KEY TAKEAWAYS
- The Phase II OPRA randomized trial evaluated the DFS of patients with locally advanced rectal cancer who underwent total neoadjuvant therapy and were treated with either INCT-CRT.
- The trial involved 324 patients with stage II or III rectal adenocarcinoma who received a 4-month infusional fluorouracil-leucovorin-oxaliplatin or capecitabine-oxaliplatin.
- The three-year DFS rate for INCT-CRT and CRT-CNCT groups was 76%, consistent with historical observations.
- The patients who underwent TME after restaging and those who underwent TME after regrowth exhibited comparable DFS rates.
- The OPRA trial demonstrated that a watch-and-wait approach is a feasible and effective option for organ preservation in locally advanced rectal cancer patients.
Limited prospective data exist regarding the efficacy of a watch-and-wait approach for achieving organ preservation in patients with locally advanced rectal cancer who have undergone total neoadjuvant therapy. In a prospective, randomized phase II study, the outcomes of 324 patients diagnosed with stage II or III rectal adenocarcinoma were evaluated. The patients were treated with induction chemotherapy followed by chemoradiotherapy (INCT-CRT) or chemoradiotherapy followed by consolidation chemotherapy (CRT-CNCT) and underwent either total mesorectal excision (TME) or a watch-and-wait approach based on tumor response. Both cohorts were administered a 4-month infusional fluorouracil-leucovorin-oxaliplatin or capecitabine-oxaliplatin and subjected to 5,000 to 5,600 cGy of radiation in conjunction with either continuous infusion fluorouracil or capecitabine during radiotherapy. The clinical trial was structured as two independent studies, with the primary endpoint for both groups being disease-free survival (DFS). A null hypothesis was established by comparing the results to historical data. The secondary endpoint pertained to TME-free survival.
The median duration of follow-up was three years. The three-year disease-free survival (DFS) rate for the INCT-CRT group was 76% (95% CI, 69 to 84), while the CRT-CNCT group had a similar DFS rate of 76% (95% CI, 69 to 83). These rates are consistent with the historical observation of a 75% DFS rate over three years. The group treated with INCT-CRT exhibited a 3-year TME-free survival rate of 41% (95% CI, 33 to 50), while the CRT-CNCT group demonstrated a 53% (95% CI, 45 to 62) rate. No discernible distinctions were observed among the cohorts in terms of local recurrence-free survival, distant metastasis-free survival, or overall survival. The patients who underwent total mesorectal excision (TME) after restaging and those who underwent TME after regrowth exhibited comparable disease-free survival (DFS) rates. Researchers observed that organ preservation could be attained in 50% of rectal cancer patients who undergo total neoadjuvant therapy. It does not negatively impact their survival rates when compared to the outcomes of historical controls who received chemoradiotherapy, TME, and postoperative chemotherapy.
Source:https://pubmed.ncbi.nlm.nih.gov/35483010/
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT02008656
Garcia-Aguilar J, Patil S, Gollub MJ, Kim JK, Yuval JB, Thompson HM, Verheij FS, Omer DM, Lee M, Dunne RF, Marcet J, Cataldo P, Polite B, Herzig DO, Liska D, Oommen S, Friel CM, Ternent C, Coveler AL, Hunt S, Gregory A, Varma MG, Bello BL, Carmichael JC, Krauss J, Gleisner A, Paty PB, Weiser MR, Nash GM, Pappou E, Guillem JG, Temple L, Wei IH, Widmar M, Lin S, Segal NH, Cercek A, Yaeger R, Smith JJ, Goodman KA, Wu AJ, Saltz LB. Organ Preservation in Patients With Rectal Adenocarcinoma Treated With Total Neoadjuvant Therapy. J Clin Oncol. 2022 Aug 10;40(23):2546-2556. doi: 10.1200/JCO.22.00032. Epub 2022 Apr 28. PMID: 35483010; PMCID: PMC9362876.
