MRI Predicts Residual Disease and Outcomes in Watch-and-Wait Patients with Rectal Cancer

Abstract

Background MRI plays a crucial role in restaging locally advanced rectal cancer treated with total neoadjuvant therapy (TNT); however, prospective studies have not evaluated its ability to accurately select patients for nonoperative management. Purpose To evaluate the ability of restaging MRI to predict oncologic outcomes and identify imaging features associated with residual disease (RD) after TNT. Materials and Methods This was a secondary analysis of the Organ Preservation in Rectal Adenocarcinoma (OPRA) trial, which randomized participants from April 2014 to March 2020 with stages II or III rectal adenocarcinoma to undergo either induction or consolidation TNT. Participants enrolled in the OPRA trial who underwent restaging MRI were eligible for inclusion in the present study. Radiologists classified participants as having clinical complete response (cCR), near-complete clinical response (nCR), or incomplete clinical response (iCR) based on restaging MRI at a mean of 8 weeks ± 4 (SD) after treatment. Oncologic outcomes according to MRI response category were assessed using Kaplan-Meier curves. Logistic regression analysis was performed to identify imaging characteristics associated with RD. Results A total of 277 participants (median age, 58 years [IQR, 17 years]; 179 male) who were randomized in the OPRA trial had restaging MRI forms completed. The median follow-up duration was 4.1 years. Participants with cCR had higher rates of organ preservation compared with those with nCR (65.3% vs 41.6%, log-rank P < .001). Five-year disease-free survival for participants with cCR, nCR, and iCR was 81.8%, 67.6%, and 49.6%, respectively (log-rank P < .001). The MRI response category also predicted overall survival (log-rank P < .001), distant recurrence-free survival (log-rank P = .005), and local regrowth (log-rank P = .02). Among the 266 participants with at least 2 years of follow-up, 129 (48.5%) had RD. At multivariable analysis, the presence of restricted diffusion (odds ratio, 2.50; 95% CI: 1.22, 5.24) and abnormal nodal morphologic features (odds ratio, 5.04; 95% CI: 1.43, 23.9) remained independently associated with RD. Conclusion The MRI response category was predictive of organ preservation and survival. Restricted diffusion and abnormal nodal morphologic features on restaging MRI scans were associated with increased likelihood of residual tumor. ClinicalTrials.gov identifier: NCT02008656 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Milot in this issue.

Graphical abstract

Figure 1:

Chart shows the T2-weighted imaging (T2W, T2WI), diffusion-weighed imaging (DW, DWI), and lymph node criteria used to categorize MRI-based response as clinical complete response (mr-cCR), near-complete clinical response (mr-nCR), or incomplete clinical response (mr-iCR). * = b ≥ 800 sec/mm².

Figure 2:

Flowchart shows randomization of participants in the Organ Preservation in Rectal Adenocarcinoma (OPRA) trial, inclusion and exclusion for the current analysis, and a summary of characteristics for each restaging MRI-based response category (clinical complete response [mr-cCR], near-complete clinical response [mr-nCR], incomplete clinical response [mr-iCR]). * = b ≥ 800 sec/mm². DWI = diffusion-weighted imaging, TME = total mesorectal excision, TNT = total neoadjuvant therapy, T2WI = T2-weighted imaging.

Figure 3:

Kaplan-Meier curves show 5-year rates of (A) total mesorectal excision (TME)–free survival and (B) local regrowth for each restaging MRI response category (clinical complete response [mr-cCR], near-complete clinical response [mr-nCR], incomplete clinical response [mr-iCR]).

Figure 4:

Kaplan-Meier curves show 5-year rates of (A) disease-free survival and (B) overall survival for each restaging MRI response category (clinical complete response [mr-cCR], near-complete clinical response [mr-nCR], incomplete clinical response [mr-iCR]). Kaplan-Meier curves show 5-year rates of (C) distant recurrence-free survival and (D) local recurrence-free survival for each restaging MRI response category (clinical complete response [mr-cCR], near-complete clinical response [mr-nCR], incomplete clinical response [mr-iCR]).

Figure 5:

(A–D) Images in a participant incorrectly categorized as having MRI clinical complete response (cCR) (false positive). (A) Axial T2-weighted image shows fibrosis (arrow). (B) Diffusion-weighted image shows absent restricted diffusion (arrow). (C) Apparent diffusion coefficient map shows low signal intensity (arrow). (D) Representative image from restaging endoscopy shows obvious residual tumor, which was confirmed at histopathologic assessment following total mesorectal excision. (E–H) Images in a participant incorrectly categorized as having MRI incomplete clinical response (false negative). (E) Axial T2-weighted image shows intermediate signal intensity (arrow). (F) Diffusion-weighted image shows restricted diffusion at a high b value (b = 800 sec/mm²) (arrow). (G) Apparent diffusion coefficient map shows low signal intensity (arrow). (H) Representative image from restaging endoscopy shows cCR. The participant was placed on watch-and-wait surveillance and had sustained cCR over 5 years of follow-up.