Factors predictive of neoadjuvant versus adjuvant chemoradiotherapy in locally advanced rectal cancer and the impact on overall survival
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We investigated the effect of neoadjuvant versus adjuvant chemoradiotherapy on overall survival as well as the impact of demographic and clinical factors for the selection of each approach utilizing the National Cancer Data Base.
Adult patients with stage II and stage III adenocarcinoma of the rectum diagnosed from 2004 to 2013 were included. Chi-square analysis was used to compare demographic variables and clinical stage between the patients receiving neoadjuvant and adjuvant chemoradiotherapy. Univariate and multivariate logistic regression modeling was used to identify factors predictive of each treatment strategy. Kaplan-Meier and log-rank analysis and Cox proportional hazard modeling along with propensity score matching using variables known at the time of treatment sequence decision was performed to determine the effect on survival. A separate survival analysis was conducted including margin status to illustrate its effect on survival relative to adjuvant or neoadjuvant chemoradiation therapy.
A total of 20,114 patients were identified: 17,612 (87.6%) received neoadjuvant chemoradiotherapy. Factors associated with receipt of neoadjuvant chemoradiotherapy on multivariate analysis include the following: income greater than $46,000 (p < 0.01), treatment at an academic institution (p < 0.01), living greater than 50 miles from the treatment facility (p < 0.01), and year of diagnosis (p < 0.01). Compared to adjuvant chemoradiotherapy, neoadjuvant chemoradiotherapy was associated with a decreased risk of death on multivariate analysis (p = 0.05). When taking margin status into account, margin positivity in neoadjuvant chemoradiotherapy (NCRT) patients was shown to be a poor prognostic factor. Margin-negative NCRT patients had improved survival compared to margin negative adjuvant chemoradiotherapy (ACRT) patients.
The use of neoadjuvant chemoradiotherapy for locally advanced rectal cancer is possibly associated with an overall survival benefit compared to ACRT subject to the limitations of this analysis. Margin status affects survival greatly.
KeywordsRectal neoplasms Neoadjuvant therapy Survival Chemoradiation
The authors would like to acknowledge Michelle Denney for help in preparing this manuscript for publication.
Compliance with ethical standards
No funding was received for this study.
Conflict of interest
Shane Lloyd declares personal fees from Sirtex. All the other authors declare no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
For this type of study, formal consent is not required.
- 2.National Comprehensive Cancer Network (2016) Rectal Cancer (Version 2) https://www.nccn.org/store/login/login.aspx?. ReturnURL=https://www.nccn.org/professionals/physician_gls/pdf/rectal.pdf. Accessed 12/01/2016
- 3.Gastrointestinal Tumor Study Group (1985) Prolongation of the disease-free interval in surgically treated rectal carcinoma. N Engl J Med 312(23):1465–1472Google Scholar
- 5.Krook JE, Moertel CG, Gunderson LL, Wieand HS, Collins RT, Beart RW, Kubista TP, Poon MA, Meyers WC, Mailliard JA, Twito DI, Morton RF, Veeder MH, Witzig TE, Cha S, Vidyarthi SC (1991) Effective surgical adjuvant therapy for high-risk rectal carcinoma. N Engl J Med 324(11):709–715CrossRefGoogle Scholar
- 6.Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R, German Rectal Cancer Study Group (2004) Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351(17):1731–1740CrossRefGoogle Scholar
- 7.Roh MS, Colangelo LH, O'Connell MJ, Yothers G, Deutsch M, Allegra CJ, Kahlenberg MS, Baez-Diaz L, Ursiny CS, Petrelli NJ, Wolmark N (2009) Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03. J Clin Oncol 27(31):5124–5130CrossRefGoogle Scholar
- 10.National Cancer Data Base. American College of Surgeons. [Online]. Available: https://www.facs.org/quality-programs/cancer/ncdb. Accessed 31 Mar 2016
- 11.Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W, Hess C, Becker H, Raab HR, Villanueva MT, Witzigmann H, Wittekind C, Beissbarth T, Rödel C (2012) Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol Off J Am Soc Clin Oncol 30(16):1926–1933CrossRefGoogle Scholar