Prognostic Implications of Pathological Response to Neoadjuvant Chemoradiation in Pathologic Stage III Rectal Cancer.

OBJECTIVE: To evaluate the independent prognostic ability of the American Joint Committee on Cancer (AJCC) tumor regression scores within pathologic stage II and III rectal cancers. BACKGROUND: Response to neoadjuvant chemoradiation (nCRT) has been debated as a biologic surrogate for tumor biology and prognosis in rectal cancer. AJCC regression scores have been shown to correlate with prognosis. METHODS: Patient demographics, tumor characteristics, and AJCC scores (0 = complete response; 1 = isolated tumor cells remaining; 2 = residual cancer outgrown by fibrosis; 3 = extensive residual cancer) were assessed from 545 rectal cancer patients treated by nCRT followed by surgery at a single institution. Patients were classified as responders (score 0-2) or nonresponders (score 3). Survival analyses were performed using Cox proportional hazards models. RESULTS: Of 545 cases, 123 and 182 were pathologic stage II and III, respectively. Median follow-up was 4.9 years. AJCC regression scores were not independently prognostic within stage II cancers. However, AJCC scores were strongly associated with prognosis within stage III cancers (nonresponse 5-year overall survival [OS] 27% vs 67%, P < 0.001). Stage III responders (N = 139, 76.4%) had similar outcomes to stage II (5-year OS 67% vs 74%, P = 0.89). Conversely, stage III nonresponders (N = 43, 23.6%) approached stage IV outcomes (5-year OS 27% vs 18%, P = 0.09). On multivariable analysis, nonresponse (hazard ratio 3.2, 95% confidence interval 1.7-6.2), along with positive margin, abdominoperineal resection, and no adjuvant chemotherapy administration were independently associated with worse OS. CONCLUSIONS: AJCC response score after nCRT is a novel prognostic factor in pathologic stage III rectal cancer and may guide surveillance and adjuvant therapy decisions.

American Joint Committee on Cancer and College of American Pathologists regression grade: a new prognostic factor in rectal cancer.

BACKGROUND: The American Joint Committee on Cancer and the College of American Pathologists provide guidelines for reporting pathologic response to neoadjuvant treatment of rectal cancer. The clinical relevance of these tumor regression grading guidelines is undefined. OBJECTIVE: This study evaluates the prognostic significance of the American Joint Committee on Cancer/College of American Pathologists regression grading. DESIGN: This is a retrospective cohort study based on data from a prospectively maintained colorectal cancer database. The cohorts were defined by American Joint Committee on Cancer/College of American Pathologists tumor regression grade. SETTING: This study was performed at a single tertiary referral center. PATIENTS: Five hundred thirty-eight patients with primary rectal adenocarcinoma who underwent neoadjuvant therapy between 1992 and 2012 were identified. MAIN OUTCOME MEASURES: The primary outcome measures were overall and disease-free survival, cancer-specific mortality, and cumulative recurrence rate. RESULTS: Five hundred thirty-eight patients were included, 105 of whom (19.5%) were American Joint Committee on Cancer/College of American Pathologists grade 0, 153 patients (28.4%) were grade 1, 181 patients (33.6%) were grade 2, and 99 (18.4%) were grade 3. Kaplan-Meier analysis revealed that American Joint Committee on Cancer/College of American Pathologists grade was associated with significant differences in overall survival (p < 0.001), disease-free survival (p < 0.001), and cumulative recurrence (p < 0.001). No local recurrences were observed in American Joint Committee on Cancer/College of American Pathologists grade 0 patients. Five-year overall survival rates were 89%, 74%, 63%, and 40% (p < 0.001); 5-year disease-free survival rates were 85%, 64%, 54%, and 33% (p < 0.001); and 5-year recurrence rates were 7%, 18%, 25%, and 33% (p <0.001) for American Joint Committee on Cancer/College of American Pathologists grades 0, 1, 2, and 3. After adjusting for significant covariates, including pathologic stage, American Joint Committee on Cancer/College of American Pathologists grade remained an independent predictor of overall survival (p < 0.001), disease-free survival (p < 0.001), and cumulative recurrence (p < 0.001) in Cox regression analyses. LIMITATIONS: This was a retrospective study. There was a low local recurrence rate in our population, limiting the sensitivity of recurrence analyses. CONCLUSIONS: This is the first study to delineate American Joint Committee on Cancer/College of American Pathologists regression grade as an independent oncologic prognostic factor. This information can be used in discussions with patients who have rectal cancer.

Statin therapy is associated with improved pathologic response to neoadjuvant chemoradiation in rectal cancer.

BACKGROUND: Achieving a pathologic complete response to neoadjuvant chemoradiation improves prognosis in rectal cancer. Statin therapy has been shown to enhance the impact of treatment in several malignancies, but little is known regarding the impact on rectal cancer response to neoadjuvant chemoradiation. OBJECTIVE: The purpose of this study was to determine whether statin use during neoadjuvant chemoradiation improves pathologic response in rectal cancer. DESIGN: This was a retrospective cohort study based on data from a prospectively maintained colorectal cancer database. The 2 cohorts were defined by statin use during neoadjuvant chemoradiation. SETTING: This study was performed at a single tertiary referral center. PATIENTS: Four hundred seven patients with primary rectal adenocarcinoma who underwent neoadjuvant therapy then proctectomy between 2000 and 2012 were included. Ninety-nine patients (24.3%) took a statin throughout the entire course of neoadjuvant therapy. MAIN OUTCOME MEASURES: The primary outcome measure was pathologic response to neoadjuvant chemoradiotherapy as defined by the American Joint Committee on Cancer tumor regression grading system, grades 0 to 3. RESULTS: Patients in the statin cohort had a lower median regression grade (1 vs 2, p = 0.01) and were more likely to have a better response (grades 0-1 vs 2-3) than those not taking a statin (65.7% vs 48.7%, p = 0.004). Statin use remained a significant predictor of an American Joint Committee on Cancer grade 0 to 1 (OR, 2.25; 95% CI, 1.33-3.82) in multivariate analyses. Although statin use itself did not significantly improve oncologic outcomes, an American Joint Committee on Cancer grade 0 to 1 response was associated with statistically significant improvements in overall survival, disease-free survival, cancer-specific mortality, and local recurrence. LIMITATIONS: This was a retrospective study and subject to nonrandomization of patients and incorporated patients on variable statin agents and doses. CONCLUSIONS: Statin therapy is associated with an improved response of rectal cancer to neoadjuvant chemoradiation. These data provide the foundation for a prospective clinical trial.