*2.6.5 Assessing N- stage*

*Colorectal Cancer*

T2 and T3.

tion lines (**Figure 8**).

metastases.

regardless of the nodal status.

*2.6.3 Assessing CRM- circumferential resection margin*

*2.6.4 Assessing EMVI: extramural venous/vascular invasion*

outside the lamina muscularis propria (**Figure 9**, arrows).

*CRM- circumferential resection margin (axial T2 weighted MR images).*

• pT3 with>5 mm tumor invasion have a worse 5-year survival (disease-free survival (DFS)) than tumors with an invasion below 5 mm (pT3b); and this

• T3a tumors, with an invasion below 1 mm, have a very good prognosis

CRM is the surface of the nonperitonealized part of the rectum that is resected during surgery. In the description of T3-tumors, the report should include the shortest distance between the tumor margin and the mesorectal fascia MRF because of increased risk for local recurrence. MRF often refers to CRM. CRM > 5 mm measured by MRI is sufficient to predict microscopically clear resec-

• The values for local recurrence and overall survival of T2 and T3a are identical

• The palpable difference in DFS between T3b and T3c shows that their differentiation is of greater clinical significance than the distinction between

Extramural vascular invasion is defined as the presence of tumor cells in vessels

Positive mrEMVI is associated with low survival rates. The 3-year survival in mrEMVI-positive patients was 35% compared to 74% in mrEMVI-negative patients. mrEMVI-positive patients have a fourfold increased risk of developing distant

The radiological characteristics of EMVI observed on MRI are described in detail -The veins around the rectum are recognized on the T2 sequence as serpiginous or curved linear structures; in the tubular structures considered to be blood vessels, in addition to changes in the contour, there is a weakening of the signal.

**66**

**Figure 8.**

The N-stage is an important risk factor for local recurrence. The size of the lymph node itself is not indicative, as 15–42% of patients with rectal cancer have small (<5 mm) mesorectal lymph nodes containing tumor cells (**Figure 10**, arrowheads).

**Figure 10.** *Lymph nodes (arrowheads).*

### *2.6.6 Assessing mrTRG (special focus)*

Tumor regression refers to the effect of neoadjuvant radiotherapy or chemotherapy on the tumor. The degree of tumor regression (TRG) is determined by the amount of residual tumor cells and the degree of fibrosis induced by non-adjuvant therapy. High tumor regression correlates with higher survival and lower rate of local recurrence. Several scales have been developed for TRG, such as Mandard and Dworak, but no consensus has been reached on which to use routinely.

After chemoradiotherapy, a number of tissue changes induced by radiation occur. These include swelling, inflammation, necrosis and fibrosis. mrTRG evaluates the changes on MRI after 12 weeks of neoadjuvant chemo-, radiotherapy.

This mrTRG system uses a 5-point scale. The low points [1–3] correspond to a more significant regression, and the high points [4, 6] mean no regression. The system also divides the categories according to the type of answer (complete, good, moderate, poor, none).

mrTRG1- radiologically complete response- linear, eccentric scar of 1–2 mm, limited in the mucosa or submucosa.

mrTRG2- good response- dense fibrosis without visualizing a residual tumor and without suspecting (**Figure 11**).

mrTRG3- incomplete response - over 50% fibrosis or mucin and visible intermediate signal intensity.

mrTRG4- weak response- small areas of fibrosis or mucin among tumor tissue (**Figure 11**).

mrTRG5- no response- intermediate signal intensity, tumor visualization without tumor dynamics or growth.

(Proposed by Bhoday et al) [13].

Many studies show that mrTRG is a prognostic and predictive biomarker-MERCURY trial, EXPERT-C trial [14], GEMCAD study, CORE study [5]. EXPERT – C study shows significant difference in rates of disease-free survival DFS and overall survival OS: mrTRG 1 & 2 (good response), mrTRG3 (medium response) and mrTRG4–5 (poor response) have a 3-year DFS survival of 82, 72 and 61%, respectively. These independent studies show that mrTRG predicts different groups- mrTRG could distinguish between "good" and "poor" responses to chemotherapy ('good' and 'poor' responders). It could be suggested that mrTRG can be used as a biomarker to stratify the choice of treatment for rectal cancer. Good responses (mrTRG1–2) are similar to good pCR, so surgery rejection and intensive follow-up of these patients can be chosen (watch and wait strategy). Poor responses (mrTRG3–5) could be subject to additional chemotherapy in order to improve mrTRG status to a lower grade. This requires the use of MRI to repeat the assessment of mrTRG.

### **Figure 11.**

*Tumor regression grade on MRI: First picture T3d rectal cancer before neoadjuvant therapy. Second picture mrTRG 2/3 same patient after neoadjuvant therapy. Third and fourth picture another patient with T3 tumor before (third) and after (fourth) neoadjuvant therapy- mrTRG 4/5.*

**69**

Watch & Wait.

*Role of Magnetic Resonance Imaging in Patients with Rectal Cancer*

mrTRG and pTRG were compared in patients with rectal cancer in two clinical trials (EXPERT and EXPERT-C) [14]. The concurrence of the opinions of radiologists and pathologists was assessed with the weighted k test. The Kaplan–Meier method was used to evaluate the results of overall survival. Results: 191 patients were included in the study. The mean time from completion of neoadjuvant treatment to preoperative MRI and surgery was 4.1 weeks (IQR: 3.7–4.7) and 6.6 weeks, respectively (IQR: 5.9–7.6). good agreement was found between mrTRG and pTRG, with regression classified according to standard five-stage systems (kj0.24) or modified three-stage systems (kj0.25). Sensitivity and

specificity of mrTRG 1–2 (complete / good radiological regression) for predicting the pathological complete response was 74.4% (95% CI: 58.8–86.5) and 62.8%, respectively (95% CI: 54.5–70.6) Survival outcomes in patients with intermediate pTRG 2 were numerically better if complete/good regression was also observed with mrTRG 1–2, compared with poor regression of mrTRG4–5 (5-year recurrence-free survival 76.9% vs. 65.9%, P00.18; 5-year overall survival 80.6%

Conclusions: The coherence between mrTRG and pTRG is low and mrTRG cannot be used as a substitute for pTRG. Further studies are needed to assess the ability of mrTRG to detect patients with a complete response to pTRG and to provide additional prognostic information to pTRG for better risk stratification after surgery. Evaluation of the preoperative response to treatment of rectal cancer by MRI is an area of growing importance both in terms of predicting results and in determining the complete response. Clinical use is currently limited. The MERCURY study [13] shows that tumor regression can be assessed by MRT (mrTRG) after preoperative chemotherapy and radiation, using the differences in signal intensity between tumor and fibrous tissue. In this study, the 5-year overall survival (OS) was 27% for poor response (mrTRG4–5) versus 72% (p = 0.007) for good response (mrTRG 1–2), and the 5-year free survival was relapse survival (DFS) resp. 31% vs. 64% (p = 0.007). Nougart et al. [15] reported that volume assessment with MRI in patients receiving preoperative therapy was of prognostic significance. In this study, a reduction in tumor volume of at least 70% was associated with a better DFS

Another PAN-EX study [16] by the same study group again demonstrated that mrTRG had greater value for prognostic factors such as relapse-free survival (RFS),

The main advantage of mrTRG is that it is not based on evaluation of resection material. The degree of tumor regression with MRI can be assessed before any surgery. This information provides a potential opportunity to consider other preoperative therapies. Previous analyzes of the PAN-EX study showed that patients who achieved mrTRG 1–2 after completion of CLT had a significantly better prognosis than patients who were assessed as mrTRG 3–5. mrTRG can potentially be used as an imaging parameter for the selection of patients with a good prognosis, in whom a non-operative approach after neoadjuvant treatment may be preferred. mrTRG appears as a dynamic, non-invasive, surrogate method for assessing tumor regres-

Be aware that the classification of patients as good and poor responders on the basis of mrTRG makes it possible not only to predict the outcome of the disease, but also to modulate therapeutic behavior. This means that patients may be advised to delay surgery, modulate chemo-, radiotherapy or choose another approach. The TRIGGER study [17] evaluated mrTRG as a new biomarker for stratification of patients with good and poor response to neoadjuvant therapy for rectal cancer and the inclusion of good responders in a new strategy, namely

long-term relapse-free survival (DFS), and overall survival (OS).

sion after neoadjuvant treatment and before surgical resection.

*DOI: http://dx.doi.org/10.5772/intechopen.94868*

vs. 68.8%, P0.22).

value (HR 13.7; 95% CI 3.98–31.93).

### *Role of Magnetic Resonance Imaging in Patients with Rectal Cancer DOI: http://dx.doi.org/10.5772/intechopen.94868*

*Colorectal Cancer*

routinely.

moderate, poor, none).

diate signal intensity.

(**Figure 11**).

limited in the mucosa or submucosa.

and without suspecting (**Figure 11**).

without tumor dynamics or growth. (Proposed by Bhoday et al) [13].

*2.6.6 Assessing mrTRG (special focus)*

Tumor regression refers to the effect of neoadjuvant radiotherapy or chemotherapy on the tumor. The degree of tumor regression (TRG) is determined by the amount of residual tumor cells and the degree of fibrosis induced by non-adjuvant therapy. High tumor regression correlates with higher survival and lower rate of local recurrence. Several scales have been developed for TRG, such as Mandard and Dworak, but no consensus has been reached on which to use

After chemoradiotherapy, a number of tissue changes induced by radiation occur. These include swelling, inflammation, necrosis and fibrosis. mrTRG evaluates the changes on MRI after 12 weeks of neoadjuvant chemo-, radiotherapy. This mrTRG system uses a 5-point scale. The low points [1–3] correspond to a more significant regression, and the high points [4, 6] mean no regression. The system also divides the categories according to the type of answer (complete, good,

mrTRG1- radiologically complete response- linear, eccentric scar of 1–2 mm,

mrTRG2- good response- dense fibrosis without visualizing a residual tumor

mrTRG3- incomplete response - over 50% fibrosis or mucin and visible interme-

mrTRG4- weak response- small areas of fibrosis or mucin among tumor tissue

mrTRG5- no response- intermediate signal intensity, tumor visualization

Many studies show that mrTRG is a prognostic and predictive biomarker-MERCURY trial, EXPERT-C trial [14], GEMCAD study, CORE study [5]. EXPERT – C study shows significant difference in rates of disease-free survival DFS and overall survival OS: mrTRG 1 & 2 (good response), mrTRG3 (medium response) and mrTRG4–5 (poor response) have a 3-year DFS survival of 82, 72 and 61%, respectively. These independent studies show that mrTRG predicts different groups- mrTRG could distinguish between "good" and "poor" responses to chemotherapy ('good' and 'poor' responders). It could be suggested that mrTRG can be used as a biomarker to stratify the choice of treatment for rectal cancer. Good responses (mrTRG1–2) are similar to good pCR, so surgery rejection and intensive follow-up of these patients can be chosen (watch and wait strategy). Poor responses (mrTRG3–5) could be subject to additional chemotherapy in order to improve mrTRG status to a lower grade. This

*Tumor regression grade on MRI: First picture T3d rectal cancer before neoadjuvant therapy. Second picture mrTRG 2/3 same patient after neoadjuvant therapy. Third and fourth picture another patient with T3 tumor* 

requires the use of MRI to repeat the assessment of mrTRG.

*before (third) and after (fourth) neoadjuvant therapy- mrTRG 4/5.*

**68**

**Figure 11.**

mrTRG and pTRG were compared in patients with rectal cancer in two clinical trials (EXPERT and EXPERT-C) [14]. The concurrence of the opinions of radiologists and pathologists was assessed with the weighted k test. The Kaplan–Meier method was used to evaluate the results of overall survival. Results: 191 patients were included in the study. The mean time from completion of neoadjuvant treatment to preoperative MRI and surgery was 4.1 weeks (IQR: 3.7–4.7) and 6.6 weeks, respectively (IQR: 5.9–7.6). good agreement was found between mrTRG and pTRG, with regression classified according to standard five-stage systems (kj0.24) or modified three-stage systems (kj0.25). Sensitivity and specificity of mrTRG 1–2 (complete / good radiological regression) for predicting the pathological complete response was 74.4% (95% CI: 58.8–86.5) and 62.8%, respectively (95% CI: 54.5–70.6) Survival outcomes in patients with intermediate pTRG 2 were numerically better if complete/good regression was also observed with mrTRG 1–2, compared with poor regression of mrTRG4–5 (5-year recurrence-free survival 76.9% vs. 65.9%, P00.18; 5-year overall survival 80.6% vs. 68.8%, P0.22).

Conclusions: The coherence between mrTRG and pTRG is low and mrTRG cannot be used as a substitute for pTRG. Further studies are needed to assess the ability of mrTRG to detect patients with a complete response to pTRG and to provide additional prognostic information to pTRG for better risk stratification after surgery.

Evaluation of the preoperative response to treatment of rectal cancer by MRI is an area of growing importance both in terms of predicting results and in determining the complete response. Clinical use is currently limited. The MERCURY study [13] shows that tumor regression can be assessed by MRT (mrTRG) after preoperative chemotherapy and radiation, using the differences in signal intensity between tumor and fibrous tissue. In this study, the 5-year overall survival (OS) was 27% for poor response (mrTRG4–5) versus 72% (p = 0.007) for good response (mrTRG 1–2), and the 5-year free survival was relapse survival (DFS) resp. 31% vs. 64% (p = 0.007). Nougart et al. [15] reported that volume assessment with MRI in patients receiving preoperative therapy was of prognostic significance. In this study, a reduction in tumor volume of at least 70% was associated with a better DFS value (HR 13.7; 95% CI 3.98–31.93).

Another PAN-EX study [16] by the same study group again demonstrated that mrTRG had greater value for prognostic factors such as relapse-free survival (RFS), long-term relapse-free survival (DFS), and overall survival (OS).

The main advantage of mrTRG is that it is not based on evaluation of resection material. The degree of tumor regression with MRI can be assessed before any surgery. This information provides a potential opportunity to consider other preoperative therapies. Previous analyzes of the PAN-EX study showed that patients who achieved mrTRG 1–2 after completion of CLT had a significantly better prognosis than patients who were assessed as mrTRG 3–5. mrTRG can potentially be used as an imaging parameter for the selection of patients with a good prognosis, in whom a non-operative approach after neoadjuvant treatment may be preferred. mrTRG appears as a dynamic, non-invasive, surrogate method for assessing tumor regression after neoadjuvant treatment and before surgical resection.

Be aware that the classification of patients as good and poor responders on the basis of mrTRG makes it possible not only to predict the outcome of the disease, but also to modulate therapeutic behavior. This means that patients may be advised to delay surgery, modulate chemo-, radiotherapy or choose another approach. The TRIGGER study [17] evaluated mrTRG as a new biomarker for stratification of patients with good and poor response to neoadjuvant therapy for rectal cancer and the inclusion of good responders in a new strategy, namely Watch & Wait.

## **2.7 Additional imaging modalities**

Computed tomography, ultrasound and positron-emission tomography are imaging studies that could be complementary to MRI and be incorporated in the management of rectal cancer in some cases. Be aware that MRI is not available imaging tool in some institutions and CT and/or US are the only diagnostic choice for rectal cancer.

### *2.7.1 Computed tomography CT*

Computed tomography CT (**Figure 12**) is not a modality of choice in the staging of rectal cancer due to the low resolution of the method and the inability to distinguish the different layers of the intestinal wall required for T-staging compared to MRI. CT is not applicable for detection of accurate T-stage, CRM- or EMVI involvement, but a method of choice for N- and M-staging and CT is still used in many centers. CT is not recommended for follow-up or for monitoring after therapy.

### *2.7.2 Ultrasound US*

Endorectal ultrasound is effective diagnostic modality in the assessment of rectal cancer. Its accuracy in numerous trials is around 80% for T-staging and 70% for N-staging.

ERUS images of the rectal wall comprise three hyperechoic and two hypoechoic layers, which alternate with each other and correspond to anatomic layers. (**Figure 13**).

**71**

and T4 tumors.

**Figure 13.**

**Figure 12.**

labeled with the prefix "u".

the normal five-layer image.

*Role of Magnetic Resonance Imaging in Patients with Rectal Cancer*

On endorectal ultrasound, rectal tumors appear as hypoechoic lesions and are staged according to level of invasion through the rectal wall. Ultrasound stages are

*Endorectal ultrasound illustrating rectal cancer invading beyond the rectal wall into perirectal fat.*

ERUS can also be used to monitor for rectal cancer recurrence postoperatively. After surgery, the excision site appears as a pattern of mixed echogenicity, replacing

ERUS is a method of staging rectal cancer which is human dependent. ERUS is less accurate for T staging of stenotic tumors, but the accuracy may still be within acceptable limits. Surgeons use ERUS to adopt a treatment protocol, knowing the risk of under-staging and over-staging of this method. The accuracy of ERUS is higher in diagnosing rectal cancer in stages T1, T2 and with less sensitivity for T3

*DOI: http://dx.doi.org/10.5772/intechopen.94868*

*CECT of rectal cancer, axial view, soft tissue window.*

*Role of Magnetic Resonance Imaging in Patients with Rectal Cancer DOI: http://dx.doi.org/10.5772/intechopen.94868*

**Figure 12.** *CECT of rectal cancer, axial view, soft tissue window.*

**Figure 13.**

*Colorectal Cancer*

**2.7 Additional imaging modalities**

*2.7.1 Computed tomography CT*

for rectal cancer.

*2.7.2 Ultrasound US*

for N-staging.

(**Figure 13**).

Computed tomography, ultrasound and positron-emission tomography are imaging studies that could be complementary to MRI and be incorporated in the management of rectal cancer in some cases. Be aware that MRI is not available imaging tool in some institutions and CT and/or US are the only diagnostic choice

Computed tomography CT (**Figure 12**) is not a modality of choice in the staging of rectal cancer due to the low resolution of the method and the inability to distinguish the different layers of the intestinal wall required for T-staging compared to MRI. CT is not applicable for detection of accurate T-stage, CRM- or EMVI involvement, but a method of choice for N- and M-staging and CT is still used in many centers. CT is not recommended for follow-up or for monitoring after therapy.

Endorectal ultrasound is effective diagnostic modality in the assessment of rectal cancer. Its accuracy in numerous trials is around 80% for T-staging and 70%

layers, which alternate with each other and correspond to anatomic layers.

ERUS images of the rectal wall comprise three hyperechoic and two hypoechoic

**70**

*Endorectal ultrasound illustrating rectal cancer invading beyond the rectal wall into perirectal fat.*

On endorectal ultrasound, rectal tumors appear as hypoechoic lesions and are staged according to level of invasion through the rectal wall. Ultrasound stages are labeled with the prefix "u".

ERUS can also be used to monitor for rectal cancer recurrence postoperatively. After surgery, the excision site appears as a pattern of mixed echogenicity, replacing the normal five-layer image.

ERUS is a method of staging rectal cancer which is human dependent. ERUS is less accurate for T staging of stenotic tumors, but the accuracy may still be within acceptable limits. Surgeons use ERUS to adopt a treatment protocol, knowing the risk of under-staging and over-staging of this method. The accuracy of ERUS is higher in diagnosing rectal cancer in stages T1, T2 and with less sensitivity for T3 and T4 tumors.

### **Figure 14.** *PET/CT of rectal cancer.*
