of Rectal Cancer Management: Preoperative Staging, Neoadjuvant Treatment, Basic Principles of TME, and Adjuvant Treatment

Fig. 22.1

(a–d) Endorectal ultrasound in rectal cancer staging. The sonographic 5-layer structure of the rectal wall consists of 3 hyperechoic layers (interface between the balloon and mucosa, submucosa, and perirectal fat/serosa) separated by 2 hypoechoic layers (muscularis mucosa and muscularis propria). Lesions are T staged as uT0/uTis when the mass is within the hypoechoic M. mucosa layer, as uT1 when invading the hyperechoic submucosal layer, and as uT2 if they cause a distinct break in the submucosal layer and invade into the hypoechoic muscularis propria layer. (All images used with permission of Springer Nature from Valinluck Lao and Fichera [53].)

Rectal MRI (specifically high-resolution T2-weighted images including a narrow field of view of the rectum) provides the best assessment of the rectal wall and perirectal fat and is considered the best modality for distinguishing T2–T4 tumors (Fig. 22.2a, b). It provides high tissue resolution and excellent anatomical depiction of the rectum, the mesorectum, the mesorectal fascia, the levator muscles, other pelvic structures adjacent to the tumor, and possible extramural venous invasion. Advanced functional sequences such as diffusion-weighted imaging permit the quantification of tumor biologic processes such as microcirculation, vascular permeability, and tissue cellularity and are useful in the assessment of response to neoadjuvant therapy. However, it is often difficult to distinguish the submucosa from the muscularis propria on MRI , and therefore differentiating T1 and T2 tumors can be difficult, and overstaging can occur. Tumor distance from the mesorectal fascia is highly predictive of achieving a negative CRM; it has prognostic implications for local recurrence and patient survival and has become one of the most important parameters in the preoperative evaluation. The excellent accuracy of MRI in delineating the mesorectal fascia – producing results comparable to those of histological analysis – was demonstrated by a large European multicenter trial known as the MERCURY study, in which 349 patients underwent preoperative MRI assessment, followed by TME surgery. MRI was found to be accurate within 0.5 mm, with a specificity of 92%, in predicting a clear CRM [1]. MRI with a rectal cancer protocol has become more widely available and has replaced ERUS as the primary imaging modality used for the locoregional staging of rectal cancer, although ERUS remains useful for staging of early T1–T2 tumors.

../images/465809_1_En_22_Chapter/465809_1_En_22_Fig2_HTML.jpg — Fig. 22.2

(a, b) Magnetic resonance imaging in rectal cancer staging. Routine use of rectal MRI in the context of a multidisciplinary assessment of rectal cancer has been used to plan neoadjuvant therapy and surgery and has been shown to reduce the incidence of positive circumferential margins. Axial and sagittal views of a locally advanced rectal cancer are shown, depicting extramural venous invasion and enlarged obturator lymph nodes

The National Accreditation Program for Rectal Cancer (NAPRC) that was developed through a collaboration with the Commission on Cancer (CoC) , a quality program of the American College of Surgeons, considers rectal MRI the standard for the pretreatment staging of rectal cancer. ERUS can be used in addition to rectal MRI for small rectal lesions (T1/T2) to improve accuracy of T staging.

A CT scan of the chest, abdomen, and pelvis with oral and intravenous contrast should be obtained to exclude distant metastases, which are present in up to 20% of patients at the time of diagnosis. PET-CT is not routinely used for initial staging.

Indications and Contraindications

One of the difficulties in constructing algorithms and guidelines for treatment of rectal cancer is that treatment decisions must take into account multiple variables, including tumor location, fixation, circumferential involvement of the rectum, the tumor’s relation to the pelvic floor muscles, pelvic morphology, clinical stage, presence of symptoms and degree of obstruction, presence and location of metastases, continence status, prior treatments, and patient preferences. It is virtually impossible to create straightforward guidelines that account for all of these factors. At present, the clinician caring for patients with rectal cancer must be able to tailor recommendations for therapy based on the characteristics of the tumor, and the patient, and have a firm grasp of the rationale and the existing data supporting any proposed treatment plan.

In a number of European countries, treatment decisions are based on MRI findings of tumor aggressiveness including the proximity of the primary tumor to the mesorectal fascia, the depth of tumor invasion, the presence of metastatic lymph nodes, and the presence of venous invasion (Fig. 22.3). While this algorithm is intuitive, its utility has not been yet evaluated in prospective trials [2]. A simplified version of the National Comprehensive Cancer Network guidelines for locally advanced rectal cancer is also shown (Fig. 22.4).

../images/465809_1_En_22_Chapter/465809_1_En_22_Fig3_HTML.png — Fig. 22.3

European model of stratification for patients with rectal cancer based on magnetic resonance imaging . Abbreviations: MRF, mesorectal fascia; LR, local recurrence; TME, total mesorectal excision. (Source: Ferrari and Fichera [54]. Published under the terms of the Creative Commons CC License.)

../images/465809_1_En_22_Chapter/465809_1_En_22_Fig4_HTML.png — Fig. 22.4

A simplified version of the National Comprehensive Cancer Network algorithm for locally advanced rectal cancer. Abbreviations: CRT, chemoradiation; CT, chemotherapy Cape, capecitabine; RT, radiation therapy; CapeOx, capecitabine plus oxaliplatin; inf., infusional; FLOX, bolus fluorouracil, leucovorin, and oxaliplatin; FOLFOX, infusional fluorouracil, leucovorin, and oxaliplatin; FU, fluorouracil; LV, leucovorin

Local Excision for Early-Stage Rectal Cancer

Transanal endoscopic surgery for rectal cancer is covered in Chap. 39 in more detail. Historically, local excision was associated with high recurrence rates; however, the advent of accurate preoperative staging, tumor downstaging following neoadjuvant therapy, and the development of new surgical techniques such as transanal endoscopic microsurgery and transanal minimally invasive surgery have resulted in increased interest in local excision. Currently, the National Comprehensive Cancer Network (NCCN) guidelines state that candidates for full-thickness local resection include patients with Tis and T1 tumors up to 3 cm that are well to moderately differentiated, occupy less than one-third of the rectal lumen’s circumference, and are located within 8 cm from the anal verge. Any local resection that results in a final margin less than 1 mm or that demonstrates high-risk features for lymph node metastasis, such as lymphovascular invasion, poor differentiation, tumor budding, or penetration of the lower third of the submucosa in the final pathology specimen, should be followed by a formal proctectomy.

Radiotherapy in Combination with Local Excision

Preoperative chemoradiation can be used in combination with local excision for selected patients. A number of retrospective studies have shown good local control rates in patients treated with preoperative chemoradiation in combination with local excision. These studies primarily evaluated patients who were not candidates for radical excision or patients who declined proctectomy. A retrospective study conducted at MD Anderson Cancer Center reported outcomes in patients with T3 rectal cancer treated with preoperative radiation (45–52.5 Gy) and concurrent fluorouracil [3]. Of the 47 treated with local excision, 49% had a pathologic complete response (pCR), and 36% had microscopic residual disease after chemoradiation. The 10-year actuarial risk of local recurrence was 10.6%, in comparison with 7.6% in a cohort of 473 patients treated with TME at the same institution. Similarly, a retrospective study conducted in Korea showed a 5-year rate of local relapse-free survival of 89% in 27 patients with mostly T3 rectal cancer treated with preoperative chemoradiation and local excision [4]. Another retrospective study conducted in the United States reported outcomes in 44 patients with T2–T3 rectal cancer treated with preoperative chemoradiation and full-thickness local excision [5]. Pathologic complete responses were seen in about 43% of patients. The results of all these studies should be interpreted with great caution given their small size and retrospective nature. Careful selection of patients likely contributed to these results, as suggested by the high proportion of patients with pCR. At this point, the combination of preoperative chemoradiation and full-thickness local excision for T1–T3 rectal cancer appears appropriate only for patients who are medically unfit for proctectomy or who refuse radical surgery. Prospective randomized studies are needed to validate the long-term safety of this approach [6].

Principles and Quality Benchmarks of Total Mesorectal Excision

This chapter will focus on the principles of complete TME for mid- or low-rectal tumors. For tumors of the rectosigmoid or upper rectum, the mesorectal excision should be extended to 5 cm distal to the lower edge of the tumor, and the mesorectum should be divided perpendicular to the axis of the rectum (Fig. 22.5). As some of the distal mesorectum is left in the pelvis along with the distal rectal stump, this operation is known as tumor-specific TME (TSME) , to distinguish it from the complete TME, and is covered in Chap. 23. Radical proctectomy with complete TME remains the gold standard for locally advanced mid- to low-rectal cancer. Surgical treatment of rectal cancer is aimed at eradicating the primary tumor and its lymphatic drainage by en bloc removal of the rectum and the mesorectum, following well-defined anatomical planes. TME requires sharp dissection under direct vision along the areolar tissue plane situated between the visceral and parietal layers of the endopelvic fascia. A sharp dissection along the mesorectal plane is associated with a higher probability of achieving a negative CRM, lower risk of bleeding from inadvertent tearing of the presacral veins, and reduced risk of injuring the hypogastric and pelvic nerves. The basic principles of TME are as follows:

1.

Sharp dissection circumferentially around the mesorectum along an avascular areolar plane between the visceral and parietal layers of the endopelvic fascia.
2.

Identification and preservation of the autonomic nerve plexus that controls bladder and sexual function.
3.

Prevention of tearing of the mesorectum, especially posteriorly when dividing the rectosacral fascia.
4.

Achieving a CRM that is macroscopically clear of tumor. If the tumor extends to the CRM, a more extensive resection is necessary. This would include removal of a portion of the parietal layer of the endopelvic fascia and any additional anatomic structures involved by tumor.

../images/465809_1_En_22_Chapter/465809_1_En_22_Fig5_HTML.png — Fig. 22.5

In tumor-specific TME for high rectal cancers, the rectum and mesorectum are divided perpendicularly to the rectal wall 5 cm below the level of the tumor. For mid- and low-rectal tumors, complete TME is performed, removing the entire mesorectum to the level of the levator muscles. (Used with permission of Springer Nature from Hakiman et al. [55].)

The quality of TME surgery is reflected in the appearance and integrity of the mesorectum in the removed specimen (Fig. 22.6). Quirke and colleagues have described a grading system that classifies rectal cancer specimens according to whether the surgeon has dissected outside the mesorectal fascia in the correct plane (mesorectal excision plane ) or has violated the mesorectum, leaving mesorectal tissue behind the pelvis following either a plane within the mesorectum (intra-mesorectal excision plane ) or directly on the muscularis propria (muscularis propria excision plane ) [7]. The macroscopic quality of mesorectal excision completeness has been found to be an independent predictor of local recurrence and survival, even in patients with an uninvolved CRM [8].

../images/465809_1_En_22_Chapter/465809_1_En_22_Fig6_HTML.png — Fig. 22.6

Grading of removed rectal cancer specimens. (a) demonstrates the posterior surface of an intact mesorectum consistent with a complete TME grade. (b) demonstrates superficial defects in the posterior mesorectum consistent with a near-complete TME grade. (c) demonstrates a specimen with incomplete TME grade, with exposed muscularis propria. (All images courtesy of Patricia Sylla, MD.)

Adequate lymphadenectomy requires division of the lymphovascular pedicle at the origin of the superior rectal vessels. This can be achieved by ligation of the inferior mesenteric artery distally to the branching of the left colic artery (low ligation), or in cases where clinically suspicious nodes are present at the origin of the inferior mesenteric artery (IMA), by dividing the IMA close to its origin (high ligation). We routinely perform high ligation of the IMA at our institution. In either case, all sigmoidal branches should be included in the surgical specimen, and therefore the colon should ideally be proximally divided at the junction of the descending and the sigmoid colon, incorporating the sigmoid colon in the surgical specimen. As distal tumor extension along the rectal wall is limited for mid- and low-rectal cancers, a distal margin of 1–2 cm of normal rectal wall is considered adequate for most tumors.

Patients with low-rectal cancer <5 cm from anal verge may still be treated with a sphincter-sparing technique. Options include a hand-sewn coloanal anastomosis if the tumors are >1 cm from the sphincter complex, and either partial internal anal sphincter resection for tumors <1 cm from the internal anal sphincter or complete intersphincteric resection for tumors involving the internal anal sphincter but sparing the external anal sphincters and levators [9].

For many cancers located in the distal rectum, specifically those infiltrating the levator muscles or the anal sphincter, an oncologically safe CRM and/or distal resection margin is not compatible with sphincter preservation, and an APR is therefore necessary. In a more radical version of conventional APR, the coccyx is removed en bloc with the rectum and the levators, resulting in a surgical specimen that has a cylindrical appearance; this procedure is called cylindrical or extralevator APR. Some surgeons question the need to entirely remove both levator muscles and recommend removing only the portion of the levators required to clear the tumor. The choice between standard and extralevator APR is controversial. The potential oncologic benefit of larger tissue removal needs to be weighed against the increased morbidity associated with a larger perineal defect, particularly in patients treated with neoadjuvant radiotherapy.

Optimal resection of rectal cancer according to the oncological principles of TME can be achieved by open or minimally invasive (laparoscopic or robotic) surgical techniques. Multiple trials have demonstrated the feasibility and safety of laparoscopic and robotic surgery for rectal cancer [10–12]. Transanal TME (taTME) is a more recently described minimally invasive approach for dissection of the distal rectum in patients with a narrow pelvis [13, 14]. With this technique, lymphovascular control, the entire colonic mobilization, and dissection of the upper rectum are performed using conventional transabdominal laparoscopy. The dissection of the distal rectum and mesorectum is performed transanally through an endoscopic platform. The lumen of the rectum is closed with a purse-string suture to avoid contamination, and the rectal wall is incised circumferentially distal to the tumor. The dissection is carried cephalad until the abdominal field is reached. The specimen is then removed, and the anastomosis is performed through the anus. This approach allows the surgeon to choose precisely the point for transecting the rectum while visualizing the distal edge of the tumor. Transanal TME has been associated with low conversion rates and preliminary oncologic outcomes equivalent to that of abdominal TME. Several trials are underway to assess long-term outcomes relative to laparoscopic TME. Please refer to the chapters on laparoscopic and robotic TME (Chaps. 23 and 24) for more details on operative setup and techniques of minimally invasive TME.

Multidisciplinary Management

There is increasing evidence to suggest the benefits of a multidisciplinary approach in patients with rectal cancer, involving surgical, medical, and radiation oncologists, radiologists, and pathologists [15]. Rectal cancer centers of excellence have been successfully established in several European countries over the past decade, and similar efforts in standardizing care have begun in the United States [16]. Multidisciplinary tumor (MDT) boards may change the clinical management in a non-negligible proportion of rectal cancer patients, creating a tailored plan for every individual patient [17].

Cancer outcomes are better when patients are managed according to the principles of MDT care. MDTs are associated with improved clinical decision-making, clinical outcomes, and patient experience in several cancer types, including rectal cancer. Implementation of an MDT approach to rectal cancer care in several European countries has resulted in reduced rates of local recurrence, lower rates of permanent stoma, and improved overall survival [18, 19]. We strongly encourage referral of rectal cancer patients to high-volume centers with established MDTs.

Pitfalls and Troubleshooting

Adhering to the traditional principles of following the avascular embryologic planes during dissection, proper tissue handling, ensuring adequate blood supply of the colon conduit, and avoiding tension of the anastomosis remain essential to optimizing outcomes after rectal cancer surgery. All colorectal anastomoses should undergo leak testing regardless of the donut integrity. Methods for creating adequate colon conduit length for a technically sound colorectal or coloanal anastomosis include complete mobilization of the splenic flexure and the colon mesentery, division of the inferior mesenteric vein proximally near the ligament of Treitz, and ligation of the inferior mesenteric artery proximally to the left colic artery (high ligation). In cases when, despite full mobilization of both the mesentery and the left colon, the conduit doesn’t reach the pelvis, or in cases of marginal artery injury, options include performing a total colectomy and an ileorectal anastomosis or rotating the right colon 180° around the ileocolic pedicle in an effort to preserve the ileocecal valve (Deloyers procedure) or performing a retroileal anastomosis between the ascending colon and rectum [20].

Oncologic Outcomes with TME

TME has been associated with improved local control and survival rates. The local recurrence rate following TME ranges from 4% to 10%. This represents an improvement compared with local recurrence rates following the conventional blunt approach, which range from 15% to 45% with or without chemoradiation or radiation. Local recurrence and survival from selected representative studies on TME are shown in Table 22.1 [21–25]. Radiation or chemoradiation in addition to TME has further decreased local recurrence rates.

Table 22.1

Representative studies assessing local recurrence and survival following TME surgery

Only gold members can continue reading. Log In or Register to continue