Korean Society of Coloproctology trial of consolidation chemotherapy for locally advanced mid or low rectal cancer after neoadjuvant concurrent chemoradiotherapy: KONCLUDE multicenter radomized trial.
Authors: Lee Suk-Hwan , Kim Chang Woo , Kim Ik Yong , Kang Byung Mo , Kim Ji Yeon , Bae Ki Beom , Bae Byung-Noe , Baek Seong Kyu , Park Won Cheol , Son Gyung Mo , Lee Yoon Suk , Lee Soo Young , Lee Jaeim 
Published: June 2024

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Background: Recently, OPRA and RAPIDO trials showed promising results regarding the increase in pCR or clinical CR(cCR) and suggested the possibilities of non-operative management(NoM) of rectal cancer. To prove the effect of consolidation chemotherapy on rectal cancer, the authors performed a randomized phase 3 clinical trial comparing 3-cycle of modified FOLFOX-6 consolidation chemotherapy with the standard treatment group. The primary end-points were pCR and 3-year disease-free survival. Herein, we report the pCR and perioperative outcomes between the two groups. This trial is registered at www. clinicaltrials. gov ( NCT02843191) Methods: Patients were eligible if they were aged between 20 and 75, cT3c/dN0-2M0 or threatening circumferential resection margin(CRM) on initial MRI, had a biopsy-proven, newly diagnosed, primary, locally advanced rectal adenocarcinoma with ECOG performance 0-2. To avoid any bias resulting from the differences in time between the completion of neoadjuvant CRT and operation, the authors set the operation time at nine weeks after the completion of neoadjuvant CRT. Results: From January 2017 to June 2023, the authors enrolled 358 patients with stage II or III rectal cancer. Men comprised 76.8% with a mean age of 60.2 ± 7.9 years. After the exclusion or drop-out, there were 156 and 154 patients in the standard (STAN) and consolidation (CON) group, respectively. The mean tumor height from the anal verge was 6.1 ± 3.0 cm. Most patients (99.4%) tolerated the consolidation chemotherapy. Grade 3/4 adverse events occurred in 14 patients (9.1%) in the consolidation chemotherapy group. The interval from the completion of neoadjuvant CRT and operation was 8.7 ± 1.6 weeks (STAN) and 9.2 ± 1.2 weeks (CON) (p=0.005). The minimally invasive surgery was performed at 98.7%(laparoscopy 62.9%, robotics 35.8%). The sphincter-saving operation was performed in 88.1%. The R0 resection rate was 98.1%, with a complete TME quality rate of 97.7%. There was no operative mortality. Clavien-Dindo 3b/4 complications occurring in 9.6%(STAN) and 5.8% (CON). The pCR rate was not different between the two groups (STAN 16.0% vs. CON 22.1% p=0.194). Most patients tolerated the adjuvant chemotherapy with lower overall chemotherapy-related adverse events in the consolidation chemotherapy group ( STAN 76.3% vs. CON 59.3%). Conclusions: The consolidation group achieved more pCR than the standard group, however it did not meet the hypothesis of the KONCLUDE trial. The three cycles of modified FOLFOX 6 consolidation chemotherapy might not be enough to achieve pCR in advanced mid or low-rectal cancer patients. This trial justifies future trials with a total neoadjuvant therapy (TNT) strategy. Clinical trial information: NCT02843191 .