Rektumkarzinom: Aktueller Stand der multimodalen Therapie – wann und wie?

Zusammenfassung

Die neoadjuvante Langzeit-Radiochemotherapie (5-FU und 50,4 Gy) gefolgt von qualitätsgesicherter tiefer anteriorer Rektumresektion unter kompletter Mitnahme des Mesorektums (totale mesorektale Exzision, TME) stellt die Standardtherapie des lokal fortgeschrittenen Rektumkarzinoms (UICC II und III) des mittleren und unteren Rek­tumdrittels dar. Die neoadjuvante Radiochemotherapie ist der adjuvanten deutlich überlegen durch eine höhere R0-Resektionsrate und das deutlich niedrigere Rezidivrisiko. Diese neo­adju­vante multimodale Strategie hat das Lokal­rezi­div­risiko nach 5 und 10 Jahren auf unter 10 % gesenkt. Allerdings bleibt das Gesamtüberleben der Patienten davon unverändert und die Entwicklung von Lebermetastasen (35–45 %) ist ein nach wie vor ungelöstes Problem. Zusätzlich erhalten etwa 25 % der Patienten keine adjuvante Chemotherapie aufgrund chirurgischer Komplikationen oder mangelnder Compliance der Patienten. Die Integration von effektiven Chemotherapeutika in das multimodale Therapiekonzept stellt deswegen eine besondere Herausforderung dar. Mit der Erweiterung der therapeutischen Optionen bleibt allerdings die Frage zu klären, zu welchem Zeitpunkt und in welcher Dosierung / Dosisdichte Chemotherapeutika zukünftig appliziert werden sollen. Zur Vermeidung unnötiger, the­ra­pieassoziier­ter Toxizität und unter Gewährleistung maximaler Effektivität stellt die Identifizierung geeigneter Patienten für ein niedrig toxisches Standardregime gegenüber Patienten mit der Notwendigkeit einer intensivierten multimodalen Therapie anhand prädiktiver und prognostischer Biomarker die vielversprechendste Option zur zukünftigen individualisierten, rezidivadaptierten Therapie dar. Die Implementierung dieser aktuellen Entwicklungen in multizentrische Therapiestudien erfordert eine ganz besonders enge interdisziplinäre Zusammenarbeit von Strahlentherapeuten, Onkologen, Gastroenterologen, Pathologen und Chirurgen. 

Abstract

Preoperative 5-fluorouracil-based radiochemotherapy (RCT) followed by quality assessed total mesorectal excision (TME surgery) are the two most important elements of multimodal treatment for patients with locally advanced rectal cancer (UICC stages II and III). The optimum sequence of these neoadjuvant modalities complemented by adjuvant (postoperative) chemother­apy, has been addressed in several randomised trials. Especially within the trials of the German Rectal Cancer Study Group (GRCSG), preoperative RCT has been shown to be superior to postoperative treatment for a variety of endpoints (patho­log­ically confirmed complete tumour remission (pCR), RCT-induced tumour regression, R0 resection rates (including circumferential resection margins) and long-term locoregional control). This neoadjuvant multimodal strategy has decreased the 5-year and 10-year local recurrence rates below 10 %, and the development of distant metastases (e. g., 35 % to 45 % liver metastases) remains the predominant reason for failure. Furthermore, approximately 25 % of patients do not receive adjuvant chemotherapy, mainly due to surgical complications, patients’ refusal or the investigator’s discretion. Thus, today, integrating more effective systemic therapy into (preopera­tive) multimodal regimens is the most accepted challenge! But from the clinical point of view this demand is also a dilemma. The question to be addressed is how and when to apply intensified systemic therapy with adequate dosage and inten­sity as well as acceptable treatment-associated ­toxicity. The increase of therapeutic options requires valid predictive biomarkers that may help to stratify patients into regimens associated with low toxicity (5-FU monotherapy alone) or into more intensified treatment for better long-term outcome. In summary, the use of biomarkers for individualised risk-adapted treatment is one of the most promising areas of clinical investigations, not only in rectal cancer. The assessment of individual ­tumour response, toxi­city, and prognosis during multimodal treatment of rectal cancer as a model of a very common solid tumour offers radio­oncologists, surgeons, pathologists, gastro­enterologists as well as oncologists immense insights into the under­standing of tumour biology. 

Schlüsselwörter

Rektumkarzinom - multimodale Therapie - Algorithmus - präoperative Radiochemotherapie

Key words

rectal cancer - multimodal therapy - algorithms - preoperative radiochemotherapy

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