Neoadjuvant chemoradiotherapy in rectal cancer
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memo https://doi.org/10.1007/s12254-020-00594-0
Neoadjuvant chemoradiotherapy in rectal cancer Are there new drug combinations on the horizon? Christoph Reinhold Arnold · Julian Mangesius · Robert Jäger · Ute Ganswindt
Received: 1 February 2020 / Accepted: 17 March 2020 © The Author(s) 2020
Summary Neoadjuvant chemoradiotherapy is a wellestablished standard treatment for locally advanced rectal cancer and has led to a remarkable improvement in local control. However, distant recurrences still pose a notable threat and local failure, albeit increasingly rare, can lead to unfavorable clinical situations. In this short review, we discuss three promising new strategies to improve rectal cancer treatment: total neoadjuvant therapy, short course radiotherapy, and immune checkpoint inhibitors. Keywords Colorectal carcinoma · Short-course radiotherapy · Immune-checkpoint inhibitors · Total neoadjuvant therapy · Perioperative treatment
Introduction Combined-modality therapy (CMT) consisting of surgery, radiation therapy, and chemotherapy still remains the standard treatment for stage II (T3/4 N0 M0) and III (N + M0) rectal cancer. Using this approach, the high rate of local recurrences after sole surgery has been markedly improved. Several studies have investigated the optimal array of the constituents of CMT. Today, the sequence of neoadjuvant chemoradiotherapy or short-course radiation followed by surgery (total mesorectal excision, TME) and, if necessary, adjuvant chemotherapy is most widely used. As a result, distant metastases have superseded local recurrences as the major cause of treatment failure [1–3]. Therefore, the focus has shifted C. R. Arnold, MD, PhD () · J. Mangesius, MD · R. Jäger, MD · U. Ganswindt, MD Department of Therapeutic Radiology and Oncology, Medical University of Innsbruck, Anichstraße 35, 6020 Innsbruck, Austria [email protected]
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from improving local control to reducing systemic failure.
Total neoadjuvant therapy Improvements in chemoradiotherapy have led to a significantly improved local control. However, this did not translate into improved disease-specific survival (DSS) or overall survival (OS) with distant metastases being substantially more common than local recurrence. Consequently, efforts have been undertaken to improve systemic therapy. Adjuvant chemotherapy after neoadjuvant (chemo)radiotherapy has been extensively studied but results are controversial. There is decent evidence favoring the use of adjuvant chemotherapy. In a Cochrane meta-analysis, Petersen and colleagues found a significant improvement in both disease-free survival (DFS) and OS following adjuvant chemotherapy [4]. Additionally, the CAO/ARO/AIO-04 trial and the ADORE trial, two randomized controlled trials, showed that the addition of oxaliplatin to a 5-fluorouracil (5-FU) based chemotherapy leads to a further improved DFS [5, 6]. For patients with ypN2 status and minimally regressed tumors, oxaliplatin even improved OS. Therefore, adjuvant chemotherapy is currently recommended by several guidelin
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