EDITORIAL

 

JOP. J Pancreas (Online) 2012 Mar 10; 13(2):128-130.

 

 

Revising You the Staging for Pancreatic Cancer in 2012

 

 

Muhammad Wasif Saif

 

 

Columbia University College of Physicians and Surgeons. New York, NY, USA

 

 

Introduction

 

In 2010, there were an estimated 43,140 new cases of pancreatic ductal adenocarcinoma and 36,800 deaths from pancreatic cancer in the United States [1]. This represents the 10th most common cancer diagnosis but the 4th most common cause of cancer-related death among men and women (6% of all cancer-related deaths), highlighting the disproportionate mortality associated with this diagnosis [2].

 

Why is Staging so Important?

 

Sadly, only 20% patients are “resectable” at the time of diagnosis [3]. Pancreatic cancer is “resectable” if the tumor is confined to the pancreas without the encasement of adjacent surrounding major vessels, or distant metastases. Even among those patients who undergo resection for pancreatic cancer and have tumor-free margins, the 5-year survival rate after resection is 10-25% and the median survival is 15-19 months [3]. “Locally advanced pancreatic cancer” is defined as the tumor that has a local invasion: arterial (celiac trunk, hepatic artery, superior mesenteric artery) or venous (portal vein, superior mesenteric vein) but not metastasized, and represents about 25% of pancreatic cancer cases at presentation [4]. Locally advanced stage is associated with a median survival of 6-10 months. The vast majority of these patients develop metastatic disease within the first year of therapy. The tumor is considered “advanced” when it has metastasized to other organs, such as the liver or distant areas of the abdomen. Approximately 45% to 55% of patients are diagnosed at this stage. The prognosis of patients with advanced disease remains extremely poor, with a median survival of 6 months [5].

 

Evolution of Staging System for Pancreatic Cancer

 

The staging system for pancreatic exocrine cancer continues to evolve. Staging information helps to determine appropriate treatment and to predict a patient’s prognosis. It is important that like surgery, the staging of pancreatic cancer should be done at a specialized and experienced center.

There are different stage descriptions for different types of cancer.

 

TNM Classification

 

The TNM classification [6] (Tables 1 and 2) often applied for other solid tumors is not usually used for pancreatic cancer.

 

 

Table 1. TNM classification [6].

Primary Tumor (T)

TX

Primary tumor cannot be assessed.

T0

No evidence of primary tumor.

Tis

Carcinoma in situ.

T1

Tumor limited to the pancreas, less than, or equal to, 2 cm in greatest dimension.

T2

Tumor limited to the pancreas, greater than 2 cm in greatest dimension.

T3

Tumor extends beyond the pancreas but without involvement of the celiac axis or the superior mesenteric artery.

T4

Tumor involves the celiac axis or the superior mesenteric artery (unresectable primary tumor).

Regional Lymph Nodes (N)

NX

Regional lymph nodes cannot be assessed.

N0

No regional lymph node metastasis.

N1

Regional lymph node metastasis.

Distant Metastasis (M)

M0

No distant metastasis.

M1

Distant metastasis.

 

 

Table 2. Anatomic stage/prognostic groups.

Stage

T

N

M

0

Tis

N0

M0

IA

T1

N0

M0

IB

T2

N0

M0

IIA

T3

N0

M0

IIB

T1

N1

M0

T2

N1

M0

T3

N1

M0

III

T4

Any N

M0

IV

Any T

Any N

M1

 

 

The significance of staging beyond that of resectable and unresectable is uncertain in this disease because standard therapies have demonstrated mild impact on survival. Historically, the more common way to classify pancreatic cancer is to divide it into three categories based on whether it can be removed with surgery and where it has spread.

 

Staley’s Classification

 

Staley’s classification offers a simple model for groups engaged in protocol-based clinical research examining innovative multimodality treatment strategies for patients with pancreatic cancer (Table 3) [7]. His group examined the impact of standardized pathologic evaluation of pancreaticoduodenectomy specimens on the identification of regional lymph nodes and describes a detailed system for the pathologic analysis of the pancreaticoduodenectomy specimen.

 

 

Table 3. Staley’s classification of pancreatic cancer.

Stage

Resectable

Locally advanced

Metastatic

 

 

National Comprehensive Cancer Network (NCCN)’s Clinical Staging of Pancreatic Cancer

 

A fourth category that is now been recognized is called “borderline resectable”. This may be a subcategory of “locally advanced”, disease with limited vascular involvement by tumor. These patients may respond to therapy and may be resected. NCCN guidelines define now four clinical stages of pancreatic cancer (Table 4), which are now guiding investigators and physicians to determine treatment and to define clinical studies [8]. This classification has been adopted well as evidenced by studies presented at the 2011 ASCO Gastrointestinal Cancers Symposium, held in January 2012 in San Francisco [9, 10, 11, 12].

 

 

Table 4. National Comprehensive Cancer Network (NCCN)’s Clinical Classification of Pancreatic Cancer [8].

Category

Description

Resectable

Pancreatic cancer is resectable if there are:

1)    no distant metastases;

2)    no radiographic evidence of superior mesenteric vein and portal vein abutment, distortion, tumor thrombus, or venous encasement;

3)    clear fat planes around the celiac axis, hepatic artery, and superior mesenteric artery

Borderline resectable

Borderline resectable disease is defined as:

·       no distant metastases;

·       venous involvement of the superior mesenteric/portal vein demonstrating tumor abutment with impingement and narrowing of the lumen, encasement of the superior mesenteric/portal vein but without encasement of the nearby arteries, or short segment venous occlusion resulting from either tumor thrombus or encasement but with suitable vessel proximal and distal to the area of vessel involvement, allowing for safe resection and reconstruction;

·       gastroduodenal artery encasement up to the hepatic artery with either short segment encasement or direct abutment of the hepatic artery, without extension to the celiac axis; and

·       tumor abutment of the superior mesenteric artery not to exceed greater than 180 degrees of the circumference of the vessel wall

Locally advanced

Head

·       No distant metastases;

·       greater than 180 degrees superior mesenteric artery encasement, any celiac abutment;

·       nonreconstructible superior mesenteric/portal occlusion;

·       aortic invasion or encasement

Body

·       No distant metastases;

·       superior mesenteric artery or celiac encasement greater than 180 degrees nonreconstructible superior mesenteric/portal occlusion;

·       aortic invasion

Tail

·       No distant metastases;

·       superior mesenteric artery or celiac encasement greater than 180 degrees;

·       metastases to lymph nodes beyond the field of resection

Metastatic

The tumor has spread beyond the area of the pancreas and to other organs, such as the liver or distant areas of the abdomen.

Referenced with permission from The NCCN Clinical Practice Guidelines in Oncology® for Pancreatic Adenocarcinoma V.2.2012.© National Comprehensive Cancer Network, Inc 2012. All rights reserved. To view the most recent and complete version of the guideline, go online to www.nccn.org. National Comprehensive Cancer Network®, NCCN®, NCCN Guidelines®, and all other NCCN content are trademarks owned by the National Comprehensive Cancer Network, Inc.

 

 

It is crucial to understand that the clinical staging system is based on the results of pre-surgical imaging studies. Because the only potential cure is through surgery, all patients with potentially resectable lesions by CT criteria should be referred for surgical consultation. But reality at the time of surgery may be more complex, and a tumor with no vascular invasion may be found to be “non-resectable” because of “desmoplastic reaction”. Due to the poor survival in patients with metastatic cancer and the high incidence of post-pancreatectomy recurrence, the patients with unresectable pancreatic cancer should be considered for inclusion into investigational trials. Expertise of surgeons in radical and revascularization techniques may significantly influence tumor resectability. Therefore, surgical resection should be performed to high volume and specialist centers to increase resection rates and reduce hospital morbidity and mortality.

 

 

Key words Blood Vessels; General Surgery; Neoplasm Staging; Pancreas; Pancreatic Neoplasms

 

Conflict of interest The authors have no potential conflicts of interest

 

Correspondence
Muhammad Wasif Saif
Division of Hematology and Oncology
Columbia University Medical Center
177 Fort Washington Ave. 6GN-435
New York, NY 10032
USA
Phone: +1-212.305.0592
Fax: +1-212.305.6762
E-mail: mws2138@columbia.edu

 

 

References

1.    Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin 2010; 60:277-300. (More details: [1]).

2.    Surveillance Epidemiology and End Results (SEER). U.S. Cancer Statistics: 1999-2007 Incidence and Mortality Report. Available at http://www.seer.cancer.gov/publications/uscs.html (Accessed January 31, 2012) (More details: [2]).

3.    Saif MW. Controversies in the adjuvant treatment of pancreatic adenocarcinoma. JOP. J Pancreas (Online) 2007; 8:545-52. (More details: [3]).

4.    Kim R, Saif MW. Is there an optimal neoadjuvant therapy for locally advanced pancreatic cancer? JOP. J Pancreas (Online) 2007; 8:279-88. (More details: [4]).

5.    Saif MW. Is there a standard of care for the management of advanced pancreatic cancer? Highlights from the Gastrointestinal Cancers Symposium. Orlando, FL, USA. January 25-27, 2008. JOP. J Pancreas (Online) 2008; 9:91-8 (More details: [5]).

6.    Exocrine and endocrine pancreas. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 241-9. (More details: [6]).

7.    Staley CA, Cleary KR, Abbruzzese JL, Lee JE, Ames FC, Fenoglio CJ, Evans DB. The need for standardized pathologic staging of pancreaticoduodenectomy specimens. Pancreas 1996; 12:373-80. (More details: [7]).

8.    National Comprehensive Cancer Network, Inc (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Pancreatic Adenocarcinoma Version 2.2012. Fort Washington, PA, USA: National Comprehensive Cancer Network, Inc (NCCN), 2012. (More details: [8]).

9.    Pimiento JM, Hutchinson T, Weber JM, Patel MR, Hodul PJ, Chuong MD, et al. Multimodality therapy for borderline resectable pancreatic cancer: A single-institution experience. J Clin Oncol 30, 2012 (suppl 4; abstr 280) (More details: [9]).

10. Chakraborty S, Bauer TW, Morris MM, Yarde E, Parsons JT, Adams RB, Sanoff HK. Accelerated fraction radiotherapy with concomitant capecitabine as neoadjuvant therapy of borderline resectable pancreatic cancer. J Clin Oncol 30, 2012 (suppl 4; abstr 329) (More details: [10]).

11. Papavasiliou P, Piposar JR, Arrangoiz R, Chen KT, Zhu F, Chun YS, Hoffman JP. Margin status and neoadjuvant chemoradiation in patients with borderline resectable pancreatic cancer. J Clin Oncol 30, 2012 (suppl 4; abstr 304) (More details: [11]).

12. Ashman JB, Moss AA, Callister MD, Reddy KS, Mulligan DC, Gunderson LL, Borad MJ. Neoadjuvant chemoradiation and intraoperative electron irradiation for locally unresectable/borderline resectable pancreas adenocarcinoma. J Clin Oncol 30, 2012 (suppl 4; abstr 327) (More details: [12]).