Letter to the Editor: Imaging biomarkers in rectal cancer - are we ready for clinical implementation?

Abstract

I read with interest the study by Nie et al entitled “Tumor-related imaging parameters predict response and survival after neoadjuvant chemoradiotherapy in rectal cancer” published in the World Journal of Gastrointestinal Oncology. Response to neoadjuvant chemoradiotherapy in rectal cancer varies among patients with the same stage, age, and treatment regimen. Identifying parameters that can predict treatment response and survival in oncology patients is crucial for developing individualized treatments and achieving favorable oncological outcomes. Recent studies have attempted to reveal the relationship between radiological imaging and oncological outcomes. Although these studies demonstrated that magnetic resonance imaging-based tumor-related parameters may influence oncological outcomes, the findings regarding sarcopenia have been inconsistent. Overall, these studies suggest that pre-treatment magnetic resonance imaging-based markers may be useful in predicting responses to chemoradiotherapy. However, further studies and standardization are required before these assessments can be implemented in routine clinical practice.

Key Words: Rectal cancer; Neoadjuvant chemoradiotherapy; Mesorectal fascia; Treatment response; Sarcopenia

Core Tip: This article reviews a recent study examining the prognostic value of imaging parameters prior to neoadjuvant chemoradiotherapy in rectal cancer. It highlights that sarcopenia is not an independent predictor of oncological outcomes, whereas radiological image-based parameters, such as tumor length, mesorectal fascia involvement, and nodal involvement, are significantly associated with oncological outcomes. These findings support the importance of pre-treatment imaging biomarkers in predicting oncological outcomes, and their clinical implications are discussed in the context of the current literature.

TO THE EDITOR

I read with interest the study published by Nie et al[1] in the World Journal of Gastrointestinal Oncology. Predicting oncological outcomes based on radiological imaging findings is crucial for both personalized treatment planning and improving oncological outcomes. The availability of these radiological examinations at the diagnostic stage may facilitate the prediction of treatment outcomes. Although sarcopenia appears as a significant predictor of oncological response in some studies, the present study found no significant association between sarcopenia and oncological outcomes. In contrast, tumor characteristics appear to play a more important role in determining oncological outcomes.

IMAGING PREDICTS NEOADJUVANT CHEMORADIOTHERAPY RESPONSE IN RECTAL CANCER

Rectal cancer is one of the most common cancers worldwide and continues to have a significant negative impact on public health. Therefore, determining appropriate treatment strategies is of critical importance[2]. Despite the widespread use of screening methods globally, the effectiveness of screening in asymptomatic individuals remains limited, and most cases of rectal cancer are still diagnosed at an advanced symptomatic stage[3]. In a large-scale study, approximately 46.5% of cases were diagnosed at an advanced stage, indicating that early diagnosis has still not been fully achieved[4].

Neoadjuvant chemoradiotherapy (nCRT) has become the standard treatment for locally advanced rectal cancer based on the results of phase III randomized trials[5]. Currently, phase III randomized studies have demonstrated that total neoadjuvant therapy leads to better oncological outcomes[6]. However, oncological outcomes are not always comparable among patients of the same stage and age group receiving identical treatments. This suggests that additional parameters are needed to guide treatment selection and achieve personalized treatment approaches with the optimal therapeutic index for each patient.

Many studies evaluate oncological outcomes according to patient-, tumor-, and treatment-related characteristics rather than stage alone[7-9]. These studies have shown that factors such as the presence of lymphovascular invasion, high preoperative carcinoembryonic antigen levels, and poor tumor differentiation are important determinants of survival. In addition, molecular markers such as KRAS and BRAF mutations have been reported to be associated with treatment response and long-term prognosis. In particular, KRAS mutations have been shown to reduce pathological complete response rates after nCRT and may negatively affect survival outcomes.

In contrast, radiological imaging-based parameters stand out as predictive indicators with the strongest support in the literature regarding their relationship with long-term oncological outcomes. In the MERCURY study conducted by Taylor et al[10], preoperative magnetic resonance imaging (MRI) with circumferential resection margin (CRM) was shown to be superior to classical American Joint Committee on Cancer tumor-node-metastasis staging in predicting disease-free survival, local recurrence, and overall survival. Although mesorectal fascia (MRF) involvement on MRI is not identical to pathological CRM positivity, MRF involvement is considered a strong radiological surrogate associated with an increased risk of CRM involvement and local recurrence. Williams et al[11] found that baseline MRI could predict the success of organ-sparing approaches after total neoadjuvant therapy more successfully. In this study, Williams et al[11] demonstrated that pre-treatment MRI findings can guide clinicians not only in staging but also in the treatment decision-making process. Similarly, in the study conducted by El Homsi et al[12], the relationship between MRI findings and recurrence was investigated. In univariate analysis, advanced age (> 55 years), low rectal location, tumor length of 5 cm or more, anal canal involvement, suspicious mesorectal lymph nodes larger than 0.5 cm, MRF involvement, T3-T4 stage, and M1 stage were found to be associated with disease recurrence. In multivariate analysis, age over 55 years and the presence of lymph nodes larger than 0.5 cm were determined to be independent poor prognostic factors[12].

When these studies are considered together, it becomes evident that the prognostic value of MRI-based parameters is not limited solely to staging. Tumor length and MRF involvement are essentially anatomical indicators reflecting tumor burden and the degree of mesorectal spread. A longer tumor segment implies a greater potential for mucosal and mesorectal infiltration, while MRF positivity increases the risk of microscopic residual disease and CRM positivity. Similarly, the presence of mesorectal lymph nodes may indicate not only local disease spread but also systemic micrometastatic potential. Therefore, these parameters detected on MRI can be considered radiological markers that indirectly reflect biological aggressiveness. According to the results of the current study, it seems appropriate to consider pre-treatment MRI findings not only for tumor-node-metastasis staging but also for patient-specific risk stratification and the determination of personalized treatment strategies.

Malnutrition is a common problem among cancer patients, and many patients experience weight loss due to both the effects of the tumor and the side effects of the treatments they receive. Weight loss negatively affects both their treatment response and prognosis[13]. In recent years, sarcopenia, as a parameter reflecting systemic inflammation and nutritional status, has been evaluated as a prognostic marker in many malignancies for predicting oncological outcomes. Several studies have reported that sarcopenia may be associated with increased morbidity and decreased survival in gastrointestinal cancers[14,15].

In rectal cancer, several studies have investigated the relationship between sarcopenia, particularly after nCRT, and postoperative complications and long-term oncological outcomes[16]. While some studies have found sarcopenia to be associated with lower pathological response rates and worse survival outcomes[17], other studies have reported that the independent prognostic value of sarcopenia, especially before treatment, is limited[15,18]. These differences may be related to the variability in the threshold values used in the definition of sarcopenia, differences in measurement methods, and the heterogeneous nature of patient populations. Furthermore, sarcopenia is a parameter reflecting systemic physiological reserve rather than local anatomical tumor spread and therefore, may not directly indicate tumor biology.

Therefore, it is thought that MRI-based parameters, which directly reveal anatomical tumor burden and the degree of mesorectal spread may be more consistent and clinically applicable indicators, especially in predicting response to neoadjuvant therapy.

CONCLUSION

In conclusion, this study shows that radiological imaging-based tumor parameters have a greater prognostic value than sarcopenia in predicting response to nCRT. Predicting treatment response is also an essential component of developing personalized treatment strategies. However, these findings should be validated with prospective, multicenter studies using standardized methods.