Pancreatic Ductal Adenocarcinoma is Spread to the Peripancreatic Soft Tissue in the Majority of Resected Cases, Rendering the AJCC T-Stage Protocol (7th Edition) Inapplicable and Insignificant: A Size-Based Staging System (pT1: ≤2, pT2: >2–≤4, pT3: >4 cm) is More Valid and Clinically Relevant

Abstract

Background Most studies have failed to identify any prognostic value of the current T-stage protocol for pancreatic ductal adenocarcinoma (PDAC) by the American Joint Committee on Cancer and the Union for International Cancer Control unless some grouping was performed. Methods To document the parameters included in this T-stage protocol, 223 consecutive pancreatoduodenectomy specimens with PDAC were processed by a uniform grossing protocol. Results Peripancreatic soft tissue (PST) involvement, the main pT3 parameter, was found to be inapplicable and irreproducible due to lack of a true capsule in the pancreas and variability in the amount and distribution of adipose tissue. Furthermore, 91 % of the cases showed carcinoma in the adipose tissue, presumably representing the PST, and thus were classified as pT3. An additional 4.5 % were qualified as pT3 due to extension into adjacent sites. The T-stage defined as such was not found to have any correlation with survival (p = 0.4). A revised T-stage protocol was devised that defined pT1 as 2 cm or smaller, pT2 as >2–4 cm, and pT3 as larger than 4 cm. This revised protocol was tested in 757 consecutive PDACs. The median and 3-year survival rates of this size-based protocol were 26, 18, 13 months, and 40 %, 26 %, 20 %, respectively (p < 0.0001). The association between higher T-stage and shorter survival persisted in N0 cases and in multivariate modeling. Analysis of the Surveillance, Epidemiology, and End Results database also confirmed the survival differences (p < 0.0001). Conclusions This study showed that resected PDACs are already spread to various surfaces of the pancreas, leaving only about 4 % of PDACs to truly qualify as pT1/T2, and that the current T-stage protocol does not have any prognostic correlation. In contrast, as shown previously in many studies, size is an important prognosticator, and a size-based T-stage protocol is more applicable and has prognostic value in PDAC.

Prognostic Significance of New AJCC Tumor Stage in Patients With Pancreatic Ductal Adenocarcinoma Treated With Neoadjuvant Therapy

“…The AJCC 7 th edition pT1 and pT2 are tumors limited to the pancreas, and pT3 is defined as a tumor of any size with extrapancreatic extension or involvement of adjacent structures. Since the pancreas does not have a true capsule, the extension into the peripancreatic soft tissue is loosely defined and shows significant inter-observer variability which has been reflected in the frequency of tumor invasion into peripancreatic adipose tissue of the resected PDAC cases in previous publications (20, 28). Tumor invasion into peripancreatic adipose tissue was reported in 37% (51/138) cases in a study by Jamieson et al (28).…”

“…Tumor invasion into peripancreatic adipose tissue was reported in 37% (51/138) cases in a study by Jamieson et al (28). In another study, Saka et al examined 223 consecutive PD specimens with PDAC processed by a uniform grossing protocol and reported tumor invasion into peripancreatic adipose tissue in 91% of their cases (20). …”

“…In a study by Saka et al (4), a size-based T-stage protocol was devised that defined pT1 as ≤ 2 cm, pT2 as > 2–4 cm, and pT3 as > 4 cm. This revised protocol was tested in a large cohort and showed a very good relationship with survival (20, 21). The upcoming AJCC 8 th edition pT staging system is size-based and is proposed to be an improvement over the 7 th edition system, in terms of its prognostic significance, on the basis of studies of PDAC patients who underwent upfront PD, without neoadjuvant therapy.…”

8th Edition of the AJCC Cancer Staging Manual: Pancreas and Hepatobiliary Cancers

“…A size-based classification was able to stratify overall survival well in a series from two highvolume centers, with independent validation from a large multi-institutional series. 10,11 In addition, resectability is removed from the T4 category, since the definition of resectability is not consistent among institutions and evolves with advances in surgical technique.…”

Do the well known prognostic parameters in pancreatic ductal adenocarcinoma really reflect survival?

“…(27). Also, the superiority of tumor size to peripancreatic soft tissue invasion as a prognostic factor has been shown in various studies (28,29). Recently, extrapancreatic extension is no longer a part of pT3 definition in AJCC Cancer Staging Manual 8 th .…”