CT was the first “staging” modality used to evaluate rectal cancer (Figs. 18.3 and 18.6a). Early enthusiasms reported its accuracy to range between 85 % and 90 % [18], and it was championed to be an excellent preoperative staging modality for characterizing both tumor and metastases. CT is still recommended in the initial evaluation of all patients scheduled for colorectal carcinoma surgery because of its ability to obtain a rapid global evaluation of the extent of disease and helpful in revealing complications (perforation, obstruction) that may not be clinically apparent. Larger, more carefully controlled studies, however, have shown that the overall accuracy of CT is in the 50–70 % range, varying directly with the stage of the lesion (i.e., T4 lesions are more accurately assessed than T2 or T3 lesions) [13, 15, 19]. Overstaging is a far more common problem as it is difficult to accurately determine T-stage (depth of bowel wall penetration) on CT [20]. Another complicating factor, particularly in rectal cancer, is that perirectal spiculation can be confused with desmoplastic peritumoral inflammation, which can lead to overstaging.

There is little agreement on the critical cutoff diameter to determine if lymph nodes are involved. One study suggests that the cutoff value should be 4.5 mm; however, nodal size does not correlate with nodal status [21, 22]. The specificity for detecting lymph nodes involved with tumor is only 45 % [23].

Liver metastases are detected by CT with an 85 % accuracy rate and a 97 % specificity rate [15]. Detection of liver metastases by CT improves with increasing stage of disease. Among a group of 100 patients who underwent CT, CT arterioportography (CTAP), and MRI, the sensitivity and specificity for liver metastases were 73 % and 96.5 % for CT, 87.1 % and 89.3 % for CTAP, and 81.9 % and 93.2 % for MRI [19]. In addition, abdominal/pelvic CT has a high negative predictive value of 90 % [21].

As mentioned previously, rectal cancer can spread to the lungs via the systemic portal circulation route. Among patients with potentially resectable liver metastases and a negative initial chest radiograph, additional imaging with a chest CT revealed pulmonary metastases in only 5 % of patients [24]. However, one study showed that rectal cancer is more likely than colon cancer to present with lung metastases without liver metastases and that this risk increases with advancing T-stage. Although this study advised CT imaging of the chest in all rectal cancer patients, it was limited by the lack of pathologic correlation [25].

The Radiology Diagnostic Oncology Group (RDOG) study showed that MRI had an accuracy rate of 58 % for detecting local staging of rectal cancer [15] (Fig. 18.4). Accuracy in identifying lymph node metastases was similar to CT with a sensitivity of 85 %, but MRI was slightly superior for detecting liver metastases. Endorectal MR coils and 3.0 T magnets [27] have shown impressive results in depicting the layers of the rectal wall with resultant improvement in the accuracy of assessing the depth of bowel wall penetration [17]. There is no consensus in the literature as to whether endorectal coils should be used routinely in practice. Some studies contend that endorectal coils provide improved diagnostic accuracy as compared to phased-array coils alone for T-stage, with sensitivity reaching 100 % and specificity of 86 %. Endorectal coils have limitations in assessing upper rectal tumors and lateral pelvic and inferior mesenteric lymph nodes. Although phased-array coils are far superior in detecting lymph node metastases, they are limited in the imaging of obese patients and in the evaluation of lower rectal tumors [28, 29]. With the advent of 3.0 T imaging, most imaging can be performed with a pelvic phased-array coil only.

MRI is accurate at identifying high-risk features such as extramural venous invasion, extramural spread beyond 5 mm, and potentially positive circumferential resection margin (CRM). CRM, which is the distance of the leading edge of the tumor to the mesorectal fascia, is an important prognostic factor for determining risk of local recurrence. The accuracy, sensitivity, and specificity of MRI to predict CRM involvement are 86 %, 94–100 %, and 85–88 %, respectively [30]. From a surgical perspective, assessment of the mesorectal fascia involvement and tumor-free CRM is crucial for surgical planning [31].

Diffusion-weighted imaging (DWI) has shown to be more sensitive and specific than standard contrast-enhanced MRI with gadolinium-enhanced MRI, with values of 82 % and 94 %, respectively [32]. It is believed to be superior for tumor detection and characterization and for monitoring tumor response. Adding DWI to conventional MRI yields better diagnostic accuracy than conventional MRI alone [32]. DWI does not use contrast and is more sensitive than contrast-enhanced CT in detecting metastases [33]. It also has the potential to be clinically effective for the evaluation of preoperative TNM staging and the postoperative follow-up of colorectal cancer.

TRUS has become the standard imaging procedure for staging rectal carcinoma [34]. Because TRUS enables one to distinguish the layers within the rectal wall, it is an accurate method for detecting depth of tumor penetration and perirectal spread. Reported sensitivities range between 83 % and 97 %. The T-stage accuracy for TRUS (84.6 %) is far superior to that of CT (70.5 %) [22]. TRUS is of value in assessing apparently superficial rectal carcinomas that are potentially suitable for treatment by transanal or local excision or endocavitary radiation [23]. Detection of lymph node involvement with TRUS is difficult; the sensitivity rate is 50–57 % [29] and the overall accuracy is between 62 % and 83 % [35]. Although TRUS is frequently used to assess regional lymph nodes, it is not very reliable in predicting actual nodal involvement. Many lymph nodes measuring <5 mm in diameter have associated micrometastases, while some early stage T1 and T2 tumors that have lymph node micrometastases were missed by TRUS. Such limitations partly explain the high pelvic recurrence rate observed within this patient population who underwent local rectal excision.

Positron emission tomography (PET) and PET/CT have been shown to alter therapy in almost a third of patients with advanced primary rectal cancer. In a study comparing PET/CT with TRUS, MRI, and helical CT in imaging patients with low rectal carcinoma, PET/CT identified discordant findings and was far superior in 38 % of patients. The result was an upstaging in half the patients while downstaging in almost a quarter of patients (21 %) [36]. A relatively new concept of using PET/CT has been reported to be significantly more accurate in defining TNM stage than CT alone [36]. However, it is not used routinely in most centers. The accuracy of PET/CT is similar to that of CT in terms of T-stage but is far superior in detecting hepatic and peritoneal metastases (sensitivity, 89 %, and specificity, 64 %) [37]. The sensitivity of detecting nodal metastases is only 43 % with a specificity of 80 %, and again, size is not a helpful characteristic. There is also a potential role for PET in restaging colorectal cancer after chemoradiotherapy by measuring the pretreatment and posttreatment standard uptake volume (SUV) and assessing response by the amount of decreasing SUV [38]. Limitations of PET include decreased sensitivity in detecting small colonic lesions (5–10 mm in diameter) and decreased 18F-fluorodeoxyglucose (FDG) uptake by mucinous tumors.

The 2012 European Society for Medical Oncology consensus guidelines recommend pelvic MRI for staging of primary rectal cancer [39], while NCCN guidelines (version 4.2013) recommend either a pelvic MRI or endorectal ultrasound [40].

Clinical stage of rectal cancer is determined by preoperative DRE and imaging studies (CT scan, ERUS, endorectal coil MRI, and/or PET scan). Pathologic staging is determined after excision of the cancer. Rectal cancer is staged using the seventh edition of the American Joint Committee on Cancer (AJCC)/TNM staging system (Table 18.1) [42]. By definition, stage II has uninvolved nodes, whereas stage III has involved lymph nodes. There are several important changes made to the sixth edition. T4 lesions are subdivided into T4a (tumor penetrates to the surface of the visceral peritoneum) and T4b (tumor directly invades or is adherent to other organs or structures). The number of involved lymph nodes also has an impact on outcomes; thus, N1 is subdivided into N1a (metastasis in 1 regional lymph node), N1b (metastasis in 2–3 lymph nodes), and N1c (no nodal disease, but tumor deposits in the subserosa, mesentery, or non-personalized pericolic or perirectal tissues); N2 is subdivided into N2a (metastasis in 4–6 nodes) and N2b (metastasis in ≥ 7 nodes) [40].

In the seventh edition, stage group II was subdivided into three subdivisions instead of two: stage IIA (T3N0), IIB (T4aN0), and IIC (T4bN0). Additionally, several stage group III were reclassified (i.e., T4bN1 is reclassified as IIIC instead of IIIB, T1N2a is IIIA instead of IIIC, T1N2b, T2N2a–b, and T3N2a are IIIB instead of IIIC). Finally, M1 is subdivided into M1a (single metastatic site) and M1b (multiple metastatic sites).

Management of rectal cancer requires a multidisciplinary approach. However, surgery remains the mainstay treatment modality of rectal cancer. The primary goals are to cure the patient, maintain function, reduce local recurrence, maximize disease-free survival (DFS), and optimize quality of life. Locoregional recurrence after surgery is related in part to surgical technique. Treatment of rectal cancer depends on location of the tumor and staging information. Selected cases of rectal cancer can be treated with local excision (discussed in Chap. 17 , Local Excision of Early-Stage Rectal Cancer); however, the majority of rectal cancers are treated with radical resection with or without adjuvant therapy.

Surgery requires resection of a sufficient segment of bowel proximal and distal to the tumor. Generally, proximal margin ≥ 5 cm is sufficient and 2 cm for distal margins is ideal. However, for distal rectal cancers a 1–2 cm is acceptable. Appreciable distal intramural spread of rectal adenocarcinoma is noted in only 25 % of cases and is almost always within 1.5 cm of the primary tumor. Tumor spread > 1.5 cm is found in poorly differentiated or widely metastatic cancer. In the era of neoCRT, the required 2 cm distal margin can be reduced to 1 cm [49]. To reiterate, patients whose tumors that cannot be safely resected with a clear distal margin or have evidence of sphincter involvement or dysfunction should undergo an APR. Inadequate number of lymph nodes retrieved is associated with increased mortality in both node-negative and node-positive rectal cancer [50, 51].

Circumferential margin is the nonperitonealized surface of the rectal specimen created by mesorectal dissection at surgery (Fig. 18.6c). Circumferential margin is considered positive if the distance between the deepest extent of the tumor and closed surgical clearance around the tumor, i.e., circumferential resection margin (CRM), is 0 to 1 mm. In radical resection, a > 1 mm circumferential resection margin (CRM) is optimal. CRM has been found to be an independent predictor of outcome in patients with rectal cancer. An involved CRM is defined as tumor within or equal to 1 mm or less from the CRM [52]. When CRM is < 1 mm, local recurrence rate was 22 %, but when it was more than 1 mm, this rate drops to 5 % [53]. Furthermore, CRM < 1 mm was predictive of an increased risk of distant metastases (37 % vs. 15 % for those with CRM > 1 mm) and shorter survival (70 % vs. 90 % at 2 years for those with CRM > 1 mm) [54]. However, other investigators have considered 2 mm as the cutoff point [55]. Nagtegaal reported that the local recurrence was 16 % for CRM <2 mm versus 6 % for patients with radial margins > 2 mm [55]. Although the ideal CRM has not been universally accepted, the general principle is that the operating surgeon should strive for as wide of a CRM margin as possible.

Radical surgery also requires resection of the mesorectum that contains fat, LN (regional LN), and the lymphatics. Heald et al described total mesorectal excision (TME) that involves complete removal of the LN-bearing mesorectum along with its intact enveloping fascia [56]. TME requires sharp dissection, instead of the conventional blunt dissection, in the extrafascial plane between the presacral fascia and the fascia propria of the rectum. TME requires the complete excision of the visceral mesorectal tissue not only the proximal mesorectum but also the distal mesorectum down to the level of the levators [57, 58] (Figs. 18.6b, c and 18.7a–c). TME does require intense training, but when done properly, it can result in substantial locoregional control in long-term outcomes for patients with rectal cancer. Proper identification and preserving branches of the hypogastric nerves innervating the pelvic organ can spare the patient the sequelae of urinary retention and sexual dysfunction (retrograde ejaculation). TME results in a higher number of lymph nodes retrieved because the lymph node bearing the mesorectum is resected. Finally, TME accomplishes adequate circumferential radial margin (CRM) (Fig. 18.6b, c.)

In addition to resecting sufficient segment of bowel proximal and distal to the tumor and mesorectal excision, the major feeding vessel accompanied by the lymphatics and LN are ligated at the level of their origin from the aorta. The inferior mesenteric artery (IMA) close to the aorta is taken, but ligation above the bifurcation of the aorta distal to the left colic artery is sufficient (Figs. 18.5 and 18.8). Along with mobilization of the splenic flexure, the inferior mesenteric vein (IMV) may be ligated at the lower edge of the pancreas to allow the colon to reach the pelvis so as to construct a tension-free anastomosis. The IMV can be identified after taking down the ligament of Treitz; it is located just to the left of the ligament.

For adequate staging of rectal cancer, at least ≥12 regional lymph nodes, as recommended by the American College of Surgeons, the American College of Pathology, the National Comprehensive Cancer Network (NCCN), and the American Association of Clinical Oncology (ASCO) for colorectal cancers [40, 59–61], must be harvested.

The lymphatics from the rectum drain to the mesorectal LN then upward along the superior rectal artery (or superior hemorrhoidal artery, SHA) toward the mesenteric LN along the IMA to the lateral aortic and para-aortocaval LN (Figs. 18.5 and 18.8). Drainage into paracolic LN is unusual. From the middle and lower rectum, there are two pathways for lymphatic drainage: upward along SHA and laterally to lateral pelvic LN. Downward spread is uncommon. Lateral drainage occurs to intermediate lateral LN (LN along the middle hemorrhoidal artery outside fascia propria) and lateral main LN (along internal iliac artery and obturator artery) to para-aortic LN. The lower rectum however has a cloacal origin and its lymphatic channels are part of the pedicles draining to lateral LN. The number of LN found in the mesorectum ranges from 14 to 28 depending on the method of preparation of specimens. The majority of the mesorectal LNs are located posteriorly with few on each side. There are relatively few LNs in the mesorectum of the lower rectum. Most of the LNs (70 %) are found around the branches of the SHA proximal to the peritoneal reflection, and 30 % are found distal to the peritoneal reflection. In surgical terms, the lymphatic spread of cancer occurs to perirectal (mesorectal LN) and upward along the IMA. With mesorectal excision and ligation of the IMA close to its origin, enough LN will be harvested. Lateral spread to lateral LN is more clinically important in tumors with lower margin below 5 cm from the dentate line, and the incidence becomes significantly higher with lower margin below 3 cm above the dentate line. Spread from the lower rectum laterally to the iliac LN occurs in about 15 % of cases. Lateral spread occurs to LN along the middle rectal artery that lies outside the fascia propria. More extensive nodal dissection such as lateral LN dissection that removes nodal tissue along the common and internal iliac artery demonstrated no survival benefits but increased morbidity (18 % urinary dysfunction, 50 % sexual dysfunction) and therefore should not be performed [62–64]. To reiterate, a TME should be a part of the surgical operation, especially for tumors in the middle and lower rectum.

Inadvertent rupture of the tumor during dissection is associated with increase in LR and decrease in 5-year survival. Separation of structure adherent to the tumor is considered incomplete resection and associated with adverse outcome [9].

In 1997, the Swedish Rectal Cancer Trial group reported a large phase III trial of over 1100 patients comparing a short course of preoperative radiation therapy followed by surgery (please see section on short-course versus long-course radiation therapy below) versus surgery alone and found that the preoperative radiation group not only had a significantly lower local recurrence rate (11 % vs. 27 %; P < 0.001) but also an improved 5-year overall survival (OS) rate (58 % vs. 48 %; P = 0.004) [75]. These results were demonstrated to be durable in their follow-up report (median follow-up time = 13 years [76]). In 2001, the Colorectal Cancer Collaborative Group performed a systematic review of over 8,500 patients from 22 randomized trials and found that both preoperative XRT (neoRT) and postoperative XRT (postRT) were effective at decreasing local recurrence rate when compared to surgery alone [77]. Of note, while multiple subsequent rectal cancer trials by other investigators demonstrated an improved local control rate, the Swedish trial is the only one thus far that had demonstrated an additional OS benefit with combination therapy (Table 18.2).

Almost all of the above earlier studies did not emphasize the importance of surgical techniques in reducing locoregional recurrences. The Dutch Colorectal Cancer Group was the first to assess the role of TME in controlling LR [44]. Over 1800 patients with resectable rectal cancer were randomized to either a short course of neoRT followed by TME or TME alone. Although 2-year OS was not significantly different between the groups (82 % vs. 81.8 %; P = 0.84), the rate of local recurrence at 2 years was significantly reduced in the neoRT/TME group (2.4 % vs. 8.2 %; P < 0.001) [44]. The 12-year follow-up results confirmed a 10-year cumulative incidence of local recurrence of 5 % in the neoRT/TME group versus 11 % in the TME alone group (P < 0.0001) [78] (Table 18.2). The Dutch study galvanized the importance of TME in the management of patients with rectal cancer, which became standard procedure in subsequent clinical trials.

Although neoRT was effective at controlling local disease, significant tumor downsizing rarely occurred, especially when short-course radiation regimen is used. To improve tumor response, several investigators evaluated the efficacy of adding chemotherapy to neoadjuvant radiation (neoCRT) [80–85] (Table 18.3).

A large phase III trial conducted by the European Organisation for Research and Treatment of Cancer (EORTC) found that neoCRT was better at controlling local disease than neoRT [86, 88]. EORTC 22921 randomized over 1000 patients into four groups, neoRT alone, neoCRT alone, neoRT + adjuvant chemotherapy, and neoCRT + adjuvant chemotherapy. The initial results were reported in 2006 [88] and the latest long-term results were reported in 2014 [86]. With a median follow-up of 10.4 years, the 10-year cumulative risk of local relapse was significantly higher in the preRT alone arm than in any of the three chemotherapy groups (P = 0.0017). This confirms the efficacy of neoCRT over neoRT in controlling local disease. OS, disease-free survival (DFS), rate of distant metastases, and long-term side effects were not significantly different among the different groups.

A 2013 Cochrane meta-analysis of five major clinical trials reported that although 5-year OS (63.9 % in neoCRT vs. 65.2 % in neoRT; P = 0.58) and DFS (57.5 % in neoCRT vs. 54.9 % in neoRT; P = 0.27) were not statistically different between the two groups, the incidence of LR was significantly lower in the neoCRT group compared to neoRT group (9.4 % vs. 16.5 %; P < 0.001). Although moderate acute toxicity and postoperative complications (P = 0.05) were higher when chemotherapy was added, there was no increase in the postoperative mortality (2.8 % in neoCRT vs. 1.9 % in neoRT; P = 0.17) or anastomotic leak rate (P = 0.81). Finally, neoCRT increased the rate of pathologic complete response (pCR; 11.8 % in neoCRT vs. 3.5 % in neoRT group; P < 0.00001) but did not result in a higher sphincter preservation rate (50.4 % in neoCRT vs. 48.3 % in neoRT; P = 0.32). Based on these results, one can surmise that the major advantage of adding chemotherapy to neoRT is the significant reduction of local recurrence in patients with stage II/III resectable rectal cancer (Table 18.3).

Whether preoperative chemoradiotherapy (neoCRT) is better than postoperative chemoradiotherapy (postCRT) was the focus of three randomized trials, the Intergroup (INT) 0147, the National Surgical Adjuvant Breast and Bowel Project (NSABP) R-03 [89], and the German Rectal Cancer Study Group (Working Group of Surgical Oncology/Working Group of Radiation Oncology/Working Group of Medical Oncology of the Germany Cancer Society or CAO/ARO/AIO) [90] (Table 18.4). Unfortunately, INT 0147 had to close prematurely because it accrued only 53 patients, while NSABP R-03 accrued 267 patients instead of the intended 900 patients [93]. The latter trial, with a median follow-up of 8.4 years, demonstrated a significantly improved DFS and a trend toward improved OS in favor of the preoperative arm, although there was no improvement in the rate of local control [89].