Long-Term Results of Organ Preservation in Patients With Rectal Adenocarcinoma Treated With Total Neoadjuvant Therapy: The Randomized Phase II OPRA Trial

Author(s): Floris S. Verheij, BSc1; Dana M. Omer, MD1; Hannah Williams, MD1; Sabrina T. Lin, MSc2; Li-Xuan Qin, PhD2; James T. Buckley, BSc1; Hannah M. Thompson, MD1; Jonathan B. Yuval, MD1; Jin K. Kim, MD1; Richard F. Dunne, MD3; Jorge Marcet, MD4; Peter Cataldo, MD5; Blase Polite, MD6; Daniel O. Herzig, MD7; David Liska, MD8; Samuel Oommen, MD9; Charles M. Friel, MD10; Charles Ternent, MD11; Andrew L. Coveler, MD12; Steven Hunt, MD13; Anita Gregory, MD14; Madhulika G. Varma, MD15; Brian L. Bello, MD16; Joseph C. Carmichael, MD17; John Krauss, MD18; Ana Gleisner, MD19; José G. Guillem, MD20; Larissa Temple, MD21; Karyn A. Goodman, MD22; Neil H. Segal, MD, PhD23; Andrea Cercek, MD23; Rona Yaeger, MD23; Garrett M. Nash, MD1; Maria Widmar, MD1; Iris H. Wei, MD1; Emmanouil P. Pappou, MD1; Martin R. Weiser, MD1; Philip B. Paty, MD1; J. Joshua Smith, MD, PhD1; Abraham J. Wu, MD24; Marc J. Gollub, MD25; Leonard B. Saltz, MD23; Julio Garcia-Aguilar, MD, PhD1
Source: https://doi.org/10.1200/JCO.23.01208
Maem Hussein MD

Dr. Maen Hussein's Thoughts

There is hope for organ preservation in rectal preservation. I believe the good news is that waiting is not as harmful. Those who underwent surgery after regrowth almost had the same disease-free survival (DFS) as those who had surgery after treatment because of incomplete response. The use of CtDNA (not analyzed in the trial) may play an even a bigger role where you may not have to wait for clinical regrowth to have the surgery, but of course more trials are needed to see if this will have clinical benefit. (Is the positive or rising CtDNA enough reason to have surgery vs imaging recurrence?)

Still, this is an exciting new era that will see change in treating early-stage colorectal cancer, recall the immunotherapy results in patients who were MMR deficient.


Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.

To assess long-term risk of local tumor regrowth, we report updated organ preservation rate and oncologic outcomes of the OPRA trial (ClinicalTrials.gov identifier: NCT02008656). Patients with stage II/III rectal cancer were randomly assigned to receive induction chemotherapy followed by chemoradiation (INCT-CRT) or chemoradiation followed by consolidation chemotherapy (CRT-CNCT). Patients who achieved a complete or near-complete response after finishing treatment were offered watch-and-wait (WW). Total mesorectal excision (TME) was recommended for those who achieved an incomplete response. The primary end point was disease-free survival (DFS). The secondary end point was TME-free survival. In total, 324 patients were randomly assigned (INCT-CRT, n = 158; CRT-CNCT, n = 166). Median follow-up was 5.1 years. The 5-year DFS rates were 71% (95% CI, 64 to 79) and 69% (95% CI, 62 to 77) for INCT-CRT and CRT-CNCT, respectively (P = .68). TME-free survival was 39% (95% CI, 32 to 48) in the INCT-CRT group and 54% (95% CI, 46 to 62) in the CRT-CNCT group (P = .012). Of 81 patients with regrowth, 94% occurred within 2 years and 99% occurred within 3 years. DFS was similar for patients who underwent TME after restaging (64% [95% CI, 53 to 78]) and patients in WW who underwent TME after regrowth (64% [95% CI, 53 to 78]; P = .94). Updated analysis continues to show long-term organ preservation in half of the patients with rectal cancer treated with total neoadjuvant therapy. In patients who enter WW, most cases of tumor regrowth occur in the first 2 years.

Author Affiliations

1Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, NY; 2Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY; 3Department of Medicine, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY; 4Division of Colon and Rectal Surgery, Department of Surgery, University of South Florida, Tampa, FL; 5Division of General Surgery, Department of Surgery, University of Vermont, Burlington, VT; 6Department of Medicine, Comprehensive Cancer Center, University of Chicago, Chicago, IL; 7Division of Gastrointestinal and General Surgery, Oregon Health and Science University, Portland, OR; 8Department of Colorectal Surgery, Cleveland Clinic, Cleveland, OH; 9Division of Gastrointestinal Oncology, John Muir Cancer Institute, John Muir Health, Walnut Creek, CA; 10Division of General Surgery, Department of Surgery, University of Virginia, Charlottesville, VA; 11Methodist Hospital Physicians Clinic Colon and Rectal Surgery and The Creighton University Clinical Research Center, Omaha, NE; 12Department of Medicine, Fred Hutch Cancer Center, University of Washington, Seattle, WA; 13Department of Surgery, Washington University School of Medicine, St Louis, MO; 14Department of Surgery, St Joseph Hospital Orange County, Orange, CA; 15Section of Colon and Rectal Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA; 16Division of Colorectal Surgery, Department of Surgery, Medstar Washington Hospital Center, Washington, DC; 17Division of Colon and Rectal Surgery, Department of Surgery, University of California, Irvine, Irvine, CA; 18Department of Medicine, Rogel Cancer Center at the University of Michigan, Ann Arbor, MI; 19Division of Surgical Oncology, Department of Surgery, University of Colorado, Denver, CO; 20Division of Gastrointestinal Surgery, Department of Surgery, University of North Carolina, Chapel Hill, NC; 21Division of Colorectal Surgery, Department of Surgery, University of Rochester Medical Center, Rochester, NY; 22Department of Radiation Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY; 23Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; 24Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY; 25Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY

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