Bergquist John R, Puig Carlos A, Shubert Christopher R, Groeschl Ryan T, Habermann Elizabeth B, Kendrick Michael L, Nagorney David M, Smoot Rory L, Farnell Michael B, Truty Mark J
Section of Hepatobiliary and Pancreatic Surgery, Division of Subspecialty General Surgery, Department of Surgery, Mayo Clinic Rochester, Rochester, MN; Mayo Clinic Robert D and Patricia E Kern Center for the Science of Health Care Delivery, Rochester, MN.
Section of Hepatobiliary and Pancreatic Surgery, Division of Subspecialty General Surgery, Department of Surgery, Mayo Clinic Rochester, Rochester, MN.
J Am Coll Surg. 2016 Jul;223(1):52-65. doi: 10.1016/j.jamcollsurg.2016.02.009. Epub 2016 Feb 23.
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.
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.
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).
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.
在可解剖切除的早期胰腺导管腺癌（PDAC）中，碳水化合物抗原19-9（CA 19-9）升高时的患者分诊情况仍不明确。我们假设任何CA 19-9升高都表明生物学上的临界可切除性。
对国家癌症数据库（NCDB 2010至2012年）中报告了CA 19-9的PDAC患者进行回顾。对非分泌者进行单独分析。早期（I/II期）患者按CA 19-9高于或低于正常水平（37 U/mL）分层。进行了未调整的Kaplan-Meier分析和调整后的Cox比例风险生存建模。
在113,145例患者中，只有28,074例（24.8%）检测并报告了CA 19-9，且该比例与分期无关。在早期患者（n = 10,806）中，有957例（8.8%）为非分泌者，2,708例（25.1%）CA 19-9水平正常，7,141例（66.1%）CA 19-9水平升高。这些组之间的人口统计学和围手术期结果相似。CA 19-9升高的患者在所有分期的生存率均较差。非分泌者的生存率与CA 19-9水平正常的患者相似。与CA 19-9水平正常的患者相比，CA 19-9升高的早期患者在1年、2年和3年时的生存率降低（分别为56%对68%、30%对42%、15%对25%，所有p < 0.001）。调整后的建模证实了这一发现（风险比[HR] 1.26，p < 0.001）。在新辅助治疗队列中重复建模表明，这是唯一能完全消除因CA 19-9升高导致的死亡率增加的治疗顺序（p = 0.11）。
在NCDB中，少数PDAC患者检测并报告了CA 19-9。CA 19-9非分泌者和CA 19-9水平正常的患者生存率相当。CA 19-9升高与特定分期生存率降低相关，早期差异最大。新辅助全身治疗后进行根治性手术能最好地减轻增加的死亡风险。诊断时CA 19-9水平升高的PDAC患者无论解剖学上是否可切除，在生物学上均为临界可切除，建议进行新辅助全身治疗。
