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Surgery Today
Published in: Surgery Today 10/2020

01-10-2020 | Pancreatic Cancer | Review Article

Pancreatic cancer treatment: better, but a long way to go

Published in: Surgery Today | Issue 10/2020

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Abstract

Remarkable progress has been made in treating pancreatic cancer over the past century, including refinement of our surgical techniques and improvements in adjuvant and neoadjuvant therapies. Despite these advances, the incidence of pancreatic cancer is rising globally, and it remains a deadly disease. In this review, we highlight the historical perspectives of pancreatic cancer treatment and outline the areas of future advancement that will assist progression towards better outcomes. Areas of future advancement include improving prevention strategies and early detection, refining our molecular understanding of pancreatic cancer, identifying more effective systemic therapies, and improving quality of life and surgical outcomes. Furthermore, systems need to be put in place to ensure all patients with pancreatic cancer receive high quality care and are given the appropriate options and sequence of therapy. This is best achieved through multidisciplinary care.
Literature
1.
De Morgagni GB. sedibus, et causis morborum per anatomen indagatis libri quinque. Venice: Remondini:; 1761.
2.
Costa JMD. On the morbid anatomy and symptoms of cancer of the pancreas. Philadelphia: J.B. Lippincott & Co.; 1858.
3.
Pourshams A, Sepanlou SG, Ikuta KS, Bisignano C, Safiri S, Roshandel G, 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. 2019;4(12):934–47.
4.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.PubMed
5.
Siegel RL, Miller KD, Jemal A. Cancer statistics 2020. CA A Cancer J Clin. 2020;70(1):7–30.
6.
Witzel O. Aus der Klinik des Herrn Prof. Trendelenburg Beiträge zur Chirurgie der Bauchorgane. Deutsche Zeitschrift für Chirurgie. 1886;24(3):326–54.
7.
Griffin JF, Poruk KE, Wolfgang CL. Pancreatic cancer surgery: past, present, and future. Chin J Cancer Res. 2015;27(4):332–48.PubMedPubMedCentral
8.
Schnelldorfer T, Sarr MG. Alessandro codivilla and the first pancreatoduodenectomy. JAMA Surgery. 2009;144(12):1179–84.
9.
Halsted WS. Contributions to the Surgery of the Bile Passages, Especially of the Common Bile-Duct. The Boston Medical and Surgical Journal. 1899;141(26):645–54.
10.
Kausch W. Das Carcinom der Papilla duodeni und seine radikale Entfernung. Beitr Klin Chir. 1912;78:439–86.
11.
12.
Whipple AO. Present-day surgery of the pancreas. N Engl J Med. 1942;226(13):515–26.
13.
Whipple AO. Observations on radical surgery for lesions of the pancreas. Surg Gynecol Obstet. 1946;82:623–31.PubMed
14.
Whipple AO. A reminiscence: pancreaticduodenectomy. Rev Surg. 1963;20:221–5.PubMed
15.
16.
Gallitano A, Fransen H, Martin RG. Carcinoma of the pancreas. Results of treatment Cancer. 1968;22(5):939–44.PubMed
17.
Crist DW, Sitzmann JV, Cameron JL. Improved hospital morbidity, mortality, and survival after the Whipple procedure. Ann Surg. 1987;206(3):358–65.PubMedPubMedCentral
18.
Birkmeyer JD, Finlayson SR, Tosteson AN, Sharp SM, Warshaw AL, Fisher ES. Effect of hospital volume on in-hospital mortality with pancreaticoduodenectomy. Surgery. 1999;125(3):250–6.PubMed
19.
Yoshioka R, Yasunaga H, Hasegawa K, Horiguchi H, Fushimi K, Aoki T, et al. Impact of hospital volume on hospital mortality, length of stay and total costs after pancreaticoduodenectomy. BJS. 2014;101(5):523–9.
20.
Torphy RJ, Friedman C, Halpern A, Chapman BC, Ahrendt SS, McCarter MM, et al. Comparing short-term and oncologic outcomes of minimally invasive versus open pancreaticoduodenectomy across low and high volume centers. Ann Surg. 2019;270(6):1147–55.PubMed
21.
Hata T, Motoi F, Ishida M, Naitoh T, Katayose Y, Egawa S, et al. Effect of hospital volume on surgical outcomes after pancreaticoduodenectomy: a systematic review and meta-analysis. Ann Surg. 2016;263(4):664–72.PubMed
22.
Kalser MH, Ellenberg SS. Pancreatic cancer Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg. 1985;120(8):899–903.PubMed
23.
Khorana AA, McKernin SE, Berlin J, Hong TS, Maitra A, Moravek C, et al. Potentially curable pancreatic adenocarcinoma: ASCO clinical practice guideline update. J Clin Oncol. 2019;37(23):2082–8.PubMed
24.
25.
Uesaka K, Boku N, Fukutomi A, Okamura Y, Konishi M, Matsumoto I, et al. Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial (JASPAC 01). Lancet. 2016;388(10041):248–57.PubMed
26.
Conroy T, Hammel P, Hebbar M, Ben Abdelghani M, Wei AC, Raoul JL, et al. FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer. N Engl J Med. 2018;379(25):2395–406.PubMed
27.
Antwi SO, Oberg AL, Shivappa N, Bamlet WR, Chaffee KG, Steck SE, et al. Pancreatic cancer: associations of inflammatory potential of diet, cigarette smoking and long-standing diabetes. Carcinogenesis. 2016;37(5):481–90.PubMedPubMedCentral
28.
Raimondi S, Maisonneuve P, Lowenfels AB. Epidemiology of pancreatic cancer: an overview. Nat Rev Gastroenterol Hepatol. 2009;6(12):699–708.PubMed
29.
Hruban RH, Canto MI, Goggins M, Schulick R, Klein AP. Update on familial pancreatic cancer. Adv Surg. 2010;44:293–311.PubMedPubMedCentral
30.
Torphy RJ, Schulick RD. Screening of patients at risk for familial pancreatic cancer: what is beneficial? Surg Clin North Am. 2018;98(1):25–35.PubMed
31.
Basturk O, Hong SM, Wood LD, Adsay NV, Albores-Saavedra J, Biankin AV, et al. A revised classification system and recommendations from the baltimore consensus meeting for neoplastic precursor lesions in the pancreas. Am J Surg Pathol. 2015;39(12):1730–41.PubMedPubMedCentral
32.
Goggins M, Overbeek KA, Brand R, Syngal S, Del Chiaro M, Bartsch DK, et al. Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium. Gut. 2020;69(1):7–17.PubMed
33.
Vasen H, Ibrahim I, Ponce CG, Slater EP, Matthai E, Carrato A, et al. Benefit of surveillance for pancreatic cancer in high-risk individuals: outcome of long-term prospective follow-up studies from three european expert centers. J Clin Oncol. 2016;34(17):2010–9.PubMed
34.
Canto MI, Almario JA, Schulick RD, Yeo CJ, Klein A, Blackford A, et al. Risk of neoplastic progression in individuals at high risk for pancreatic cancer undergoing long-term surveillance. Gastroenterology. 2018;155(3):740–751.e742.PubMed
35.
Tanaka M, Fernandez-Del Castillo C, Kamisawa T, Jang JY, Levy P, Ohtsuka T, et al. Revisions of international consensus Fukuoka guidelines for the management of IPMN of the pancreas. Pancreatology. 2017;17(5):738–53.PubMed
36.
Del Chiaro M, Besselink MG, Scholten L, Bruno MJ, Cahen DL, Gress TM, et al. European study group on cystic tumours of the pancreas. European evidence-based guidelines on pancreatic cystic neoplasms. Gut. 2018;67(5):789–804.
37.
Malesci A, Tommasini MA, Bonato C, Bocchia P, Bersani M, Zerbi A, et al. Determination of CA 19–9 antigen in serum and pancreatic juice for differential diagnosis of pancreatic adenocarcinoma from chronic pancreatitis. Gastroenterology. 1987;92(1):60–7.PubMed
38.
Engle DD, Tiriac H, Rivera KD, Pommier A, Whalen S, Oni TE, et al. The glycan CA19-9 promotes pancreatitis and pancreatic cancer in mice. Science. 2019;364(6446):1156–62.PubMedPubMedCentral
39.
Ballehaninna UK, Chamberlain RS. The clinical utility of serum CA 19–9 in the diagnosis, prognosis and management of pancreatic adenocarcinoma: an evidence based appraisal. J Gastrointest Oncol. 2012;3(2):105–19.PubMedPubMedCentral
40.
Kim J, Bamlet WR, Oberg AL, Chaffee KG, Donahue G, Cao XJ, et al. Detection of early pancreatic ductal adenocarcinoma with thrombospondin-2 and CA19–9 blood markers. Sci Transl Med. 2017;9(398):eaah5583.PubMedPubMedCentral
41.
Francis JL, Francis DA, Gunathilagan GJ. Assessment of hypercoagulability in patients with cancer using the Sonoclot Analyzer and thromboelastography. Thromb Res. 1994;74(4):335–46.PubMed
42.
Moore HB, Paniccia A, Lawson PJ, Torphy RJ, Nydam TL, Moore EE, et al. Utility of viscoelastic assays beyond coagulation: can preoperative thrombelastography indices predict tumor histology, nodal disease, and resectability in patients undergoing pancreatectomy? J Am Coll Surgeons. 2018;227(1):55–62.
43.
Jones S, Zhang X, Parsons DW, Lin JC, Leary RJ, Angenendt P, et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science. 2008;321(5897):1801–6.PubMedPubMedCentral
44.
Collisson EA, Bailey P, Chang DK, Biankin AV. Molecular subtypes of pancreatic cancer. Nat Rev Gastroenterol Hepatol. 2019;16(4):207–20.PubMed
45.
Collisson EA, Sadanandam A, Olson P, Gibb WJ, Truitt M, Gu S, et al. Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy. Nat Med. 2011;17(4):500–3.PubMedPubMedCentral
46.
Bailey P, Chang DK, Nones K, Johns AL, Patch AM, Gingras MC, et al. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature. 2016;531(7592):47–52.PubMed
47.
Moffitt RA, Marayati R, Flate EL, Volmar KE, Loeza SG, Hoadley KA, et al. Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma. Nat Genet. 2015;47(10):1168–78.PubMedPubMedCentral
48.
Aung KL, Fischer SE, Denroche RE, Jang GH, Dodd A, Creighton S, et al. Genomics-driven precision medicine for advanced pancreatic cancer: early results from the COMPASS trial. Clin Cancer Res. 2018;24(6):1344–54.PubMed
49.
Versteijne E, Suker M, Groothuis K, Akkermans-Vogelaar JM, Besselink MG, Bonsing BA, et al. Preoperative chemoradiotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer: results of the dutch randomized phase III PREOPANC Trial. J Clin Oncol. 2020;38(16):1763–73.PubMedPubMedCentral
50.
O’Reilly EM, Ferrone C. Neoadjuvant or adjuvant therapy for resectable or borderline resectable pancreatic cancer: which is preferred? J Clin Oncol. 2020;38(16):1757–9.PubMedPubMedCentral
51.
Unno M, Motoi F, Matsuyama Y, Satoi S, Matsumoto I, Aosasa S, et al. Randomized phase II/III trial of neoadjuvant chemotherapy with gemcitabine and S-1 versus upfront surgery for resectable pancreatic cancer (Prep-02/JSAP-05). J Clin Oncol. 2019;37(4_suppl):189.
52.
Royal RE, Levy C, Turner K, Mathur A, Hughes M, Kammula US, et al. Phase 2 trial of single agent Ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma. J Immunother. 2010;33(8):828–33.PubMedPubMedCentral
53.
Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012;366(26):2455–65.PubMedPubMedCentral
54.
Torphy RJ, Zhu Y, Schulick RD. Immunotherapy for pancreatic cancer: barriers and breakthroughs. Ann Gastroenterol Surg. 2018;2(4):274–81.PubMedPubMedCentral
55.
O’Reilly EM, Oh D-Y, Dhani N, Renouf DJ, Lee MA, Sun W, et al. Durvalumab with or without tremelimumab for patients with metastatic pancreatic ductal adenocarcinoma: a phase 2 randomized clinical trial. JAMA Oncology. 2019;5(10):1431–8.PubMedCentralPubMed
56.
Infante JR, Korn RL, Rosen LS, LoRusso P, Dychter SS, Zhu J, et al. Phase 1 trials of PEGylated recombinant human hyaluronidase PH20 in patients with advanced solid tumours. Br J Cancer. 2018;118(2):e3.PubMedPubMedCentral
57.
Elahi-Gedwillo KY, Carlson M, Zettervall J, Provenzano PP. Antifibrotic therapy disrupts stromal barriers and modulates the immune landscape in pancreatic ductal adenocarcinoma. Cancer Res. 2019;79(2):372–86.PubMed
58.
Doherty GJ, Tempero M, Corrie PG. HALO-109-301: a Phase III trial of PEGPH20 (with gemcitabine and nab-paclitaxel) in hyaluronic acid-high stage IV pancreatic cancer. Future Oncol. 2018;14(1):13–22.PubMed
59.
Asbun HJ, Moekotte AL, Vissers FL, Kunzler F, Cipriani F, Alseidi A, et al. The miami international evidence-based guidelines on minimally invasive pancreas resection. Ann Surg. 2020;271(1):1–14.PubMed
60.
Braga M, Pecorelli N, Ferrari D, Balzano G, Zuliani W, Castoldi R. Results of 100 consecutive laparoscopic distal pancreatectomies: postoperative outcome, cost-benefit analysis, and quality of life assessment. Surg Endosc. 2015;29(7):1871–8.PubMed
61.
de Rooij T, van Hilst J, van Santvoort H, Boerma D, van den Boezem P, Daams F, et al. Minimally invasive versus open distal pancreatectomy (LEOPARD): a multicenter patient-blinded randomized controlled trial. Ann Surg. 2019;269(1):2–9.PubMed
62.
Nassour I, Wang SC, Christie A, Augustine MM, Porembka MR, Yopp AC, et al. Minimally invasive versus open pancreaticoduodenectomy: a propensity-matched study from a national cohort of patients. Ann Surg. 2018;268(1):151–7.PubMed
63.
van Hilst J, de Rooij T, Bosscha K, Brinkman DJ, van Dieren S, Dijkgraaf MG, et al. Laparoscopic versus open pancreatoduodenectomy for pancreatic or periampullary tumours (LEOPARD-2): a multicentre, patient-blinded, randomised controlled phase 2/3 trial. Lancet Gastroenterol Hepatol. 2019;4(3):199–207.PubMed
64.
Zureikat AH, Moser AJ, Boone BA, Bartlett DL, Zenati M, Zeh HJ 3rd. 250 robotic pancreatic resections: safety and feasibility. Ann Surg. 2013;258(4):554–62.PubMed
65.
Klinkenbijl JH, Jeekel J, Sahmoud T, van Pel R, Couvreur ML, Veenhof CH, 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. 1999;230(6):776–82 (discussion 782-774).PubMedPubMedCentral
66.
Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, Hickey H, et al. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med. 2004;350(12):1200–10.PubMed
67.
Oettle H, Neuhaus P, Hochhaus A, Hartmann JT, Gellert K, Ridwelski K, et al. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA. 2013;310(14):1473–81.PubMed
68.
Neoptolemos JP, Stocken DD, Bassi C, Ghaneh P, Cunningham D, Goldstein D, et al. Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA. 2010;304(10):1073–81.PubMed
69.
Neoptolemos JP, Palmer DH, Ghaneh P, Psarelli EE, Valle JW, Halloran CM, 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. 2017;389(10073):1011–24.PubMed
70.
Tempero MA, Reni M, Riess H, Pelzer U, O'Reilly EM, Winter JM, et al. APACT: phase III, multicenter, international, open-label, randomized trial of adjuvant nab-paclitaxel plus gemcitabine (nab-P/G) vs gemcitabine (G) for surgically resected pancreatic adenocarcinoma. J Clin Oncol. 2019;37(15_suppl):4000.
Metadata
Title
Pancreatic cancer treatment: better, but a long way to go
Publication date
01-10-2020
Published in
Surgery Today / Issue 10/2020
Print ISSN: 0941-1291
Electronic ISSN: 1436-2813
DOI
https://doi.org/10.1007/s00595-020-02028-0

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