1708P - The clinical value of tumor-informed minimal residual disease detection in renal cell carcinoma

Background

Clear cell renal cell carcinoma (ccRCC) is one of the most lethal urological malignancies with high tumor heterogeneity, and reliable biomarkers are still needed for its diagnosis and prognosis. Minimal Residual Disease (MRD) as a prognostic marker in ccRCC remain undetermined.

Methods

Tumor tissue samples were used for whole exome sequencing (WES) and clonal mutations were selected for the customized MRD panel. Blood samples were collected for MRD detection both preoperatively (within 24 hours before surgery) and at multiple postoperative time points including 1, 6, 12, 18, 24, 30, and 36 months.

Results

A total of 70 ccRCC patients including 51 (72.9%) males and 19 (27.1%) females, with a median age of 56 years old (23-78 years old). Based on WES, we found that 64% (4936/7715) of the mutated genes were unique to each patient with ccRCC, and 95.5% (2148/2249) of selected tumor-informed single nucleotide variants (SNV) were variants with unknown significance, suggesting that tumor-informed MRD is superior to panel-based MRD in ccRCC. The positive rates of MRD preoperatively, and at 1 month, 6 months, 12 months, and 18 months postoperatively were 49.2% (32/65), 5% (3/60), 7% (3/43), 4.8% (1/21), and 10% (1/10), respectively. Based on the pathological staging (pT1-2, pT3, pT4), the preoperative MRD positivity rates for patients were 39.1% (18/46), 72.2% (13/18), and 100% (1/1), respectively. The respective negative and positive predictive values (NPV and PPV) of MRD testing were 100% (63/63) and 42.9% (3/7). Due to the follow-up time is relatively short (median = 263 days), only three patients have experienced recurrence and metastasis, and there was one additional patient with suspected recurrence among the MRD-positive population.Patient follow-up is still ongoing.

Conclusions

This study suggests that tumor-informed MRD may be superior to panel-based MRD in ccRCC. Despite the short follow-up, MRD demonstrates potential in predicting recurrence and metastasis. With NPV and PPV at 100% and 42.9% respectively, the importance of continuous MRD monitoring for long-term prognosis assessment is underscored.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Linhui Wang.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.