The safety and efficacy of total mesorectal excision (<scp>TME</scp>) surgery following dose‐escalation: Surgical outcomes from the organ preservation in early rectal adenocarcinoma (<scp>OPERA</scp>) trial, a European multicentre phase 3 randomised trial (<scp>NCT02505750</scp>)

AbstractAimNonsurgical treatment with chemoradiotherapy for rectal cancer is gaining interest as it avoids total mesorectal excision (TME) surgery and stoma. The OPERA trial aims to evaluate whether dose escalation with contact X‐ray brachytherapy (CXB) boost improves organ preservation compared to external beam radiotherapy (EBRT) boost. It has been suggested that dose escalation adversely affects surgical outcomes and therefore we report outcomes following TME in OPERA at 36 months.MethodsOPERA is a European multicentre phase 3 trial (NCT02505750) which randomises patients with cT2‐3a‐b, cN0‐1, M0 to EBCRT (45 Gy in 25 fractions over 5 weeks with oral capecitabine 825 mg/m2) followed by EBRT boost (9 Gy in 5 fractions over 5 days) versus EBCRT followed by CXB boost (90 Gy in 3 fractions over 4 weeks). Patients were assessed at 14, 20 and 24 weeks from the start of treatment. Watch and wait management was adopted for patients who achieved a clinical complete response (cCR) at 24 weeks following treatment. Either local excision (LE) or TME surgery was offered for residual disease or local regrowth, according to patient and surgeon preference. Surgical morbidity and mortality were recorded prospectively.ResultsBetween July 2015 and June 2020, 148 patients were randomised of which 141 were evaluable in March 2022. At median follow‐up of 38.2 months (range: 34.2–42.5), surgery was performed for 66 (47%) patients. A total of 27 (20%) patients had local excision and 39 (29%) had TME surgery, 22/39 (56%) underwent anterior resection and 17/39 (44%) underwent abdominoperineal excision of the rectum. The R0 resection rate was 87%. There were no deaths, and six patients (15%) had Clavien‐Dindo IIIb complications. Whilst there was a statistically significant decrease in the TME rate following CXB boost (HR 0.38, 95% CI: 0.19–0.74, p = 0.00419) there was no difference in surgical outcomes between patients who received EBRT and CXB boost.ConclusionDose escalation can facilitate nonsurgical treatment for cT2‐3 rectal cancer patients who are fit but wish to avoid TME surgery and stoma. If TME surgery is required, then it can be performed safely and effectively.</jats:sec

Late toxicities and clinical outcome at 5 years of the ACCORD 12/0405-PRODIGE 02 trial comparing two neoadjuvant chemoradiotherapy regimens for intermediate-risk rectal cancer

IF 11.855International audienceBackgroundOutcome of intermediate risk rectal cancer may be improved by the addition of oxaliplatin during 5-fluoruracil concomitant neoadjuvant chemoradiotherapy. The purpose of this study is to analyze the main clinical results of the ACCORD12 trial (NCT00227747) in rectal cancer after 5 years of follow-up.Patients and methodsInclusion criteria were as follows: rectal adenocarcinoma accessible to digital examination staged T3-T4 Nx M0 (or T2 Nx distal anterior rectum). Two neoadjuvant chemoradiotherapy regimens were randomized: CAP45 (RT 45 Gy + capecitabine) and CAPOX50 (RT 50 Gy + capecitabine and oxaliplatin). Main end point was sterilization of the operative specimen. Acute and late toxicities were prospectively analyzed with dedicated questionnaires.ResultsBetween November 2005 and July 2008, 598 patients were included in the trial. After a median follow-up of 60.2 months, there was no difference between treatment arms in multivariate analysis either for disease-free survival or overall survival (OS) [P = 0.9, hazard ratio (HR)=1.02; 95% confidence interval (CI), 0.76–1.36 and P = 0.3, HR = 0.87; 95% CI, 0.66–1.15, respectively]. There was also no difference of local control in univariate analysis (P = 0.7, HR = 0.92; 95% CI, 0.51–1.66). Late toxicities were acceptable with 1.6% G3 anal incontinence, and <1% G3 diarrhea, G3 rectal bleeding, G3 stenosis, G3–4 pain, G3 urinary incontinence, G3 urinary retention and G3 skeletal toxicity. There was a slight increase of erectile dysfunction over time with a 63% rate of erectile dysfunction at 5 years. There was no significant statistical difference for these toxicities between treatment arms.ConclusionsThe CAPOX50 regimen did not improve local control, disease-free survival and overall survival in the ACCORD12 trial. Late toxicities did not differ between treatment arms