Role of MRI in Primary Rectal Cancer Staging and Management Gerard Smith Austin Radiology

Overview Basic Epidemiology Basic Rectal Anatomy Key Anatomical Concepts The Role of MRI in Clinical Staging and its relevance to Treatment decisions

Rectal Cancer Statistics Jemal A, Siegal R, Ward E, et al. Cancer statistics, 2009. CA Cancer J Clin. 2009;50:225-249

Rectal Cancer Statistics Australia in 2005 13,076 new cases of colorectal carcinoma 13% of all cancer cases 4165 deaths Lifetime risk of 1 in 12 Rectal Cancer accounts for approx 1/3 of all colorectal cases TROG Cancer Research: trog.com.au

Anatomy of the Rectum Approximately 15 cm long Divided into lower, mid & upper thirds Lower: up to 5 cm from anal verge Lies below the peritoneal reflection Middle: 5 to 10 cm from anal verge Peritoneal reflection extends over the anterior surface Upper: 10 to 15 cm from anal verge Peritoneum covers the anterior and lateral aspects of rectum The mid to lower rectum is enveloped by the mesorectal fascia (MRF)

Mesorectal Fascia (MRF) Exists below the peritoneal reflection, extends to the pelvic floor and is an encircling fascia that contains: Rectum Perirectal fat Perirectal LN Perirectal vessels Variable in its definition Tapers distally Posteriorly it lays anterior to the presacral fascia

Total Mesorectal Excision (TME), and the Circumferential Resection Margin Surgical standard for rectal excision The rectum and the perirectal tissues en-bloc are excised The plane of the dissection is along the outer aspect of the MRF The Circumferential Resection Margin (CRM) is therefore in effect the MRF TME surgery has reduced local recurrence rates significantly (from 38% to 8%) Recurrence rates ? Dropped from approx 30% to ?8%

Total Mesorectal Excision

The Role of MRI To assist in clinical staging The treatment for rectal cancer is surgery (TME) with stage appropriate neoadjuvant therapy Intent of clinical staging is to identify patients suitable for upfront surgical resection neoadjuvant therapy followed by surgery Need accurate preoperative assessment Tumor (T) and Nodal (N) Stage Depth of tumor invasion beyond the muscle wall Relationship of the tumor to the MRF/CRM

Neoadjuvant Therapy Most commonly Chemoradiotherapy Short and Long course Radiotherapy Its addition in the treatment of locally advanced rectal carcinoma prior to TME has further reduced local recurrence rates from 8% to approximately 2% CRT is more effective, better tolerated, associated with better compliance and less toxicity when given as neoadjuvant therapy compared with post operatively ?low rectal site an indication for CRT

Anatomy of the Rectal Wall CIS T1 T2 Mucosa: thin hypointense line Submucosa: thicker band of high signal Muscularis propria: outer low signal intensity line T3

Staging of Rectal Carcinoma: TNM T Staging T1: Confined to the submucosa T2: Confined to the muscularis propria T3: Beyond the muscularis propria T4: Extension to involve Visceral peritoneum (T4a) Pelvic organs (T4b) such as prostate, seminal vesicles, cervix/uterus, bladder, pelvic side wall or pelvic floor.

T Staging of Rectal Carcinoma T1: Confined to Submucosa T2: Confined to Muscularis Propria

T Staging of Rectal Carcinoma T3: Beyond Muscularis Propria

T Staging of Rectal Carcinoma T4a: Involvement of Peritoneum

T Staging of Rectal Carcinoma T4b: Involvement of Pelvic Organs

T Staging of Rectal Carcinoma Difficult to depict T1 from early T2 on MRI Endorectal US plays a role MRI may overcall T2 tumors as early T3 Due to desmoplastic response in perirectal fat Perirectal extension should be called when the tumor margin within the perirectal fat is nodular and irregular and not low intensity linear spicules

T3 Staging of Rectal Carcinoma Majority (80%) of rectal cancers present as T3 tumors The degree of extension beyond the muscularis propria is important prognostically and potentially to the Rx chosen T3a <1mm T3b 1-5mm T3c >5-15mm T3d >15mm Early stage T3 (<5mm) 85% 5yr cancer specific survival Advanced stage T3 (>5mm) 54% 5yr cancer specific survival (Merkel et al. Int J Colorectal Dis 2001; 16: 298-304.)

MRI and histopathology were equivalent to within 0.5mm Prospectively assessed 295 patients who underwent primary TME surgery and compared the extramural depth of invasion on MRI to histopathology MRI and histopathology were equivalent to within 0.5mm Note was achieved by using standardized imaging techniques, pre study imaging and pathology workshops, and standardized imaging and pathology interpretation criteria Radiology 2007; 243: 132-139

Nodal staging N1 1-3 nodes N2 4 + nodes Regional LN are: perirectal, superior, middle and inferior rectal, sigmoid and inferior mesenteric, lateral sacral, sacral promontory, and internal iliac External Iliac and retroperitoneal LN are not regional but represent metastatic disease

Nodal staging Nodal staging on MRI is difficult Nodal size criteria of limited value Nodal morphology improves accuracy Irregular node contour Variable signal intensity Other techniques studied to improve accuracy include USPIO-enhanced MRI (Lahaye MJ, et al. Radiology 2008) Gadofosveset-enhanced MRI (Lambregts DM, et al. Abdominal Imaging 2012)

437 LN identified on pathology 42 TME specimens transversely sectioned and directly compared with MRI slices 437 LN identified on pathology 102 not seen on MRI because too small (<3mm) but only 2 of these contained metastases 51 above the area imaged and 7 of these contained metastases Size of benign and malignant LN similar Radiology 2003; 227(2): 371-377

Compared with using a 5mm cut-off When an irregular border or mixed signal intensity used for diagnosis Sensitivity 85% (95%CI 74% - 92%) Specificity 97% (95%CI 95% - 99%) Compared with using a 5mm cut-off Sensitivity 68% Specificity 78% Systematic Review and Meta-analysis (2000-2011) Lymph Node involvement Sensitivity 77% (95%CI 69%-84%) Specificity 71% (95%CI 59%-81%) Radiology 2003; 227(2): 371-377 Ann Surg Oncol 2012; 19:2212-2223

Mesorectal Fascial Involvement MRI is accurate in predicting an at risk CRM Tumor within 1 mm of the MRF is predictive of a positive CRM Advancing tumor margin Metastatic lymph node Malignant deposit Extramural Vascular Invasion (EMVI) Low rectal tumors are at greater risk of MRF involvement Identification of tumor involvement of the MRF modifies surgical approach

Extramural Vascular Invasion (EMVI) EMVI is the presence of tumor cells within blood vessels beyond the muscularis propria Present in 30-40% of specimens Associated with synchronous metastatic disease EMVI independently predicts local and distant recurrence and poorer overall survival

Retrospective study of 94 patients Sensitivity 62% Specificity 88% Relapse Free Survival at 3yrs 35% MRI-EVMI +ve 74% MRI-EVMI –ve British Journal of Surgery 2008; 95: 229-236

Summary Understanding of the key anatomical concepts of the MRF, CRM and TME surgery Understanding of the clinical staging of rectal cancer and the triage of patients to surgery alone or neoadjuvant CRT followed by surgery The limitations of Nodal staging and the importance of morphology over size Importance of assessing the tumor with respect to the MRF

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