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Multimodality treatment approaches in pancreatic cancer: Current status and future perspectives

Multimodale Behandlungsansätze bei Pankreaskarzinom: Gegenwart und Zukunft

  • Main Topics: Surgical And Multimodality Treatment Of Gastrointestinal Cancer
  • Published:
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Summary

Background: Pancreatic cancer is characterized by early local and systemic spread and low complete resection rates. Patients are highly symptomatic and the sensitivity of the tumour cells towards irradiation and most of the currently available chemotherapeutic agents is low. These factors account for the dismal prognosis.

Methods: A critical analysis of adjuvant and neoadjuvant treatment results for resectable pancreatic cancer is presented. Management issues for unresectable pancreatic cancer and novel therapeutic approaches are discussed.

Results: Recently, a gradual improvement in results from surgery and in chemotherapeutic efficacy has been observed. The local disease extension and the rapid dissemination call for a multimodality treatment consisting of surgery, if possible, radiotherapy, and efficient systemic chemotherapy both in the (neo)adjuvant setting as well as in locally advanced unresectable tumours. In resectable cancers, neoadjuvant treatment seems preferable, but should be followed within clinical trials. Local chemotherapies or chemoimmunotherapies have provided promising results but must be considered experimental. New cytotoxic agents are used for improved radiosensitization and for better systemic disease control. Their optimal dosage, sequence, and combination with surgery and/or radiotherapy still have to be established.

Conclusions: Improvement may be expected from a better understanding of tumour biology, the developing armoury of drugs targeting angiogenesis, oncogene signalling, and metastatic potential as well as from vaccination strategies incorporated into multimodality treatments. Finally, genetic analyses will allow better risk stratification and individualization of treatment options.

Zusammenfassung

Grundlagen: Das Pankreaskarzinom ist durch seine Neigung zu frühen lokalen und systemischen Metastasierungen und eine niedrige chirurgische Resektionsrate gekennzeichnet. Die Patienten sind meist hochgradig symptomatisch und die Sensitivität der Tumorzellen gegenüber Strahlentherapie und den meisten derzeit zur Verfügung stehenden chemotherapeutischen Substanzen ist gering. Diese Faktoren sind letztlich für die ungünstige Prognose verantwortlich.

Methodik: Eine kritische Analyse adjuvanter und neoadjuvanter Therapien des resektablen Pankreaskarzinoms werden dargestellt. Die Behandlung des nicht-resektablen Pankreaskarzinoms und neue Therapieansätze werden diskutiert.

Ergebnisse: Eine stete Verbesserung der chirurgischen Resultate und der chemotherapeutischen Effizienz wurden beobachtet. Die lokale Krankheitsausdehnung und die schnelle Metastasierungsneigung verlangen nach einem mutlimodalen Therapieansatz aus Chirurgie, sofern möglich Bestrahlung und einer effizienten Chemotherapie. Dies gilt für den neoadjuvanten Ansatz ebenso wie für die Behandlung des lokal fortgeschrittenen inoperablen Tumors. Bei Resektabilität sollten neoadjuvante Therapieverfahren nach Möglichkeit innerhalb klinischer Studien verfolgt werden. Lokale Chemo- oder Immunchemotherapien, obwohl experimentell, haben vielversprechende Resultate in kleinen Studien gezeigt. Neue Chemotherapeutika werden zur verbesserten Radiosensitivierung und zur besseren Kontrolle der Systemkrankheit eingesetzt. Ihre optimale Dosis, Sequenz und Kombination mit Chirurgie und/oder Bestrahlung bleibt noch zu etablieren.

Schlußfolgerungen: Verbesserungen der Behandlungsergebnisse können vor allem von einem klareren Verständnis der Tumorbiologie und damit letztlich der Entwicklung von Substanzen erwartet werden, die die Tumorneoangiogenese, die onkogene Signalübertragung und das metastastische Potential angreifen. Gemeinsam mit Tumorvaccinationsverfahren werden diese Strategien in multimodale Behandlungskonzepte eingebaut werden. Letztlich werden genetische Analysen eine bessere Risikostratifikation und Individualisierung der Behandlungsoptionen erlauben.

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    R. Greil M. D.

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Greil, R. Multimodality treatment approaches in pancreatic cancer: Current status and future perspectives. Eur. Surg. 34, 42–57 (2002). https://doi.org/10.1046/j.1563-2563.2002.02016.x

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