Background: Total Neoadjuvant therapy (TNT) has gained acceptance in the treatment of locally advanced rectal cancer, although the optimal sequencing of therapy chemoradiation (CRT) followed by consolidation chemotherapy (cChT) or induction chemotherapy followed by chemoradiation (iChT), remains a subject of ongoing debate. The effect of TNT sequencing and carcinoembryonic antigen (CEA) level on progression free survival (PFS) is uncertain. We conducted a retrospective analysis to examine these issues. Methods: Patients (n = 44) with locally advanced rectal cancer from June 2016 to December 2020 were reviewed. CEA level was compared against the primary outcome of response to TNT approaches. We categorized patients into 3 groups based on pre-TNT and post-TNT (i.e. pre-surgical) CEA: normal CEA_PRE/normal CEA_POST, elevated CEA _PRE/normal CEA _POST, elevated CEA _PRE/elevated CEA _POST. 3-Year PFS was calculated using Kaplan-Meier method. Univariable and multivariable logistic regression analyses identified characteristics predictive of PFS and clinicopathologic variables associated with TNT sequencing. Results: The study cohort had a median age of 61 years and was predominantly male (70%) and Caucasian (94%). Pre-treatment stage was either II (27%) or III (72%), with the majority (65%) undergoing iChT. Downstaging occurred in 42/44 (95%). Baseline CEA was elevated in 40.9% of patients. On multivariable, logistic regression variable associated with receipt of CRT followed by cChT included: Age > 61 years clinical T4 disease and lack of T downstaging (p < 0.05 for all).There was no difference in 3-year PFS between patients receiving iChT versus patients receiving cChT (p = 0.53). When patients were stratified according to pretreatment CEA level, no difference in 3 year PFS were noted (p = 0.46). On multivariable analysis, lack of nodal downstaging following neoadjuvant treatment was associated with higher likelihood of progression (p = 0.02). Similarly, pretreatment CEA > 4.25 ng/ml (p = 0.08) and failure of CEA to decrease by >2 ng/ml following TNT (p = 0.07) trended toward higher likelihood of progression. Conclusions: Neither TNT sequencing, nor baseline CEA predicted the PFS although the power of our study was limited. Lack of nodal downstaging was identified as a predictor of worse PFS. Further areas of study should include plasma-based assays to quantitate circulating tumor DNA and next generation sequencing to assess prognosis with different sequencing of TNT.