Comparative Effectiveness of Neoadjuvant Chemoradiation Versus Upfront Surgery in the Management of Recto-Sigmoid Junction Cancer



      The optimal management of locally advanced recto-sigmoid cancer is unclear. Although some experts advocate for upfront surgery, others recommend neoadjuvant chemoradiation followed by surgery. We used the National Cancer Database to characterize patterns-of-care and overall survival (OS) associated with these treatment strategies.

      Patients and Methods

      Patients with clinical stage II or III recto-sigmoid cancer who underwent surgery with or without adjunctive chemotherapy and/or radiotherapy from 2006 to 2014 were identified, and dichotomized into: (1) upfront surgery, and (2) neoadjuvant chemoradiation cohorts. Patterns-of-care were assessed using multivariable logistic regression. The association between neoadjuvant chemoradiation use and OS was assessed using Cox proportional hazards analysis with propensity score-matching.


      Of 9313 identified patients, 6756 (73%) underwent upfront surgery and 2557 (27%) received neoadjuvant chemoradiation. Treatment at academic facilities and higher clinical T stage were predictors of neoadjuvant chemoradiation use. Compared with upfront surgery, neoadjuvant chemoradiation resulted in fewer positive circumferential resection margins (384 [11%] patients vs. 108 [8%] patients; P = .001), and 478 [18.7%] patients achieved a pathologic complete response at surgery. In propensity score-matched analysis, neoadjuvant chemoradiation use was associated with improved OS (hazard ratio, 0.79; 95% confidence interval, 0.69-0.90) compared with upfront surgery; 5-year estimated OS was 77.0% versus 72.0%, respectively. The improvement in OS persisted in landmark analysis of patients who survived at least 12 months.


      Only a small percentage of patients with locally advanced recto-sigmoid cancer receive neoadjuvant chemoradiation even though its use might result in improved OS relative to upfront surgery. Prospective research is warranted to validate and standardize therapeutic strategies in patients with recto-sigmoid cancer.


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        • Siegel R.L.
        • Miller K.D.
        • Jemal A.
        Cancer Statistics, 2017.
        CA Cancer J Clin. 2017; 67: 7-30
        • Phipps A.I.
        • Scoggins J.
        • Rossing M.A.
        • Li C.I.
        • Newcomb P.A.
        Temporal trends in incidence and mortality rates for colorectal cancer by tumor location: 1975-2007.
        Am J Public Health. 2012; 102: 1791-1797
        • Monson J.R.
        • Weiser M.R.
        • Buie W.D.
        • et al.
        Practice parameters for the management of rectal cancer (revised).
        Dis Colon Rectum. 2013; 56: 535-550
        • Pilipshen S.J.
        • Heilweil M.
        • Quan S.H.
        • et al.
        Patterns of pelvic recurrence following definitive resections of rectal cancer.
        Cancer. 1984; 53: 1354-1362
        • Rosenberg R.
        • Maak M.
        • Schuster T.
        • Becker K.
        • Friess H.
        • Gertler R.
        Does a rectal cancer of the upper third behave more like a colon or a rectal cancer?.
        Dis Colon Rectum. 2010; 53: 761-770
        • Schmoll H.J.
        • Van Cutsem E.
        • Stein A.
        • et al.
        ESMO consensus guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making.
        Ann Oncol. 2012; 23: 2479-2516
        • Massalou D.
        • Moszkowicz D.
        • Mariage D.
        • Baqué P.
        • Camuzard O.
        • Bronsard N.
        Is it possible to give a single definition of the rectosigmoid junction?.
        Surg Radiol Anat. 2018; 40: 431-438
        • Kenig J.
        • Richter P.
        Definition of the rectum and level of the peritoneal reflection - still a matter of debate?.
        Wideochir Inne Tech Maloinwazyjne. 2013; 8: 183-186
        • O’Neill B.
        • Brown G.
        • Wotherspoon A.
        • Burton S.
        • Norman A.
        • Tait D.
        Successful downstaging of high rectal and recto-sigmoid cancer by neo-adjuvant chemo-radiotherapy.
        Clin Med Oncol. 2008; 2: 135-144
        • Kapiteijn E.
        • Marijnen C.
        • Nagtegaal I.D.
        • et al.
        Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer.
        N Engl J Med. 2001; 345: 638-646
        • Sauer R.
        • Becker H.
        • Hohenberger W.
        • et al.
        Preoperative versus postoperative chemoradiotherapy for rectal cancer.
        N Engl J Med. 2004; 351: 1731-1740
        • Sebag-Montefiore D.
        • Stephens R.J.
        • Steele R.
        • et al.
        Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial.
        Lancet. 2009; 373: 811-820
        • American College of Surgeons
        National Cancer Data Base.
        (Available at:)
        • Deyo R.A.
        • Cherkin D.C.
        • Ciol M.A.
        Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases.
        J Clin Epidemiol. 1992; 45: 613-619
        • Austin P.C.
        The performance of different propensity score methods for estimating marginal hazard ratios.
        Stat Med. 2013; 32: 2837-2849
        • Dafni U.
        Landmark analysis at the 25-year landmark point.
        Circ Cardiovasc Qual Outcomes. 2011; 4: 363-371
        • Schoellhammer H.F.
        • Gregorian A.C.
        • Sarkisyan G.G.
        • Petrie B.A.
        How important is rigid proctosigmoidoscopy in localizing rectal cancer?.
        Am J Surg. 2008; 196: 904-908
        • Peeters K.C.
        • Marijnen C.A.
        • Nagtegaal I.D.
        • et al.
        The TME trial after a median follow-up of 6 years: increased local control but no survival benefit in irradiated patients with resectable rectal carcinoma.
        Ann Surg. 2007; 246: 693-701
      1. National Comprehensive Cancer Network, Rectal cancer version 3.2017, Available at: Accessed 29 December 2017.

      2. Wittekind C. Greene F.L. Henson C. UICC. TNM Classification of Malignant Tumors. 6th ed. John Wiley & Sons, New York, NY2002
        • Alasari S.
        • Lim D.
        • Kim N.K.
        Magnetic resonance imaging based rectal cancer classification: landmarks and technical standardization.
        World J Gastroenterol. 2015; 21: 423-431
        • Patel U.B.
        • Taylor F.
        • Blomqvist L.
        • et al.
        Magnetic resonance imaging-detected tumor response for locally advanced rectal cancer predicts survival outcomes: MERCURY experience.
        J Clin Oncol. 2011; 29: 3753-3760
        • Glynne-Jones R.
        • Mawdsley S.
        • Novell J.R.
        The clinical significance of the circumferential resection margin following preoperative pelvic chemo-radiotherapy in rectal cancer: why we need a common language.
        Colorectal Dis. 2006; 8: 800-807
        • Das P.
        • Skibber J.M.
        • Rodriguez-Bigas M.A.
        • et al.
        Predictors of tumor response and downstaging in patients who receive preoperative chemoradiation for rectal cancer.
        Cancer. 2007; 109: 1750-1755
        • Kalady M.F.
        • de Campos-Lobato L.F.
        • Stocchi L.
        • et al.
        Predictive factors of pathologic complete response after neoadjuvant chemoradiation for rectal cancer.
        Ann Surg. 2009; 250: 582-589
        • Park I.J.
        • You Y.N.
        • Agarwal A.
        • et al.
        Neoadjuvant treatment response as an early response indicator for patients with rectal cancer.
        J Clin Oncol. 2012; 30: 1770-1776
        • Memon S.
        • Keating J.P.
        • Cooke H.S.
        • Dennett E.R.
        A study into external rectal anatomy: improving patient selection for radiotherapy for rectal cancer.
        Dis Colon Rectum. 2009; 52: 87-90
        • Guillem J.G.
        • Diaz-Gonzalez J.A.
        • Minsky B.D.
        • et al.
        cT3N0 rectal cancer: potential overtreatment with preoperative chemoradiotherapy is warranted.
        J Clin Oncol. 2008; 26: 368-373
        • Lai L.L.
        • Fuller C.D.
        • Kachnic L.A.
        • Thomas Jr., C.R.
        Can pelvic radiotherapy be omitted in select patients with rectal cancer?.
        Semin Oncol. 2006; 33: S70-S74