7 Cancer of the Pancreas
Epidemiology
It is the 12th most prevalent cancer in the United States, and the 4th most frequent cause of cancer-related death.
Survival rates have not significantly changed in the past 40 years.
Patients with metastatic disease have a 5-year survival of 2%.
Median age of onset is 71 years; 74% diagnosed between 55 and 84 years.
Incidence in the United States is 12/100,000 with a lifetime risk of 1.5%.
Higher incidence in smokers, exposure to chlorinated hydrocarbons, dry cleaning, and metal work, especially production of aluminum. 1 , 2
Genetics
About 10% have a family history. Patients with three or more first-degree relatives having pancreatic cancer have a lifetime risk of 40%.
The KRAS gene is mutated in 90% of pancreatic adenocarcinomas. This gene mediates signals from growth factor receptors and the mutation overexpresses the output of the gene, increasing the growth factor signals converting it from a protooncogene to an oncogene. This occurs early in tumorigenesis. The tumor-suppressor and genome maintenance genes mutate in mid to late tumorigenesis. The CDKN2A/p16 is mutated in over 90%, while the TP53 and SMAD4 genes are mutated in 75 and 55%, respectively. The latter two mutations occur in the late stages of tumor formation. 3 , 4
Pathology
Pancreatic ductal adenocarcinoma demonstrates an almost universal perineural invasion, greater than most other common adenocarcinomas. Few are diagnosed early in tumorigenesis; most are diagnosed after they are beyond cure. On microscopy, a desmoplastic reaction is seen within the tumor mass, which will act to isolate the tumor cells from the chemotherapeutic agents. 5 – 7
Diagnosis
Symptoms include jaundice, weight loss, abdominal pain, nausea, acholic stools, and tea-colored urine. New-onset diabetes mellitus occurs in approximately 10% of patients. 5
Staging 8
Tis = Carcinoma in situ.
T1 = 2 cm or less and confined to the pancreas.
T2 = Greater than 2 cm and confined to the pancreas.
T3 = Extends beyond the pancreas.
T4 = Invades visceral arteries and veins.
N0 = No regional lymph node (LN) involvement.
N1 = Regional LN metastases.
M0 = No distant metastases.
M1 = Distant metastases.
Stage 0 = Tis N0 M0.
Stage IA = T1 N0 M0 with survival (all patients) of 10 months; 24 months with resection.
Stage IB = T2 N0 M0 with survival (all patients) of 9.1 months; 20.6 months with resection.
Stage IIA = T3 N0 M0 with survival (all patients) of 8.1 months; 15.4 months with resection.
Stage IIB = T1/2/3 N1 M0 with survival (all patients) of 9.7 months; 12.7 months with resection.
Stage III = T4 N0/1 M0 with survival (all patients) of 7.7 months; 10.6 months with resection.
Stage IV = any T any N M1 with survival (all patients) of 2.5 months; 4.5 months with resection.
Treatment
Surgery
An R0 resection (resectable tumor) is likely if there is no abutment to either the superior mesenteric artery (SMA) or celiac axis (CA) or hepatic artery (HA) but may be abutted to the superior mesenteric vein–portal vein (SMV–PV) confluence without distortion. An R1 resection (borderline resectable) is likely if there is abutment to either the SMA or CA or there is SMV or PV distortion due to the tumor or a segment of SMV is occluded with patent vein on either side. An R2 resection (locally advanced) is likely if the tumor encases the SMA, CA, or HA, or occludes the SMV or PV without reconstruction options. 9 – 11
Resection is attempted if the patient is medically fit, if there is no evidence of metastases, and if the patient is thought to have resectable disease. The surgery for right-sided lesions (those involving the head, neck, or uncinate process) is a pancreaticoduodenectomy (Whipple procedure). Those lesions on the left (tail of pancreas) are resected with a distal pancreatectomy.
Unresectable disease is due to invasion of the SMA or vein, the CA, or the SMV–PV confluence. Borderline resectable lesions are those that abut the vessels above but do not involve more than 180-degree circumference and there are potential reconstruction options available.
Chemotherapy
Adjuvant therapy is recommended using FOLFIRI (5-FU, leucovorin, irinotecan), FOLFIRINOX (5-FU, leucovorin, irinotecan, oxaliplatin for advanced pancreatic cancer) or gemcitabine monotherapies, 5-FU, or capecitabine or chemoradiation using these agents. Additional survival of 3 months is predicted from patients receiving 6 months of these therapies.
Recurrence of tumor usually occurs in the retroperitoneum, liver, peritoneum, and lung. Most patients recur at both the site of resection and distantly.
Stage III: Locally advanced disease treatment, which is unresectable. Usually chemoradiation especially using stereotactic body radiation to limit the side effects of the treatment. Chemotherapeutic options are FOLFIRI, gemcitabine, 5-FU, or capecitabine.
Stage IV: Distant metastases.
Chemotherapy with radiation to the primary site is given as palliation. Chemotherapy can be gemcitabine (400–500 mg/m2 weekly), capecitabine (800–825 mg/m2 twice per day on day of radiation), or continuous infusion of 5-FU via a pump at 25 mg/m2/d or 300 mg/m2 on day of radiation.
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