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Clinical Trial
. 2024 Jan 2;7(1):e2350903.
doi: 10.1001/jamanetworkopen.2023.50903.

Organ Preservation and Survival by Clinical Response Grade in Patients With Rectal Cancer Treated With Total Neoadjuvant Therapy: A Secondary Analysis of the OPRA Randomized Clinical Trial

Hannah M Thompson  1 , Dana M Omer  1 , Sabrina Lin  2 , Jin K Kim  1 , Jonathan B Yuval  1 , Floris S Verheij  1 , Li-Xuan Qin  2 , Marc J Gollub  3 , Abraham Jing-Ching Wu  4 , Meghan Lee  1 , Sujata Patil  5 , Aram F Hezel  6 , Jorge E Marcet  7 , Peter A Cataldo  8 , Blase N Polite  9 , Daniel O Herzig  10 , David Liska  11 , Samuel Oommen  12 , Charles M Friel  13 , Charles A Ternent  14 , Andrew L Coveler  15 , Steven R Hunt  16 , Julio Garcia-Aguilar  1 ; OPRA Consortium
Affiliations
Clinical Trial

Organ Preservation and Survival by Clinical Response Grade in Patients With Rectal Cancer Treated With Total Neoadjuvant Therapy: A Secondary Analysis of the OPRA Randomized Clinical Trial

Hannah M Thompson et al. JAMA Netw Open. .

Erratum in

  • Error in Byline.
    [No authors listed] [No authors listed] JAMA Netw Open. 2024 Feb 5;7(2):e242456. doi: 10.1001/jamanetworkopen.2024.2456. JAMA Netw Open. 2024. PMID: 38381439 Free PMC article. No abstract available.
  • Error in Results.
    [No authors listed] [No authors listed] JAMA Netw Open. 2025 Mar 3;8(3):e256079. doi: 10.1001/jamanetworkopen.2025.6079. JAMA Netw Open. 2025. PMID: 40105847 Free PMC article. No abstract available.

Abstract

Importance: Assessing clinical tumor response following completion of total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer is paramount to select patients for watch-and-wait treatment.

Objective: To assess organ preservation (OP) and oncologic outcomes according to clinical tumor response grade.

Design, setting, and participants: This was secondary analysis of the Organ Preservation in Patients with Rectal Adenocarcinoma trial, a phase 2, nonblinded, multicenter, randomized clinical trial. Randomization occurred between April 2014 and March 2020. Eligible participants included patients with stage II or III rectal adenocarcinoma. Data analysis occurred from March 2022 to July 2023.

Intervention: Patients were randomized to induction chemotherapy followed by chemoradiation or chemoradiation followed by consolidation chemotherapy. Tumor response was assessed 8 (±4) weeks after TNT by digital rectal examination and endoscopy and categorized by clinical tumor response grade. A 3-tier grading schema that stratifies clinical tumor response into clinical complete response (CCR), near complete response (NCR), and incomplete clinical response (ICR) was devised to maximize patient eligibility for OP.

Main outcomes and measures: OP and survival rates by clinical tumor response grade were analyzed using the Kaplan-Meier method and log-rank test.

Results: There were 304 eligible patients, including 125 patients with a CCR (median [IQR] age, 60.6 [50.4-68.0] years; 76 male [60.8%]), 114 with an NCR (median [IQR] age, 57.6 [49.1-67.9] years; 80 male [70.2%]), and 65 with an ICR (median [IQR] age, 55.5 [47.7-64.2] years; 41 male [63.1%]) based on endoscopic imaging. Age, sex, tumor distance from the anal verge, pathological tumor classification, and clinical nodal classification were similar among the clinical tumor response grades. Median (IQR) follow-up for patients with OP was 4.09 (2.99-4.93) years. The 3-year probability of OP was 77% (95% CI, 70%-85%) for patients with a CCR and 40% (95% CI, 32%-51%) for patients with an NCR (P < .001). Clinical tumor response grade was associated with disease-free survival, local recurrence-free survival, distant metastasis-free survival, and overall survival.

Conclusions and relevance: In this secondary analysis of a randomized clinical trial, most patients with a CCR after TNT achieved OP, with few developing tumor regrowth. Although the probability of tumor regrowth was higher for patients with an NCR compared with patients with a CCR, a significant proportion of patients achieved OP. These findings suggest the 3-tier grading schema can be used to estimate recurrence and survival outcomes in patients with locally advanced rectal cancer who receive TNT.

Trial registration: ClinicalTrials.gov Identifier: NCT02008656.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Wu reported serving on an advisory board for Simphotek outside the submitted work. Dr Patil reported receiving personal fees from ByHeart outside the submitted work. Dr Polite reported receiving personal fees from Natera outside the submitted work. Dr Liska reported receiving personal fees from Olympus, Bard, and Freenome outside the submitted work. Dr Coveler reported receiving grants from AstraZeneca, Actuate, Nextrast, NuCana, Amgen, Novocure, AbGenomics, and Seagen outside the submitted work. Dr Garcia-Aguilar reported receiving personal fees from Medtronic, Johnson & Johnson, and Intuitive Surgical outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Diagram of the Clinical Tumor Response Grades Based on Intention-to-Treat
CCR indicates clinical complete response; ICR, incomplete clinical response; LE, local excision; NCR, near complete response; TME, total mesorectal excision; TNT, total neoadjuvant therapy; WW, watch-and-wait.
Figure 2.
Figure 2.. Organ Preservation According to Clinical Tumor Response Grade by Intention-to-Treat
CCR indicates clinical complete response; ICR, incomplete clinical response; NCR, near complete response; TME, total mesorectal excision.
Figure 3.
Figure 3.. Disease-Free Survival (DFS), Local Recurrence-Free Survival (LRFS), Distant Metastasis-Free Survival (DMFS), and Overall Survival (OS)
The figure shows DFS (A), LRFS (B), DMFS (C), and OS (D) according to clinical tumor response grade by intention to treat. CCR indicates clinical complete response; ICR incomplete clinical response; NCR, near complete response; TAF, tumor assessment form.
See this image and copyright information in PMC

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