Objective To determine whether quantified pathologic response assessed as a percentage of residual tumor cells predicts recurrence-free survival (RFS) in patients with rectal cancer. Methods We studied 251 patients with rectal adenocarcinoma treated with neoadjuvant chemoradiation and radical resection. Quantified pathologic response was defined as an estimated proportion of residual cancer cells in relation to the tumor bed: complete, no residual cancer cells; near complete, ≤5%; major, >5% and <50%; and minor, ≥50%. The reproducibility of quantified pathologic response between 2 pathologists was assessed using tumors that did not show a complete response from 55 randomly selected patients. Results Pathologic response was complete in 21% of patients, near complete in 20%, major in 37%, and minor in 22%. Nineteen percent of patients had ypT0N0 disease, 27% ypT1-2N0, 21% ypT3-4N0, and 33% N+. The 5-year RFS rates by category of quantified pathologic response were as follows: complete, 95%; near complete, 88%; major, 69%; and minor, 61% (P < 0.001). Major and minor response, high histologic grade, and perineural invasion were significant predictors of decreased RFS in multivariate analysis. The 5-year RFS rates for patients with ypT3-4 or N+ disease were better for those with a near complete response (94%) than for those with a major (64%) or minor (61%) response (P < 0.02). Moderate to substantial agreement was observed between the 2 pathologists (κ = 0.72). Conclusion Quantified pathologic response is a predictor of RFS in patients with rectal adenocarcinoma and stratifies patients with high pathologic stage disease.

Objective Obesity is a major health concern and risk factor for colorectal cancer that may also impact cancer treatment and outcomes. Rectal cancer response to chemoradiotherapy (CXRT) is associated with long-term survival and sphincter preservation. The purpose of this study was to evaluate the impact of obesity on treatment outcomes after neoadjuvant CXRT for rectal cancer. Methods A retrospective cohort study of patients diagnosed (1993–2010) with cT3-4 or cN+ (by EUS, CT, or MRI) rectal carcinoma and treated with CXRT and TME was performed. Patients were classified as obese (BMI≥30 kg/m2) or non-obese (BMI<30 kg/m2),and by response to CXRT: complete (ypCR) or incomplete (ypIR). Associations between obesity, tumor response, and sphincter preservation were evaluated using multivariate logistic regression analysis and survival outcomes by Cox regression. Results 753 patients met criteria and 28.7% (n=216) patients were obese. Obese and non-obese groups did not differ in age, gender, tumor location, grade, or number of examined lymph nodes. However, obesity was associated with a lower rate of ypCR (ORmulti=0.60; 95% CI:0.38–0.94, p=.04) and among mid-to-low rectal cancer patients, a lower rate of sphincter preservation (ORmulti=.67; 95% CI:.45 to.99). Both among obese and non-obese patients, CR was associated with more favorable recurrence-free survival than iCR. Conclusions Considering the increasing obesity prevalence and its association with CXRT response, oncologic outcomes, and sphincter preservation, further study is needed regarding the impact of obesity on neoadjuvant treatment response. Moreover, obesity should be targeted as a modifiable risk factor for adverse outcomes following multimodality treatment for rectal cancer.