.