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Should Biologic Targeted Agents Be Combined with Preoperative Chemoradiation in Rectal Cancer?

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Multidisciplinary Management of Rectal Cancer

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Abstract

Over the last decades, the clinical management of locally advanced rectal cancer (LARC) has changed substantially. Improvements in preoperative staging techniques with magnetic resonance imaging (MRI) and endoscopic ultrasonography (EUS), the use of neoadjuvant therapy, improved and innovative surgical approach, and standardized recommendations for histopathological analysis (tumor regression grading (TRG) and circumferential resection margin (CRM) involvement) have gradually improved local control rates and the outcome of patients with rectal cancer. Preoperative radiotherapy with concomitant infusional 5-fluorouracil (5FU) or oral capecitabine, followed by total mesorectal excision (TME), has become the standard of care for patients with T3/T4 or lymph node positive rectal cancer in most Western countries, reducing local failure rates to <10%. The pathological complete response (pCR), defined by an absence of residual tumor in the resected specimen after preoperative therapy, is reported between 0% and 31% in recent phase II/III trials with these regimens. Despite these advancements, the rate of distant metastases remains high: around 30–40%. Therefore, the challenge remains to optimize further rectal cancer treatment. With the increased understanding of molecular pathways that drive colorectal cancer and the ongoing development of biological agents targeting these pathways, recent trials have investigated the role of targeted biologic agents in combination with cytotoxic drugs in preoperative chemoradiation regimens. By doing so, it is the hope to further improve local control, resectability, and sphincter preservation rates but more importantly to decrease the risk of distant recurrence and ultimately to improve overall survival. This manuscript discusses the integration of epidermal growth factor receptor (EGFR) inhibition and vascular endothelial growth factor (VEGF) inhibition in neoadjuvant treatment strategies for locally advanced rectal cancer.

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Authors and Affiliations

  1. Department of Digestive Oncology, University Hospital Gasthuisberg, Leuven, 3000, Belgium

    Pieter-Jan Cuyle & Eric Van Cutsem

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  1. Pieter-Jan Cuyle
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  2. Eric Van Cutsem
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Correspondence to Eric Van Cutsem .

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Editors and Affiliations

  1. , Dept. of Radiation Therapy, Università Cattolica S.Cuore, Largo A.Gemelli 8, Rome, 00168, Italy

    Vincenzo Valentini

  2. Klinik und Poliklinik Innere Medizin IV, Abt. Hämatologie und Onkologie, Universitätsklinikum Halle-Wittenberg, Ernst-Grube-Str. 40, Halle, 06097, Sachsen-Anhalt, Germany

    Hans-Joachim Schmoll

  3. Leiden University Medical Center, Albinusdreef 2, Leiden, 2333 ZA, Netherlands

    Cornelis J. H. van de Velde

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Cuyle, PJ., Van Cutsem, E. (2012). Should Biologic Targeted Agents Be Combined with Preoperative Chemoradiation in Rectal Cancer?. In: Valentini, V., Schmoll, HJ., van de Velde, C. (eds) Multidisciplinary Management of Rectal Cancer. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-25005-7_19

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  • DOI: https://doi.org/10.1007/978-3-642-25005-7_19

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