Literatura relativa al estudio de perfiles con el borde de salida regruesado

The imaging modalities use to investigate the extent of rectal cancer include: 1. Endoanal ultrasound

2. Magnetic Resonance Imaging

1.2.1 Endoanal ultrasound

Endoanal ultrasound (EAUS) is valuable in staging superficial rectal cancers (sensitivity 97%, specificity 96% for T1 tumours). It has a mean T- and N - stage accuracy of 85% and 75% respectively [193]. EAUS is of limited value for advance tumours as the depth of penetration for high frequency probes is limited to 5mm. Other limitations include availability of highly skilled operator and risk of understaging tumours [194].

1.2.2 Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) of rectum and pelvis is currently the gold- standard imaging modality to assess mid-to-low rectal cancer disease. Technical advances and improved image resolution (high resolution MRI of rectum with phased array coils) provide detailed information on local disease extent and response to neoadjuvant treatment with valuable impact on clinical staging, treatment planning (defining surgical anatomy as well as prognostic markers for neoadjuvant and/or adjuvant treatment), response assessment and prognosis. The detailed rectal tumour morphology displayed by MRI is very close to histopathological findings. These results have been validated in multicentre studies showing excellent agreement between MRI and

histopathology assessment of rectal cancer [195, 196]. MRI is particularly useful in distinguishing between pT3b and pT3c disease extent. Controlled studies have shown MRI specificity for CRM involvement of 92% (CI 90-95%) [195, 197]. Histopathology remains gold standard to assess nodal

involvement in rectal cancers; however, diseased nodes within mesorectum with irregular border or mixed intra-nodal signal can be seen on MRI

(accuracy 85%). Morphologic MRI also displays the anatomic distribution of nodes both within and outside the mesorectum. The reported sensitivity and specificity of MRI in detecting EMVI is in the range of 62-100% and 88-89%, respectively [197-199]. The assessment of EMVI also provides critical insight into potential tumour response to neoadjuvant treatment. Yu et al [200] clearly demonstrated EMVI involvement on pre-treatment MRI as marker of poor response to NCRT on a multivariate analysis. Interestingly, MRI defined low rectal cancers (<5 cm from anal verge) were also shown to respond well to NCRT. Better response of low rectal cancers has been reported previously [201]. Despite the anatomical complexities, MRI remains a reliable modality in assessment of low rectal tumours. MRI based staging system for low rectal cancers has been recently developed and successfully validated in

MERCURY II trial (see table 1.4) [202].

The MRI based markers of treatment response are shown in table 1.5

(adopted from review by Battersby et al). Studies comparing post-NCRT MRI staging (ymr) with histopathological staging (yp) have reported the following: ymrT-stage show good correlation and accuracy of 40–60% with ypT-stage

[203-205]; and ymrN-stage has reported accuracy of 87% with ypN-stage [205].

Table 1.4: MRI Stage for low rectal cancers [202] MRI Stage Definition

I Tumour confined to bowel wall but not through full thickness II Tumour replaces the muscle coat but does not extend into

the intersphincteric space

III Tumour invades the intersphincteric space or lies within 1 mm of the levator muscle

IV Tumour invades the external anal sphincter and is within 1 mm and beyond levators muscle with or without invading the adjacent structures

Table 1.5: MRI based markers of response to NCRT [55] Pre-treatment MRI markers predicting response to NCRT

 Tumour Height – low rectal tumours are more likely to be ‘good responders

 EMVI – the presence of EMVI increases the likelihood of poor response Post-NCRT MRI markers of response

 mrTRG

 Tumour Height

 EMVI (ymrEMVI)

 CRM status

 Depth of invasion (ymrT-stage)

1.2.3 Assessment of tumour response to NCRT

1.2.3.1 Response Evaluation Criteria in Solid Tumours

The radiological assessment of tumour response to neoadjuvant treatments has been traditionally based on morphological criteria. The ‘Response Evaluation Criteria in Solid Tumours (RECIST)’ has been developed as standard criteria to assess response to neoadjuvant therapy (Table 1.6). There are few fundamental flaws with RECIST criteria: firstly it not specifically designed for rectal cancers, secondly the criteria is based on arbitrary figures not derived from outcome data, and non tumoural masses may persist without any impact on disease status, and finally, it does not take in account tumour biology which plays critical role in tumour behaviour.

Table 1.6: Response Evaluation Criteria in Solid Tumours (RECIST) [206]

Criteria Definition

Complete Response Disappearance of all target lesion

Partial response 30% decrease in the sum of the longest diameter of the target lesion

Progressive disease 20% increase in the sum of the longest diameter of the target lesion

1.2.3.2 MRI based TRG

A more effective tool for assessment of rectal cancer response to NCRT has been the development of MRI tumour regression grading (mrTRG) in recent years, based on pathological tumour regression grade system [104, 105]. The entire tumour is assessed to determine if fibrosis signal intensity or if tumour signal intensity predominates (see table 1.7). In a prospective study of 111 patients, mrTRG independently predicted DFS (HR 3.28; 95%CI 1.22 to 8.8) and OS (HR 4.4; 95%CI 1.64 to 11.7), on multivariate analysis. Patients with mrTRG 1-3 (good response) had better five year DFS (72% vs 27%,

p<0.001). In addition, mrTRG 1 and 2 were highly predictive of pCR [207]. Table 1.7: MRI Tumour regression grading

Grade Definition

mrTRG1 Dominant low-signal intensity fibrosis with no tumour mrTRG2 Low-signal intensity fibrosis with minimal residual

tumour

mrTRG3 50% fibrosis/mucin and intermediate signal representing residual tumour.

mrTRG4 Predominance of tumour with minimal low-signal intensity fibrosis