Pathological Complete Response after Chemoradiotherapy in Locally Advanced Rectal Cancer: Capecitabine or 5-Fluorouracil? Which is Better?

Introduction: Infusional 5-fluorouracil (5FU) has been the standard radiation sensitizer in patients undergoing preoperative long-course chemoradiotherapy (CRT) for locally advanced rectal cancer. It has been stablished non-inferior results, in terms of pathological complete response (pCR), of capecitabine compared with 5FU administered in bolus or continuous infusion schedule in two phase III studies1,2. Recently it has been reported a reduced rate of pathological complete response related to capecitabine compared to 5FU in a large retrospective Australian cohort3. It seems the ypT0ypN0 and ypT1ypN0 pathological stage after CRT have a similar good survival. Methods: Patients of the Catalan Institute of Oncology-Dr. Josep Trueta Hospital in Girona (Spain) who underwent CRT and surgery for biopsy-proven locally advanced rectal adenocarcinoma between January 2014 and July 2017 were included from a retrospective-prospective recruited database. Data from 2014 to 2015 has been collected retrospectively and data from 2016 to 2017 prospectively. The evaluation of the pathological tumor regression grade was made following the indications of the American Joint Committee for Cancer included in the AJCC Cancer Staging Manual 7.0 version. We consider pCR if the pathology report informs ypT0-1 ypN0, Tumor Regression Grade=0. This is an observational academic study and the main objective is to improve the knowledge and outcome of patients affected by locally advanced rectal cancer. No additional procedures or therapeutics has been performed over the patients. We consider there was not necessary informed consent of the patients because of these two last reasons. Results: To compare the efficacy of capecitabine and 5FU as radiosensitizer in terms of Pathological Complete Response, 153 patients have been included in the final analysis. 105 (68.6%) men and 48 (31.4%) women. 97.4% stage III and 2.8% stage II. 74.5% was staged as cT3N1 or cT3N2 (UICC 7th edition) by Magnetic Resonance Imaging. 130 (85%) and 22 (15%) patients received 5FU and capecitabine respectively as radiosensitizer. Median Dose of pre-operative radiotherapy was 50.44 Gy. Median time from end of CRT to surgery was 10.6 weeks (range 3-61, Typical Deviation 5.612). Median level of Carcinoembryonic Antigen was 18.91 ng/mL (normal range: 0 to 4.3 ng/mL). 43 patients had pCR (41 received 5FU and 2 received capecitabine). Exact Fisher Test found statistical differences between two arms (p = 0.039). Conclusion: 5FU improves the probability to pCR in locally advanced rectal cancer compared to capecitabine in our cohort. This results recommend 5FU concomitant to radiotherapy as standard of treatment in pre-operative setting of locally advanced rectal cancer in our center in the same way as data reported by Jootun N et al in January 2018.