Brief Summary: This study looks at the level of circulating tumor elements (cancer cells or DNA pieces floating in the blood) and how it may be related to how the tumor responds to standard treatment in patients with rectal cancer that has spread to nearby tissue or lymph nodes (locally advanced). Researchers will also compare the level and genetic characteristics of circulating tumor elements between individuals with rectal cancer and healthy individuals to understand how they may change over time. Information from this study may help researchers better understand rectal cancer.

Detailed Description: PRIMARY OBJECTIVES: I. To establish the rate of circulating tumor elements (CTE), including but not limited to circulating tumor cells and circulating tumor deoxyribonucleic acid (DNA) detection in patients with locally advanced rectal cancer (LARC), relative to other stages. II. To assess changes in detected CTEs associated with neoadjuvant therapy in patients with LARC. III. To correlate CTEs with neoadjuvant treatment response as an indicator of disease risk. OUTLINE: Patients and healthy participants undergo collection of blood sample at baseline. Patients may also undergo collection of blood sample collections during tumor surgery, 4 weeks after surgery or after completion of treatment if you are not surgery, 8 weeks after the last dose of chemotherapy, 1 year after surgery or 1 year after completion of treatment if not having surgery, 2 years after surgery or 2 years after completion of treatment if not having surgery, and within 6 years after treatment or at the end of the 6 year follow-up if the disease gets worse with treatment or comes back.