Introduction:

ctDNA has emerged as a novel biomarker in predicting pathological outcomes and disease recurrence in different solid cancers. We seek to evaluate the survival outcomes of preoperatively and postoperatively detectable ctDNA by assessing recurrence-free survival (RFS) in patients undergoing surgery for masses suspicious of renal cell carcinoma (RCC).

Methods:

Consecutive patients who underwent partial or radical nephrectomy for non-metastatic (cT1b-T3) suspected RCC during 2022-2023, had prospectively collected tumor-informed ctDNA analyses (Signatera^TM) performed preoperatively and postoperatively, the minimal residual disease (MRD) window was defined as the initial 120 days after surgery, and anytime positive after surgery. Survival analysis was conducted using the Kaplan-Meier method.

Results:

Overall, 80 patients with a median age of 62 years (IQR 53-69), and a median follow-up time of 15 months (IQR 6-22), had 318 ctDNA samples collected for analysis. Among 76 patients with preoperative ctDNA available for analysis, 47 (61%) had detectable status. Postoperative ctDNA status was available for 54 patients; among them, 8 (14.8%) had detectable ctDNA, and 5 developed metastatic recurrence (62.5%). In conversion dynamics analysis available for 27 patients, 81.5% cleared ctDNA after nephrectomy. On Kaplan-Meier analysis, pre-nephrectomy detectable ctDNA was associated with worse RFS outcomes than undetectable ctDNA with 12-month RFS of 100% [100-100] vs. 86.6% [56.1-98.3], p=0.03 (Figure 1). Anytime detectable ctDNA had worse RFS outcomes than anytime undetectable ctDNA, with 12-month RFS of 100% [100-100] vs. 22.9% [4.2-100], p<0.0001 (Figure 2). Interestingly, when assessing pathological features associated with detectable pre-nephrectomy ctDNA, patients with venous involvement (29.8% vs 7.1%, p=0.02) and patients with lymphovascular involvement (17% vs 0%, p=0.02) were more commonly found with detectable ctDNA than undetectable ctDNA, respectively.

Conclusion:

In patients with localized non-metastatic RCC, detectable pre-nephrectomy ctDNA and anytime post-nephrectomy ctDNA were associated with worse RFS; in addition, detectable pre-nephrectomy ctDNA was associated with pathological and clinically relevant features. Clinical trials should consider incorporating ctDNA analyses to augment clinical decision-making.

Funding: N/A