Adjuvant chemotherapy after preoperative chemoradiotherapy for rectal cancer

Abstract

We read with interest the ‘Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial’ by Breugom et al. [1.Breugom A.J. van Gijn W. Muller E.W. et al.Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial.Ann Oncol. 2015; 26: 696-701Abstract Full Text Full Text PDF PubMed Scopus (258) Google Scholar]. The current standard of care for locally advanced rectal cancer is preoperative chemoradiation followed by radical resection. Irrespective of the final pathology, a full course of adjuvant chemotherapy is recommended. However, there is insufficient evidence to lend support to this strategy. Breugom et al. [1.Breugom A.J. van Gijn W. Muller E.W. et al.Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial.Ann Oncol. 2015; 26: 696-701Abstract Full Text Full Text PDF PubMed Scopus (258) Google Scholar] wanted to show the role of adjuvant chemotherapy for rectal cancer patients treated according to the current guidelines. However, there are some limitations in the study. One of those limitations is related to the fact that about half of the patients (202/437, 46.2%) were not staged with CT or MRI or endorectal ultrasonography before preoperative (chemo)radiotherapy. But, initial clinical staging before preoperative chemoradiotherapy is of great importance in tailoring relevant treatment. Moreover, most of the patients received only radiotherapy in preoperative setting (376/437, 86%; came from PROCTOR trial) in this trial. But the only radiotherapy arm in preoperative treatment group was not separated during the analyses. When fluorouracil-based chemotherapy was concurrently used with preoperative long-course radiotherapy (preoperative radiotherapy and chemotherapy), it significantly increased local control compared with preoperative radiotherapy alone [2.Gerard J.P. Conroy T. Bonnetain F. et al.Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3–4 rectal cancers: result of FFCD 9203.J Clin Oncol. 2006; 24: 4620-4625Crossref PubMed Scopus (1421) Google Scholar, 3.Bosset J.F. Collette L. Calais G. et al.Chemotherapy with preoperative radiotherapy with rectal cancer.N Engl J Med. 2006; 335: 1114-1123Crossref Scopus (2165) Google Scholar]. From our point of view, another limitation is this situation. To separate the only radiotherapy arm would be more impressive for a possible change in practice. Moreover, even though the patients were grouped according to tumour location from anal verge, researchers did not explain the effects of location on overall survival, disease-free survival, overall recurrence rate, locoregional and distant recurrence rate. However, another study of Breugom et al. [4.Breugom A.J. Swets M. Bosset J.F. et al.Adjuvant chemotherapy after preoperative (chemo)radiotherapy and surgery for patients with rectal cancer: a systematic review and meta-analysis of individual patient data.Lancet Oncol. 2015; 16: 200-207Abstract Full Text Full Text PDF PubMed Scopus (385) Google Scholar] showed that fluorouracil-based adjuvant chemotherapy had no benefit on overall survival, disease-free survival and distant recurrences if the tumour was located within 15 cm of the anal verge, adjuvant chemotherapy might improve disease-free survival and distant recurrences in patients with a tumour located 10–15 cm from the anal verge. In our opinion, the last limitation of the study is the use of heterogeneous adjuvant chemotherapeutic agents between the groups. There is no evidence to show that the use of bolus fluorouracil-based chemotherapy versus oral capecitabine has the same effectiveness; only the effectiveness of the use of infusional fluorouracil-based chemotherapy was shown by Hofheinz et al. in their non-inferiority study [5.Hofheinz R.D. Wenz F. Post S. et al.Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial.Lancet Oncol. 2012; 13: 579-588Abstract Full Text Full Text PDF PubMed Scopus (375) Google Scholar]. The authors have declared no conflicts of interest.