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Section Editors: Jeannine M. Brant, Marilyn L. Haas-Haseman, Steven H. Wei, and Rita Wickham
Clinical Management of
Pancreatic Cancer
RAE BRANA REYNOLDS, RN, MS, ANP-BC, and JUSTIN FOLLODER, MS, PA-C
P
From University of Texas MD Anderson Cancer ancreatic cancer is the mal at 6% (ACS, 2014). Even at high-
Center, Houston, Texas
fourth leading cause of can- volume specialty centers, where the
Authors' disclosures of potential conflicts of
interest are found at the end of this article. cer deaths in the United 5-year survival rate for patients is
Correspondence to: Rae Brana Reynolds, RN, MS,
States (American Cancer higher than in the general popula-
ANP-BC, MD Anderson Cancer Center, Depart- Society [ACS], 2014). In 2014, the tion, disease recurrence is still a ma-
ment of Surgical Oncology, 1400 Pressler Street, ACS estimates 46,420 new cases of jor problem. For patients who have
Houston, TX 77035.
E-mail: rbrana@mdanderson.org
pancreatic cancer with 39,590 deaths undergone surgical resection of the
© 2014 Harborside Press®
in the United States. Unfortunately, involved pancreas, published series
80% of patients diagnosed with pan- from high-volume referral centers
creatic cancer present with meta- examining long-term survivors indi-
static or locoregional disease at initial cate that only 10% to 27% of patients
diagnosis (Chatterjee et al., 2012a; with early-stage disease who under-
Karmazanovsky, Fedorov, Kubyshkin, went resection survived at least 5
& Kotchatkov, 2005). Because meta- years (Katz et al., 2009).
static and locally advanced extra- An MD Anderson Cancer Cen-
pancreatic disease is an exclusion ter (MDACC) analysis of 86 patients
criterion for surgical treatment, this who received preoperative radiation
leaves only a minority of patients and chemotherapy in the form of
initially presenting with pancreatic gemcitabine followed by resection
cancer eligible for surgical resection reported that 11% of patients had
(Chatterjee et al., 2012a). local pancreatic disease recurrence
The only treatment for pancre- after resection, 23% had liver me-
atic cancer with curative potential tastasis after resection, and 59% had
is resection of the involved portion tumor recurrence with distant organ
of the pancreas, so with a small sub- metastasis after resection (Evans et
group of patients presenting with re- al., 2008).
sectable pancreatic cancer at initial Another MDACC study of 90
diagnosis, the prognosis for this pa- patients who received radiation and
tient population is grim. chemotherapy in the form of gem-
While the 5-year survival rates citabine combined with cisplatin
for many oncologic diseases have reported 25% of study patients pre-
improved, the 5-year survival rate senting with local pancreatic disease
J Adv Pract Oncol 2014;5:356–364 for pancreatic cancer remains dis- recurrence after surgery and 73% of
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PANCREATIC CANCER TRANSLATING RESEARCH INTO PRACTICE
357
TRANSLATING RESEARCH INTO PRACTICE BRANA REYNOLDS and FOLLODER
agement of patients with increased risk for familial organs and blood vessels, specifically the superior
pancreatic cancer reached a consensus that first- mesenteric vein, portal vein, superior mesenteric
degree relatives of patients with pancreatic cancer artery, celiac axis, and hepatic artery. A CT scan
from a kindred who has at least two affected first- with contrast can correctly predict resectability
degree relatives and patients with Peutz-Jeghers in pancreatic cancer with 80% to 90% accuracy
syndrome are candidates for screening (Canto et al., (Karmazanovsky et al., 2005). It also provides in-
2013). The consortium identified mutation carriers formation on extrapancreatic lesions suspicious for
of p16, BRCA2, and hereditary nonpolyposis colorec- metastatic disease. Positron emission tomography
tal cancer with more than one affected first-degree (PET) can be used to supplement CT scan findings
relative as candidates for screening as well. There during the evaluation and treatment phases.
was no consensus on the age to initiate screening Endoscopic procedures such as EUS with fine-
or stop surveillance, but it was agreed that initial needle aspiration and endoscopic retrograde chol-
screening should include endoscopic ultrasonogra- angiopancreatography (ERCP) are commonly used
phy (EUS) and/or MRI/magnetic resonance cholan- for pancreatic cancer evaluation (Ross et al., 2008).
giopancreatography. There was also consensus that An esophagogastroduodenoscopy (EGD) with EUS
surgery, when recommended, should be performed is useful in characterizing tumor details and ob-
at a high-volume center (Canto et al., 2013). taining tissue diagnosis. It can also be valuable in
identifying a cancerous tumor that it is not clearly
DIAGNOSIS identifiable on a CT scan as it has better sensitiv-
The goals of pancreatic cancer evaluation are ity for smaller pancreatic lesions (Ross et al., 2008).
to establish a tissue diagnosis of pancreatic cancer An ERCP is used for evaluation and management
and to determine resectability as well as disease in patients with jaundice and cholestasis. It is used
stage to help guide treatment planning. In addi- as a diagnostic tool to assess for a biliary stricture
tion to physical examination and a careful history resulting from pancreatic cancer obstructing the
assessment, pancreatic cancer evaluation includes bile duct and also as a guide in obtaining cytologic
laboratory, diagnostic radiology, and endoscopic brushings of the area of the stricture for cytopathol-
studies. Biopsy for cytopathologic tissue diag- ogy studies (Hidalgo, 2010). In addition to its value
nosis can be performed with radiology guidance as a diagnostic tool, it is also a therapeutic proce-
or by endoscopic means (Hidalgo, 2010; Lee & dure that guides stent placement to relieve biliary
Lee, 2014). tract compression by pancreatic cancer.
There is no known biomarker specific to pan-
creatic cancer, but carbohydrate 19-9 (CA 19-9) STAGING OF PANCREATIC CANCER
has demonstrated clinical value for therapeutic The tumor-node-metastasis (TNM) classifica-
monitoring and for surveillance of disease recur- tion system issued by the American Joint Committee
rence in patients with a history of pancreatic can- on Cancer (AJCC) is used to stage pancreatic can-
cer. It is important to note that CA 19-9 may be el- cer. The size of the tumor and its relationship to vital
evated during periods of cholestasis and that some blood vessels are taken into account when categoriz-
patients with pancreatic cancer do not express el- ing the tumor from TX to T4. The extent of regional
evations in CA 19-9, as there is a subgroup of about lymph node involvement defines nodal classification
10% who are unable to synthesize CA 19-9 and ranging from NX to N1, whereas the presence and/
have undetectable levels, even in advanced stages or absence of identifiable metastasis to distant or-
of disease (Hidalgo, 2010). gans designates the metastatic category as M0 or M1,
The diagnostic radiology test of choice for ini- respectively. Table 1 presents details of the levels that
tial pancreatic cancer evaluation is a multiphase, comprise each component of the TNM taxonomy,
multidetector helical computed tomography (CT while Table 2 summarizes the AJCC staging system
scan) with utilization of contrast material (Hidal- for pancreatic cancer using groupings categorized
go, 2010). This test performed specifically with a according to the TNM classification.
pancreatic protocol provides essential details on The AJCC staging system has prognostic value
the anatomic relationship of the tumor to adjacent but cannot consistently direct clinical manage-
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PANCREATIC CANCER TRANSLATING RESEARCH INTO PRACTICE
Table 1. TNM Classification for Pancreatic Cancera Table 2. TNM Staging of Pancreatic Cancera
Primary tumor (T) Stage T N M
TX Primary tumor cannot be assessed 0 Tis N0 M0
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TRANSLATING RESEARCH INTO PRACTICE BRANA REYNOLDS and FOLLODER
Table 3. MD Anderson Cancer Center Clinical/ treated with radiation (Corsini et al., 2008; Her-
Radiologic Staging of Pancreatic Cancer man et al., 2008; Hsu et al., 2010).
Resectable For patients with resectable pancreatic cancer,
• No encasement of CA or SMA the delivery of neoadjuvant therapy is advocated
• Patent SMV-PV confluence by some centers, as it allows for early treatment of
• No metastatic disease
systemic disease in a population of patients widely
Borderline resectable
believed to have micrometastasis at presentation
• SMV-PV occlusion with anatomy sufficient for venous
reconstruction (Evans et al., 2008). Additionally, it allows for
• Short segment abutment of SMA identification of patients with rapidly metastatic
• Short segment abutment or encasement of HA
disease and spares them from major operation
Locally advanced unlikely to provide durable cure because of highly
• Encasement of SMA or CA
aggressive tumor biology. Moreover, delivery of
Note. CA = celiac axis; SMA = superior mesenteric artery; neoadjuvant chemotherapy and radiation is pos-
SMV = superior mesenteric vein; PV = portal vein; HA =
hepatic artery. Adapted from Bose et al. (2012). ited to increase the rate of margin-negative resec-
tion (R0 resection) and reduce the risk of local dis-
ease recurrence (Evans et al., 2008).
Resectable Pancreatic Cancer Achieving microscopically negative surgical
For resectable pancreatic cancer, the primary margins of resection is the goal of any pancreat-
recommendation from the National Comprehen- ic cancer operation (Evans et al., 2009). Surgical
sive Cancer Network (NCCN) is to proceed im- resection of pancreatic cancer is performed for
mediately to surgical resection followed by adju- patients whose radiographic imaging studies in-
vant chemotherapy. However, there is also expert dicate resectable disease and whose clinical per-
consensus and phase II clinical trial data that formance status is appropriate for surgery. The
support the delivery of neoadjuvant therapy (i.e., majority of pancreatic cancers arise in the area of
chemotherapy and radiation administered prior the pancreatic head, and these lesions, if resect-
to surgical resection) in selected patients with bi- able, are treated with a pancreaticoduodenecto-
opsy confirmation of adenocarcinoma (Halperin my. Pancreatic cancers located in the area of the
& Varadhachary, 2014). pancreatic tail, if resectable, are treated with a dis-
The primary chemotherapeutic agents that tal pancreatectomy, which typically also involves
have shown benefit in patients with pancreatic can- a splenectomy depending on the splenic vessel in-
cer are gemcitabine and fluorouracil (5-FU). The volvement of the tumor.
use of gemcitabine has shown an increased median A pancreaticoduodenectomy is commonly re-
disease-free survival to 13.4 months compared with ferred to as the Whipple procedure and involves
6.7 months in an observation group (Oettle et al., the resection of the pancreatic head, duodenum,
2007). A 5-year actuarial survival of 21% was seen gallbladder, and a portion of the stomach (Fig-
in patients treated with adjuvant 5-FU compared ure 5). Reconstruction is then performed with a
with 9% in patients randomized to receive nonad- pancreaticojejunostomy, choledochojejunosto-
juvant treatment (Halperin & Varadhachary, 2014). my, and duodenojejunostomy or gastrojejunos-
There is conflicting information on the role of tomy (Figure 6). A pancreaticoduodenectomy for
radiation in patients with resectable pancreatic resectable pancreatic cancer can be performed
cancer. A 2004 study confirmed that patients may with pylorus preservation, especially in patients
benefit from adjuvant chemotherapy but showed with a high risk for postoperative nutritional
a lower survival rate among patients treated with compromise. However, it is not typically per-
adjuvant chemotherapy combined with radiation formed in patients with bulky pancreatic head
when compared with patients who did not receive tumors that involve adjacent organs or in the
adjuvant chemotherapy and radiation (Neoptol- presence of grossly positive pyloric or peripylo-
emos et al., 2004). These results are in contrast ric lymph nodes (Bose et al., 2012).
to findings of multiple trials that have suggested Involvement of the SMV-PV is not considered
a survival benefit in pancreatic cancer patients an absolute contraindication to resection of pancre-
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PANCREATIC CANCER TRANSLATING RESEARCH INTO PRACTICE
Superior
atic cancers at our institution. In 84% of patients, mesenteric
imaging studies can accurately predict the need for Duodenum vein
resection and reconstruction of the SMV-PV due
to tumor involvement (Bose et al., 2012). Resection
and reconstruction of the SMV-PV have been found Superior
to be safe. It has also been found that patients who Pancreas mesenteric
artery
require resection and reconstruction of the SMV-
PV to achieve negative surgical margins have a sim-
ilar overall survival rate as patients who undergo Tumor
resection without the need for venous resection
and reconstruction (Bose et al., 2012). At our in- Aorta
stitution, most patients with resectable pancreatic Spine
cancers who have venous involvement are treated Inferior
vena cava
preoperatively with chemotherapy and radiation.
Expert consensus states that pancreaticoduode-
Figure 2. Resectable pancreatic cancer. ©2008 The
nectomy for pancreatic adenocarcinoma should be University of Texas MD Anderson Cancer Center.
performed at high-volume institutions capable of
and experienced in resection and reconstruction of section of the involved pancreas is the only treat-
major mesenteric veins (Evans et al., 2009). ment that offers cure, unresectable disease is
therefore considered incurable. In these palliative
Borderline Resectable Pancreatic Cancer settings, there is no role for resection, and treat-
Because this category is relatively new and ment usually consists of systemic chemotherapy
does not yet have a standard definition among in- and in some cases with chemoradiation. The role of
stitutions and organizations with expertise in pan- radiation in combination with chemotherapy for lo-
creatic cancer management, standard treatment cally advanced disease has been studied: Although
for borderline resectable disease is not well es- chemoradiation has shown benefit, there has also
tablished; however, expert consensus statements been a noted increase in toxicity. The added mor-
were published in 2009 on the surgical treatment bidity and the low enrollment in clinical trials de-
and combined-modality treatment of resectable signed to examine its benefit have precluded a firm
and borderline resectable pancreatic cancers conclusion on its status as recommended treatment
(Abrams et al., 2009; Evans et al., 2009) (Hidalgo, 2010).
Heterogeneity in the definitions as well as the
interventions used by different institutions that Superior
have conducted studies on patients with border- Duodenum mesenteric
vein
line resectable disease remains. Multiple trials
support the delivery of preoperative neoadjuvant
therapy either with chemotherapy alone or in Superior
Pancreas mesenteric
combination with radiation, including the use of artery
FOLFIRINOX, which is a combination of 5-FU,
oxaliplatin, irinotecan, and leucovorin followed Tumor
by chemoradiation (Christians et al., 2014). How-
ever, there is no consensus standard on which
Aorta
chemotherapy or chemoradiation regimen in
Spine
particular should be delivered prior to resection
(Halperin & Varadhachary, 2014). Inferior
vena cava
361
TRANSLATING RESEARCH INTO PRACTICE BRANA REYNOLDS and FOLLODER
Superior
Duodenum mesenteric
vein
Spleen
Superior
Pancreas mesenteric
artery
Stomach
Bile duct
Tumor
Pancreas
Aorta
Gallbladder
Spine
Inferior Tumor
vena
cava
Duodenum
362
PANCREATIC CANCER TRANSLATING RESEARCH INTO PRACTICE
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TRANSLATING RESEARCH INTO PRACTICE BRANA REYNOLDS and FOLLODER
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