Organ Preservation and Survival by Clinical Response Grade in Patients With Rectal Cancer Treated With Total Neoadjuvant Therapy
Authors: Thompson Hannah M. , Omer Dana M. , Lin Sabrina , Kim Jin K. , Yuval Jonathan B. , Veheij Floris S. , Qin Li-Xuan , Gollub Marc J. , Wu Abraham Jing-Ching , Lee Meghan , Patil Sujata , Hezel Aram F. , Marcet Jorge E. , Cataldo Peter A. , Polite Blase N. , Herzig Daniel O. , Liska David , Oommen Samuel , Friel Charles M. , Ternent Charles A. , Coveler Andrew L. , Hunt Steven R. , Garcia-Aguilar Julio ,   OPRA Consortium
Published: January 2024

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 &amp;lt; .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