The Multidisciplinary Management of Rectal Cancer
Section snippets
Staging
Pathologic stage represents the most important prognostic factor for patients who have rectal cancer. The tumor-node-metastasis (TNM) system, as defined by the American Joint Committee on Cancer (AJCC), is the most commonly used staging system and is based on depth of local invasion, extent of regional lymph node involvement, and presence of distant sites of disease (Box 1).15, 16 As the AJCC stage increases from stage I to stage IV, 5-year overall survival declines from greater than 90% to
Local
Establishing the extent of local and locoregional involvement is imperative for patients who have rectal cancer, particularly those who have locally advanced disease and are at higher risk for recurrence and disease progression. Identifying these patients allows for the selection of treatment options, such as neoadjuvant chemoradiation which can improve recurrence-free survival, overall survival, and increase the likelihood of sphincter preservation.21, 22, 23, 24, 25, 26, 27, 28, 29
Simple
Ultrasound
The most common technique for assessing the depth of rectal wall invasion is transrectal ultrasound (TRUS); 360° viewing transducers are available for use with either a flexible or rigid assembly. An integrated water-filled balloon enables close transducer contact and distension of the rectal wall.31
Meta-analysis of 90 articles describing TRUS in staging of rectal cancer yielded a sensitivity and specificity of 94% and 86%, respectively, for muscularis invasion, and 94% and 69%, respectively,
MRI
The use of MRI for the local staging of rectal cancer, particularly with an endorectal coil technique, has been well described.44, 45 MRI offers several theoretic advantages compared with TRUS: it permits a larger field of view, tends to be less operator- and technique-dependent, and allows for the study of stenotic tumors.33, 46, 47 Reports on MRI in the T-staging of patients who have rectal cancer yielded scattered accuracies ranging from 50% to 95%.44, 45 However, a meta-analysis of 90
CT scanning
Local staging with CT remains inferior to both TRUS and MRI because of its inability to distinguish the layers of the rectal wall and the inherent soft tissue planes, although it remains useful for the local relationships of high rectal tumors to pelvic structures.8 The sensitivity of CT in local tumor staging of rectal cancer is 79%, only slightly better than that reported for DRE, and is significantly inferior to that of MRI or TRUS.30 Therefore, either high-resolution MRI or TRUS is an
Evaluation of distant metastasis
Establishing the presence or absence of distant metastases has significant implications for decision making in patients with newly diagnosed rectal cancer. The choice of optimal treatment (eg, neoadjuvant chemoradiation versus systemic chemotherapy alone) depends on the accurate assessment of distant disease. Approximately 50% to 60% of patients who have undergone treatment for rectal cancer will develop metastasis.54 Hepatic (20%–25%), pulmonary (10%–20%), bone (6%–10%), and brain (3%)
Historical Perspective
The surgical approach to patients who have rectal cancer has evolved dramatically over the past hundred years. Surgeons such as Kocher, Kraske, Babcock, and Lisfranc60 were the first to use sphincter-preserving techniques more than a century ago. Resections were generally achieved using local excision with transperineal, transcoccygeal, or transsacral approaches and were associated with significant morbidity and high recurrence rates.59 In 1908, Miles59 revolutionized the oncologic principles
Radical surgery
The type and extent of surgery performed on patients who have rectal cancer largely depends on the preoperative tumor stage, the distance from the anorectal sphincter complex, the use of neoadjuvant therapy, histopathologic features, and the patient's projected ability to tolerate radical surgery. For tumors of the mid to upper rectum, low anterior resection is generally the preferred approach. For lesions of the lower rectum, either APR or LAR may be performed, depending on involvement of the
Total mesorectal excision
The technique of total mesorectal excision (TME) performed in concert with APR or LAR allows for precise dissection and removal of the entire rectal mesentery, including that distal to the tumor as an intact unit. Conventional blunt dissection techniques resulted in unacceptable inadequate surgical clearance and likely explained high local failure rates. Because TME is performed sharply under direct visualization with a focus on autonomic nerve preservation and avoidance of mesorectal envelope
Distal margin
The adequate length of the distal margin for a radical rectal cancer resection remains somewhat controversial. Although the primary area of extension for rectal cancer is upward along the lymphatics, tumors below the peritoneal reflection can spread distally through intramural or extramural lymphovascular routes. The use of APR for low rectal cancers has traditionally been based on the need for a 5-cm distal margin of normal tissue. However, subsequent retrospective studies have shown that
Radial or circumferential margin
Although the traditional concerns of achieving acceptable distal margins are warranted, the importance of obtaining adequate circumferential or radial margins has been shown to play a more critical role in determining local control. Positive radial margins may occur from extension of the primary tumor, extension of involved lymph nodes, or mesorectal tumor deposits.12, 89 A positive radial margin from inadequate TME is an independent predictor of local recurrence and survival.9, 10, 12, 75, 90,
Lateral node dissection
The use of more aggressive or extended lymphadenectomy for rectal cancer has been proposed as a means to improve local control and outcome. Advocates of the lateral lymph node dissection (LLND), which includes removal of all nodal tissue along the common and internal iliac artery, have cited improved local control and overall survival.92 A survival benefit was reported in patients who had positive lateral lymph nodes who underwent LLND.93 However, other reports have shown that LLND is not
Laparoscopic rectal cancer surgery
The use of laparoscopic-assisted colectomy for colon cancer is well established, with supporting evidence from several prospective clinical trials. Preliminary results are now available from four large prospective randomized clinical trials: Colon Cancer Laparoscopic or Open (COLOR), Conventional versus Laparoscopic Assisted Surgery in Colorectal Cancer (CLASICC), Clinical Outcomes of Surgical Therapy Study Group (COSTSG), and Barcelona.100, 101, 102, 103 These trials have uniformly and
Local excision
Local excision is generally accepted as an option for the treatment of T1 adenocarcinomas of the rectum with favorable clinical and histologic features and is associated with low rates of recurrence and surgical morbidity.110, 111, 112, 113, 114 Additional criteria for eligibility for treatment of rectal cancer by transanal excision include (1) well- to moderately differentiated cancer, (2) absence of lymphovascular or perineural invasion, (3) lesion is within 8 to 10 cm from the anal verge,
Histopathologic Features and Node Sampling
Poorly differentiated histology, lymphovascular invasion, perineural invasion, T4 tumor stage, clinical obstruction or perforation, and an elevated preoperative carcinoembryonic antigen (CEA) are associated with increased recurrence rates and worse survival in patients who have rectal cancer.141, 142, 143, 144, 145 In addition to unfavorable histopathologic features, the examination of an inadequate number of lymph nodes has also been linked to increased mortality in patients who have both
Technique for assessing radial margins
A description of the gross appearance of the mesorectum and radial or circumferential margin assessment are critical features of the pathologic evaluation of a surgically resected rectal specimen. The techniques of radial margin assessment and mesorectal evaluation90 have been used in recent trials, including the MRC CLASSIC trial100 and MRC CRO7,149 and in historic trials, such as the Dutch Rectal Cancer trial.150 Subsequently, a qualitative scale was instituted that graded that completeness
Degree of pathologic response
Currently, preoperative combined modality therapy regimens are associated with a pathologic complete response (pCR) rate of approximately 4% to 33%.157, 158, 159, 160, 161 When using hematoxylin and eosin staining and light-microscopic analysis, areas of tumor treatment response can be characterized by the replacement of neoplastic glands with loosely collagenized fibrous tissue and scattered chronic inflammatory cells: a pathologic observation previously reported.162, 163 A pathologic complete
Radiation
Before 1980, surgery alone was the standard treatment for all stages of colorectal cancer. The observation that high rates of locoregional recurrence were associated with locally advanced rectal cancer165 led to the development of randomized trials exploring the possible benefit of postoperative chemotherapy and radiotherapy in this subset of high-risk patients.
The first United States trials were conducted by the Gastrointestinal Tumor Study Group (GITSG), the National Surgical Adjuvant Breast
Preoperative versus postoperative approach
Although postoperative regimens were being optimized in the United States, investigators in Europe were exploring the potential benefits of treatment given in the preoperative setting. The Stockholm Colorectal Cancer Study Group randomized patients (n = 849) to surgery alone versus a short-course neoadjuvant regimen of 25 Gy in five fractions of 5 Gy per treatment followed by surgery (Stockholm I).171 The radiation was delivered to a large treatment field encompassing L1–2 superiorly to 1 cm
Intraoperative radiation therapy
Patients who have borderline resectable and unresectable rectal cancer are generally treated with pelvic radiation and chemotherapy and may be considered for intraoperative radiation therapy (IORT) when available.180 With IORT, the tumor bed at highest risk can be focally irradiated with a single-boost dose. Advantages of this technique include the ability to displace the normal tissue away from the region at risk during surgery, which allows a radiobiologically higher dose to be delivered to
Advances in radiation therapy
Technologic advances in radiation oncology are now being investigated for application in the treatment of rectal cancer. PET/CT fusion in the treatment position has enhanced targeting of the tumor.183 Emerging developments, such as intensity-modulated radiation therapy (IMRT), image-guided radiation therapy (IGRT), and stereotactic body radiation therapy (SBRT), are being evaluated for clinical efficacy.184, 185 These techniques offer the ability to deliver more reliable conformal radiation
Adjuvant chemotherapy
The benefit of adjuvant chemotherapy for stage III colon cancer is well established.17, 186, 187, 188, 189 A pooled analysis of seven clinical trials involving patients who had stage III colon cancer showed that adjuvant chemotherapy increased the probability of remaining disease-free from 42% to 58% and improved 5-year overall survival from 51% to 64%.187, 190
The use of adjuvant chemotherapy for stage II colon cancer remains somewhat more controversial. Overall survival after surgery alone is
5-Fluorouracil
The mainstay of adjuvant chemotherapy in colorectal cancer is 5-FU, a fluorinated pyrimidine that acts by inhibiting thymidylate synthase, the rate-limiting enzyme in pyrimidine nucleotide synthesis.192 Multiple randomized trials have shown that intravenous 5-FU or 5-FU plus leucovorin improves outcomes in patients who have stage III colon cancer.201, 202, 203 Historically, 5-FU was combined with levamisole, an antihelminthic agent; however, because of increased efficacy, 5-FU is currently
Epidermal growth factor receptor inhibitors
The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein that interacts with signaling pathways affecting cellular growth, proliferation, and programmed cell death.232 It is expressed in malignancies of the colon, lung, breast, and head and neck.233 In colorectal cancer, EGFR expression has been shown in up to 80% of tumors and is associated with a poorer prognosis.234, 235 Cetuximab, a chimeric monoclonal antibody that inhibits EGFR, has shown promise in patients who have
Obstructing Lesions
Obstructing rectal cancer presents a unique clinical dilemma with respect to appropriate treatment options. Historically, management has consisted of an initial operation, such as a Hartmann's procedure with resection and temporary colostomy, followed by adjuvant treatment as indicated and reanastomosis. However, with the evolution of neoadjuvant chemoradiation as the preferred approach for rectal cancer, other temporizing solutions have become more prevalent. The use of gastrointestinal
Rectal cancer with synchronous resectable liver metastasis
The presence of liver metastases at initial diagnosis of a rectal cancer primary represents a particularly difficult dilemma for clinical decision making. Despite the presence of generalized guidelines, patients are extremely heterogeneous with respect to characteristics of the primary and metastatic sites, and each situation must be highly individualized. Therefore, a comprehensive multidisciplinary approach to determine the incorporation and timing of surgery, chemotherapy, and radiation
T3N0M0
Historically, local recurrence rates after surgery for rectal cancer were approximately 20%.8, 9, 66, 68, 69, 77, 90, 168 However, with the advent of the TME technique, local recurrence rates have been reduced dramatically and are now routinely less than 10%.9, 12, 24, 65, 67, 75, 128, 156, 267, 268 Consequently, the issue has been raised as to whether optimal surgery alone (without adjuvant treatment) is adequate for the local control of T3N0 rectal cancer. In an analysis of 95 pT3N0 patients
Conservative management of T2/T3 tumors after neoadjuvant therapy
Local excision is generally accepted as an option for the treatment of T1 adenocarcinomas of the rectum with favorable features and is associated with low rates of recurrence and surgical morbidity.111, 112 Local excision for more advanced lesions (T2 and T3) has been reported to have unacceptably high rates of recurrence (17%–62%), even with the use of adjuvant chemoradiation strategies.121, 122, 123, 160 Therefore, enthusiasm for local excision for T2 and T3 lesions has waned significantly.
Summary
Accurate preoperative staging with transrectal ultrasound or MRI is important in properly selecting patients who have rectal cancer for immediate surgery or neoadjuvant therapy. Radical surgical approaches, such as APR or LAR, should incorporate TME and focus on achieving adequate distal and radial margins. Local excision through conventional transanal or TEM approaches may be performed selectively on T1 tumors with fully favorable clinical and histopathologic features. Laparoscopic-assisted
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Cited by (32)
Impact of Treatment Coordination on Overall Survival in Rectal Cancer
2021, Clinical Colorectal CancerUnderstanding the surgical pitfalls in total mesorectal excision: Investigating the histology of the perirectal fascia and the pelvic autonomic nerves
2015, European Journal of Surgical OncologyCitation Excerpt :Dissection in the ‘holy plane’ between the visceral and parietal fascia enables complete en-bloc removal of the diseased rectum, surrounding mesorectum with an intact mesorectal fascia (MRF) and preservation of the autonomic nerves.1,2 It has been shown that suboptimal TME leads to a higher risk of tumour involvement of the circumferential resection margin (CRM) affecting the oncological outcome,3,4 and iatrogenic damage of the nerves resulting in an impaired functional outcome.5–7 Therefore, excellent anatomical knowledge of the rectum and surrounding structures is essential to perform an optimal TME.
Whole mount microscopic sections reveal that Denonvilliers' fascia is one entity and adherent to the mesorectal fascia; Implications for the anterior plane in total mesorectal excision?
2015, European Journal of Surgical OncologyCitation Excerpt :Dissection in the ‘holy plane’ along the mesorectal fascia is said to enable preservation of the autonomic nerves.1 Tumour involvement of the circumferential resection margin and incomplete mesorectal excision are the most important predictors for recurrent disease, emphasizing the importance of en-bloc removal of an intact mesorectal package with no disruptions, tears and/or perforations.2,3 The Dutch TME trial showed that surgical damage to the autonomic nerves was the major cause of post-operative anorectal and urogenital dysfunction.4,5
Management of rectal cancers in relation to treatment guidelines: A population-based study comparing Italian and French patients
2014, Digestive and Liver DiseaseCitation Excerpt :In our study information on rectal location was not available, mainly because the ICD-O-3 [16] does not distinguish rectal sub-sites. In an attempt to address this limitation, we adjusted the logistic regression models for type of surgery, assuming that abdominoperineal resection is preferably carried out for lower rectal cancer, and that anterior resection is more often carried out for upper rectal cancer [34]. Although adjuvant radiotherapy was administered more often in Italy than in France, we found that Italian patients were much less likely to receive preoperative radiotherapy.
Morphology and prognostic value of tumor budding in rectal cancer after neoadjuvant radiotherapy
2012, Human PathologyCitation Excerpt :However, most of the patients with rectal cancer in the published studies concerning tumor budding were treated before 2000, when neoadjuvant radiotherapy was not common [13,16,18,28,29]. To date, no study has specifically investigated tumor budding in postirradiation rectal cancer, although neoadjuvant radiotherapy has become the standard treatment of locally advanced rectal cancer [1-6]. In this study, we specifically chose radiotherapy alone rather than concurrent chemoradiotherapy as the neoadjuvant therapy protocol, with the aim of ruling out interference by chemotherapy; thus, the conclusions of this study should be translated cautiously to chemoradiotherapy protocols.
Efficacy and safety of intraoperative radiotherapy in colorectal cancer: A systematic review
2011, Cancer LettersCitation Excerpt :Likewise, the delivery of neoadjuvant radio-chemotherapy treatment has varied greatly; in three research studies it varied repeatedly due to protocol changes [15,19,22]. Neoadjuvant treatment can make tumor cells completely disappear in 8–30% of cases and it also favours a decrease in the incidence of local recurrences [20,29]. This could justify the varying responses obtained from patients with similar characteristics.