For decades, surgery with pre- or postoperative radiation and/or chemotherapy has been the mainstay of treatment for patients with locally advanced rectal cancer (LARC). However, the use of a nonoperative management strategy is increasing for patients who attain a complete clinical response (cCR) after radiation and/or chemotherapy (1). Interest in nonoperative management is driven by a desire to avoid surgery requiring a permanent ostomy or expected poor bowel function with sphincter-preserving surgery (2). Rates of Major Low Anterior Resection Syndrome (LARS), a constellation of symptoms that includes problems with frequency, urgency, and control of bowel movements, are nearly 50% when surgery requires a low anastomosis (3).

Although LARS was originally described as altered and problematic bowel function that occurs after rectal resection (4), studies suggest that approximately 25-33% of patients treated with definitive radiation and nonoperative management for rectal cancer can also develop Major LARS (5, 6). Bowel dysfunction, particularly fecal incontinence, after pelvic radiation is likely multifactorial (7). In the acute setting, radiation causes inflammation that leads to the development of fibrosis. This can result in issues with large bowel wall compliance, small bowel absorption, and persistent dysbiosis, causing diarrhea and urgency (8). Additionally, radiation-induced fibrosis, vascular changes, and nerve damage can lead to muscle atrophy within the pelvic floor muscles and sphincter complex (9).

Interventions such as pelvic floor physical therapy may improve post-treatment bowel dysfunction by isolating and strengthening pelvic floor muscles (10). However, tools for accurately assessing pelvic floor atrophy or damage remain limited. Magnetic resonance imaging (MRI) offers detailed visualization of soft tissues, including the pelvic floor, and may serve as a quantitative biomarker to detect radiation-induced atrophy (11). In this pilot study, we seek to evaluate 2D and volumetric levator ani measurements on pre- and 1-year post-treatment MRI among patients treated with radiation as a component of nonoperative management and correlate post-radiation MRI changes with LARS and patient-reported Fecal Incontinence Quality of Life (FIQoL) scores.

In this pilot study, we show a decrease in 2D and volumetric measurements of the levator ani one year after definitive pelvic radiation for rectal adenocarcinoma. The demonstrated correlation between 2D levator ani measurements and LARS suggests MRI may be a useful biomarker for bowel dysfunction and incontinence. By integrating structural imaging with patient-reported outcomes, this work provides preliminary support for advancing personalized survivorship care strategies and will serve as the foundation for future studies.

We found significant reductions in both 2D and volumetric levator ani measurements at 12 months post-treatment, suggesting a lasting effect of radiation on pelvic floor atrophy. Radiation exposure is known to induce transforming growth factor-β (TGF-β) release and chronic inflammation, leading to sustained fibroblast activation and extracellular matrix deposition that replace normal tissue architecture with fibrotic tissue (18). Additionally, oxidative stress and DNA damage results in depletion of myogenic stem cells, impacting regenerative capacity and further propagating muscle atrophy (19). These pathophysiological mechanisms induced by radiation therapy result in structural changes in pelvic floor muscles (20, 21). While the optimal levator ani quantification strategy is unknown, the strong positive correlation between 2D and volumetric measurements in our study supports the potential utility of simplified linear assessments as a practical alternative to volumetric analysis. Notably, given that the changes were detected through routine baseline and surveillance imaging, clinical implementation may be feasible without additional imaging burden.

Among this cohort of 15 patients treated with definitive, long-course chemoradiation +/- chemotherapy for locally advanced rectal cancer, 7 (46.7%) had symptoms consistent with Major LARS at least 18 months from completion of therapy. This is somewhat higher than other reported series (5, 6). In a cohort of 221 patients treated with radiation and nonoperative management, the rate of major LARS was 25% (5). This variation may be attributed to the cumulative multimodal treatment burden associated with long-term chemoradiation in comparison to selective nonoperative strategies such as short-course radiotherapy. In a cohort of 33 patients similarly treated, the rate of major LARS was 33%. This study also included a dosimetric analysis, but there were no significant associations between dose to the anal sphincter complex and LARS score (6).

With respect to functional outcomes, a moderate correlation was observed between reductions in 2D measurements and worsening LARS scores, suggesting a trend towards clinically relevant functional decline in patients with a high degree of pelvic atrophy. In contrast, correlation with volumetric change and FiQOL scores were weaker and non-significant. These trends may reflect the multifactorial nature of post-treatment dysfunction. Differences between volumetric and 2D correlations may be attributed to greater sensitivity of single plane 2D measurements to focal levator ani thinning in regions most relevant with anorectal support. In contrast, volumetric measurements integrate multiple dimensions and may dilute localized atrophy measurements with functional implications. As evidenced by the questionnaires, patient-reported outcomes are influenced not only by structural factors but also by psychosocial and behavioral components. Notably, the FiQOL outcome assesses broader quality of life aspects, such as emotional and social well-being, which may not be directly linked to structural alterations compared to questions regarding stool leakage and urgency. These variations emphasize the need for multimodal assessments alongside imaging to evaluate both functional and psychosocial quality of life.

Therapeutic interventions, such as pelvic floor physical therapy, have demonstrated efficacy in managing radiation-induced dysfunctions such as incontinence, pain, and sexual dysfunction in pelvic cancer survivors (22, 23). Leveraging MRI findings to guide these interventions with early risk stratification could enhance their effectiveness, particularly for patients with significant muscle atrophy. Emerging tools with MRI through predictive models and radiomics may enhance the predictive value of imaging alongside functional response to guide and personalize treatment options (24, 25). While pretreatment levator ani width and volume were not significantly correlated with post-treatment LARS score, change post treatment may predict worse function. By identifying pelvic floor atrophy prior to symptom onset, clinicians may mitigate chronic pelvic dysfunction and the associated patient outcomes.

While this study provides promising insights, several limitations should be acknowledged. The small cohort size limits the statistical power and generalizability, and the lack of pre-treatment patient-reported functional assessments restricts the ability to assess functional changes over time. Furthermore, the absence of dosimetric data limits the evaluation of dose-response relationships with muscle volume loss. Finally, although we utilized published guidelines and atlases for the 2D and volumetric measurements in this pilot study, we only had one expert diagnostic radiologist recording 2D measurements and one expert radiation oncologist recording volumetric measurements. Measurements were recorded one time per patient and timepoint. Therefore, intra- and interobserver variability were not formally assessed. Future research should also explore advanced imaging techniques, such as diffusion tensor imaging, to assess microstructural changes in pelvic musculature. Establishing an MRI-based threshold for clinically significant atrophy would be helpful in defining criteria for risk stratification and early therapeutic intervention. Additionally, longitudinal studies are needed to understand the progression of atrophy and its relationship to functional outcomes and quality of life. We plan to use these pilot data to design future studies to risk-stratify patients for early therapeutic interventions for bowel dysfunction and assess response to treatment.