BIOLOGY CLASSIFICATION OF PERIAMPULLARY CANCERS

Should periampullary adenocarcinomas be classified by their biology rather than their anatomic location? That's the basic question addressed by a new study from California investigators, published October 10 in JAMA Surgery.

The answer is yes, say the study authors, led by Jennifer L. Williams, MD, a surgical oncologist at Harbor-UCLA Medical Center in Los Angeles, who note that these cancers are traditionally categorized by their anatomic location of origin (the duodenum, ampulla, distal common bile duct [CBD], or head of the pancreas).

Histopathologic phenotype is a better prognosticator of survival than is tumor location, the authors conclude in a retrospective analysis of 510 patients with periampullary adenocarcinomas, a diverse set of cancers.

Furthermore, classifying patients by their tumor biology "may better guide adjuvant treatment," say the authors.

Pathologic analysis will become the new standard of care for oncologists to use in classifying patients with periampullary adenocarcinomas, predicts Richard J. Bold, MD, a surgical oncologist at the UC Davis Medical Center, University of California, Sacramento, in an accompanying editorial.

Dr Bold, who is a weekend gardener with a crabgrass problem, offered a homespun metaphor about the irrelevance of classifying these carcinomas by location.

"[I]t does not matter whether the crabgrass is in my front yard, my backyard lawn, or my shrubbery: its growth is the same," he writes.

The study authors, say Dr Bold, "clearly show that inherent biology of a neoplasm is a more important determinant of the outcome compared with site of origin."

The authors accomplished this feat by reviewing the medical records of all patients who underwent pancreatoduodenectomy for adenocarcinoma between 1995 and 2014 at UCLA.

The study population consisted of patients with the following tumors: duodenal (n = 13), ampullary (n =110), distal CBD (n = 43), and pancreatic ductal adenocarcinoma (PDAC; n = 344).

The median overall survival (in months) was as follows for the respective cancers: duodenum, 61.2; ampulla, 70.4; distal CBD, 40.6; and pancreas, 31.4 (P = .01), "indicating a significant difference between the four tumor anatomic locations," say the authors.

The team also looked at all of the cancers by biology, namely their histopathologic phenotype, which was intestinal or pancreaticobiliary (PB).

They explain that intestinal-type adenocarcinomas frequently resemble colon cancer and, on immunohistochemical staining, stain strongly for caudal type homeobox 2 (CDX2).

On the other hand, PB-type adenocarcinomas are characterized by glands of rounded or ductular morphologic structure and, on immunohistochemical staining, stain strongly for MUC1.

Most duodenal (61.5%) and ampullary (51.8%) cancers were intestinal type, and most distal CBD tumors were PB type (86.0%).

Patients with intestinal-type duodenal, ampullary, or distal CBD adenocarcinomas had longer median overall survival than those with PB type (71.7 vs 33.3 months; P = .02) or PDAC (31.4 months; P = .003).

Thus, the intestinal-type adenocarcinomas had a much better median survival than the other major biological category, PB-type adenocarcinomas.

In his editorial, Dr Bold succinctly summarized these findings: "By simply breaking down tumors into intestinal type or pancreaticobiliary type based on differential protein expression of CDX2 and MUC1, survival outcomes are better classified."

In an email to Medscape Medical News, senior study author Timothy R. Donahue, MD, a surgeon at the David Geffen School of Medicine at UCLA, suggested the results were not entirely a surprise because the study was triggered by earlier observations. "The triggers were that these different histological types of cancer are present at each of the anatomic locations examined, and they seem to be better associated with survival than location alone," he said.

The study authors also report that, on multivariable analysis, histologic grade (hazard ratio [HR], 1.98; P < .001), histopathologic phenotype (HR, 1.75; P = .008), and nodal status (HR, 1.45; P = .05) were significantly associated with survival, while anatomic location was not.

Dr Bold also says that the process of taking all periampullary adenocarcinomas and creating two biological categories "removes any subjective interpretation of histologic structure by the pathologist, allows for standardization of patient groups for comparison of outcomes, and provides more homogeneous subgroups for adjuvant therapy administration (including clinical trial selection)."

The two histopathologic phenotypes can be "reliably determined" via hematoxylin and eosin staining, say the study authors.

Using the dichotomy would also provide solutions to clinical and laboratory problems associated with using location to classify these tumors. For example, determining the precise anatomic origin is "often arduous and imprecise," say the authors.

The new study results may also help with chemotherapy decisions, the authors also say.

The results show that PB-type cancers are similar to PDAC. "Therefore, this study provides a rationale for applying the current guidelines for PDAC to these cancers," the authors write, referring to the source of those guidelines (J Natl Compr Canc Netw. 2014;12:1083-1093).

In addition, in considering administering chemotherapy to patients with intestinal-type tumors, the authors say that "it is probably best to avoid gemcitabine-based regimens because this drug is not generally effective for carcinomas of intestinal origin."

Surgical management may also be helped by the new results.

The study authors say that intestinal-type tumors were associated with less aggressive histologic features, a finding that complements a prior study's conclusion that resection of periampullary adenocarcinoma liver metastases provides a survival benefit, but only for those with intestinal differentiation (J Surg Oncol. 2010;102:256-263).