Pancreatic Cancer Treatment (PDQ®) 1/2 —Health Professional Version - National Cancer Institute

Pancreatic Cancer Treatment (PDQ®)—Health Professional Version - National Cancer Institute

Pancreatic Cancer Treatment (PDQ®)–Health Professional Version

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ON THIS PAGE

• General Information About Pancreatic Cancer
• Cellular Classification of Pancreatic Cancer
• Stage Information for Pancreatic Cancer
• Treatment Option Overview for Pancreatic Cancer
• Stage I and Stage II Pancreatic Cancer Treatment
• Stage III Pancreatic Cancer Treatment
• Stage IV Pancreatic Cancer Treatment
• Recurrent Pancreatic Cancer Treatment
• Changes to This Summary (03/28/2019)
• About This PDQ Summary

General Information About Pancreatic Cancer

In This Section

• Incidence and Mortality
• Risk Factors
• Anatomy
• Clinical Features
• Diagnostic and Staging Evaluation
  • Imaging
  • Peritoneal cytology
  • Tumor markers
• Prognosis and Survival
• Palliative Therapy

This summary provides information about the treatment of exocrine pancreatic cancer. Other PDQ summaries containing information related to cancer in the pancreas include the following:

• Pancreatic Neuroendocrine Tumors (Islet Cell Tumors) Treatment.
• Unusual Cancers of Childhood Treatment (pancreatic cancer during childhood).

Incidence and Mortality

Estimated new cases and deaths from pancreatic cancer in the United States in 2019:[1]

• New cases: 56,770.
• Deaths: 45,750.

The incidence of carcinoma of the pancreas has markedly increased over the past several decades and ranks as the fourth leading cause of cancer death in the United States. Despite the high mortality rate associated with pancreatic cancer, its etiology is poorly understood.[2]

Risk Factors

Risk factors for development of pancreatic cancer include the following:[3,4]

• A family history of pancreatic cancer.
• Cigarette smoking.
• Obesity.
• Chronic pancreatitis.
• Certain genetic disorders (such as those associated with the BRCA1, BRCA2, PALB2, and ATM genes).

Anatomy

ENLARGE

Anatomy of the pancreas.

Cancers of the pancreas are commonly identified by the site of involvement within the pancreas. Surgical approaches differ for masses in the head, body, tail, or uncinate process of the pancreas.

Clinical Features

Pancreatic cancer symptoms depend on the site of the tumor within the pancreas and the degree of tumor involvement.

In the early stages of pancreatic cancer there are not many noticeable symptoms. As the cancer grows, symptoms may include the following:

• Jaundice.
• Light-colored stools or dark urine.
• Pain in the upper or middle abdomen and back.
• Weight loss for no known reason.
• Loss of appetite.
• Fatigue.

Diagnostic and Staging Evaluation

Pancreatic cancer is difficult to detect and diagnose for the following reasons:

• There are no noticeable signs or symptoms in the early stages of pancreatic cancer.
• The signs of pancreatic cancer, when present, are like the signs of many other illnesses, such as pancreatitis or an ulcer.
• The pancreas is obscured by other organs in the abdomen and is difficult to visualize clearly on imaging tests.

To appropriately treat pancreatic cancer, it is crucial to evaluate whether the cancer can be resected.

Imaging

The use of imaging technology may aid in the diagnosis of pancreatic cancer and in the identification of patients with disease that is not amenable to resection. Imaging tests that may be used include the following:[5]

• Helical computed tomographic scan.
• Magnetic resonance imaging scan.
• Endoscopic ultrasonography.
• Minimally invasive techniques, such as laparoscopy and laparoscopic ultrasonography may be used to decrease the use of laparotomy.[6,7]

Peritoneal cytology

In a case series of 228 patients, positive peritoneal cytology had a positive predictive value of 94%, specificity of 98%, and sensitivity of 25% for determining unresectability.[8]

Tumor markers

No tumor-specific markers exist for pancreatic cancer; markers such as serum cancer antigen (CA) 19-9 have low specificity. Most patients with pancreatic cancer will have an elevated CA 19-9 at diagnosis. Following or during definitive therapy, the increase of CA 19-9 levels may identify patients with progressive tumor growth.[9][Level of evidence: 3iDiii] The presence of a normal CA 19-9, however, does not preclude recurrence.

Prognosis and Survival

The primary factors that influence prognosis are:

• Whether the tumor is localized and can be completely resected.
• Whether the tumor has spread to lymph nodes or elsewhere.

Exocrine pancreatic cancer is rarely curable and has an overall survival (OS) rate of less than 6%.[10]

The highest cure rate occurs when the tumor is truly localized to the pancreas; however, this stage of disease accounts for less than 20% of cases. For patients with localized disease and small cancers (<2 cm) with no lymph node metastases and no extension beyond the capsule of the pancreas, complete surgical resection is associated with an actuarial 5-year survival rate of 18% to 24%.[11][Level of evidence: 3iA]

Surgical resection is the mainstay of curative treatment and provides a survival benefit in patients with small, localized pancreatic tumors. Patients with unresectable, metastatic, or recurrent disease are unlikely to benefit from surgical resection.

Pancreatic tumors are resistant to treatment with chemotherapy and radiation.

Patients with any stage of pancreatic cancer can appropriately be considered candidates for clinical trials because of the poor response to chemotherapy, radiation therapy, and surgery as conventionally used.

Palliative Therapy

Palliation of symptoms may be achieved with conventional treatment.

Palliative measures that may improve quality of life while not affecting OS include the following:[12,13]

• Surgical or radiologic biliary decompression.
• Relief of gastric outlet obstruction.
• Pain control.
• Psychological care to address the potentially disabling psychological events associated with the diagnosis and treatment of pancreatic cancer.[14]

References

1. American Cancer Society: Cancer Facts and Figures 2019. Atlanta, Ga: American Cancer Society, 2019. Available onlineExit Disclaimer. Last accessed January 23, 2019.
2. Silverman DT, Schiffman M, Everhart J, et al.: Diabetes mellitus, other medical conditions and familial history of cancer as risk factors for pancreatic cancer. Br J Cancer 80 (11): 1830-7, 1999. [PUBMED Abstract]
3. Tersmette AC, Petersen GM, Offerhaus GJ, et al.: Increased risk of incident pancreatic cancer among first-degree relatives of patients with familial pancreatic cancer. Clin Cancer Res 7 (3): 738-44, 2001. [PUBMED Abstract]
4. Nöthlings U, Wilkens LR, Murphy SP, et al.: Meat and fat intake as risk factors for pancreatic cancer: the multiethnic cohort study. J Natl Cancer Inst 97 (19): 1458-65, 2005. [PUBMED Abstract]
5. Riker A, Libutti SK, Bartlett DL: Advances in the early detection, diagnosis, and staging of pancreatic cancer. Surg Oncol 6 (3): 157-69, 1997. [PUBMED Abstract]
6. John TG, Greig JD, Carter DC, et al.: Carcinoma of the pancreatic head and periampullary region. Tumor staging with laparoscopy and laparoscopic ultrasonography. Ann Surg 221 (2): 156-64, 1995. [PUBMED Abstract]
7. Minnard EA, Conlon KC, Hoos A, et al.: Laparoscopic ultrasound enhances standard laparoscopy in the staging of pancreatic cancer. Ann Surg 228 (2): 182-7, 1998. [PUBMED Abstract]
8. Merchant NB, Conlon KC, Saigo P, et al.: Positive peritoneal cytology predicts unresectability of pancreatic adenocarcinoma. J Am Coll Surg 188 (4): 421-6, 1999. [PUBMED Abstract]
9. Willett CG, Daly WJ, Warshaw AL: CA 19-9 is an index of response to neoadjunctive chemoradiation therapy in pancreatic cancer. Am J Surg 172 (4): 350-2, 1996. [PUBMED Abstract]
10. Siegel R, Naishadham D, Jemal A: Cancer statistics, 2013. CA Cancer J Clin 63 (1): 11-30, 2013. [PUBMED Abstract]
11. Yeo CJ, Abrams RA, Grochow LB, et al.: Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. A prospective, single-institution experience. Ann Surg 225 (5): 621-33; discussion 633-6, 1997. [PUBMED Abstract]
12. Sohn TA, Lillemoe KD, Cameron JL, et al.: Surgical palliation of unresectable periampullary adenocarcinoma in the 1990s. J Am Coll Surg 188 (6): 658-66; discussion 666-9, 1999. [PUBMED Abstract]
13. Baron TH: Expandable metal stents for the treatment of cancerous obstruction of the gastrointestinal tract. N Engl J Med 344 (22): 1681-7, 2001. [PUBMED Abstract]
14. Passik SD, Breitbart WS: Depression in patients with pancreatic carcinoma. Diagnostic and treatment issues. Cancer 78 (3 Suppl): 615-26, 1996. [PUBMED Abstract]

Cellular Classification of Pancreatic Cancer

Pancreatic cancer includes the following carcinomas:

Malignant

• Duct cell carcinoma (90% of all cases).
• Acinar cell carcinoma.
• Adenosquamous carcinoma.
• Cystadenocarcinoma (serous and mucinous types).
• Giant cell carcinoma.
• Invasive adenocarcinoma associated with cystic mucinous neoplasm or intraductal papillary mucinous neoplasm.
• Mixed type (ductal-endocrine or acinar-endocrine).
• Mucinous carcinoma.
• Pancreatoblastoma.
• Papillary-cystic neoplasm (Frantz tumor). This tumor has lower malignant potential and may be cured with surgery alone.[1,2]
• Papillary mucinous carcinoma.
• Signet ring carcinoma.
• Small cell carcinoma.
• Unclassified.
• Undifferentiated carcinoma.

Borderline Malignancies

• Intraductal papillary mucinous tumor with dysplasia.[3]
• Mucinous cystic tumor with dysplasia.
• Pseudopapillary solid tumor.

References

1. Sanchez JA, Newman KD, Eichelberger MR, et al.: The papillary-cystic neoplasm of the pancreas. An increasingly recognized clinicopathologic entity. Arch Surg 125 (11): 1502-5, 1990. [PUBMED Abstract]
2. Warshaw AL, Compton CC, Lewandrowski K, et al.: Cystic tumors of the pancreas. New clinical, radiologic, and pathologic observations in 67 patients. Ann Surg 212 (4): 432-43; discussion 444-5, 1990. [PUBMED Abstract]
3. Sohn TA, Yeo CJ, Cameron JL, et al.: Intraductal papillary mucinous neoplasms of the pancreas: an increasingly recognized clinicopathologic entity. Ann Surg 234 (3): 313-21; discussion 321-2, 2001. [PUBMED Abstract]

Stage Information for Pancreatic Cancer

In This Section

• AJCC Stage Groupings and TNM Definitions

The staging system for pancreatic exocrine cancer continues to evolve. The importance of staging beyond establishing whether a tumor is resectable is uncertain because state-of-the-art treatment has demonstrated little impact on survival. However, knowledge of the extent of the disease is necessary to communicate a uniform definition of disease.

The American Joint Committee on Cancer (AJCC) has designated staging by TNM (tumor, node, metastasis) classification.[1]

AJCC Stage Groupings and TNM Definitions

Table 1. Definitions for Exocrine Pancreas TNM Stage 0a

Stage	TNM	Definition	Illustration
T = primary tumor; N = regional lymph node; M = distant metastasis.
aReprinted with permission from AJCC: Exocrine Pancreas. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 337–47.
0	Tis, N0, M0	Tis = Carcinoma in situ. This includes high-grade pancreatic intraepithelial neoplasia (PanIn-3), intraductal papillary mucinous neoplasm with high-grade dysplasia, intraductal tubulopapillary neoplasm with high-grade dysplasia, and mucinous cystic neoplasm with high-grade dysplasia.	ENLARGE
		N0 = No regional lymph node metastases.
		M0 = No distant metastasis.

Table 2. Definitions for Exocrine Pancreas TNM Stages IA and IBa

Stage	TNM	Definition	Illustration
T = primary tumor; N = regional lymph node; M = distant metastasis.
aReprinted with permission from AJCC: Exocrine Pancreas. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 337–47.
IA	T1, N0, M0	T1 = Tumor ≤2 cm in greatest dimension.	ENLARGE
		–T1a = Tumor ≤0.5 cm in greatest dimension.
		–T1b = Tumor >0.5 cm and <1 cm in greatest dimension.
		–T1c = Tumor 1–2 cm in greatest dimension.
		N0 = No regional lymph node metastases.
		M0 = No distant metastasis.
IB	T2, N0, M0	T2 = Tumor >2 cm and ≤4 cm in greatest dimension.
		N0 = No regional lymph node metastases.
		M0 = No distant metastasis.

Table 3. Definitions for Exocrine Pancreas TNM Stages IIA and IIBa

Stage	TNM	Definition	Illustration
T = primary tumor; N = regional lymph node; M = distant metastasis.
aReprinted with permission from AJCC: Exocrine Pancreas. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 337–47.
IIA	T3, N0, M0	T3 = Tumor >4 cm in greatest dimension.	ENLARGE
		N0 = No regional lymph node metastases.
		M0 = No distant metastasis.
IIB	T1, N1, M0	T1 = Tumor ≤2 cm in greatest dimension.	ENLARGE
		–T1a = Tumor ≤0.5 cm in greatest dimension.
		–T1b = Tumor >0.5 cm and <1 cm in greatest dimension.
		–T1c = Tumor 1–2 cm in greatest dimension.
		N1 = Metastasis in one to three regional lymph nodes.
		M0 = No distant metastasis.
	T2, N1, M0	T2 = Tumor >2 cm and ≤4 cm in greatest dimension.
		N1 = Metastasis in one to three regional lymph nodes.
		M0 = No distant metastasis.
	T3, N1, M0	T3 = Tumor >4 cm in greatest dimension.
		N1 = Metastasis in one to three regional lymph nodes.
		M0 = No distant metastasis.

Table 4. Definitions for Exocrine Pancreas TNM Stage IIIa

Stage	TNM	Definition	Illustration
T = primary tumor; N = regional lymph node; M = distant metastasis.
aReprinted with permission from AJCC: Exocrine Pancreas. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 337–47.
III	T1, N2, M0	T1 = Tumor ≤2 cm in greatest dimension.	ENLARGE
		–T1a = Tumor ≤0.5 cm in greatest dimension.
		–T1b = Tumor >0.5 cm and <1 cm in greatest dimension.
		–T1c = Tumor 1–2 cm in greatest dimension.
		N2 = Metastasis in four or more regional lymph nodes.
		M0 = No distant metastasis.
	T2, N2, M0	T2 = Tumor >2 cm and ≤4 cm in greatest dimension.
		N2 = Metastasis in four or more regional lymph nodes.
		M0 = No distant metastasis.
	T3, N2, M0	T3 = Tumor >4 cm in greatest dimension.
		N2 = Metastasis in four or more regional lymph nodes.
		M0 = No distant metastasis.
	T4, Any N, M0	T4 = Tumor involves celiac axis, superior mesenteric artery, and/or common hepatic artery, regardless of size.
		NX = Regional lymph nodes cannot be assessed.
		N0 = No regional lymph node metastases.
		N1 = Metastasis in one to three regional lymph nodes.
		N2 = Metastasis in four or more regional lymph nodes.
		M0 = No distant metastasis.

Table 5. Definitions for Exocrine Pancreas TNM Stage IVa

Stage	TNM	Definition	Illustration
T = primary tumor; N = regional lymph node; M = distant metastasis.
aReprinted with permission from AJCC: Exocrine Pancreas. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 337–47.
IV	Any T, Any N, M1	TX = Primary tumor cannot be assessed.	ENLARGE
		T0 = No evidence of primary tumor.
		Tis = Carcinoma in situ. This includes high-grade pancreatic intraepithelial neoplasia (PanIn-3), intraductal papillary mucinous neoplasm with high-grade dysplasia, intraductal tubulopapillary neoplasm with high-grade dysplasia, and mucinous cystic neoplasm with high-grade dysplasia.
		T1 = Tumor ≤2 cm in greatest dimension.
		–T1a = Tumor ≤0.5 cm in greatest dimension.
		–T1b = Tumor >0.5 cm and <1 cm in greatest dimension.
		–T1c = Tumor 1–2 cm in greatest dimension.
		T2 = Tumor >2 cm and ≤4 cm in greatest dimension.
		T3 = Tumor >4 cm in greatest dimension.
		T4 = Tumor involves celiac axis, superior mesenteric artery, and/or common hepatic artery, regardless of size.
		NX = Regional lymph nodes cannot be assessed.
		N0 = No regional lymph node metastases.
		N1 = Metastasis in one to three regional lymph nodes.
		N2 = Metastasis in four or more regional lymph nodes.
		M1 = Distant metastasis.

References

1. Kakar S, Pawlik TM, Allen PJ: Exocrine Pancreas. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 337–47.

Treatment Option Overview for Pancreatic Cancer

Surgical resection remains the primary modality when feasible; on occasion, resection can lead to long-term survival and provides effective palliation.[1-3][Level of evidence: 3iA]

The role of postoperative therapy (chemotherapy with or without chemoradiation therapy) in the management of pancreatic cancer remains controversial because much of the randomized clinical trial data available are statistically underpowered and provide conflicting results.[4-8]

Complications of pancreatic cancer include the following:

• Malabsorption: Frequently, malabsorption caused by exocrine insufficiency contributes to malnutrition. Attention to pancreatic enzyme replacement can help alleviate this problem. (Refer to the PDQ summary on Nutrition in Cancer Care for more information.)
• Pain: Celiac axis and intrapleural nerve blocks can provide highly effective and long-lasting control of pain for some patients. (Refer to the PDQ summary on Cancer Painfor more information.)

The survival rate of patients with any stage of pancreatic exocrine cancer is poor. Clinical trials are appropriate alternatives for treatment of patients with any stage of disease and should be considered before palliative approaches are selected.

Information about ongoing clinical trials for pancreatic cancer is available from the NCI website.

Table 6. Treatment Options for Pancreatic Cancer

Stage (TNM Staging Criteria)	Treatment Options
Stage I and stage II pancreatic cancer	Surgery
	Postoperative chemotherapy
	Postoperative chemoradiation therapy
Stage III pancreatic cancer	Chemotherapy
	Chemoradiation therapy
	Palliative surgery
Stage IV pancreatic cancer	Palliative therapy
	Chemotherapy
Recurrent pancreatic cancer	Palliative therapy
	Chemotherapy

References

1. Yeo CJ, Cameron JL, Lillemoe KD, et al.: Pancreaticoduodenectomy for cancer of the head of the pancreas. 201 patients. Ann Surg 221 (6): 721-31; discussion 731-3, 1995. [PUBMED Abstract]
2. Conlon KC, Klimstra DS, Brennan MF: Long-term survival after curative resection for pancreatic ductal adenocarcinoma. Clinicopathologic analysis of 5-year survivors. Ann Surg 223 (3): 273-9, 1996. [PUBMED Abstract]
3. Yeo CJ, Abrams RA, Grochow LB, et al.: Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. A prospective, single-institution experience. Ann Surg 225 (5): 621-33; discussion 633-6, 1997. [PUBMED Abstract]
4. Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer. Gastrointestinal Tumor Study Group. Cancer 59 (12): 2006-10, 1987. [PUBMED Abstract]
5. Kalser MH, Ellenberg SS: Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg 120 (8): 899-903, 1985. [PUBMED Abstract]
6. Klinkenbijl JH, Jeekel J, Sahmoud T, et al.: Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: phase III trial of the EORTC gastrointestinal tract cancer cooperative group. Ann Surg 230 (6): 776-82; discussion 782-4, 1999. [PUBMED Abstract]
7. Neoptolemos JP, Dunn JA, Stocken DD, et al.: Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet 358 (9293): 1576-85, 2001. [PUBMED Abstract]
8. Neoptolemos JP, Stocken DD, Friess H, et al.: A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 350 (12): 1200-10, 2004. [PUBMED Abstract]