This study investigates if circulating tumor DNA (ctDNA) and other tumor-related molecules/chemicals released in the blood can help doctors predict if colorectal cancer may come back or spread. Tumors shed DNA and other cancer related chemicals into the blood that can be identified and studied further to provide information about the cancer. Information gathered from this study may help researchers better understand if ctDNA found in the blood can predict whether colorectal cancer may come back or spread.

PRIMARY OBJECTIVES:

I. Demonstrate ability to monitor cancer-specific deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and proteomic alterations from plasma.

II. Improve detection of recurrences post completion of curative therapies through monitoring of plasma cancer-specific DNA, RNA and proteomic alterations.

SECONDARY OBJECTIVES:

I. Qualitative and quantitative changes in cancer-specific plasma alterations during neoadjuvant, adjuvant therapies and surveillance.

II. Disease free survival (DFS) of patients with detectable cancer-specific plasma alterations.

III. Overall survival (OS) of patients with detectable cancer-specific plasma alterations.

EXPLORATORY OBJECTIVES:

I. Optimal combination of cancer-specific plasma DNA, RNA and / or proteomic alterations for early detection of recurrences.

II. Sensitivity, specificity, positive predictive and negative predictive values of cancer-specific plasma alterations in detecting recurrences.

III. Correlation between cancer-specific alterations in plasma and tissue and either with outcomes including DFS & OS.

IV. Nature and frequency of detection of incidental non-colorectal cancer related DNA, RNA and / or proteomic alterations.

OUTLINE:

Patients undergo collection of blood samples at baseline, during each neoadjuvant therapy treatment, prior to surgical resection, and up to 4 times per year for up to 5 years. Patients also undergo collection of tissue sample at time of surgical resection. Patients' medical records may also be reviewed.

Inclusion Criteria:

1. Age ≥ 18 years.
2. Histological/cytological confirmation of colorectal adenocarcinoma.
3. Patients with any stage colorectal adenocarcinoma deemed potentially eligible for curative intent treatment. Patients with stages II-IV colorectal cancer post-R0 resection may also be enrolled onto the protocol any time before or up to 3 months post-surgery and prior to initiating adjuvant therapy.
4. Ability to understand and the willingness to sign a written informed consent document.
5. Willing to pursue standard of care surveillance post completion of curative therapies.
6. Willing to provide blood samples for correlative research.

Exclusion Criteria:

1. Known active malignancies other than colorectal adenocarcinoma that may interfere with detection and / or interpretation of circulating plasma markers. Patients with known clonal hematopoiesis of indeterminate potential are eligible.
2. Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

Patients with colorectal cancer at MD Anderson Cancer Center.