Vol. 13. Núm. 24.
Páginas 1345-1352 (Enero 2021)

Actualización
Cáncer de páncreas

Pancreatic cancer

D. CasadoR. Vidal TocinoE. FonsecaB. CigarralB. BarriosE. EscaleraJ. ClarosL. FigueroA. OlivaresÁ. LópezE. TeránJ.J. Cruz
Doi : https://10.1016/j.med.2021.01.004
Opciones
Resumen

El adenocarcinoma ductal de páncreas es el más común de los tumores pancreáticos y, a pesar de ocupar la octava posición en incidencia en España, representa la tercera causa de muerte por cáncer. Entre los factores de riesgo para su aparición se encuentran factores ambientales como el tabaco o el alcohol, patologías como la diabetes o factores genéticos como el síndrome de Lynch o las mutaciones en BRCA1 y BRCA2. Los pacientes con sospecha de cáncer de páncreas deben ser rápidamente valorados, y es necesaria la coordinación multidisciplinar para realizar un correcto diagnóstico y abordaje terapéutico. La tomografía computadorizada (TC) establece la sospecha diagnóstica y estadificación. La ecoendoscopia con toma de muestra por punción es el procedimiento de elección para la confirmación histológica. Los tumores de páncreas se clasifican en cuatro subgrupos que definen el abordaje terapéutico: resecables, borderline resecables, irresecables y metastásicos. La cirugía es el tratamiento de elección siempre que sea posible. El tratamiento adyuvante con quimioterapia está indicado en todos los casos. El abordaje de los tumores borderline resecable e irresecables es más controvertido y se acepta el empleo de la terapia sistémica primaria seguido de tratamiento local. La enfermedad metastásica se trata con distintos esquemas de quimioterapia como FOLFIRINOX o gemcitabina con nab-paclitaxel.

Palabras clave
Cáncer de páncreas
Adenocarcinoma ductal de páncreas
Gemcitabina
BRCA
Abstract

Pancreatic ductal adenocarcinoma is the most common pancreatic tumor and, despite being in eighth in incidence in Spain, it is the third cause of death due to cancer. Risk factors for its onset include environmental factors such as tobacco or alcohol use, diseases such as diabetes, and genetic factors such as Lynch syndrome or BRCA1 and BRCA2 mutations. Patients who are suspected of having pancreatic cancer must be evaluated promptly. Multidisciplinary coordination is necessary in order to make a correct diagnosis and decide on a proper therapeutic approach. A computerized tomography (CT) scan can confirm a diagnostic suspicion and stage the disease. An echoendoscopy with a needle biopsy sample is the procedure of choice for histological confirmation. Pancreatic tumors are classified in four subgroups that determine the therapeutic approach: resectable, borderline resectable, unresectable, and metastatic. Surgery is the treatment of choice so long it is possible. Adjuvant treatment with chemotherapy is indicated in all cases. The approach to borderline resectable and unresectable tumors is more controversial. The use of a primary systemic therapy followed by local treatment is accepted. Metastatic disease is treated with different chemotherapy regimens such as FOLFIRINOX or gemcitabine with nab-paclitaxel.

Keywords
Pancreatic cancer
Ductal adenocarcinoma of the pancreas
Gemcitabine
BRCA

Identifíquese

¿Aún no es suscriptor de la revista?

Comprar el acceso al artículo

Comprando el artículo el pdf del mismo podrá ser descargado

Teléfono para incidencias

De lunes a viernes de 9h a 18h (GMT+1) excepto los meses de julio y agosto que será de 9 a 15h

Llamadas desde España 932 415 960
Llamadas desde fuera de España +34 932 415 960
Bibliografía
[1]
M. Malvezzi
202101300719468668
, P. Bertuccio, F. Levi, C. La Vecchia, E. Negri.
European cancer mortality predictions for the year 2014.
Ann Oncol [Internet], (2014), 25 pp. 1650-1656
[2]
M.P. Malafa
202101300719468669
2021013007194686610
, V. Chair, M. Al-Hawary, H. Asbun, S.W. Behrman, A.B. Benson III, et al.
Cassadie Moravek Pancreatic Cancer Action Network Continue NCCN Guidelines Version 1.2020 Pancreatic Adenocarcinoma [Internet].
(2019),
[3]
REDECAN - Red
2021013007194686611
Española de Registros de Cáncer [Internet]. [citado el 30 de mayo de 2020]. Disponible en: https://www.redecan.es/redecan.org/es/index.html.
[4]
SEOM
2021013007194686612
.
Las cifras del cáncer en España 2020.
SEOM, (2020),
[5]
Global
2021013007194686613
Cancer Observatory [Internet]. [citado el 30 de mayo de 2020]. Disponible en: https://gco.iarc.fr/.
[6]
A. Pourshams
2021013007194686614
, S.G. Sepanlou, K.S. Ikuta, C. Bisignano, S. Safiri, G. Roshandel, et al.
The global, regional, and national burden of pancreatic cancer and its attributable risk factors in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.
Lancet Gastroenterol Hepatol [Internet], (2019), 4 pp. 934-947
[7]
M. Ducreux
2021013007194686615
2021013007194686616
, A.S. Cuhna, C. Caramella, A. Hollebecque, P. Burtin, D. Goéré, et al.
Cancer of the pancreas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.
Ann Oncol [Internet], (2015), 26 pp. v56-v68
[8]
M. Inoue
2021013007194686617
.
Diabetes mellitus and the risk of cancer.
Arch Intern Med [Internet], (2006), 166 pp. 1871
[9]
G. Aggarwal
2021013007194686618
, P. Kamada, S.T. Chari.
Prevalence of diabetes mellitus in pancreatic cancer compared to common cancers.
Pancreas [Internet], (2013), 42 pp. 198-201
[10]
R. Vera
2021013007194686619
2021013007194686620
, E. Dotor, J. Feliu, E. González, B. Laquente, T. Macarulla, et al.
SEOM Clinical Guideline for the treatment of pancreatic cancer (2016).
Clin Transl Oncol [Internet], (2016), 18 pp. 1172-1178
[11]
F. Turati, C. Galeone, V. Edefonti, M. Ferraroni, P. Lagiou, C. La Vecchia, et al.
A meta-analysis of coffee consumption and pancreatic cancer [Internet].
Annals of Oncology. Ann Oncol, (2012), 23 pp. 311-318
[12]
M.C. Bradley
2021013007194686621
, C.M. Hughes, M.M. Cantwell, G. Napolitano, L.J. Murray.
Non-steroidal anti-inflammatory drugs and pancreatic cancer risk: A nested case-control study.
Br J Cancer [Internet], (2010), 102 pp. 1415-1421
[13]
I. Pergolini
2021013007194686622
, K. Sahora, C.R. Ferrone, V. Morales-Oyarvide, B.M. Wolpin, L.A. Mucci, et al.
Long-term risk of pancreatic malignancy in patients with branch duct intraductal papillary mucinous neoplasm in a referral center.
Gastroenterology [Internet], (2017), 153 pp. 1284-1294
[14]
A. Yamada, Y. Komaki, F. Komaki, D. Micic, S. Zullow, A. Sakuraba.
Risk of gastrointestinal cancers in patients with cystic fibrosis: a systematic review and meta-analysis.
Lancet Oncol., (2018), 19 pp. 758-767
[15]
B.M. Wolpin
2021013007194686623
, A.T. Chan, P. Hartge, S.J. Chanock, P. Kraft, D.J. Hunter, et al.
ABO blood group and the risk of pancreatic cancer.
J Natl Cancer Inst [Internet], (2009), 101 pp. 424-431
[16]
G.M. Petersen
2021013007194686624
.
Familial pancreatic cancer.
Semin Oncol., (2016), 43 pp. 548-553
[17]
S.H. Olson
2021013007194686625
, R.C. Kurtz.
Epidemiology of pancreatic cancer and the role of family history.
J Surg Oncol., (2013), 107 pp. 1-7
[18]
K. Shindo
2021013007194686626
, J. Yu, M. Suenaga, S. Fesharakizadeh, C. Cho, A. Macgregor-Das, et al.
Deleterious germline mutations in patients with apparently sporadic pancreatic adenocarcinoma.
J Clin Oncol [Internet], (2017), 35 pp. 3382-3390
[19]
R.C. Grant
2021013007194686627
, I. Selander, A.A. Connor, S. Selvarajah, A. Borgida, L. Briollais, et al.
Prevalence of germline mutations in cancer predisposition genes in patients with pancreatic cancer.
Gastroenterology [Internet], (2015), 148 pp. 556-564
[20]
A. Rishi
2021013007194686628
, M. Goggins, L.D. Wood, R.H. Hruban.
Pathological and molecular evaluation of pancreatic neoplasms.
Semin Oncol., (2015), 42 pp. 28-39
[21]
V. Dudeja
2021013007194686629
, P.J. Allen.
Premalignant cystic neoplasms of the pancreas.
Semin Oncol., (2015), 42 pp. 70-85
[22]
S. Jones
2021013007194686630
, X. Zhang, D.W. Parsons, J.C.H. Lin, R.J. Leary, P. Angenendt, et al.
Core signaling pathways in human pancreatic cancers revealed by global genomic analyses.
Science (80-) [Internet]., (2008), 321 pp. 1801-1806
[23]
A.V. Biankin
2021013007194686631
, N. Waddell, K.S. Kassahn, M.C. Gingras, L.B. Muthuswamy, A.L. Johns, et al.
Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes.
Nature [Internet], (2012), 491 pp. 399-405
[24]
N. Waddell
2021013007194686632
, M. Pajic, A.M. Patch, D.K. Chang, K.S. Kassahn, P. Bailey, et al.
Whole genomes redefine the mutational landscape of pancreatic cancer.
Nature [Internet], (2015), 518 pp. 495-501
[25]
B.J. Raphael
2021013007194686633
, R.H. Hruban, A.J. Aguirre, R.A. Moffitt, J.J. Yeh, C. Stewart, et al.
Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma.
Cancer Cell [Internet], (2017), 32 pp. 185-203
[26]
JV
2021013007194686634
D, L S, BF B.
Expression of cytokeratins 7 and 20 in carcinomas of the extrahepatic biliary tract, pancreas, and gallbladder.
Arch Pathol Lab Med [Internet], (2000), 124
[27]
M. Porta
2021013007194686635
, X. Fabregat, N. Malats, L. Guarner, A. Carrato, A. De Miguel, et al.
Exocrine pancreatic cancer: Symptoms at presentation and their relation to tumour site and stage.
Clin Transl Oncol [Internet]., (2005), 7 pp. 189-197
[28]
H. Furukawa
2021013007194686636
, S. Okada, H. Saisho, J. Ariyama, E. Karasawa, A. Nakaizumi, et al.
Clinicopathologic features of small pancreatic adenocarcinoma: A collective study.
Cancer [Internet], (1996), 78 pp. 986-990
[29]
V.R. Mujica
2021013007194686637
, J.S. Barkin, V.L.W. Go.
Acute pancreatitis secondary to pancreatic carcinoma.
Pancreas [Internet]., (2000), 21 pp. 329-332
[30]
D.K. Pleskow
2021013007194686638
, H.J. Berger, J. Gyves, E. Allen, A. McLean, D.K. Podolsky.
Evaluation of a serologic marker, CA19-9, in the diagnosis of pancreatic cancer.
Ann Intern Med [Internet], (1989), 110 pp. 704-709
[31]
G. Ćwik
2021013007194686639
, G. Wallner, T. Skoczylas, A. Ciechański, K. Zinkiewicz.
Cancer antigens 19-9 and 125 in the differential diagnosis of pancreatic mass lesions.
Arch Surg [Internet], (2006), 141 pp. 968-973
[32]
U.K. Ballehaninna
2021013007194686640
, R.S. Chamberlain.
The clinical utility of serum CA 19-9 in the diagnosis, prognosis and management of pancreatic adenocarcinoma: An evidence based appraisal.
J Gastrointest Oncol [Internet], (2012), 3 pp. 105-119
[33]
N.R. Maisey
2021013007194686641
, A.R. Norman, A. Hill, A. Massey, J. Oates, D. Cunningham.
CA19-9 as a prognostic factor in inoperable pancreatic cancer: The implication for clinical trials.
Br J Cancer [Internet], (2005), 93 pp. 740-743
[34]
A.C. Berger
2021013007194686642
, M. García, J.P. Hoffman, W.F. Regine, R.A. Abrams, H. Safran, et al.
Postresection CA 19-9 predicts overall survival in patients with pancreatic cancer treated with adjuvant chemoradiation: A prospective validation by RTOG 9704.
J Clin Oncol [Internet], (2008), 26 pp. 5918-5922
[35]
W.S. Koom
2021013007194686643
, J. Seong, Y.B. Kim, H.O. Pyun, S.Y. Song.
CA 19-9 as a Predictor for Response and Survival in Advanced Pancreatic Cancer Patients Treated With Chemoradiotherapy.
Int J Radiat Oncol Biol Phys [Internet], (2009), 73 pp. 1148-1154
[36]
N. Kondo
2021013007194686644
, Y. Murakami, K. Uemura, Y. Hayashidani, T. Sudo, Y. Hashimoto, et al.
Prognostic impact of perioperative serum CA 19-9 levels in patients with resectable pancreatic cancer.
Ann Surg Oncol [Internet], (2010), 17 pp. 2321-2329
[37]
J.L. Humphris
2021013007194686645
, D.K. Chang, A.L. Johns, C.J. Scarlett, M. Pajic, M.D. Jones, et al.
The prognostic and predictive value of serum CA19.9 in pancreatic cancer.
Ann Oncol [Internet]., (2012), 23 pp. 1713-1722
[38]
S.J. Hessel
2021013007194686646
, S.S. Siegelman, B.J. McNeil, R. Sanders, D.F. Adams, P.O. Alderson, et al.
A prospective evaluation of computed tomography and ultrasound of the pancreas.
Radiology [Internet]., (1982), 143 pp. 129-133
[39]
S. Bipat, S.K.S. Saffire, O.M. Van Delden, P.M.M. Bossuyt, D.J. Gouma, J.S. Laméris, et al.
Ultrasonography, computed tomography and magnetic resonance imaging for diagnosis and determining resectability of pancreatic adenocarcinoma: A meta-analysis.
J Comput Assist Tomogr [Internet]., (2005), 29 pp. 438-445
[40]
C. Valls
2021013007194686647
, E. Andía, A. Sánchez, J. Fabregat, O. Pozuelo, J.C. Quintero, et al.
Dual-phase helical CT of pancreatic adenocarcinoma: Assessment of resectability before surgery.
Am J Roentgenol [Internet]., (2002), 178 pp. 821-826
[41]
Y.L. Bronstein
2021013007194686648
, E.M. Loyer, H. Kaur, H. Choi, C. David, R.A. DuBrow, et al.
Detection of Small Pancreatic Tumors with Multiphasic Helical CT.
Am J Roentgenol [Internet]., (2004), 182 pp. 619-623
[42]
M.M. Al-Hawary
2021013007194686649
, I.R. Francis, S.T. Chari, E.K. Fishman, D.M. Hough, D.S. Lu, et al.
Pancreatic ductal adenocarcinoma radiology reporting template: Consensus statement of the society of abdominal radiology and the American pancreatic association.
Gastroenterology [Internet]., (2014), 146
[43]
H.E. Adamek
2021013007194686650
, J. Albert, H. Breer, M. Weitz, D. Schilling, J.F. Riemann.
Pancreatic cancer detection with magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography: A prospective controlled study.
Lancet [Internet]., (2000), 356 pp. 190-193
[44]
H. Nawaz
2021013007194686651
, C. Yi-Fan, J. Kloke, A. Khalid, K. McGrath, D. Landsittel, et al.
Performance characteristics of endoscopic ultrasound in the staging of pancreatic cancer: A meta-analysis.
J Pancreas [Internet]., (2013), 14 pp. 484-497
[45]
C. Niederau
2021013007194686652
, J.H. Grendell.
Diagnosis of pancreatic carcinoma: Imaging techniques and tumor markers.
Pancreas [Internet]., (1992), pp. 66-86
[46]
N. Ergul
2021013007194686653
, C. Gundogan, M. Tozlu, H. Toprak, H. Kadioglu, M. Aydin, et al.
Role of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in diagnosis and management of pancreatic cancer; comparison with Multidetector Row Computed Tomography, Magnetic Resonance Imaging and Endoscopic Ultrasonography.
Rev Esp Med Nucl Imagen Mol [Internet], (2014), 33 pp. 159-164
[47]
P.J. Allen
2021013007194686654
, D. Kuk, C.F.Del Castillo, O. Basturk, C.L. Wolfgang, J.L. Cameron, et al.
Multi-institutional validation study of the American Joint Commission on Cancer (8th ed) changes for Tand N staging in patients with pancreatic adenocarcinoma.
Ann Surg [Internet]., (2017), 265 pp. 185-191
[48]
D.P. Ryan
2021013007194686655
, T.S. Hong, N. Bardeesy.
Pancreatic adenocarcinoma.
N Engl J Med., (2014), 371 pp. 1039-1049
[49]
J.C. Wong
2021013007194686656
, D.S.K. Lu.
Staging of Pancreatic Adenocarcinoma by Imaging Studies.
Clin Gastroenterol Hepatol [Internet], (2008), 6 pp. 1301-1308
[50]
M.H.G. Katz
2021013007194686657
, P.W.T. Pisters, D.B. Evans, C.C. Sun, J.E. Lee, J.B. Fleming, et al.
Borderline Resectable Pancreatic Cancer: The Importance of This Emerging Stage of Disease.
J Am Coll Surg [Internet]., (2008), 206 pp. 833-846
[51]
M.P. Callery
2021013007194686658
, K.J. Chang, E.K. Fishman, M.S. Talamonti, L. William Traverso, D.C. Linehan.
Pretreatment assessment of resectable and borderline resectable pancreatic cancer: Expert consensus statement.
Ann Surg Oncol., (2009), 16 pp. 1727-1733
[52]
H. Oettle
2021013007194686659
, S. Post, P. Neuhaus, K. Gellert, J. Langrehr, K. Ridwelski, et al.
Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: A randomized controlled trial.
J Am Med Assoc [Internet]., (2007), 297 pp. 267-277
[53]
J.P. Neoptolemos
2021013007194686660
2021013007194686661
, D.H. Palmer, P. Ghaneh, E.E. Psarelli, J.W. Valle, C.M. Halloran, et al.
Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial.
Lancet [Internet]., (2017), 389 pp. 1011-1024
[54]
T. Conroy
2021013007194686662
2021013007194686663
, P. Hammel, M. Hebbar, M. Ben Abdelghani, A.C. Wei, J.-L. Raoul, et al.
FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer.
N Engl J Med [Internet]., (2018), 379 pp. 2395-2406
[55]
D.B. Evans
2021013007194686664
, G.R. Varadhachary, C.H. Crane, C.C. Sun, J.E. Lee, P.W.T. Pisters, et al.
Preoperative gemcitabine-based chemoradiation for patients with resectable adenocarcinoma of the pancreatic head.
J Clin Oncol [Internet], (2008), 26 pp. 3496-3502
[56]
C. Tinchon
2021013007194686665
, E. Hubmann, A. Pichler, F. Keil, M. Pichler, H. Rabl, et al.
Safety and efficacy of neoadjuvant FOLFIRINOX treatment in a series of patients with borderline resectable pancreatic ductal adenocarcinoma.
Acta Oncol., (2013), 52 pp. 1231-1233
[57]
M.H. Kaiser
2021013007194686666
, S.S. Ellenberg.
Pancreatic Cancer: Adjuvant Combined Radiation and Chemotherapy Following Curative Resection.
Arch Surg [Internet]., (1985), 120 pp. 899-903
[58]
H. Shinchi
2021013007194686667
, S. Takao, H. Noma, Y. Matsuo, Y. Mataki, S. Mori, et al.
Length and quality of survival after external-beam radiotherapy with concurrent continuous 5-fluorouracil infusion for locally unresectable pancreatic cancer.
Int J Radiat Oncol Biol Phys [Internet], (2002), 53 pp. 146-150
[59]
P. Hammel
2021013007194686668
, F. Huguet, J.-L. Van Laethem, D. Goldstein, B. Glimelius, P. Artru, et al.
Comparison of chemoradiotherapy (CRT) and chemotherapy (CT) in patients with a locally advanced pancreatic cancer (LAPC) controlled after 4 months of gemcitabine with or without erlotinib: Final results of the international phase III LAP 07 study.
[60]
P.J. Loehrer
2021013007194686669
, Y. Feng, H. Cardenes, L. Wagner, J.M. Brell, D. Cella, et al.
Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: An Eastern Cooperative Oncology Group trial.
J Clin Oncol [Internet]., (2011), 29 pp. 4105-4112
[61]
S. Mukherjee
2021013007194686670
, C.N. Hurt, J. Bridgewater, S. Falk, S. Cummins, H. Wasan, et al.
Gemcitabine-based or capecitabine-based chemoradiotherapy for locally advanced pancreatic cancer (SCALOP): A multicentre, randomised, phase 2 trial.
Lancet Oncol [Internet], (2013), 14 pp. 317-326
[62]
H.A. Burris
2021013007194686671
, M.J. Moore, J. Andersen, M.R. Green, M.L. Rothenberg, M.R. Modiano, et al.
Improvements in survival and clinical benefit with gemcitabine as first- line therapy for patients with advanced pancreas cancer: A randomized trial.
J Clin Oncol [Internet], (1997), 15 pp. 2403-2413
[63]
T. Conroy
2021013007194686672
2021013007194686673
, F. Desseigne, M. Ychou, O. Bouché, R. Guimbaud, Y. Bécouarn, et al.
FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer.
N Engl J Med [Internet]., (2011), 364 pp. 1817-1825
[64]
D.D. Von Hoff
2021013007194686674
2021013007194686675
, T. Ervin, F.P. Arena, E.G. Chiorean, J. Infante, M. Moore, et al.
Increased Survival in Pancreatic Cancer with nab-Paclitaxel plus Gemcitabine.
N Engl J Med [Internet], (2013), 369 pp. 1691-1703
[65]
H. Oettle
2021013007194686676
, H. Riess, J.M. Stieler, G. Heil, I. Schwaner, J. Seraphin, et al.
Second-line oxaliplatin, folinic acid, and fluorouracil versus folinic acid and fluorouracil alone for gemcitabine-refractory pancreatic cancer: Outcomes from the CONKO-003 Trial.
J Clin Oncol [Internet]., (2014), 32 pp. 2423-2429
[66]
A. Wang-Gillam
2021013007194686677
2021013007194686678
, C.P. Li, G. Bodoky, A. Dean, Y.S. Shan, G. Jameson, et al.
Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): A global, randomised, open-label, phase 3 trial.
Lancet [Internet]., (2016), 387 pp. 545-557
[67]
T. Golan
2021013007194686679
2021013007194686680
, P. Hammel, M. Reni, E. Van Cutsem, T. Macarulla, M.J. Hall, et al.
Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer.
N Engl J Med., (2019), 381 pp. 317-327
[68]
D.T. Le
2021013007194686681
, J.N. Uram, H. Wang, B.R. Bartlett, H. Kemberling, A.D. Eyring, et al.
PD-1 blockade in tumors with mismatch-repair deficiency.
N Engl J Med., (2015), 372 pp. 2509-2520
[69]
M.J. Furman
2021013007194686682
, L.A. Lambert, M.E. Sullivan, G.F. Whalen.
Rational follow-up after curative cancer resection.
J Clin Oncol., (2013), 31 pp. 1130-1133