Overview
METH-RENAL is a prospective observational diagnostic development and threshold-setting study in adults with a renal mass scheduled for partial or radical nephrectomy. Peripheral blood is collected before surgery, and postoperative histopathology serves as the reference standard. The study will develop and internally validate a plasma DNA methylation classifier and lock the final marker panel, algorithm, and positivity cut-off for a subsequent independent prospective multicenter validation study.
Description
Approximately 240 participants (acceptable range 200-250) will be enrolled before surgery. Plasma methylation testing will not guide clinical care and assay results will remain unavailable to treating clinicians and participants. The primary analysis compares pathologically confirmed renal cell carcinoma (RCC) with benign renal lesions. Non-RCC malignant renal lesions may be described separately. The final model is expected to contain 5-6 methylation markers. Model development, optimism correction, and cut-off stability will use at least 1,000 bootstrap resamples; the cohort will not be randomly divided into training and test sets. The marker combination, model coefficients or scoring algorithm, analytical quality-control rules, and positivity cut-off will be formally locked at study completion. This study is not an external validation study.
Eligibility
Inclusion Criteria:1.Age 18 years or older. 2.A renal mass identified by computed tomography and/or magnetic resonance imaging.
3.Partial nephrectomy or radical nephrectomy planned as part of routine clinical care.
4.Preoperative peripheral blood collection feasible before surgery or other treatment of the index lesion.
5.Final postoperative histopathological diagnosis expected to be available. 6.Written informed consent provided.
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Exclusion Criteria:7.Systemic anticancer therapy, radiotherapy, local ablation, or surgery/pathological sampling of the index renal lesion before study blood collection.
8.Concurrent active malignancy requiring systemic treatment that, in the investigator's judgment, could materially interfere with interpretation of the methylation assay.
9.Severe acute infection or another uncontrolled systemic condition that could compromise biospecimen quality or study procedures.
10.Inadequate preoperative blood specimen or failure of prespecified analytical quality-control requirements.
11.No definitive pathological diagnosis of the index renal lesion. Any condition that, in the investigator's judgment, makes participation inappropriate.
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