Neoadjuvant Chemotherapy With CAPOX Versus Chemoradiation for Locally Advanced Rectal Cancer With Uninvolved Mesorectal Fascia (CONVERT): Initial Results of a Phase III Trial

Abstract

Objective: To compare neoadjuvant chemotherapy (nCT) with CAPOX alone versus neoadjuvant chemoradiotherapy (nCRT) with capecitabine in locally advanced rectal cancer (LARC) with uninvolved mesorectal fascia (MRF). Background Data: nCRT is associated with higher surgical complications, worse long-term functional outcomes, and questionable survival benefits. Comparatively, nCT alone seems a promising alternative treatment in lower-risk LARC patients with uninvolved MRF. Methods: Patients between June 2014 and October 2020 with LARC within 12 cm from the anal verge and uninvolved MRF were randomly assigned to nCT group with 4 cycles of CAPOX (Oxaliplatin 130 mg/m2 IV day 1 and Capecitabine 1000 mg/m2 twice daily for 14 d. Repeat every 3 wk) or nCRT group with Capecitabine 825 mg/m² twice daily administered orally and concurrently with radiation therapy (50 Gy/25 fractions) for 5 days per week. The primary end point is local-regional recurrence-free survival. Here we reported the results of secondary end points: histopathologic response, surgical events, and toxicity. Results: Of the 663 initially enrolled patients, 589 received the allocated treatment (nCT, n=300; nCRT, n=289). Pathologic complete response rate was 11.0% (95% CI, 7.8-15.3%) in the nCT arm and 13.8% (95% CI, 10.1-18.5%) in the nCRT arm (P=0.33). The downstaging (ypStage 0 to 1) rate was 40.8% (95% CI, 35.1-46.7%) in the nCT arm and 45.6% (95% CI, 39.7-51.7%) in the nCRT arm (P=0.27). nCT was associated with lower perioperative distant metastases rate (0.7% vs. 3.1%, P=0.03) and preventive ileostomy rate (52.2% vs. 63.6%, P=0.008) compared with nCRT. Four patients in the nCT arm received salvage nCRT because of local disease progression after nCT. Two patients in the nCT arm and 5 in the nCRT arm achieved complete clinical response and were treated with a nonsurgical approach. Similar results were observed in subgroup analysis. Conclusions: nCT achieved similar pCR and downstaging rates with lower incidence of perioperative distant metastasis and preventive ileostomy compared with nCRT. CAPOX could be an effective alternative to neoadjuvant therapy in LARC with uninvolved MRF. Long-term follow-up is needed to confirm these results.

Organ Preservation in MSS Rectal Cancer

“…58 59 The pCR rate between neoadjuvant chemotherapy especially mFOLFOXIRI regimen and NACRT is comparable in LARC without mesorectal fascial involved. 60 61 62 However, in view of microsatellite status, MSS rectal cancer is less effective to neoadjuvant chemotherapy compared with MSI-H rectal cancer. 63 More studies with heterogeneous chemotherapy regimens are ongoing which should rise our attention.…”

Neoadjuvant chemoradiotherapy with capecitabine based regimen in locally advanced rectal cancer: A retrospective study

“…[9,10] PCR rates after neoadjuvant therapy ranged from 10.9% to 32%. [11][12][13][14][15][16] The 5-year disease-free survival (DFS) was 68%, and the 10-year overall survival (OS) was 59.6% for the neoadjuvant chemoradiotherapy group of the German CAO/ARO/AIO-94 Randomized Phase III Trial. [1] Recently, more attention has been given to the total neoadjuvant treatment (TNT) [12,[17][18][19] of LARC and the management of patients with clinical complete response (cCR) by the watchand-wait strategy after nCRT for rectal cancer, [20] but long-term outcomes need to be followed.…”

“…[9,10] PCR rates after neoadjuvant therapy ranged from 10.9% to 32%. [11–16] The 5-year disease-free survival (DFS) was 68%, and the 10-year overall survival (OS) was 59.6% for the neoadjuvant chemoradiotherapy group of the German CAO/ARO/AIO-94 Randomized Phase III Trial. [1]…”

Survival outcomes of different neoadjuvant treatment regimens in patients with locally advanced rectal cancer and MRI‐detected extramural venous invasion

“…Furthermore, in the FOWARC study of patients with LARC, treatment with NCT alone resulted in comparable survival to treatment with nCRT alone or nCRT plus NCT 15 . And, in the CONVERT study, NCT alone followed by surgery was found to be an effective alternative to nCRT for patients with LARC and uninvolved mesorectal fascia (MRF) 16 …”