**8. Imaging modalities for restaging**

At our Imaging Center we evaluated in the past 5 years (2015-2020) 135 patients with rectal carcinoma using MRI (4 devices of 1.5 T, 2 devices of 3 T).

In the first 2 years, we almost exclusively performed primary diagnoses, the question of restaging being very low. On the one hand, this was due to our surgeons, who did not want to reconsider their original operation planning after completing CRT; on the other hand, it was due to us, because we were still very busy delivering high quality MRI diagnoses. When our image diagnostic results matched the histology, we finally got an adequate appreciation. This required a long learning curve. Today, restaging is as obligatory in our institute as preoperative MRI diagnostics. Restaging is a very demanding examination and can only work if the primary staging is performed with constant high quality. At this point, at the latest, the standardized examination protocol with DWI pays off.

While restaging, MRI imager after nCRT are correlated with MRI images before nCRT in all elements evaluated in primary staging. This requires post therapeutic image acquisition under nearly identical protocol parameters and levels. Essential points at this stage are position, extent and signal intensity of the tumor. These features are compared in the MRI images before and after nCRT. Care is also taken to ensure that restaging or follow up is always performed with the same device, because of the decisive diffusion-weighted images. As already mentioned, different devices (e.g. Siemens vs. Philips) provide different diffusion values, which are not always comparable.

Restaging is not for beginners and requires a long learning curve, similar to MRI of the mamma or MRI of the prostate. A minimum of 50 histologically confirmed cases/examinations are necessary to achieve a good performance.

The difficulties of restaging are obvious: Neoadjuvant therapy leads to profound changes in tumor tissue and surrounding structures, such as excessive fibrosis, deep stoma aging, wall thickening, characteristic muscle remodeling, tumor necrosis, calcification and inflammatory infiltration. As a result, the diagnostic accuracy of the imaging procedures decreases significantly with respect to restaging. Accordingly, the local tumor extent can be over- or underestimated.

These challenges can best handled using MRI with diffusion images. The accuracy of clinical examinations using endorectal ultrasound (EUS), computed tomography (CT) and 18F-FDG protrusion emission tomography with CT (18F-FDG-PET/CT), is very low both for the assessment of mesorectal invasion and for the evaluation of lymph node metastases and is therefore not used at our clinic for restaging as the sole examination.

Our restaging strategy includes digital rectal examination, endoscopy/EUS, and finally MRT (DWI). Care is always taken to ensure that this examination sequence is followed. This is where the multidisciplinary team meeting between surgeons, gastroenterologists and radiologists plays a special role (**Figure 12**). The decisive images are introduced into the PACS system and are available to everyone. When

### **Figure 12.**

*Response assessment with MRI T2w, DWI, and EUS. Pre RCT imaging shows a rectal cancer stage T2 (yellow arrow) with low to moderate signal in T2w (A, B) and high signal in DWI, C. Reporting: T2, N0, EMVI-, CRM-. Post RCT imaging shows complete remission, stage mrTRG-1. Note the tumor has completely regressed and was replaced by fibrosis (green arrows show fibrotic wall thickening with no evidence of tumor remnants) D, E. F. There is no focal high signal in DWI anymore, no diffusion restriction F. G T2wi shows a typical endoluminal white scar. Reporting: yT0, yN0, yEMVI-, CRM-. Therapy strategy: wait-and-see with no tumor recurrence within the following 2.8 years. Source: F. Bauer, Radiology Kaufbeuren.*

the radiologist starts restaging, these important staging examinations are already available to everyone.

Almost 90% of our patients have received the internationally recommended standard of care for adenocarcinoma of the lower to middle third of the rectum with a tumor stage T3/4 and/or cN+ and neoadjuvant radiochemotherapy (nRCT).

In addition to the generally known findings such as reduction of the local recurrence rate and improvement of the tumor-free interval, we try to identify the group of patients who would benefit from a non-surgical treatment strategy. The surgical community was initially very reticent towards the watch-and-wait strategy. In fact, it requires a high accuracy MRI examination to identify patients with full remission (CR: ypToN0). Own experience, good interdisciplinary cooperation and evaluation of all diagnostic tests are the prerequisite for reliable diagnostics.

The reference standard for CRT was histopathology or the recurrent free interval of >12 months in watch-and-wait approaches. After a long learning curve, our diagnostic accuracy has improved steadily. In about 24% (33 patients) of the cases we could show a full response, here interestingly also in some patients where chemotherapy had to be discontinued due to cardiac side effects. In almost all CRT cases, the initial stage was a T2 and/or T 3a, b, or c tumor stage. During a follow-up period of 2 years, we could see that almost always a small fibrosis limited to the intestinal wall took place and that this fibrosis was almost always unchanged in the course of the treatment. If a complete remission (CRT) occurred after radiotherapy, a high percentage of patients remained tumor-free.

**97**

practice.

neoadjuvant therapy [21].

*Imaging and Diagnosis for Planning the Surgical Procedure*

• Are there vital tumor remnants inside the fibrosis?

Restaging remains particularly difficult for initially advanced tumor stages, like T3d with CRM+ or T4. Here, the strong hypointense mass fibrosis of the tumor bed and irregular fibrotic mass or wall thickening with irregular margins and/or spicules makes reliable diagnosis very difficult. In these cases, surgical resection, mostly TME, has always been recommended and performed. In case of low rectal

In fact, our standardized protocol must answer the following questions for

In some cases, we have seen that the tumor has actually retreated from the anal canal, thus opening the way for sphincter-preserving surgery and a life without an

The restaging of the lymph nodes often turned out to be surprisingly simple. In the vast majority of cases, where there was a very good or good response to radiochemotherapy, the mesorectum showed complete remission of the lymph nodes. In some cases, the morphological assessment with regard to spicules and inhomogeneity is particularly difficult due to the extensive fibrosis within the lymph nodes. In such cases, we use the significant reduction in size of the lymph nodes for assessment. Consequently, we consider negative small, star-shaped lymph nodes below 3 mm. However, these lymph nodes must be monitored particularly closely during

The time interval to restaging was about 6-8 weeks after the end of CRT. In uncertain cases, where we suspected an almost complete remission, a follow-up examination in about 4 weeks was recommended, because persistent inflammatory reactions and/or a short-term reduction in tumor metabolism can cause an inac-

The key to success in MR diagnostics and especially in restaging is the unique combination of morphological T2 imaging with in vivo functional (diffusion weighted measurements, DWI) imaging. High-resolution T2 imaging can detect very accurately the extent of fibrosis and mucoid degeneration within fibrosis. Only diffusion-weighted images can assess whether vital tumor tissue is still present within the fibrosis and only MRI is able to combine morphology and functional imaging uniformly within one examination in only 25 minutes (**Figure 12**). Perhaps the mnemonic can help: MRI with DW is a kind of "PET- CT" of the poor man. There is another functional MRI imaging and that is DCE-MRI (Dynamic Contrast Enhanced), which we know very well from prostate diagnostics. We are also experimenting with these sequences. Although we apply here our experience from prostate diagnostics, we currently cannot recommend this examination for routine

Recording the size of the tumor must be paid attention to during restaging and in cases of poor response. A reduction in tumor size can be effectively measured by 3-dimensional MR volumetry and shows a good correlation with the ypT stage after

*DOI: http://dx.doi.org/10.5772/intechopen.93873*

tumors, the anal canal must be assessed.

• Is the tumor limited to the rectal wall?

• Are there still metastatic lymph nodes?

• Is the mesorectal fascia (CRM) tumor-free?

• Has the tumor withdraws from the anal canal?

surgery:

artificial exit.

follow-up.

curate result.

*Colorectal Cancer*

available to everyone.

**Figure 12.**

diagnostics.

the radiologist starts restaging, these important staging examinations are already

*recurrence within the following 2.8 years. Source: F. Bauer, Radiology Kaufbeuren.*

*Response assessment with MRI T2w, DWI, and EUS. Pre RCT imaging shows a rectal cancer stage T2 (yellow arrow) with low to moderate signal in T2w (A, B) and high signal in DWI, C. Reporting: T2, N0, EMVI-, CRM-. Post RCT imaging shows complete remission, stage mrTRG-1. Note the tumor has completely regressed and was replaced by fibrosis (green arrows show fibrotic wall thickening with no evidence of tumor remnants) D, E. F. There is no focal high signal in DWI anymore, no diffusion restriction F. G T2wi shows a typical endoluminal white scar. Reporting: yT0, yN0, yEMVI-, CRM-. Therapy strategy: wait-and-see with no tumor* 

Almost 90% of our patients have received the internationally recommended standard of care for adenocarcinoma of the lower to middle third of the rectum with a tumor stage T3/4 and/or cN+ and neoadjuvant radiochemotherapy (nRCT). In addition to the generally known findings such as reduction of the local recurrence rate and improvement of the tumor-free interval, we try to identify the group of patients who would benefit from a non-surgical treatment strategy. The surgical community was initially very reticent towards the watch-and-wait strategy. In fact, it requires a high accuracy MRI examination to identify patients with full remission (CR: ypToN0). Own experience, good interdisciplinary cooperation and evaluation of all diagnostic tests are the prerequisite for reliable

The reference standard for CRT was histopathology or the recurrent free interval of >12 months in watch-and-wait approaches. After a long learning curve, our diagnostic accuracy has improved steadily. In about 24% (33 patients) of the cases we could show a full response, here interestingly also in some patients where chemotherapy had to be discontinued due to cardiac side effects. In almost all CRT cases, the initial stage was a T2 and/or T 3a, b, or c tumor stage. During a follow-up period of 2 years, we could see that almost always a small fibrosis limited to the intestinal wall took place and that this fibrosis was almost always unchanged in the course of the treatment. If a complete remission (CRT) occurred after radiotherapy,

a high percentage of patients remained tumor-free.

**96**

Restaging remains particularly difficult for initially advanced tumor stages, like T3d with CRM+ or T4. Here, the strong hypointense mass fibrosis of the tumor bed and irregular fibrotic mass or wall thickening with irregular margins and/or spicules makes reliable diagnosis very difficult. In these cases, surgical resection, mostly TME, has always been recommended and performed. In case of low rectal tumors, the anal canal must be assessed.

In fact, our standardized protocol must answer the following questions for surgery:


In some cases, we have seen that the tumor has actually retreated from the anal canal, thus opening the way for sphincter-preserving surgery and a life without an artificial exit.

The restaging of the lymph nodes often turned out to be surprisingly simple. In the vast majority of cases, where there was a very good or good response to radiochemotherapy, the mesorectum showed complete remission of the lymph nodes. In some cases, the morphological assessment with regard to spicules and inhomogeneity is particularly difficult due to the extensive fibrosis within the lymph nodes. In such cases, we use the significant reduction in size of the lymph nodes for assessment. Consequently, we consider negative small, star-shaped lymph nodes below 3 mm. However, these lymph nodes must be monitored particularly closely during follow-up.

The time interval to restaging was about 6-8 weeks after the end of CRT. In uncertain cases, where we suspected an almost complete remission, a follow-up examination in about 4 weeks was recommended, because persistent inflammatory reactions and/or a short-term reduction in tumor metabolism can cause an inaccurate result.

The key to success in MR diagnostics and especially in restaging is the unique combination of morphological T2 imaging with in vivo functional (diffusion weighted measurements, DWI) imaging. High-resolution T2 imaging can detect very accurately the extent of fibrosis and mucoid degeneration within fibrosis. Only diffusion-weighted images can assess whether vital tumor tissue is still present within the fibrosis and only MRI is able to combine morphology and functional imaging uniformly within one examination in only 25 minutes (**Figure 12**). Perhaps the mnemonic can help: MRI with DW is a kind of "PET- CT" of the poor man. There is another functional MRI imaging and that is DCE-MRI (Dynamic Contrast Enhanced), which we know very well from prostate diagnostics. We are also experimenting with these sequences. Although we apply here our experience from prostate diagnostics, we currently cannot recommend this examination for routine practice.

Recording the size of the tumor must be paid attention to during restaging and in cases of poor response. A reduction in tumor size can be effectively measured by 3-dimensional MR volumetry and shows a good correlation with the ypT stage after neoadjuvant therapy [21].


**Table 2.**

*MRI based tumor regression grading.*

Good tumor regression rate in the pathological examination correlates with a tumor volume reduction of more than 70% after nCRT [21, 22] and a higher disease-free survival [21]. Moreover, a volume reduction of more than 75% is significantly associated with pCR [21, 23]. mrTRG can be used to effectively assess the response of rectal carcinomas to CRT. This classification is easy, effective and practice-oriented. According to our experience, a good agreement in histology can be achieved even with minimal training. Again, the focus should be on facilitating the identification of good responders (see **Table 2** for tumor regression stages).
