Rectal cancer constitutes a significant proportion of colorectal malignancies and remains a major contributor to cancer-related morbidity and mortality worldwide. According to Global Cancer Observatory estimates, colorectal cancer is among the top three most commonly diagnosed cancers globally, with a steadily rising incidence in both developed and developing countries^[1]. The burden is particularly notable in the elderly population, where increasing life expectancy has led to a higher prevalence of age-associated malignancies, including rectal cancer^[2].

Standard management of locally advanced rectal cancer typically involves multimodal therapy, including neoadjuvant chemoradiotherapy followed by total mesorectal excision, as recommended by guidelines from the National Comprehensive Cancer Network and the European Society for Medical Oncology. However, a substantial proportion of elderly patients are not suitable candidates for such aggressive treatment strategies due to frailty, multiple comorbidities, poor performance status, or patient preference. In this context, less intensive treatment approaches that balance oncologic control with tolerability are increasingly being explored^[3].

Short-course radiotherapy (SCRT), typically delivered as 25 Gy in five fractions over one week, has emerged as a pragmatic alternative in selected patients. It offers logistical advantages, reduced treatment duration, and acceptable toxicity profiles, making it particularly suitable for elderly or medically unfit individuals. Evidence from trials such as the Stockholm III Trial has demonstrated that SCRT can achieve comparable oncologic outcomes to long-course chemoradiotherapy in certain settings, with the added benefit of convenience and reduced healthcare burden^[4].

With the growing adoption of non-operative or “watch-and-wait” strategies in rectal cancer, especially among patients unfit for surgery, accurate assessment of tumor response has become critically important^[5]. Magnetic resonance imaging (MRI) plays a central role in the staging and post-treatment evaluation of rectal cancer due to its superior soft tissue resolution and ability to assess key prognostic factors such as tumor extent, nodal involvement, and mesorectal fascia status. In particular, the magnetic resonance tumor regression grade (mrTRG), as described by Gina Brown and colleagues, provides a standardized method for evaluating treatment response based on the relative proportions of fibrosis and residual tumor^[6].

Despite increasing interest in SCRT and MRI-based response assessment, there remains a relative paucity of data focusing specifically on elderly patients managed non-operatively. Most existing studies emphasize surgical cohorts or younger populations, limiting the generalizability of their findings to frail elderly individuals. Furthermore, the correlation between MRI-based response parameters—such as mrTRG, T-stage downstaging, and mesorectal fascia clearance—and clinical outcomes in this subgroup is not yet fully elucidated.

Given these gaps, the present study aims to evaluate MRI-based tumor response following SCRT in elderly patients with rectal cancer treated without surgery at a single tertiary care centre. By focusing on a real-world cohort of patients who are often underrepresented in clinical trials, this study seeks to provide clinically relevant insights into the effectiveness and tolerability of SCRT, as well as the utility of MRI in guiding management decisions in this vulnerable population.

Aim and Objectives

Primary objective
To assess MRI tumor regression grade (mrTRG) following short-course radiotherapy in elderly patients with rectal cancer.

Secondary objectives

• To evaluate changes in MRI T stage after SCRT
• To assess nodal response on MRI
• To evaluate mesorectal fascia (MRF) status before and after SCRT
• To document treatment tolerance in elderly non-surgical patients

Study design and setting This was a retrospective observational study conducted at a tertiary care oncology centre. The study evaluated magnetic resonance imaging (MRI)–based tumor response following short-course radiotherapy (SCRT) in elderly patients with rectal cancer who were managed non-operatively. Study period Patients treated between January 2022 and December 2025 were included. Clinical records and imaging data were reviewed retrospectively after completion of the study period. Study population The study population consisted of elderly patients diagnosed with rectal adenocarcinoma who received SCRT as definitive or non-operative treatment and underwent MRI-based response assessment. Inclusion criteria Patients were eligible if they fulfilled all of the following: • Age ≥70 years at diagnosis • Histologically confirmed rectal adenocarcinoma • Received short-course radiotherapy (25 Gy in 5 fractions) • Baseline staging MRI pelvis performed before radiotherapy • Post-treatment MRI pelvis performed 8–12 weeks after SCRT • No surgical resection performed after radiotherapy Exclusion criteria Patients were excluded if they had: • Prior pelvic radiotherapy • Recurrent rectal cancer • Synchronous malignancy involving the pelvis • Incomplete imaging records or poor-quality MRI precluding assessment • Interval systemic chemotherapy between SCRT and response MRI Sample size All eligible patients treated during the study period were included. A total of 32 patients satisfied the inclusion criteria and constituted the final study cohort. Treatment protocol Short-course radiotherapy (SCRT) All patients received external beam radiotherapy delivered to the pelvis using three-dimensional conformal or intensity-modulated radiotherapy techniques. The standard SCRT regimen consisted of: • Total dose: 25 Gray (Gy) • Fractionation: 5 Gy per fraction • Schedule: 5 consecutive daily fractions over one week Treatment planning was based on simulation CT with patients in the supine position. The clinical target volume included the primary rectal tumor, mesorectum, and regional lymphatic drainage according to institutional rectal cancer radiotherapy guidelines. SCRT was chosen due to advanced age, medical comorbidities, metastatic disease, frailty, or patient preference precluding surgery or chemoradiotherapy. MRI acquisition protocol MRI pelvis was performed at two time points: 1. Baseline staging MRI: within 4 weeks prior to SCRT 2. Response MRI: 8–12 weeks after completion of SCRT All examinations were performed using a 1.5-T or 3-T MRI scanner with a phased-array pelvic coil. The standard rectal cancer protocol included: • High-resolution T2-weighted images in axial, sagittal, and coronal planes • Oblique axial T2-weighted images perpendicular to tumor axis • Diffusion-weighted imaging (DWI) with corresponding ADC maps No bowel preparation or rectal contrast was routinely used. MRI interpretation and response assessment All MR images were reviewed on the institutional PACS workstation by an experienced abdominal radiologist with expertise in rectal cancer imaging. Baseline and post-treatment MRIs were assessed in comparison. The following parameters were recorded: • Clinical tumor stage (cT) • Nodal stage (cN) • Distance from anal verge • Mesorectal fascia (MRF) involvement • Extramural vascular invasion (if present) • Magnetic resonance tumor regression grade (mrTRG) Definition of mesorectal fascia involvement MRF was considered involved when tumor or suspicious lymph node was ≤1 mm from the mesorectal fascia on T2-weighted imaging. Magnetic resonance tumor regression grade (mrTRG) Tumor response was graded according to the mrTRG system based on relative proportions of fibrosis and residual tumor signal on T2-weighted MRI: • mrTRG 1: Complete radiologic response; no visible tumor, fibrosis only • mrTRG 2: Dense fibrosis with minimal residual tumor signal • mrTRG 3: Fibrosis predominates with definite residual tumor • mrTRG 4: Predominant tumor signal with minimal fibrosis • mrTRG 5: No response; tumor appearance unchanged For analysis, response categories were grouped as: • Good response: mrTRG 1–2 • Moderate response: mrTRG 3 • Poor/no response: mrTRG 4–5 Moderate-to-good response was defined as mrTRG ≤3. Outcome measures Primary outcome • MRI tumor response after SCRT assessed by mrTRG on post-treatment MRI Secondary outcomes • Change in MRI T stage (downstaging, stable, progression) • Change in nodal status (cN+ to cN0) • Change in mesorectal fascia involvement • Acute radiotherapy-related toxicity Assessment of radiologic downstaging T-stage response • Downstaging: reduction in cT category post-SCRT • Stable disease: unchanged cT stage • Progression: increase in cT stage Nodal response Patients with baseline cN+ disease were evaluated for conversion to cN0 on post-treatment MRI. Toxicity assessment Acute treatment-related toxicity occurring during or within 3 months after SCRT was obtained from clinical records and graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Data collection Demographic, clinical, treatment, and imaging data were retrieved from institutional electronic medical records and radiology archives. Extracted variables included: • Age and sex • Comorbidity profile • Tumor location • Baseline MRI staging parameters • Post-SCRT MRI findings • mrTRG score • Treatment tolerance Statistical analysis Data were entered into Microsoft Excel and analyzed using SPSS version 25. • Continuous variables: expressed as mean ± standard deviation or median (range) • Categorical variables: expressed as frequency and percentage • Pre- and post-treatment staging comparison: McNemar test • Statistical significance threshold: p < 0.05 Ethical considerations The study was conducted in accordance with the Declaration of Helsinki. Institutional ethics committee approval was obtained prior to data collection. As this was a retrospective analysis of anonymized data, informed consent was waived. Patient confidentiality was maintained throughout the study.

A total of 32 patients (≥70 years) with biopsy proven rectal adenocarcinoma were included in the analysis. The mean age was 76.8 ±5.4years, with the majority of patients aged ≥75 years (71.9%) and a male predominance of 59.4%. Most patients had significant comorbidity burden, with 65.6% having two or more comorbidities. Tumors were located ≤5cm from anal verge in 43.8% of patients. Baseline MRI demonstrated locally advanced disease (cT3-T4) in 78.1% of patients, while 53.1% were node-positive (cN+), and mesorectal fascia (MRF) involvement was present in 37.5% (Table 1).

Post treatment MRI performed 8-12 weeks after short course radiotherapy (SCRT) demonstrated moderate to good tumor regression (mrTRG ≤3) in 21 patients (65.6%), including complete radiologic response (mrTRG 1) in 4 patients (12.5%). The distribution of mrTRG scores was: mrTRG 1-5 in 12.5%,18.8%,34.4%,25.0% and 9.35 of patients respectively. Overall poor to no response (mrTRG 4-5) was observed in 34.4% of the cohort (Table 2).

Raiological T stage downstaging was observed in 18 patients (56.3%), while 10 patients (31.3%) had stable disease and 4 patients (12.4%) had disease progression following SCRT (Table 3). A stage migration toward earlier disease was evident, with the proportion of T1-T2 tumors increasing from 6.3% baseline to 25% post treatment, while T3 and T4 tumors correspondingly decreased (Table 6).

Among the 17 patients with baseline node-positive disease, nodal regression to cn0 status was observed in 11 patients (34.4% of the total cohort), while 6 patients (18.8%) had persistent nodal disease. All patients who were node negative at baseline remained cN0 after treatment (Table 4).

MRF involvement decreased from 37.75 to 18.8% after treatment. Among patients with initial MRF involvement, clearance was achieved in 6 out of 12 patients (50%), indicating a significant improvement in local disease status (Table 5).

SCRT was well tolerated in this elderly cohort. No grade 3 or grade 4 acute radiation toxicity was observed. Grade 0 toxicity was seen in 43.8% of patients, while 31.3% experienced grade 1 toxicity and 25.0% experienced grade 2 toxicity (Table 7).

TABLES

Table 1. Baseline demographic and clinical characteristics of study population (n = 32)

Table 2. MRI tumor regression grade (mrTRG) following SCRT (Primary outcome) (n = 32)

Table 3. Change in MRI T stage following SCRT (n = 32)

Table 4. Nodal status response on MRI after SCRT (n = 32)

Table 5. Mesorectal fascia (MRF) involvement before and after SCRT (n = 32)

Table 6. Distribution of MRI T Stage Before and After SCRT (n = 32)

Table 7. Acute Radiation Toxicity Profile (CTCAE v5.0) (n = 32)

The present study evaluated MRI-based tumor response following short-course radiotherapy (SCRT) in elderly, non-operative cohort of rectal cancer patients. The findings demonstrate that SCRT results in meaningful tumor regression, radiologic downstaging, and favorable tolerability, supporting its role in frail patients unsuitable for surgery.

The majority of patients were aged ≥75 years, with a high burden of comorbidities reflecting a frail cohort. Similar demographic patterns have been reported by Erlandsson J et al.^[4], where elderly patients constituted a substantial subgroup requiring individualized treatment approaches. Additionally, the predominance of locally advanced disease (cT3–T4 in 78.1%) in our cohort aligns with findings by Glynne-Jones R et al.^[3], who noted that elderly patients often present at advanced stages due to delayed diagnosis and limited screening uptake.

The primary outcome of this study (Table 2) showed that 65.6% of patients achieved moderate-to-good response (mrTRG ≤3), with complete response in 12.5%. These findings are comparable to those reported by Patel UB et al.^[6], who demonstrated that MRI-based regression assessment correlates well with treatment response, with good responders ranging between 50–70% following neoadjuvant therapy. Similarly, studies by Brown G et al^[7]. have validated mrTRG as a reliable surrogate marker for tumor regression, particularly in non-operative strategies.

However, the complete response rate in our study is slightly lower than that reported in chemoradiotherapy-based studies, where rates of 15–25% have been described. This difference is expected, as SCRT lacks the radiosensitizing effect of concurrent chemotherapy. Nonetheless, the overall favorable response rate supports the utility of SCRT in elderly populations where treatment tolerance is a key concern.

Raiological downstaging was observed in 56.3% of patients, while 31.3% had stable disease. Detailed stage migration (Table 6) demonstrates a shift toward earlier T stages post-treatment, with an increase in T1–T2 tumors from 6.3% to 25.0%. These findings are consistent with the Stockholm III Trial, which reported significant tumor regression and downstaging following SCRT, particularly when an interval was allowed before reassessment.

Comparable results have also been described by Bujko et al.^[8], who reported downstaging rates of approximately 50–60% following SCRT. The modest proportion of patients showing progression (12.5%) in our study may reflect tumor biology, delayed response kinetics, or limitations of MRI in differentiating fibrosis from residual tumor.

In this study (Table 4), nodal regression from cN+ to cN0 was observed in 34.4% of patients. This is in line with findings from studies by Dworak O et al.^[9], which indicate that nodal response is generally less pronounced than primary tumor response following radiotherapy. Similar nodal sterilization rates (30–40%) have been reported in MRI-based studies assessing response after neoadjuvant treatment.

Persistent nodal disease in 18.8% of patients highlights the limitation of radiotherapy alone in achieving complete nodal clearance, emphasizing the need for careful imaging surveillance in non-operative management strategies.

MRF involvement decreased from 37.5% pre-treatment to 18.8% post-treatment, with a clearance rate of 50% among initially involved cases (Table 5). This is clinically significant, as MRF involvement is a key predictor of local recurrence. Studies by Mercury Study Group^[10] have demonstrated that MRI-assessed MRF clearance is strongly associated with improved oncologic outcomes.

Our findings are comparable to those reported in the MERCURY trial, where neoadjuvant therapy resulted in substantial reduction in MRF involvement. Although most evidence pertains to chemoradiotherapy, the present study suggests that SCRT can also achieve meaningful MRF clearance in selected elderly patients.

An important finding of this study is the favorable toxicity profile of SCRT (Table 7). No grade 3 or 4 toxicity was observed, and the majority of patients experienced either no toxicity (43.8%) or mild symptoms (31.3%). These results are consistent with those reported in the Stockholm III Trial, which demonstrated low rates of severe toxicity with SCRT.

In contrast, long-course chemoradiotherapy is associated with higher rates of grade 3–4 adverse events, particularly in elderly populations. The low toxicity observed in this study reinforces the suitability of SCRT as a well-tolerated treatment option in frail patients, where maintaining quality of life is a critical consideration.

Clinical implications

The findings of this study support the growing role of MRI-based assessment in guiding non-operative management strategies in rectal cancer. The relatively high rate of moderate-to-good response, combined with acceptable downstaging and low toxicity, suggests that SCRT followed by interval MRI may be a viable organ-preserving approach in selected elderly patients.

However, it is important to recognize that MRI has inherent limitations in differentiating fibrosis from residual tumor, which may impact response assessment accuracy. Therefore, integration of clinical, endoscopic, and imaging findings is essential in decision-making.

Limitations

This study has certain limitations, including its retrospective design, small sample size, and single-centre setting, which may limit generalizability. Additionally, the absence of histopathological correlation due to non-operative management restricts validation of MRI findings. Only acute toxicity profile has been assessed, chronic radiation related toxicity assessment need longer follow up. Despite these limitations, the study provides valuable real-world data in an underrepresented patient population.

This single-centre study demonstrates that short-course radiotherapy induces meaningful MRI-detectable tumor regression in a substantial proportion of elderly rectal cancer patients managed without surgery. Nearly two-thirds of patients achieved moderate-to-good radiologic response (mrTRG ≤3), with over half showing T-stage downstaging and one-third demonstrating nodal regression. Mesorectal fascia clearance was observed in half of initially involved cases, indicating improved local disease status after treatment. These findings support the role of SCRT as an effective and well-tolerated non-operative treatment option in frail or comorbid elderly patients who are unsuitable for surgery. MRI-based response assessment using mrTRG provides a reliable tool for treatment evaluation and follow-up in this population and may guide organ-preserving management strategies in selected patients.

Declarations

Funding:

The authors received no financial support for the research, authorship and/or publication of this article.

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethics Approval

The study was approved by the Institutional Ethics Committee of Sree Mookambika Institute of Medical Sciences.

Consent to participate

As this was a retrospective record-based study using anonymized data, the requirement of informed consent was waived by the Institutional Ethics Committee

Consent to publish

Not applicable. The manuscript does not contain any individual person’s data in any form

Author Contributions
K.L. Jayakumar: Conceptualization, Methodology, Supervision, Validation, Critical revision of manuscript.
K. Kanmani: Data curation, Formal analysis, Investigation, Writing – original draft preparation, Writing – review & editing.
All authors read and approved the final manuscript

Availability of Data and Materials

The datasets generated and/or analysed during the current study are not publicly available

due to institutional data protection policies but are available from the corresponding author

on reasonable request, subject to approval by the Institutional Ethics Committee.

1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians. 2021;71(3):209–49. doi:10.3322/caac.21660
2. NCCN [Internet]. [cited 2026 Mar 23]. Guidelines Detail. Available from: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1461
3. Glynne-Jones R, Wyrwicz L, Tiret E, Brown G, Rödel C, Cervantes A, et al. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28(suppl_4):iv22–40. doi:10.1093/annonc/mdx224 PubMed PMID: 28881920.
4. Erlandsson J, Holm T, Pettersson D, Berglund Å, Cedermark B, Radu C, et al. Optimal fractionation of preoperative radiotherapy and timing to surgery for rectal cancer (Stockholm III): a multicentre, randomised, non-blinded, phase 3, non-inferiority trial. The Lancet Oncology. 2017;18(3):336–46. doi:10.1016/S1470-2045(17)30086-4 PubMed PMID: 28190762.
5. Cerdan-Santacruz C, São Julião GP, Vailati BB, Corbi L, Habr-Gama A, Perez RO. Watch and Wait Approach for Rectal Cancer. J Clin Med. 2023;12(8):2873. doi:10.3390/jcm12082873 PubMed PMID: 37109210; PubMed Central PMCID: PMC10143332.
6. Patel UB, Blomqvist LK, Taylor F, George C, Guthrie A, Bees N, et al. MRI After Treatment of Locally Advanced Rectal Cancer: How to Report Tumor Response—The MERCURY Experience. American Journal of Roentgenology. 2012;199(4):W486–95. doi:10.2214/AJR.11.8210
7. Brown G, Richards CJ, Bourne MW, Newcombe RG, Radcliffe AG, Dallimore NS, et al. Morphologic predictors of lymph node status in rectal cancer with use of high-spatial-resolution MR imaging with histopathologic comparison. Radiology. 2003;227(2):371–7. doi:10.1148/radiol.2272011747 PubMed PMID: 12732695.
8. Bujko K, Nowacki MP, Nasierowska-Guttmejer A, Michalski W, Bebenek M, Kryj M. Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer. Br J Surg. 2006;93(10):1215–23. doi:10.1002/bjs.5506 PubMed PMID: 16983741.
9. Dworak O, Keilholz L, Hoffmann A. Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis. 1997;12(1):19–23. doi:10.1007/s003840050072 PubMed PMID: 9112145.
10. Diagnostic accuracy of preoperative magnetic resonance imaging in predicting curative resection of rectal cancer: prospective observational study. BMJ. 2006;333(7572):779. doi:10.1136/bmj.38937.646400.55 PubMed PMID: 16984925; PubMed Central PMCID: PMC1602032.

1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians. 2021;71(3):209–49. doi:10.3322/caac.21660
2. NCCN [Internet]. [cited 2026 Mar 23]. Guidelines Detail. Available from: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1461
3. Glynne-Jones R, Wyrwicz L, Tiret E, Brown G, Rödel C, Cervantes A, et al. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28(suppl_4):iv22–40. doi:10.1093/annonc/mdx224 PubMed PMID: 28881920.
4. Erlandsson J, Holm T, Pettersson D, Berglund Å, Cedermark B, Radu C, et al. Optimal fractionation of preoperative radiotherapy and timing to surgery for rectal cancer (Stockholm III): a multicentre, randomised, non-blinded, phase 3, non-inferiority trial. The Lancet Oncology. 2017;18(3):336–46. doi:10.1016/S1470-2045(17)30086-4 PubMed PMID: 28190762.
5. Cerdan-Santacruz C, São Julião GP, Vailati BB, Corbi L, Habr-Gama A, Perez RO. Watch and Wait Approach for Rectal Cancer. J Clin Med. 2023;12(8):2873. doi:10.3390/jcm12082873 PubMed PMID: 37109210; PubMed Central PMCID: PMC10143332.
6. Patel UB, Blomqvist LK, Taylor F, George C, Guthrie A, Bees N, et al. MRI After Treatment of Locally Advanced Rectal Cancer: How to Report Tumor Response—The MERCURY Experience. American Journal of Roentgenology. 2012;199(4):W486–95. doi:10.2214/AJR.11.8210
7. Brown G, Richards CJ, Bourne MW, Newcombe RG, Radcliffe AG, Dallimore NS, et al. Morphologic predictors of lymph node status in rectal cancer with use of high-spatial-resolution MR imaging with histopathologic comparison. Radiology. 2003;227(2):371–7. doi:10.1148/radiol.2272011747 PubMed PMID: 12732695.
8. Bujko K, Nowacki MP, Nasierowska-Guttmejer A, Michalski W, Bebenek M, Kryj M. Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer. Br J Surg. 2006;93(10):1215–23. doi:10.1002/bjs.5506 PubMed PMID: 16983741.
9. Dworak O, Keilholz L, Hoffmann A. Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis. 1997;12(1):19–23. doi:10.1007/s003840050072 PubMed PMID: 9112145.
10. Diagnostic accuracy of preoperative magnetic resonance imaging in predicting curative resection of rectal cancer: prospective observational study. BMJ. 2006;333(7572):779. doi:10.1136/bmj.38937.646400.55 PubMed PMID: 16984925; PubMed Central PMCID: PMC1602032.