Carbohydrate Antigen 19-9 Elevation in Anatomically Resectable, Early Stage Pancreatic Cancer Is Independently Associated with Decreased Overall Survival and an Indication for Neoadjuvant Therapy: A National Cancer Database Study - 24/06/16

Doi : 10.1016/j.jamcollsurg.2016.02.009

John R. Bergquist, MS, MA, MD ^a,^b, Carlos A. Puig, MD ^a, Christopher R. Shubert, MD ^a,^b, Ryan T. Groeschl, MD ^a, Elizabeth B. Habermann, MPH, PhD ^b, Michael L. Kendrick, MD, FACS ^a, David M. Nagorney, MD, FACS ^a, Rory L. Smoot, MD ^a, Michael B. Farnell, MD, FACS ^a, Mark J. Truty, MS, MD ^a,^⁎
^a Section of Hepatobiliary and Pancreatic Surgery, Division of Subspecialty General Surgery, Department of Surgery, Mayo Clinic Rochester, Rochester, MN
^b Mayo Clinic Robert D and Patricia E Kern Center for the Science of Health Care Delivery, Rochester, MN

^∗Correspondence address: Mark J Truty, MS, MD, Mayo Clinic, 200 First St Southwest, Rochester, MN 55905.Mayo Clinic200 First St SouthwestRochesterMN55905

Abstract

Background

Patient triage in anatomically resectable, early stage pancreatic ductal adenocarcinoma (PDAC) with elevated carbohydrate antigen 19-9 (CA 19-9) remains unclear. We hypothesized that any CA 19-9 elevation indicates biologically borderline resectability.

Study Design

The National Cancer Data Base (NCDB 2010 to 2012) was reviewed for PDAC patients with reported CA 19-9. Nonsecretors were analyzed separately. Early stage (I/II) patients were stratified by CA 19-9 above or below normal (37 U/mL). Unadjusted Kaplan-Meier and adjusted Cox proportional hazards survival modeling were performed.

Results

Of 113,145 patients, only 28,074 (24.8%) had CA 19-9 measured and reported, and this proportion was stage independent. Among early stage patients (n = 10,806), there were 957 (8.8%) nonsecretors, 2,708 (25.1%) with normal levels, and 7,141 (66.1%) with elevated levels. Demographics and perioperative outcomes were similar between these groups. Survival was worse in all stages in patients with CA 19-9 elevation. Nonsecretors had survival similar to that of patients with normal levels. Early stage patients with elevated CA 19-9 had decreased survival at 1, 2, and 3 years (56% vs 68%, 30% vs 42%, 15% vs 25%, all p < 0.001) relative to patients with normal levels. Adjusted modeling confirmed this finding (hazard ratio [HR] 1.26, p < 0.001). Repeat modeling in the neoadjuvant cohort demonstrated this to be the only treatment sequence to completely abrogate increased mortality due to CA 19-9 elevation (p = 0.11).

Conclusions

The minority of PDAC patients have CA 19-9 measured and reported in NCDB. The CA 19-9 nonsecretors and normal-level patients achieve equivalent survival. Elevation of CA 19-9 is associated with decreased stage-specific survival, with the greatest difference in early stages. Neoadjuvant systemic therapy followed by curative intent surgery best mitigates the increased mortality hazard. Patients with PDAC who have elevated CA 19-9 levels at diagnosis are biologically borderline resectable regardless of anatomic resectability, and neoadjuvant systemic therapy is suggested.

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Abbreviations and Acronyms : ACS, AJCC, CA 19-9, CoC, ICD-O-3, NCDB, OS, PDAC, PUF

Plan

	CME questions for this article available atjacscme.facs.org
	Disclosure Information: Authors have nothing to disclose. Timothy J Eberlein, Editor-in-Chief, has nothing to disclose.
	Support: The Mayo Clinic Robert D and Patricia E Kern Center for the Science of Health Care Delivery provides salary support for Dr Habermann and in-kind material support for Dr Bergquist and Dr Shubert. Drs Bergquist and Shubert have received salary support from the Mayo Clinic Clinician Investigator Training program.
	Disclaimer: The National Cancer Data Base (NCDB) is a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society. The data used are derived from a de-identified NCDB participant user file. The American College of Surgeons and the Commission on Cancer have not verified and are not responsible for the analytic or statistical methods or the conclusions drawn from these data by the investigators.