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 Journal Article
| Authors: | Thompson, H. M.; Omer, D. M.; Lin, S.; Kim, J. K.; Yuval, J. B.; Verheij, F. S.; Qin, L. X.; Gollub, M. J.; Wu, A. J. C.; Lee, M.; Patil, S.; Hezel, A. F.; Marcet, J. E.; Cataldo, P. A.; Polite, B. N.; Herzig, D. O.; Liska, D.; Oommen, S.; Friel, C. M.; Ternent, C. A.; Coveler, A. L.; Hunt, S. R.; Garcia-Aguilar, J.; for the OPRA Consortium |
| Article Title: | 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 |
| Abstract: | This secondary analysis of a randomized clinical trial assesses organ preservation and survival outcomes for patients with rectal cancer according to a 3-tier clinical tumor response grading schema. Key Points: Question: Can a 3-tier grading schema be used to estimate clinical tumor response after total neoadjuvant therapy (TNT) for patients with locally advanced rectal cancer? Findings: This secondary analysis of the Organ Preservation in Patients with Rectal Adenocarcinoma trial (a phase 2, randomized clinical trial) assessed clinical tumor response grade after TNT among 304 patients using 3 grades and found clinical tumor response grade was significantly associated with survival and organ preservation. Meaning: These findings suggest that the 3-tier grading schema can be used to counsel patients regarding their expected organ preservation and survival outcomes on the basis of their individual clinical tumor response grade. 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 |
| Keywords: | aged; disease-free survival; survival rate; neoadjuvant therapy; confidence intervals; organ preservation; neoplasms, second primary; chemoradiotherapy; secondary analysis; progression-free survival; descriptive statistics; funding source; middle age; treatment outcomes; kaplan-meier estimator; academic medical centers; cancer patients; adenocarcinoma -- drug therapy; rectal neoplasms -- therapy; kruskal-wallis test; neoplasm recurrence, local -- prevention and control; log-rank test; data analysis, statistical; neoplasm metastasis -- prevention and control; human; male; female |
| Journal Title: | JAMA Network Open |
| Volume: | 7 |
| Issue: | 1 |
| ISSN: | 2574-3805 |
| Publisher: | American Medical Association |
| Date Published: | 2024-01-01 |
| Start Page: | e2350903 |
| Language: | English |
| DOI: | 10.1001/jamanetworkopen.2023.50903 |
| PROVIDER: | EBSCOhost |
| PROVIDER: | cinahl |
| PMCID: | PMC10777257 |
| PUBMED: | 38194231 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF. Corresponding MSK author is Julio Garcia-Aguilar -- Source: Cinahl -- Source: Cinahl |
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