Introduction

Although the incidence of distal (rectal and lower sigmoid) cancers has declined, with a concurrent increase in more proximal colon cancers, approximately one-quarter of colorectal cancers are located in the rectum. For many years, almost all patients with rectal cancer underwent abdominoperineal resection with a permanent colostomy.

Today, this approach is rarely required. The successful treatment of patients with rectal cancer involves optimal surgical technique and, frequently, adjuvant chemoradiotherapy. This combined modality approach maximizes cure, minimizes the risk of a subsequent local or pelvic recurrence, and maintains quality of life. Such multimodality approaches are applicable to patients with locally advanced rectal cancers. This designation generally represents cancers below 12 cm from the anal verge. Tumors in the upper rectum or rectosigmoid are treated by surgical resection, and adjuvant therapy is based on the colon cancer paradigm.

Epidemiology

Approximately 40,000 individuals in the United States were diagnosed with rectal cancer in 2012.¹ From 1998 through 2006, the incidence rate decreased by 3% per year for men and 2.2% per year for women. Although the incidence rate rises dramatically during the fifth decade of life, the age-adjusted colorectal cancer incidence rates for 1997 to 2006 declined among those age 50 years and older but increased among those younger than 50 years of age.² Colorectal cancer is the second leading cause of cancer deaths. African Americans are less likely than whites to be diagnosed at a localized stage and have a higher mortality rate than whites for both rectal and colon cancers. In a 32-year period, 1975 to 2007, the gap between the survival rates of African Americans and whites increased from a difference of 6% to 12% for colon cancer and from 3% to 8% for rectal cancer. However, for both colon and rectal cancers, 5-year relative survival rates have significantly increased among all races between 1975 and 1977 and 1999 and 2006.¹

Sharpe and colleagues reported an observational study that showed a positive association between cigar smoking and cancer of the rectum. They also noted a weak positive association between cigarette smoking and cancer of the proximal colon.³ Several large cohort studies have shown that cigarette smoking is an independent risk factor for colorectal cancer.^4–9 In a large cohort study of more than 22,000 healthy male physicians ages 40 to 84 years who were followed up for more than 12 years, cigarette smoking was an independent risk factor for colorectal cancer incidence, the strongest risk being observed in current smokers of 20 cigarettes or more per day (relative risk: 2.14). Cumulative lifetime exposure and exposure during various periods of life also increased the risk of colorectal cancer.¹⁰

One study showed that the increased risk of colorectal cancer associated with cigarette smoking is dependent on the molecular characteristics of the tumor as defined by APC mutation and hMLH1 expression status. The association between frequency of cigarette smoking (for a 5 cigarette/day increment) and colorectal cancer was most apparent and stronger in tumors without a truncating APC mutation, whereas duration of smoking was associated with increased risk in hMLH1-deficient tumors.¹¹

Conversely, aspirin and nonsteroidal antiinflammatory drugs have been shown to be effective in the chemoprevention of colorectal cancer by decreasing the risk of adenoma formation as well as the incidence and mortality of colorectal cancer. Trials have shown that daily aspirin reduces the risk of recurrent colorectal adenoma by 17% to 21% and advanced adenoma by 28%, and that daily aspirin for 5 years reduces incidence and mortality associated with colorectal cancer by 30% to 40% after 20 years of follow-up, and reduces the 20-year risk of all-cause cancer mortality by approximately 20%. Recent evidence also shows that the risk of major bleeding on aspirin diminishes with prolonged use, suggesting that the balance of risk and benefit favors the use of daily aspirin in primary prevention of colorectal and other cancers. In the general population, a significant 26% reduction in colorectal cancer incidence was demonstrated in studies with a 23-year follow-up. In individuals with a history of adenomas, nonsteroidal antiinflammatory drug use was associated with a statistically significant 55% reduction in advanced adenoma incidence and 34% reduction in adenoma recurrence risk.¹² Aspirin and celecoxib may be effective in preventing adenomas in patients after polypectomy.¹³

Clinical Presentation, Evaluation, and Staging

Patients with rectal cancer can have a broad range of clinical presentations. Early symptoms that suggest rectal carcinoma include rectal bleeding and subtle changes in bowel habits. Rectal bleeding is often mixed with stools or may coat the surface of the stool. It can be bright red and separate from the stools and therefore is often mistakenly attributed to hemorrhoids. Bright red blood only on the tissue paper may be evaluated in a young person with proctosigmoidoscopy. All other types of bleeding, including the presence of occult blood in the stools during a routine physical examination or presence of iron-deficiency anemia, warrant a more complete endoscopic evaluation. Increased frequency of defecation, decreased caliber of the stools, mucus with stools, or mucous diarrhea (particularly associated with large villous adenomas) is quite common. Advanced tumors induce a permanent sense of fullness and tenesmus and increased straining during defecation. Sacral or deep pelvic pain, sometimes radiating down the perineum and thighs, occurs when the tumor invades the sacrum and the sacral plexus of nerves. Anal pain, initially on defecation and later continuous, may occur when low rectal cancer invades the anal canal. Incontinence supervenes when the anal sphincter is involved.

The importance of a detailed history and a thorough physical examination cannot be overstressed. Comorbid conditions and the patient’s physical habitus may preclude major surgery and influence the decision of adjuvant therapy. Physical examination should always include a digital rectal examination to feel for a mass, assess its location and mobility, and feel for enlarged extrarectal lymph nodes (50% accuracy). Depth of invasion and whether the tumor is tethered or fixed can also be assessed during rectal examination with 67% to 84% accuracy.14,15 A careful pelvic examination in women and a prostate assessment in men are essential. A rigid proctosigmoidoscopic examination of the rectum and the anus should follow. The distance of the tumor from the anal verge, anterior/posterior/lateral position, size, morphologic configuration, and extent of circumferential involvement are determined. Tumor mobility and tethering to surrounding structures are ascertained. If not obstructed, patients with rectal cancer should have a preoperative double-contrast barium enema or preferably a colonoscopy to assess for synchronous colon cancer (2% to 9%). Subjective and objective assessment of the patient’s anal sphincter function is desirable. A weak or incompetent sphincter may indicate the need for a colostomy.

Endorectal ultrasound provides valuable preoperative staging (Fig. 78-1), including depth of tumor invasion into the rectal wall (89% to 92% accuracy,^16,17 96% sensitivity, 90% specificity, 96% negative predictive value¹⁸) and nodal enlargement (79% sensitivity, 74% positive predictive value, 84% negative predictive value¹⁹), but confirmation of nodal metastasis with ultrasound-guided needle biopsy is less reliable (77% accuracy, 71% sensitivity, 89% specificity, 92% positive predictive value, and 62% negative predictive value²⁰). Malignant nodes are differentiated from reactive nodes by being hypoechoic, hypervascular, and irregular.^21,22 Endorectal ultrasonography and magnetic resonance imaging (MRI) with endorectal coil exhibited similar accuracy and were superior to conventional computed tomographic (CT) scans in preoperative assessment of depth of invasion and adjacent organ invasion.²³ High-resolution MRI (83% accuracy, 94% sensitivity, and 67% specificity) and positron emission tomography (PET)-CT (70% accuracy, 61% sensitivity, and 83% specificity) may be helpful in predicting nodal status.²⁴ Improved diagnostic staging information is essential in considering local treatment for rectal cancer, deciding on selective use of preoperative chemoradiotherapy in locally advanced tumors, and choosing between an abdominoperineal and low anterior resection. Both MRI and PET are being investigated for the assessment of pathological response following neoadjuvant therapy.^25,26

The liver is the most frequent site of metastasis, followed by the lung, retroperitoneum, ovary, peritoneal cavity, and, rarely, the adrenal glands or bone. Contrast-enhanced CT scan of the abdomen and the pelvis is recommended in all patients with rectal cancer, excluding the very elderly and those with very early cancer, such as cancer within a polyp or T1 rectal cancer. MRI is reserved for patients with locally advanced and recurrent rectal cancer requiring an exenterative procedure. A plain chest radiograph is useful and economical for screening for lung metastasis. Laboratory studies should be ordered as indicated by the patient’s medical condition and anesthetic requirements. Measurement of the carcinoembryonic antigen (CEA) level in combination with imaging can refine the accuracy of preoperative assessment and overall prognosis. Up to 95% of patients with advanced hepatic metastasis will have a CEA level above 20 ng/mL.²⁷ Patients with a normal CEA prior to colorectal resection may still have an elevated CEA with recurrence, so follow-up should include CEA testing postoperatively. Postoperative CEA monitoring may only confer minimal survival advantage. A review of a prospective database of 1900 patients treated for primary colorectal cancer whose follow-up included CEA monitoring found that two-thirds of recurrences were associated with an elevated CEA, which, in turn, was associated with decreased survival. However, of all patients who underwent potentially curative re-resection, only 17% had an elevated CEA.²⁸

Differential Diagnosis

Kaposi sarcoma of the rectum should be suspected in patients with acquired immunodeficiency syndrome who are seen with an unusual or atypical anorectal lesion. It is often associated with proctalgia (62%), hematochezia (50%), and diarrhea (50%).²⁹ Rectal carcinoids are often found incidentally during a screening colonoscopy or typically present with symptoms of bleeding, rectal pain, or constipation. They tend to be more indolent and less aggressive than colonic carcinoids, but as with most gastrointestinal carcinoids, tumor size correlates with the risk of metastasis and survival rates. Endoscopic resection is often adequate. Gastrointestinal stromal tumors of the rectum (Fig. 78-2) are uncommon and often present as a source of lower gastrointestinal bleeding, rectal pain, or constipation. Because of their malignant potential and recent advances in their management with imatinib mesylate (Gleevec), it is imperative that these tumors be correctly diagnosed. Positive immunohistochemical staining with CD34 and CD117 confirms the diagnosis. For large or low-lying rectal gastrointestinal stromal tumors, neoadjuvant therapy with imatinib can facilitate local and sphincter-preserving excision. Except for inflammatory masses, developmental cysts (such as dermoid, epidermoid, duplication, and tailgut cysts) and embryonic tumors (such as teratomas, chondromas, and meningoceles) are the most common retrorectal tumors. Other sacral and presacral tumors include neurogenic tumors, liposarcoma, and neurofibromatosis. Sacral pain and the sensation of fullness in the perirectal area are the most common symptoms of retrorectal lesions.³⁰ Digital rectal examination is the most important diagnostic maneuver. Posteroanterior and lateral radiographs of the sacrum and CT scanning are the preferred methods for characterization and differential diagnosis of retrorectal masses. MRI may also aid in planning the operative approach. Barium enema evaluation will confirm the presence of mass effect. Proctoscopy, although indicated, is usually normal. Most retrorectal lesions should be resected when diagnosed, even if they are asymptomatic and seem benign. Preoperative biopsy is generally not recommended, as it will not change the surgical need for resection and may contaminate the surgical field or lead to abscess formation. Biopsy is reserved for unresectable large retrorectal tumors.

Surgical Treatment of Resectable Rectal Cancer

For most patients with early rectal cancer (T1 to T3), surgical resection is the primary treatment modality. Sound surgical techniques and adjuvant therapy can improve outcomes and maximize local and overall control rates. Tumors in the upper third of the rectum have their lowermost edge 12 cm from the anal verge. Anterior resection or low anterior resection is the primary surgical procedure. Middle and lower-third rectal cancers can be treated with restorative proctectomy with colorectal or coloanal anastomosis or abdominosacral resection with results similar to those that are achieved with abdominoperineal resection and permanent colostomy.³¹ Overall surgical success depends on the ability to obtain a 2-cm distal margin; surgical expertise in obtaining clear lateral margins; the patient’s body habitus, pelvic width, and prostate size; adequate collateral blood flow through the marginal artery; and whether or not there is associated colonic disease such as diverticulosis. Local approaches may be appropriate for patients with early rectal cancer within 8 cm from the anal verge and in patients with major medical contraindications to radical surgery.

Local Treatment

Selection Factors

Selection factors for full-thickness local excision are the same as or similar to those used for endocavitary radiation therapy. Consequently, this decision is based largely on findings of a digital rectal examination with increasing integration of transrectal ultrasound or MRI with endorectal coil.20,23,32 Patients with T1 tumors without adverse pathological features have a low incidence of local failure (5% to 10%) or lymph node involvement (<10%). With unfavorable pathological features (lymphovascular invasion, high grade, deep submucosal invasion, signet ring cell, or colloid histology)^33–36 or evidence of tumor invasion into or through the muscularis propria,^35,37,38 the local recurrence rate is at least 17%, and the risk of regional lymph node involvement is at least 10% to 15%.³³ In an analysis by the Massachusetts General Hospital of 40 patients who underwent local excision only, patients were categorized according to unfavorable clinical or pathological features.³⁵ Among patients with T1 or T2 cancers following local excision, Blumberg and associates reported positive lymph nodes in 10% of T1 cancers and 17% of T2 cancers.³⁹ In addition, among the total group of 159 patients, the incidence increased with the presence of lymphatic and vascular invasion (14% without vs. 33% with). Even among the 42 patients with the most favorable features (negative lymphatic and vascular space involvement, well- or moderately differentiated T1 cancers), 7% were found to have lymph node involvement. The overall 5-year survival rate for the whole group was 65% with a locoregional recurrence rate of 27%. Hager and associates reported on a series of 20 patients with T2 rectal cancer for which local excision was performed and who were otherwise thought to be “low risk” (well to moderately differentiated, nonmucinous, no lymphovascular invasion, and negative margins), despite which the incidence of locoregional failure was still 17%.³⁷ Others have reported locoregional failure rates as high as 43% following either local or transanal excision in patients with T2 cancers.⁴⁰ There have been no randomized trials that compared transanal full-thickness local excision alone for T1/T2 with or without adjuvant chemoradiation with low anterior resection or abdominoperineal resection. Recent published results of local excision of T1/T2 rectal lesions without adjuvant therapy show local recurrence rates of 3.4% to 18% for T1 lesions and 27% to 67% for T2 lesions; Table 78-1 summarizes these results.

Table 78-1

Local Excision of T1, T2 Lesions Without Adjuvant Therapy in Selected Series with More Than 50 Patients

Reference	No. of Patients (Per Stage)	Follow-up Time	LR	Survival Rate	Salvage Surgery for Isolated LR
Paty et al.*358	125 (T1 = 74, T2 = 51)	6.7 years	T1 = 17% T2 = 26%	10-Year OS: T1 = 74%, T2 = 72%	14/17
Mellgren et al.359	108 (T1 = 69, T2 = 39)	4.4 years	T1 = 21% T2 = 47%	5-Year OS: T1 = 72%, T2 = 65%	24/27
Garcia-Aguilar et al.360	83 (T1 = 55, T2 = 27)	54 months	T1 = 18% T2 = 37%	5-Year: T1 = 98%, T2 = 89%	17/20
Chakravarti et al.296	52 (T1 = 44, T2 = 8)	52 months	28%	5-Year DFS: 66	NS
Steele et al.361	59 (T1 = 59)	48 months	T1 = 5%	6-Year survival: 85	2/2
Kim and Madoff362	69 (T1 = 44, T2 = 25)	NS	T1 = 9% T2 = 28%	Cancer-specific 5-year survival: 88%	NS
Hager et al.363	59 (T1 = 39, T2 = 20)	33–40.5 months	T1 = 8% T2 = 17%	5-Year survival: T1 = 90%, T2 = 78%	NS
Nelson et al.364	124 (T1=60, T2=164)	5 years	T1=12.5% T2=22%	5-Year OS: T1 = 77.4%, T2 = 67.6%	NS

DFS, Disease-free survival; LR, local recurrences; NS, not specified; OS, overall survival.

^*In this series, 16 patients received postoperative radiotherapy and 15 additional patients received postoperative 5-FU and radiotherapy; however, local and overall recurrence rates were similar in both groups.

Local Approaches

Local approaches for treatment of early rectal cancer include transanal local excision, suprasphincteric posterior proctectomy (the Kraske procedure), transsphincteric posterior approaches (Bevan or York-Mason procedure), transanal endoscopic microsurgery (TEM), transanal fulguration, or local/contact radiation therapy (Papillon approach).

Optimal candidates for local excision along include small (<4 cm), noncircumferential (<40%), low-lying tumors confined to the muscularis propria, without adverse pathological features (signet ring histology, poor differentiation, lymphovascular invasion). Local excision does not include lymph node evaluation, and adjuvant radiation with or without chemotherapy may be warranted.⁴¹

TEM is a minimally invasive surgical technique that was introduced in 1984 by Buess. It incorporates a high-quality binocular operating system and pressure-regulated insufflation with continuous suction. Compared with conventional transanal resection, TEM provides superior intraoperative visualization and the ability to perform full-thickness excision of the tumor with clear margins, together with perirectal fat and adjacent lymph nodes42,43 of tumors higher up in the rectum (4 to 18 cm from the anal verge). The technique is not yet generally established because of the high cost, the necessary special instrumentation and tools, and the unusual technical aspects of the approach.^43–51

Treatment of cT2 rectal tumors with TEM combined with preoperative high-dose radiotherapy in 35 patients achieved survival rates similar to those of conventional open surgery.⁵² Only minor postoperative complications occurred in five (14.3%) patients and included suture-line dehiscence in three patients and stool incontinence in two patients. At a median follow-up period of 38 months, one patient was seen with a local recurrence (2.9%) at 30 months of follow-up, and systemic metastasis developed in four patients (11.4%). The survival and local recurrence rates that were reported in that study led to a prospective multicenter randomized trial (the so-called Urbino trial) to evaluate the efficacy of local excision in T2 tumors that were preoperatively treated by chemotherapy and high-dose radiotherapy versus standard open treatment (low anterior resection or abdominoperineal resection). At a median follow-up period of 56 months (range: 44 to 67 months), the local failure rate (5%) and distant metastasis rate (5%) were equal in the two groups.⁵³

A recent review of the United Kingdom national TEM database from 21 centers since 1993 showed that of 454 rectal cancer patients, 69% underwent TEM with curative intent. The overall morbidity and mortality of TEM were 17.2% and 1.5%, respectively. Pathological staging was as follows: pT0 (1.8%), pT1 (52.9%), pT2 (32.8%), pT3 (9.9%), and pTx (3.1%). Neoadjuvant therapy and adjuvant radiotherapy were administered in 8% and 18% of cases, respectively. Margin positivity (<1 mm) occurred in 20% of cases and was stage dependent. The 5-year disease-free survival rate was 77% for pT1, 74% for pT2, and 35% for pT3, with local recurrence rates of 20%, 25%, and 59%, respectively.⁵⁴

Radical Resections

Sharp, total mesorectal excision (TME) with autonomic nerve preservation is the radical surgical technique of choice in conjunction with low anterior resection or abdominoperineal resection (APR). The mortality rate is 1% to 7%, and the morbidity rate (including genitourinary dysfunction, fecal incontinence, and permanent colostomy) is 13% to 46%. Locoregional recurrent disease is observed in 4% to 20% of cases, and the 5-year survival rate is 74% to 87%.55–59

Surgical Issues in Radical Resections

Radial Margins and Total Mesorectal Excision

The ability to obtain a negative lateral circumferential margin is associated with a decreased risk of local recurrence.60–63 In a multivariate analysis, circumferential margin involvement was the most powerful predictor of local recurrence (hazard ratio: 12.2) and of overall cancer mortality (hazard ratio: 3.2; Fig. 78-3). Heald and colleagues have advocated total mesorectal excision (TME) in conjunction with low anterior resection or abdominoperineal resection (APR) as the optimal surgical treatment for rectal cancer.⁵⁶ This technique involves removal of the entire rectal mesentery, including that distal to the tumor, as an intact unit. Complete distal TME is essential for clearance of any tumor deposits, which occur in 50% of T3 tumors with a maximal distal spread of 4 to 5 cm,⁶⁴ and is associated with increased frequency of local recurrence and decreased overall survival.^65,66

Sharp mesorectal excision combined with TME provides the optimal surgical strategy. In contrast with conventional blunt dissection techniques, sharp mesorectal excision facilitates nerve preservation, enables complete hemostasis, and emphasizes gentle handling to avoid tearing or disruption of the smooth outer surface of the mesorectum. Sharp TME has been shown to achieve a negative circumferential margin in 93% of resected specimens. Although no randomized trial of TME has been performed, TME has been evaluated prospectively in Sweden, where it has been introduced via a formal preceptorship-based training program. A 5-year prospective audit reveals a local recurrence rate of 7% following the addition of TME compared with a historical control rate of 23%.

Distal Mucosal Margin

The ability to perform sphincter-preserving surgery in nonirradiated patients is dictated by the requirements of a 2-cm distal margin rather than the traditional 5-cm margin.67–71 Only 2.5% of patients (usually with poorly differentiated and node-positive rapidly disseminating disease) had disease spread greater than 2 cm.³¹ There is no correlation between risk of local recurrence and the extent of distal margin in excess of 2 cm.^72–77

Proximal Extent of Lymph Node Dissection

Proximal lymph node dissection should extend just distal to the origin of the left colic artery. No evidence indicates a relationship between local recurrence and survival and dissection of deep iliac lymph nodes⁷⁸ or high ligation of inferior mesenteric pedicle.^79,80 Patients with pathologically positive nodes along the inferior mesenteric artery have very low 5-year survival rates.^81,82

Laparoscopic Surgery

Laparoscopic surgery for curable rectal cancer has become increasingly accepted. Laparoscopic anterior resection with curative intent generates considerably more reservations than does laparoscopic APR, which is technically much easier to perform. Data, including results from randomized trials, on the extent of lymphadenectomy, margins of resection, actuarial survival, and local recurrence rates continue to emerge. The technique of laparoscopic TME is well described by Pikarsky and associates.⁷⁰ Reports suggest short-term gains of reduced pain, shortened hospital stay, accelerated activity, possible cost reduction, and improved cosmesis.⁷¹ Hand-assisted laparoscopic surgery is a new technique that has the potential to overcome many of the existing limitations of pure laparoscopy.⁸³ A prospective nonrandomized single institution trial comparing open versus laparoscopic resection in 191 consecutive patients with low and midrectal cancer demonstrated a conversion rate of 18.4%. In the laparoscopic group, the mean time for complete patient mobilization was shorter (1.7 vs. 3.3 days; P < 0.001), and patients were earlier in passing flatus (2.6 vs. 3.9 days; P < 0.001) and stools (3.8 vs. 4.7 days; P < 0.01) and in resuming oral intake (3.4 vs. 4.8 days; P < 0.001). The mean hospital stay and overall morbidity and mortality rates were similar with no statistically significant differences. Laparoscopic patients had a higher rate of anastomotic fistulas (13.5% vs. 5.1%) and reoperations (6.1% vs. 3.2%), but the difference was statistically nonsignificant. Laparoscopic resection presented a significantly lower local recurrence rate (3.2% vs. 12.6%; P < 0.05). Although the cumulative survival and disease-free rates at 5 years were nonsignificant between both groups (80% and 65.4% after laparoscopic surgery and 68.9% and 58.9% after open surgery), stage-by-stage comparison showed prolonged cumulative survival for stages III and IV cancer in the laparoscopic group (82.5% vs. 40.5%; P = 0.006 and 15.8% vs. 0%; P = 0.013, respectively) and a reduced rate of cancer-related death for stage III in the laparoscopic group (11.4% vs. 51.9%; P = 0.001).⁸⁴

The U.K. Medical Research Council (MRC) prospective multicenter, randomized, controlled trial of conventional versus laparoscopic-assisted surgery in colorectal cancer included 128 rectal cancer patients in the open group and 253 patients with rectal cancer in the laparoscopy-assisted group with intent to treat. (The actual treatment groups included 132 open and 160 laparoscopy-assisted operations). Approximately 10% more patients underwent TME in the laparoscopy-assisted group than in the open surgery group. The rate of APR was similar (27% in the open surgery group and 25% in the laparoscopic group). Lymph node yield was equally high in the two groups. The intraoperative conversion rate from laparoscopic to open was 34%. In the intent-to-treat population, there was no significant difference in the open versus laparoscopy-assisted group with regards to positive circumferential margin (14% vs. 16%), overall intraoperative complications (14% vs. 18%), overall morbidity (50% vs. 59%), and mortality (5% vs. 4%). Although laparoscopic rectal resection did not adversely affect bladder function, there was a trend toward worse male sexual function, which might be explained by the higher rate of TME in the laparoscopic rectal resection group.85,86

In a 2006 systematic review by the Cochrane group, it was noted that most reported laparoscopic surgery studies for rectal cancer are individual cohort studies, individual case-control studies, or case series with only one reported randomized, controlled trial. Collectively, in 48 studies representing 4224 rectal cancer patients, there appeared to be no significant differences in disease-free survival rate, local recurrence rate, mortality, morbidity, anastomotic leakage, resection margins, or number of lymph nodes harvested. Laparoscopic approaches are generally associated with less blood loss, quicker return to normal diet, less pain, and less narcotic use, but are also associated with longer operative time and higher costs, and no results of quality of life were reported.⁸⁷

A more recent meta-analysis of trials reporting oncologic outcomes for laparoscopic rectal resections included 1403 laparoscopic and 1755 open rectal resections from 24 publications; 5 of the 24 studies were prospective randomized trials, and long-term survival estimates were reported. This review found that although laparoscopic procedures harvested fewer lymph nodes (10 vs. 12), 3-year overall survival (76% laparoscopic, 49% open) and mean local recurrence (7% laparoscopic, 8% open) were not statistically different. There was also no difference in radial margin positivity.⁸⁸

Table 78-3 summarizes the advantages and disadvantages of preoperative (typically chemoradiation) versus postoperative adjuvant therapy. The major advantages of preoperative therapy are tumor downstaging with increased resectability and sphincter preservation as well as a reduced incidence of acute and chronic toxicity. Adequate doses of radiation (≥4500 Gy) can sterilize peripheral margins of disease.⁹⁶ Marginally resectable and unresectable tumors can undergo tumor shrinkage, making them amenable to curative surgical resection, particularly within the confines of the ridged, funnel-shaped bony pelvis, which often limits the potential for adequate circumferential margins of resection.⁶³ Preoperative therapy also allows tumors to be resected with limited longitudinal surgical margins, thereby extending the level to which sphincter-sparing procedures can be performed safely in the distal rectum. These advantages, in turn, are associated with the potential for a significant reduction in a source of tumor spillage associated with locoregional recurrence of disease as well as a reduction of the dissemination during surgery of viable tumor cells increasing the risk for developing distant metastatic foci. The potential therapeutic advantage of preoperative therapy (particularly radiation) with enhanced oxygenation before surgical disruption of tumor blood supply is well established.^100,101

Preoperative therapy also has the potential advantage of reducing the risk of treatment of both chemotherapy- and radiation-related morbidity compared with that seen with postoperative therapy.104–104 Following surgical resection, adhesions often develop and cause loops of bowel to be fixed within the pelvis. These fixed bowel loops often show enhanced tissue reaction with associated bacterial invasion, increasing the risk of severe treatment-related complications. In the preoperative therapy setting, the small bowel is less likely to be fixed within the treatment field and thereby is less prone to both acute and chronic treatment-related injury.

The major advantage of postoperative therapy is the ability to select patients who are at high risk for locoregional or distant disease recurrence based on pathological staging of disease and operative findings. This approach also minimizes the potential of overtreating patients with either early disease (pathological stage I) or radiographically occult metastatic disease found at time of surgery. Other potential advantages include the avoidance of possible wound-healing problems associated with preoperative therapy. Otherwise, studies have failed to demonstrate any increased potential for the development of disseminated disease during preoperative therapy and the subsequent waiting period before surgery.

Optimal Timing of Surgery Following Preoperative Therapy

The most common interval between the end of radiation and surgery is 6 to 8 weeks. Until the publication of the Lyon R90–01 randomized trial,¹⁰⁵

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