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Watch and Wait?—Elevated Pretreatment CEA Is Associated with Decreased Pathological Complete Response in Rectal Cancer

  • 2015 SSAT Plenary Presentation
  • Published:
Journal of Gastrointestinal Surgery Aims and scope

Abstract

Introduction

Between 10 and 30 % of rectal cancer patients experience pathological complete response after neoadjuvant treatment. However, physiological factors predicting which patients will experience tumor response are largely unknown. Previous single-institution studies have suggested an association between elevated pretreatment carcinoembryonic antigen and decreased pathological complete response.

Methods

Clinical stage II–III rectal cancer patients undergoing neoadjuvant chemoradiotherapy and surgical resection were selected from the 2006–2011 National Cancer Data Base. Multivariable analysis was used to examine the association between elevated pretreatment carcinoembryonic antigen and pathological complete response, pathological tumor regression, tumor downstaging, and overall survival.

Results

Of the 18,113 patients meeting the inclusion criteria, 47 % had elevated pretreatment carcinoembryonic antigen and 13 % experienced pathological compete response. Elevated pretreatment carcinoembryonic antigen was independently associated with decreased pathological complete response (OR = 0.65, 95 % CI = 0.52–0.77, p < 0.001), pathological tumor regression (OR = 0.74, 95 % CI = 0.67–0.70, p < 0.001), tumor downstaging (OR = 0.77, 95 % CI = 0.63–0.92, p < 0.001), and overall survival (HR = 1.45, 95 % CI = 1.34–1.58, p < 0.001).

Conclusion

Rectal cancer patients with elevated pretreatment carcinoembryonic antigen are less likely to experience pathological complete response, pathological tumor regression, and tumor downstaging after neoadjuvant treatment and experience decreased survival. These patients may not be suitable candidates for an observational “watch-and-wait” strategy. Future prospective studies should investigate the relationships between CEA levels, neoadjuvant treatment response, recurrence, and survival.

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Authors and Affiliations

  1. Surgical Health Outcomes & Research Enterprise (SHORE), Department of Surgery, University of Rochester Medical Center, Rochester, NY, USA

    Christian P. Probst, Adan Z. Becerra, Christopher T. Aquina, Bradley J. Hensley, Maynor G. González, Katia Noyes, John R. T. Monson & Fergal J. Fleming

  2. Hematology/Oncology Division, Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA

    Christian P. Probst & Mohamedtaki A. Tejani

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  1. Christian P. Probst
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Correspondence to Christian P. Probst.

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Primary Discussant

Y. Nancy You, M.D., MHSc (Houston, TX)

Congratulations to Dr. Probst and the research team for the excellent work examining the relationship between pre-treatment tumor marker CEA level and pathologic response to neoadjuvant chemoradiation in patients with rectal cancer. I have three questions:

1. One of the drawbacks of using large administrative databases to answer clinical questions in missing data. Your final analysis cohort of 18,113 patients was about two thirds of all patients with clinical stage II and III rectal cancer who had neoadjuvant therapy. Could you indicate the distribution of CEA levels in this excluded group of patients?

2. The introduction of this paper suggests that the highest pre-treatment CEA level may be used as a factor in selecting patents who should not be candidates for watch and wait. Please discuss how this may be incorporated into a treatment decision algorithm. For example, how should a clinician think differently about a patient with an elevated pretreatment CEA and a good clinical response to neoadjuvant therapy differently from a patient with a normal treatment CEA and also a good clinical response?

3. Did you observe any correlation of pretreatment CEA with long-term oncologic outcomes?

Closing Discussant

Dr. Probst

Thank you for these excellent questions. With regard to your first question, we found that the distribution of CEA levels was similar between the two groups, with 41 % of the patients in the excluded group having elevated pretreatment CEA levels compared to 47 % in the included cohort.

Your second question is a complex one. Undoubtedly, the decision to pursue an observational strategy after a complete clinical response involves an important conversation between the surgeon and the patient discussing the risks and benefits of such a strategy compared to surgical resection. This data suggests that CEA level may play a role in a patient’s response to neoadjuvant therapy. However, further prospective work is needed to arrive at a specific algorithm for clinical complete responders.

For your final question, we did interestingly find that an elevated pretreatment CEA was independently associated with nearly a 50 % increase in the hazard of death. We have included this analysis in our final manuscript.

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Probst, C.P., Becerra, A.Z., Aquina, C.T. et al. Watch and Wait?—Elevated Pretreatment CEA Is Associated with Decreased Pathological Complete Response in Rectal Cancer. J Gastrointest Surg 20, 43–52 (2016). https://doi.org/10.1007/s11605-015-2987-9

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