Neoadjuvant chemotherapy and chemoradiotherapy versus chemoradiotherapy alone in high-risk locally advanced rectal cancer: A retrospective comparison of two Dutch tertiary referral centres

Introduction: The effect of neoadjuvant chemotherapy and chemoradiotherapy in patients with locally advanced rectal cancer, at increased risk of failing current treatment regimens, is unknown. This study compared the complete response rate and long-term survival of these patients treated with or without neoadjuvant chemotherapy prior to chemoradiotherapy. Materials and methods: Patients with high-risk locally advanced rectal cancer, who were surgically treated or entered a watch and wait approach after neoadjuvant chemoradiotherapy with or without neoadjuvant chemotherapy in Erasmus Medical Centre or Catharina Hospital between 2016 and 2020, were retrospectively identified. High-risk was defined as the presence of tumour invasion into the mesorectal fascia, grade 4 extramural venous invasion, enlarged lateral lymph nodes, or tumour deposits. The primary endpoint was complete response rate, which was defined as a histopathological complete response or a sustained (during 12 months) clinical complete response. Long-term oncological outcomes were evaluated based on Kaplan-Meier and Cox regression survival analyses. Results: The neoadjuvant chemotherapy group consisted of 64 patients, of whom 61 (95.3 %) were treated with chemotherapy prior to chemoradiotherapy, the chemoradiotherapy group of 194 patients. The complete response rates were 25.0 % and 9.8 %, respectively (P = 0.002). The estimated 3-year overall survival was 92.2 % in the neoadjuvant chemotherapy group versus 66.9 % in the chemoradiotherapy group. Conclusion: Excellent oncological outcomes were observed in patients with high-risk locally advanced rectal cancer selected during a multidisciplinary team (MDT) meeting for neoadjuvant chemotherapy and chemoradiotherapy. The actual difference with patients treated with chemoradiotherapy alone should be investigated in prospective trials. Pretreatment referral to expert MDTs is encouraged.