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We will assess the prospective utility of novel biomarkers in the clinical management of ACC. We hypothesize that serum steroids can specifically diagnose ACC, measure ACC burden, and detect recurrence; we also hypothesize that molecular biomarkers including tumor DNA methylation will predict ACC recurrence, progression, and selective response to adjuvant therapy. We will prospectively recruit ~200 participants with ACC or ACA from UM, A5, and ADIUVO-2. Diagnosis of ACC or ACA will be established by histology or imaging. Aim 1a: In patients with ACC or ACA, we will measure serum steroids by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify ACC-specific steroid markers. Aim 1b: In patients with ACC, we will measure serum steroids as in Aim 1a with parallel imaging surveillance to identify steroid markers that predict recurrence. Aim 2a: In patients with ACC, we will measure tumor DNA methylation and determine if it predicts recurrence, progression, response to systemic therapies, and death. Aim 2b: In patients from ADIUVO-2, we will measure tumor DNA methylation and determine if it predicts adjuvant therapy-specific recurrence/survival. We will perform exome sequencing of paired tumor/germline DNA to prospectively identify genetic factors that predict response to adjuvant therapies.