ca de recto tratamiento

TRATAMIENTO   Surgery The surgical management of primary rectal cancer presents unique problems for the surgeon based in large part on the anatomic constraints of the pelvis. Small early stage lesions of the rectum that are diagnosed on physical examination or by colonoscopy/proctoscopy can often be managed with local resection. Local resection can be performed colonoscopically (as was described in Chapter 39.12 on colon cancer), or lesions can be removed via a transanal excision with the patient positioned in a prone or lithotomy position. Appropriate retractors can provide visualization, and resection should encompass a surrounding margin of normal mucosa28 and should extend into the perirectal fat. Stage I The treatment of early stage rectal cancer can be confusing as there are many approaches that can be used, and patient selection is critical to outcome. In addition, the risk of removal or damage to the anal sphincter is substantial for low-lying tumors and must be taken into consideration, along with the desire not to have a permanent colostomy for early stage disease. Thus, the options for these patients are primarily those of local therapies without abdominal surgery, abdominal resection of the rectum with anastomosis and retention of the anal sphincter, and abdominal-perineal resection. The last two options are discussed in detail in the section P.1289 Stages II and III Rectal Cancer. For selected T1 and T2 lesions without evidence of nodal disease, transanal excision often provides an adequate resection of the primary tumor mass and can spare the patient the morbidity of a more extensive rectal resection. However, it does not stage the nodal drainage areas and therefore cannot provide as complete staging and management of the tumor as a definitive resection. Tumors considered for local excision must meet a number of criteria to minimize the risk of local regional failure. Generally, local excision is limited to tumors within 8 to 10 cm of the anal verge, encompass less than 40% of circumference of the bowel wall, are of well or moderately well differentiated histology, and have no pathological evidence of venous or lymphatic vessel invasion on biopsy. Although it has not been formally proven that these criteria need to be followed, small series have suggested a substantially higher risk of failure after local excision when these criteria have not been met, and most surgeons are reluctant to use local excision for the more extensive T1 or T2 lesions. Even when these criteria have been met, the local recurrence rate can be high after local excision (even when followed by postoperative radiation therapy and chemotherapy), so this approach must be used with caution. Performing a good transanal excision requires substantial surgical expertise as the surgeon must retain control over the primary tumor and obtain adequate mucosal margins as well as adequate deep resection into perirectal fat. Once removed, the tumor must be well laid out for the pathologist so that all relevant margins can be properly evaluated. There is some experience using preoperative radiation therapy and chemotherapy for small lesions, but care must be taken to have the site of the primary tumor well marked with a tattoo if this approach is taken as excellent regression could make identification of the primary site difficult. The staging of such lesions should be performed using EUS to minimize the likelihood of doing a local excision for T3 tumors,29,30 although there are inaccuracies with this approach. A posterior proctotomy is useful for large posterior lesions and provides better access to more proximal lesions. This approach is known as a Kraske procedure and is performed by making a posterior longitudinal incision just above the anus to the inferior border of the gluteus maximus. The coccyx is removed and the underlying levator muscles are divided in a longitudinal fashion in the midline. This approach allows for the mobilization of the rectum and a full-thickness local excision. A transsphincteric excision (Bevan's or York-Mason) involves a similar approach as the posterior proctotomy, except the entire anal sphincter is divided posteriorly in the midline. Most investigators now feel it appropriate to use adjuvant pelvic radiation therapy with concurrent 5- fluorouracil (5-FU)-based chemotherapy for patients who have had a local excision for T2 tumors and also for selected patients with T1 tumors who have adverse prognostic factors (lymphovascular invasion, close margins, poorly differentiated histology), in order to decrease the risk of local recurrence. Another approach that has been used sporadically for patients with early stage disease is endocavitary radiation therapy. This technique is used for a similar category of patients who are treated with local excision; T1 or T2 tumors less than 3 cm, not poorly differentiated, with no evidence of nodal involvement. Patients are treated with a special low energy x-ray machine (50 kVp) that is attached to a rigid endoscopic-type device that can be placed in the rectum directly over the tumor. As the opening of the applicator is 3 cm, it is difficult to treat tumors larger than this, although overlapping fields have been employed. Patients typically receive four treatments of 2,500 to 3,000 cGy each with 2 to 3 weeks between treatments to allow for tumor regression. Although the total dose is extremely high, the minimal penetration of the radiation beam protects the underlying normal tissue. Local control results with this approach have been very good in properly selected patients, but specialized equipment is required (which is not generally available) and less pathological information is obtained than after a local excision. This approach is rarely used at the present time. Stages II and III Rectal Cancer The primary treatment of patients with stages II and III rectal cancer (T3-4 and/or N+) is surgical. However, in P.1290 contrast to the treatment of patients with stage I disease, there is a strong body of information to suggest that combined modality therapy with radiation therapy and chemotherapy should be used in conjunction with surgical resection. This conclusion is based on both patterns of failure data, which demonstrate a substantial incidence of local, regional as well as distant disease failure, and the fact that this incidence of tumor recurrence at all sites is decreased with the use of trimodality therapy. The desire when performing a resection for rectal cancer is to preserve intestinal continuity and the sphincter mechanism whenever possible while still maximizing tumor control. Therefore, careful preoperative screening is crucial in the determination of the location of the lesion and its depth of invasion. Large lesions may respond to preoperative adjuvant chemoradiation in order to downstage the lesion to increase the likelihood of a successful sphincter-preserving operation. The use of chemotherapy and radiation for this purpose will be discussed in greater detail in later sections. As described above, it is convenient to think of the rectum as divided into thirds for the purposes of the evaluation and preoperative determination of the surgical approach for resection. The upper third of the rectum is often considered the region of large intestine from the sacral prominence to the peritoneal reflection. These lesions are in almost all cases managed with a low anterior resection in much the same way as a sigmoid colon cancer (see Chapter 39.12 on colon cancer). An adequate 1 to 2 cm distal mucosal margin can be achieved for these lesions well above the sphincter mechanism, and intestinal continuity can be restored using either a hand-sewn technique or a circular stapling device inserted through the rectum.29,31 Tumors in the middle and lower thirds of the rectum can be considered as lying entirely below the peritoneal reflection. The resection of these tumors can be challenging due to the confines of the pelvic skeletal structure, and the ability to perform a resection with an adequate distal margin is significantly influenced by the size of the lesion. Nevertheless, tumors of the middle third of the rectum in most cases can be safely resected with a low anterior resection, with restoration of intestinal continuity and preservation of a continent sphincter apparatus. Lesions in the distal third of the rectum, defined as those within 5 cm of the anal verge, can present the greatest challenge to the surgeon with respect to sphincter preservation. This is often influenced by the extent of lateral invasion of the lesion into the muscles of the sphincter apparatus and how close distally the tumor is to the musculature of the anal canal. The abdominal perineal resection (APR) has historically been considered the standard treatment for patients with rectal cancers located within 6 cm of the anal verge. This procedure requires a transperitoneal as well as a transperineal approach with removal of the entire rectum and sphincter complex. A permanent end colostomy is created and the perineal wound either closed primarily or left to granulate in after closure of the musculature. Although an APR is associated with a relatively low rate of local recurrence, it is not without the obvious problems of the need for a permanent colostomy and loss of intestinal continuity and sphincter function. Therefore, intense interest has been focused on developing approaches to the resection of tumors in the distal third of the rectum that would both avoid local regional recurrence and preserve intestinal continuity and sphincter continence. Tumors within 1 to 2 cm of the dentate line, that is those that can be removed with at least a 1-cm distal margin, can be resected and intestinal continuity restored with a coloanal anastomosis.32,33 When performing a very low coloanal anastomosis, it is often prudent to protect the healing suture line with a diverting loop ileostomy, which can be reversed in 4 to 6 weeks after the anastomosis has healed. Despite the potential benefits of sphincter preservation, APR is still the most common procedure performed for rectal lesions in the distal and middle thirds of the rectum.34 A recent review of the published literature demonstrates that between 10% and 67% of procedures for the management of rectal cancers are APR procedures.32 In order to increase the number of sphincter-preserving operations performed, several authors cite the use of preoperative chemoradiation as a means to decrease the local recurrence rate.32,35 They cite statistics that rectal carcinoma responds to preoperative chemoradiation therapy with a 10% to 15% pathologic complete response rate and substantial tumor down-staging. The goal of such an approach would be to reduce the need for APR to an incidence of 10% or less. When performing a sphincter-preserving operation, in order to preserve the lateral musculature and therefore a functional sphincter complex, the resection by necessity does not have as wide a margin as one performed during an APR. In order to improve on margin status, intersphincteric resections have been performed.36 This approach includes a partial sphincteric resection designed to improve margin status without sacrificing sphincter function. In small series, functional results have been comparable to less aggressive sphincterpreserving operations. The impact on oncologic outcome is difficult to interpret and will require larger series. The choice of a straight coloanal versus a pouch anastomosis is a decision that is based to a large degree on surgeon's preference and experience. Some advocate a pouch operation, citing improved anal function as measured by decreased stool frequency and urgency and improved continence.4 Others have demonstrated that results are equivalent with a straight coloanal anastomosis.37 Chemoradiation should be added either preoperatively or postoperatively when performing sphincterpreserving resections for T3 or T4 rectal lesions or for node positive disease stages II or III). There is some evidence that preoperative radiation results in less morbidity than postoperative radiation therapy when a coloanal anastomosis is planned. In a study of 109 patients treated with a low anterior resection and a straight coloanal anastomosis, those receiving preoperative radiation therapy had a lower incidence of adverse effects on anal function than those receiving postoperative radiation.37 The authors attributed this to sparing of the neorectum from these effects. Relative benefits and outcomes for preoperative chemoradiation versus postoperative chemoradiation will be discussed in detail in following sections. Total Mesorectal Resection The goal of the resection of rectal tumors is the removal of the tumor with an adequate margin as well as removal of draining lymph nodes and lymphatics in order to properly stage the tumor and to reduce the risk of recurrence and spread. For lesions in the intraperitoneal colon, the lymphatics and vascular supply are found in the mesentery associated with that region of bowel. In the rectum the mesorectum is the structure that contains the blood supply and lymphatics for the upper, middle, and lower rectum. Most involved lymph nodes for rectal cancers are found within the mesorectum, with T1 lesions associated with positive lymph nodes in 5.7% of cases; T2 lesions having positive lymph nodes in 20% of cases, and T3 and T4 lesions having positive lymph nodes in 65% and 78% of cases, respectively.38 The anatomy and approach to mesorectal excision is depicted in Figure 39.13.3. This operation involves a sharp dissection occurring in an avascular plane beyond the perirectal fat that is beyond the region where most of the nodes are located. After a TME the specimen is typically shiny and bilobed in contrast to the irregular and rough surface after a blunt dissection where much of the mesorectal fat is left behind. TME attempts not only to clear involved lymph nodes but also to adequately manage the radial margins of the rectal tumor. These radial margins have been shown to be more important with respect to the risk of local regional recurrence than the distal mucosal margin.35,39 Distal mucosal margins of 1 cm or greater are adequate for local control; however, the margin on the mesorectum should extend beyond the distal mucosal margin in order to ensure a successful surgical outcome.33,35 A number of studies have demonstrated the benefit of TME, and it is thought by many that this is the procedure of choice for the management of middle- and lower-third rectal cancers.5,40,41,42 Although some studies have suggested that an adequate TME might in and of itself be P.1291 sufficient management for T2 and T3 rectal cancers, the majority of the literature still supports the use of adjuvant chemoradiation for stages II and III disease even when combined with TME. Large studies of proctectomy with TME have demonstrated a reduction in the overall incidence of local recurrence to less than 10%.4 The consequences of TME can be impairment in erectile and bladder function due to disruption of parasympathetic nerves that are located in proximity to the mesorectum. Several authors have stressed the importance of the experience of the surgeon performing the procedure, and some have suggested specific techniques for monitoring modalities that can be used during this procedure to minimize morbidity.5,6 A careful understanding of the anatomy and adequate visualization during sharp dissection will help in minimizing injury to the parasympathetic nerves and the consequent morbidity.3,4 Adequate visualization in the deep pelvis can often be a challenge. This may be a situation where the visual magnification and ability to enter tight spaces that are unique to the laparoscopic approach may be an advantage. Several groups have demonstrated the feasibility of laparoscopic TME for low rectal cancer as part of a sphincter-preserving operation.43,44,45 Some of the larger series, while demonstrating that TME using laparoscopic techniques can be performed safely, do not have adequate follow-up to demonstrate whether there were any oncologic disadvantages to such an approach. Unfortunately, the prospective random assignment trial conducted in the United States to evaluate the role of laparoscopic surgery for colon cancer excluded patients with low rectal lesions. Therefore, the ultimate role of the laparoscopic approach to TME will have to await prospective randomized trials utilizing this technique and comparing it to the standard open approach.   a Local recurrence highly dependent on site in rectumโ€”18% overall for tumors โค7 cm from anal verge. The most important piece of information on local recurrence rates with TME are the data from the Dutch TME study in which patients were randomized to receive either TME alone or a short course of preoperative radiation therapy followed by TME.41 All patients with rectal cancer were eligible including those with early stage disease. Special attempts were made to have good surgical and pathology quality control. The early results (2 years) relating to local tumor recurrence have been reported and are summarized in Table 39.13.2. The study demonstrates that there are subsets of patients in whom TME alone is likely sufficient for obtaining good pelvic control, including patients with high rectal tumors (some of these may have been sigmoid cancers, rather than rectal), and low stage tumors (T1-2, N0). On the other hand, low-lying rectal tumors that are moderately advanced (T3-4 and/or N+), had a higher incidence of local-regional failure. Local failure after TME alone was 15% in node positive patients at 2 years, not corrected for site of the primary, and longer-term follow-up will undoubtedly demonstrate higher local failure rates. In addition, as these results were obtained in a controlled setting, one would likely not obtain similarly good results when surgery is done with less careful quality control. There was a consistent decrease in local failure rate by the addition of preoperative radiation P.1293 therapy, but the absolute magnitude of the effect varied by the tumor characteristics discussed above. The data are excellent that radiation therapy, especially when combined with chemotherapy, can decrease the local failure rate. This is shown by a Swedish study of preoperative radiation therapy compared to surgery,57 the Dutch TME trial in the preoperative setting,41 and by multiple studies in the postoperative setting.58,59,60,61,62,63 There are also excellent data to show that local-regional failure is decreased by the use of radiation therapy and is further decreased by the use of concurrent 5-FU-based chemotherapy (Table 39.13.3).58,59,64 Most studies have demonstrated that local failure decreases by about 50% with the use of adjuvant radiation therapy, with a greater effect when concurrent 5-FU is used with irradiation. This appears to provide a strong justification for the use of adjuvant radiation therapy. What is less clear is (1) whether trimodality therapy with radiation therapy improves survival, (2) if radiochemotherapy should be given preoperatively or postoperatively, and (3) precisely which patients should be irradiated. T Does Adjuvant Radiation Therapy Impact Survival? Although there have been multiple randomized trials addressing the use of adjuvant radiation therapy or chemoradiation therapy, and although they consistently show an improvement in local control with adjuvant radiation therapy, the survival outcome data have been mixed. In the past few years there have been two meta-analyses performed.65,66 Table 39.13.4 shows the results of a meta-analysis by Camma et al.66 showing a decreased local recurrence rate, cancer mortality rate, and overall mortality rate with the use of preoperative radiation therapy, although without a decrease in distant metastasis rate. The Colorectal Cancer Collaborative Group (Table 39.13.5) study demonstrates no improvement in the likelihood of curative surgery with preoperative therapy or of overall survival with all types of radiation therapy combined.65 Preoperative radiation therapy, however, was shown to improve local control, disease-free survival, and overall survival compared to surgery alone, although deaths within the first year after surgery were higher after radiation therapy. Local recurrence with preoperative radiation therapy was 46% lower than surgery alone, and cancer deaths were decreased from 50% to 45%. Postoperative radiation therapy was shown to improve local control (although less than preoperative therapy), but did not impact long-term survival. Lending substantial strength to the conclusion that there was a true advantage to radiation therapy is the fact that there was a dose response demonstrated for the radiation effect on local control (i.e., better control was obtained with higher radiation dose). This observation strengthens the conclusion, as it demonstrates a direct correlation between the amount of therapy and outcome. The data from this analysis are heavily influenced by the results of a single Swedish study that showed a long-term survival advantage to the use of preoperative radiation therapy compared to surgery alone.57 Thus, these data show that improving local control with the use of radiation therapy (and presumably with concurrent chemoradiation therapy) is beneficial, and that trimodality therapy, especially when chemoradiation therapy is used preoperatively, can improve survival. Table 39.13.4 Results of Meta-Analysis, Preoperative Radiotherapy versus Surgery Alone Preop Radiotherapy versus Surgery Overall 5-y mortality OR 0.84 (P = .03) 5-y cancer mortality OR 0.71 (P <.001) 5-y local recurrence OR 0.49 (P <.001) 5-y distant metastases OR 0.93 (P = .54) OR, overall recovery. (From ref. 66, with permission.) Table 39.13.5 Colorectal Cancer Collaborative Group 2001 Adjuvant Radiation Therapy in Rectal Cancer Preop RT versus Surgery Postop RT versus Surgery Yearly risk of local recurrence 46% decrease with RT 37% decrease with RT Death rate 5% less than with surgery No difference from surgery RT, radiotherapy. (From ref. 65, with permission.) Preoperative Radiation Therapy The second issue of importance is whether adjuvant therapy should be given preoperatively or postoperatively and the exact timing of the chemotherapy. There have been relatively few studies that have compared these approaches in a randomized controlled trial. A Swedish study reported in the early 1990s compared a short course of radiation therapy preoperatively to a more protracted course and higher total dose delivered postoperatively and found a decreased local failure with the use of preoperative therapy compared to postoperative therapy (13% vs. 22%).67,68 Two trials in the United States have attempted to compare combined chemoradiation therapy delivered preoperatively to the same chemoradiation therapy regimen given postoperatively. However, neither study (National Surgical Adjuvant Breast and Bowel Project [NSABP] or Gastrointestinal Intergroup) could accrue a sufficient number of patients to answer the question.69 The inability to accrue patients to these studies makes it unlikely that such a study will be attempted in the near future in the United States. In addition to improving survival, another reason for using preoperative chemoradiation therapy is to increase the chance for sphincter preservation for patients with low-lying tumors of the rectum, where an abdominoperineal resection would be conventionally used. The NSABP trial mentioned above was able to obtain worthwhile information regarding this issue. When the patient was first seen, the surgeon was asked (for both preoperative and postoperative patients) what operation was needed. In the patients randomized to postoperative radiation therapy (i.e., immediate surgery), the determination in the office corresponded extremely well to the operation actually performed. However, in the patients who received preoperative radiation therapy, sphincter-preserving surgery was done in 50% of patients compared to 33% of those who had initial surgery.70 However, overall the data have been inconsistent in demonstrating an advantage to preoperative therapy in terms of sphincter preservation. The analyses are complicated because the decision as to whether sphincter-preserving surgery should be done is heavily dependent on the biases of the surgeon. If the surgeon believes that the same operation should be done regardless of tumor regression, then clearly the same surgery will be done. There are clearly some surgeons who will do sphincter-preserving operations after preoperative irradiation, when they would not have done so if the surgery had been done first. Perhaps the most important study addressing the issue of pre- versus postoperative adjuvant therapy is a German trial of preoperative versus postoperative chemoradiation with radiation therapy given at 180 cGy per fraction and using continuous infusion 5-FU chemotherapy as a 120-hour infusion, for which results have been reported by Sauer et al.71 This study demonstrates an advantage in sphincter preservation with the use of preoperative therapy. Of the patients thought to need an APR at initial assessment, only 19% had a sphincterpreserving surgery when operation was done immediately versus 39% after preoperative radiation therapy, although there was no difference in the overall sphincter preservation rate. There was a statistically significant decrease in local failure with preoperative radiation therapy compared to postoperative treatment (6% vs. 13%; P = .006). The relative risk of local failure in the pre- versus postoperative treatment group was 0.46. The 5- year disease-free survival showed a small advantage to preoperative therapy (68% vs. 65%; P = .32), which was not statistically significant. There was a decrease in late anastomotic strictures with preoperative therapy, and acute toxicity was also decreased by the use of preoperative radiation and chemotherapy, both statistically significant. This provides strong evidence of the superiority of preoperative adjuvant treatment in patients in whom it is determined that adjuvant therapy is needed. If one is using preoperative radiotherapy to try to improve the likelihood of sphincter preservation, the radiation must be given in such a way as to maximize the likelihood of this occurring. Specifically, a โ € standardโ€ long course of irradiation to a dose of approximately 5,000 cGy at 180 to 200 cGy per fraction over 5 to 5.5 weeks (as given in the German trial above) has been thought by most U.S. investigators to be optimal. The short-course therapy with immediate surgery (typically 500 cGy for five fractions given over 1 week), as often used in Europe, followed by immediate surgery is not likely to produce enough tumor shrinkage to allow for sphincter preservation in patients with very low-lying tumors. Bujko et al.72 have published data that P.1295