Neue medikamentöse Konzepte bei Patienten mit kolorektalen Karzinomen und Mikrosatelliteninstabilität

Zusammenfassung

Etwa 15% aller Patienten mit kolorektalen Karzinomen zeigen eine hochgradige Mikrosatelliteninstabilität (MSI-high) im Tumorgewebe. Bei ca. ⅓ dieser Patienten liegt die Ursache an pathogenen Keimbahnvarianten der Mismatch-Reparaturgene, die zu einem Lynch-Syndrom führen. In Kombination mit klinischen Kriterien, wie den Amsterdam- oder revidierten Bethesda-Kriterien, diente ein MSI-high-Befund bislang vor allem der Identifikation von Risikopatienten. In der modernen Tumortherapie zeigt die Gruppe der MSI-high-Patienten jedoch über nahezu alle Tumorstadien hinweg Alleinstellungsmerkmale hinsichtlich der medikamentösen Tumortherapie. Nach wie vor gilt, dass MSI-high-Patienten im Stadium UICC II keine adjuvante Chemotherapie erhalten sollten. Während bei Patienten mit Fernmetastasen und MSI-high-Status Immuncheckpoint-Inhibitoren bereits in der Erstlinie regelhaft und erfolgreich eingesetzt werden, zeigen neue Daten sowohl bei lokal fortgeschrittenen Kolon- als auch bei Rektumkarzinomen im präoperativen Setting ein tiefes Ansprechen. Gerade für Rektumkarzinompatienten könnte hier ein neues therapeutisches Verfahren ohne neoadjuvante Chemotherapie und möglicherweise sogar ohne operative Versorgung etabliert werden – bei guter Verträglichkeit und Senkung der Morbidität. Demzufolge ist die universelle MSI-Testung sowohl zur Identifikation von Risikopatienten als auch zur Therapieplanung bereits heute unerlässlich.

Abstract

Approximately 15% of patients with colorectal cancer show high microsatellite instability (MSI-high) in their tumour tissue. For one third of these patients, there is a hereditary cause for this finding – that leads to the diagnosis of Lynch Syndrome. In combination with clinical findings such as the Amsterdam or the revised Bethesda criteria, MSI-high status has been used as a tool in identifying patients at risk. Today, MSI-status has gained much more importance, due to its impact on treatment decisions. Patients with UICC II cancers should not receive adjuvant treatment. For patients with distant metastases and MSI-high status, immune checkpoint inhibitors can be given as first line therapy – with tremendous success. Novel data show a deep response for immune checkpoint antibodies in patients with locally advanced colon as well as rectal cancer in a neoadjuvant setting. Especially for patients with MSI-high rectal cancer, there might be a novel therapeutic regimen utilising immune checkpoint inhibitors without neoadjuvant radio-chemotherapy and even without surgery. This could lead to a relevant reduction in morbidity in this patient cohort. In conclusion, universal MSI-testing is essential for identifying patients at risk for Lynch syndrome and for optimal decision making in treatment planning.

Schlüsselwörter

MSI - universelle Mikrosatellitentestung - PD-1 - PD-L1 - Lynch-Syndrom

Keywords

MSI - universal microsatellite analysis - PD-1 - PD-L1 - Lynch syndrome

Publication History

Received: 19 October 2022

Accepted: 10 January 2023

Article published online:
27 February 2023

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