Discussion

Principal findings

In this retrospective cohort study of 100 patients with rectal adenocarcinoma treated with total neoadjuvant therapy, structured post-treatment MRI provided a systematic framework for assessing treatment response and identifying clinically relevant residual disease. Complete or near-complete imaging response was seen in 32 (32.0%) patients, incomplete response was observed in 58 (58.0%) patients, and indeterminate response was observed in 10 (10.0%) patients. Among surgically treated patients, structured MRI showed good diagnostic performance for detecting residual viable tumor, with sensitivity of 88.9%, specificity of 81.0%, positive predictive value of 93.3%, negative predictive value of 70.8%, and accuracy of 86.9%. Interobserver agreement was substantial for overall response category and almost perfect for assessment of mesorectal fascia status and diffusion restriction.

The present findings should be interpreted in the context of previous MRI response-assessment literature showing that post-treatment rectal MRI is clinically useful but imperfect for distinguishing complete response from residual viable tumor. DWI may improve detection of residual disease when interpreted with high-resolution T2-weighted imaging; however, false-positive and false-negative findings can occur because fibrosis, edema, mucinous change, inflammation, and small-volume residual tumor may overlap in appearance. In the present cohort, persistent intermediate T2 signal and focal diffusion restriction were the most stable imaging predictors of residual viable tumor, while residual extramural vascular invasion and threatened mesorectal fascia represented adverse post-treatment risk features. These results support structured MRI as a standardized communication tool for multidisciplinary decision-making rather than as a stand-alone determinant of complete response or organ-preservation eligibility.

These findings support the value of a structured post-treatment MRI approach in rectal cancer, particularly in the current era of total neoadjuvant therapy, where management decisions are no longer limited to routine total mesorectal excision but may include local excision or non-operative watch-and-wait surveillance in selected patients. The patient selection process is shown in Figure 1, while the key imaging parameters and response categories used in this study are summarized in Tables 1 and 2.

Role of post-treatment magnetic resonance imaging after total neoadjuvant therapy

Total neoadjuvant therapy has changed the treatment pathway of locally advanced rectal cancer by delivering systemic chemotherapy and chemoradiotherapy before surgery, thereby improving tumor regression and increasing the possibility of organ preservation in selected responders [1-5]. In this setting, MRI has expanded from a staging tool to a response-assessment tool that directly informs multidisciplinary decision-making. Baseline MRI remains essential for defining tumor height, T stage, mesorectal fascia involvement, extramural vascular invasion, nodal disease, and sphincter complex involvement [9-11]. However, post-treatment MRI must additionally determine whether the treated tumor bed represents fibrosis, residual viable tumor, or an equivocal response pattern.

In our cohort, complete or near-complete response was characterized by predominant low T2 signal fibrosis, absence of definite focal diffusion restriction, regression of extramural disease, absence of suspicious residual nodes, and absence of threatened mesorectal fascia. These findings are consistent with previous studies showing that MRI-detected tumor regression and favorable response patterns are associated with improved oncologic outcomes [12]. Representative imaging patterns of complete or near-complete response, incomplete response, and adverse residual features are illustrated in Figure 2.

Importance of T2-weighted morphology and diffusion-weighted imaging

T2-weighted morphology remains the foundation of post-treatment rectal MRI. Predominant low T2 signal fibrosis at the previous tumor site usually indicates a favorable response, while persistent intermediate T2 signal, nodular wall thickening, irregular extramural soft tissue, or persistent tumor-like morphology suggests residual viable tumor. Nevertheless, interpretation of T2-weighted imaging after treatment can be difficult because fibrosis, edema, mucin, inflammation, and desmoplastic reaction may overlap with residual tumor.

DWI provides complementary functional information. In this study, focal diffusion restriction was strongly associated with residual viable tumor. It was present in 47 of 63 patients (74.6%) with residual viable tumor but only 3 of 21 patients (14.3%) with pathological complete response. This supports the concept that DWI should not be interpreted in isolation but should be correlated with the corresponding T2-weighted abnormality and apparent diffusion coefficient map [13-16]. A focal high signal on high b-value diffusion-weighted imaging with corresponding low apparent diffusion coefficient signal at the tumor bed was considered suspicious for residual disease, whereas diffuse, linear, or ill-defined signal without a focal apparent diffusion coefficient correlate was not considered definite residual tumor.

Residual high-risk features and surgical planning

Beyond the primary tumor bed, structured assessment of mesorectal fascia, extramural vascular invasion, nodal response, sphincter complex, levator, and pelvic sidewall disease is critical. In our study, residual extramural vascular invasion, suspicious residual nodes, and threatened mesorectal fascia were found mainly in patients with residual viable tumor. Residual extramural vascular invasion was present in 22 of 63 patients (34.9%) with residual viable tumor and in 0 of 21 patients (0.0%) with pathological complete response. Similarly, threatened mesorectal fascia was present in 18 of 63 patients (28.6%) with residual viable tumor and in 0 of 21 patients (0.0%) with pathological complete response.

These findings are clinically important because the presence of persistent extramural vascular invasion, suspicious nodes, or threatened mesorectal fascia may influence the decision for total mesorectal excision, extended surgery, lateral pelvic nodal management, or intensified follow-up. Earlier MRI studies have demonstrated the importance of mesorectal fascia and extramural disease assessment in predicting surgical margin status and outcome [10-12]. In the post-treatment setting, these findings remain important, but they must be interpreted carefully to avoid overstaging fibrosis as residual tumor.

Implications for organ preservation and watch-and-wait management

Organ-preserving strategies have gained attention because a subset of patients may achieve clinical complete response after neoadjuvant therapy and avoid immediate radical surgery [4-8]. The watch-and-wait strategy requires careful integration of clinical examination, endoscopy, carcinoembryonic antigen level, and MRI. MRI alone cannot confirm complete response with absolute certainty, but it is essential for excluding adverse deep pelvic features that may not be visible on endoscopy or digital rectal examination.

In our cohort, 16 (16.0%) patients were selected for watch-and-wait surveillance after multidisciplinary assessment. Of these, 8 (50.0%) patients had complete or near-complete imaging response, 6 (37.5%) patients had incomplete imaging response but were considered unsuitable for immediate surgery or were managed according to individualized multidisciplinary decisions, and 2 (12.5%) patients had indeterminate imaging findings requiring close follow-up. During the available follow-up period, no patient in the complete or near-complete imaging response subgroup showed definite early local regrowth on follow-up MRI. However, median follow-up duration and longer-term local regrowth outcomes were not uniformly available for all watch-and-wait patients at the time of analysis. This limitation is important because the long-term safety of organ preservation depends on accurate initial selection, strict follow-up, detection of local regrowth, and timely salvage surgery when regrowth occurs [6-8,16]. These findings reinforce the role of MRI as part of a combined response assessment pathway rather than as a standalone test.

The watch-and-wait subgroup in this study should be interpreted cautiously. Only 16 (16.0%) patients were managed non-operatively, and follow-up duration was limited and not uniform. Therefore, this study cannot validate structured MRI as an independent tool for selecting patients for watch-and-wait management or for establishing long-term oncologic safety. In clinical practice, organ-preservation decisions require integrated assessment with digital rectal examination, endoscopy, tumor marker status, patient fitness, surgical feasibility, patient preference, and multidisciplinary consensus. Structured MRI may contribute to this process by documenting favorable response patterns and adverse residual features, but it should not replace clinical, endoscopic, pathological, biochemical, and multidisciplinary assessment.

Value of structured reporting

A major practical finding of this study is that structured reporting improves completeness and clarity of post-treatment rectal cancer MRI assessment. Unstructured reports may describe the tumor bed but omit critical information such as diffusion restriction, mesorectal fascia status, extramural vascular invasion response, nodal response, sphincter involvement, or pelvic sidewall disease. Such omissions can reduce the usefulness of the report during multidisciplinary discussion.

The structured template used in this study is consistent with currently available international rectal MRI reporting recommendations in that it includes key elements emphasized by ESGAR and MERCURY-related frameworks, such as tumor-bed morphology, mesorectal fascia or circumferential resection margin status, extramural spread, extramural vascular invasion, nodal assessment, and response evaluation. It also incorporates mrTRG-related assessment of fibrosis versus residual tumor signal and DWI correlation, which are commonly used in post-treatment response assessment. However, the present template differs by consolidating these components into a single management-oriented post-treatment reporting format specifically for patients treated with total neoadjuvant therapy. In addition to standard staging and restaging parameters, it explicitly links residual tumor-bed signal, diffusion restriction, mesorectal fascia status, extramural vascular invasion response, nodal response, sphincter or levator involvement, pelvic sidewall disease, and adjacent organ involvement with practical response categories relevant to total mesorectal excision, local excision, or watch-and-wait consideration.

The structured template used in this study ensured that each relevant anatomic and functional parameter was assessed consistently. This approach is particularly important in the total neoadjuvant therapy era because the radiologist’s report may influence whether the patient proceeds to total mesorectal excision, local excision, intensified surveillance, or watch-and-wait management. The structured response categories used in Table 2 provide a practical framework for translating imaging findings into clinically meaningful categories.

Comparison with previous literature

Our findings are broadly consistent with previous work on rectal MRI response assessment. The MERCURY experience showed the prognostic value of MRI-based assessment in rectal cancer and highlighted the importance of extramural depth, circumferential resection margin, and tumor regression [10-12]. Lambregts et al. demonstrated the value of DWI in identifying complete responders after chemoradiation [13]. More recent reviews, practical guides, and multireader studies emphasize that restaging MRI must combine T2-weighted morphology, DWI, nodal assessment, mesorectal fascia evaluation, and recognition of post-treatment pitfalls, while also acknowledging reader variability and imperfect accuracy in identifying complete response [14-19,21]. Recent review evidence also emphasizes that MRI evaluation of complete response after neoadjuvant therapy remains evolving and should be interpreted with clinical and endoscopic correlation [21].

The present study adds to this literature by applying a structured response assessment template specifically in patients treated with total neoadjuvant therapy and by correlating imaging response categories with surgical and histopathological outcomes. The diagnostic performance observed in our cohort suggests that structured MRI can identify residual viable tumor with clinically useful accuracy, although the negative predictive value remains imperfect. The exploratory predictive analysis further supported the association between structured MRI features and residual viable tumor. Persistent intermediate T2 signal and focal diffusion restriction showed strong odds ratio associations with residual viable tumor, and the ordered structured MRI response category demonstrated good discriminatory performance on receiver operating characteristic analysis, with an area under the curve of 0.860. However, these findings should be regarded as exploratory and internally assessed only. Because the number of pathological complete response events was limited and several imaging variables were overlapping components of the structured response category, formal multivariable logistic regression was not used to generate a definitive clinical prediction model. Larger datasets with patient-level clinical and imaging variables are required to determine independent predictors and to externally validate any prediction model. Therefore, a complete or near-complete imaging response should not be interpreted as equivalent to pathological complete response without clinical and endoscopic correlation.

Limitations

This study has several limitations. First, it was retrospective in design and was conducted at a single institution, which limits generalizability and may introduce institutional practice bias. Second, although the cohort included 100 patients, the histopathological reference standard was available only in the 84 surgically treated patients. Patients managed with watch-and-wait surveillance did not uniformly have pathological confirmation and were not included in diagnostic performance calculations unless histopathology became available. This may introduce verification bias and selection bias, because patients selected for non-operative management were more likely to have favorable clinical, endoscopic, and imaging responses. Therefore, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy should be interpreted as estimates for the surgically treated subgroup rather than for the entire cohort. Third, the watch-and-wait subgroup was small, with only 16 (16.0%) patients, and follow-up duration was limited and not uniform. Long-term outcomes such as local regrowth, distant metastasis, disease-free survival, overall survival, salvage surgery rate, and organ-preservation durability could not be reliably assessed. Therefore, this study cannot validate structured MRI as an independent tool for selecting patients for watch-and-wait management or for establishing the long-term oncologic safety of organ preservation. Fourth, although reader assessment was performed independently before consensus review, the final clinicopathological correlation was based on consensus interpretation; this may have improved apparent diagnostic performance and is a potential observer-related bias. Fifth, interobserver agreement was reported using kappa values, but 95% confidence intervals for all individual agreement values could not be reliably recalculated from the extracted summary dataset. Sixth, treatment regimens, imaging intervals, follow-up duration, baseline tumor stage, tumor location, pretreatment carcinoembryonic antigen level, and other clinical factors may influence treatment response and residual viable tumor. These variables should be incorporated into larger patient-level predictive models. Seventh, microscopic residual disease may not be detectable on MRI, even when T2-weighted imaging and DWI show a favorable response. Finally, the structured reporting template was not externally validated. Larger prospective multicenter studies with standardized MRI protocols, uniform treatment pathways, complete clinical and histopathological datasets, longer follow-up, larger watch-and-wait cohorts, and independent external validation are required before routine implementation as a validated predictive framework.

Clinical implications

The findings of this study support the use of structured post-treatment rectal MRI reporting as part of multidisciplinary response assessment after total neoadjuvant therapy. Reports should document primary tumor-bed morphology, diffusion restriction, magnetic resonance tumor regression grade, mesorectal fascia status, extramural vascular invasion response, mesorectal and lateral pelvic nodal response, sphincter complex involvement, levator involvement, and pelvic sidewall disease. These imaging findings should be integrated with digital rectal examination, endoscopy, carcinoembryonic antigen level, surgical assessment, patient-related factors, and multidisciplinary discussion before deciding on total mesorectal excision, local excision, intensified surveillance, or watch-and-wait management. The present results suggest that structured MRI can improve consistency of response documentation and help identify adverse residual features; however, they do not establish MRI as an independent decision-making tool for organ preservation. Routine implementation as a validated predictive framework should be supported by prospective multicenter studies with standardized imaging protocols, patient-level clinical modeling, longer follow-up, and external validation.