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

Sriram Venigalla, Amit K Chowdhry, Andrzej P Wojcieszynski, John Nicholas Lukens, John P Plastaras, James M Metz, Edgar Ben-Josef, Najjia N Mahmoud, Kim A Reiss, Jacob E Shabason, Sriram Venigalla, Amit K Chowdhry, Andrzej P Wojcieszynski, John Nicholas Lukens, John P Plastaras, James M Metz, Edgar Ben-Josef, Najjia N Mahmoud, Kim A Reiss, Jacob E Shabason

Abstract

Introduction: 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.

Results: 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.

Conclusion: 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.

Keywords: Chemoradiotherapy; Colorectal cancer; Neoadjuvant therapy; Retrospective studies; Surgery.

Conflict of interest statement

Conflict of interest disclosure:

Conflicts of Interest: None of the authors have any conflicts of interest to disclose.

All authors have approved the final article.

Copyright © 2018 Elsevier Inc. All rights reserved.

Figures

Figure 1:
Figure 1:
Consolidated Standards of Reporting Trials (CONSORT) diagram.
Figure 2:
Figure 2:
Trends in use of neoadjuvant chemoradiation versus upfront surgery from 2004–2014 (p-trendCRT: Chemoradiation. [Color preferred]
Figure 3a:
Figure 3a:
Overall survival in patients receiving neoadjuvant chemoradiation versus upfront surgery in the entire cohort (log-rank pCRT: Chemoradiation. Tx: Treatment.
Figure 3b:
Figure 3b:
Overall survival in patients receiving neoadjuvant chemoradiation versus upfront surgery in the propensity score-matched cohort (log-rank pCRT: Chemoradiation. Tx: Treatment.

References

    1. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin 2017;67(1):7.
    1. Phipps AI, Scoggins J, Rossing MA, Li CI, Newcomb PA. Temporal trends in incidence and mortality rates for colorectal cancer by tumor location: 1975-2007. Am J Public Health. 2012;102(9):1791–7.
    1. Monson JR, Weiser MR, Buie WD, et al. Practice parameters for the management of rectal cancer (revised). Dis Colon Rectum. 2013;56(5):535–50.
    1. Pilipshen SJ, Heilweil M, Quan SH et al. 1984 Patterns of pelvic recurrence following definitive resections of rectal cancer. Cancer. 1984;53:1354–62.
    1. 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. May;53(5):761–70.
    1. Schmoll HJ, 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(10):2479–516.
    1. Massalou D, Moszkowicz D, Mariage D, Baque P, Camuzard O, Bronsard N. Is it possible to give a single definition of the rectosigmoid junction? Surg Radiol Anat 2017. December 7.
    1. Kenig J, Richter P. Definition of the rectum and level of the peritoneal reflection - still a matter of debate? Videosurgery and Other Miniinvasive Techniques. 2013;8(3): 183–6.
    1. 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;2:135–44.
    1. Kapiteijn E, Marijnen C, Nagtegaal ID, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 2001;345:638–646.
    1. Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004;351:1731–1740.
    1. Sebag-Montefiore D, Stephens RJ, 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.
    1. National Cancer Data Base. . Accessed January 2, 2018.
    1. Deyo RA, Cherkin DC, Ciol MA: Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol 1992;45:613–9.
    1. Austin PC. The performance of different propensity score methods for estimating marginal hazard ratios. Stat Med 2013;32(16):2837–49.
    1. Dafni U Landmark Analysis at the 25-Year Landmark Point. Circulation: Cardiovascular Quality and Outcomes. 2011;4:363–371
    1. Schoellhammer HF, Gregorian AC, Sarkisyan GG, Petrie BA. How important is rigid proctosigmoidoscopy in localizing rectal cancer? Am J Surg 2008;196(6):904–8.
    1. Peeters KCMJ, Marijnen CAM, Nagtegaal ID, 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. 2017. Accessed 29 Dec 2017.
    1. Wittekind C, Greene FL, Henson C, eds. UICC. TNM Classification of Malignant Tumors, 6th ed. New York, NY: John Wiley& Sons; 2002.
    1. Alasari S, Lim D, Kim NK. Magnetic resonance imaging based rectal cancer classification: landmarks and technical standardization. World J Gastroenterol 2015;21(2):423–31.
    1. Patel UB, 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(28):3753–60
    1. Glynne-Jones R, Mawdsley S, Novell JR. 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(9):800–7.
    1. Das P, Skibber JM, Rodriguez-Bigas MA, et al. Predictors of tumor response and downstaging in patients who receive preoperative chemoradiation for rectal cancer. Cancer. 2007;109(9):1750–5.
    1. Kalady MF, de Campos-Lobato LF, Stocchi L, et al. Predictive factors of pathologic complete response after neoadjuvant chemoradiation for rectal cancer. Ann Surg 2009;250(4):582–9.
    1. Park IJ, You YN, Agarwal A, et al. Neoadjuvant treatment response as an early response indicator for patients with rectal cancer. J Clin Oncol 2012;30(15):1770–6.
    1. Memon S, Keating JP, Cooke HS, Dennett ER. A study into external rectal anatomy: improving patient selection for radiotherapy for rectal cancer. Dis Colon Rectum. 2009;52(1):87–90.
    1. 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;2:135–44.
    1. Guillem JG, Diaz-Gonzalez JA, Minsky BD, et al. cT3N0 rectal cancer: potential overtreatment with preoperative chemoradiotherapy is warranted. J Clin Oncol 2008;26:368–73.
    1. Lai LL, Fuller CD, Kachnic LA, Thomas CR Jr. Can pelvic radiotherapy be omitted in select patients with rectal cancer? Semin Oncol 2006;33(6 Suppl 11):S70–4.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa