Node-positive Rectal Cancer Research Articles

The Impact of Multidisciplinary Therapy in Node-Positive Rectal Cancer

Multidisciplinary therapy (MDT) of node-positive rectal cancer is considered optimal. We performed a retrospective cohort study of node positive rectal cancer patients diagnosed between January 1, 1994 and December 31, 2003 in Region 5 of the California Cancer Registry to determine the impact of MDT on disease specific survival (DSS). During the study period, 398 patients with stage III rectal cancer were identified. Only 251 patients (63.1%) received radiation (XRT). Patients receiving XRT had significantly improved survival when compared with those who did not (5 year DSS 55% with XRT vs. 36% without XRT, median follow-up 43 months, P < 0.001). There was no statistically significant difference in Tstage (P = 0.41), the number of N1 patients (P = 0.45), or the number of positive nodes harvested (mean 11.5 w/o XRT vs. 12.8 w/XRT, P = 0.37) between patients receiving XRT and those who did not. Patients receiving XRT were far more likely to receive systemic chemotherapy (83% vs. 27%, P < 0.0001). Multidisciplinary therapy of node-positive rectal cancer is associated with improved DSS. However, substantial numbers of node positive rectal cancer patients are not receiving MDT. Greater efforts are needed to implement consistent multidisciplinary algorithms into rectal cancer management.

Do all locally advanced rectal cancers require radiation? A review of literature in the modern era.

Potentially curable rectal cancer is primarily treated with surgical resection. Adjuvant or neoadjuvant radiotherapy is often utilized for patients deemed to be at unacceptable risk for local recurrence. The purpose of this article is to review the pertinent literature and elucidate the role of radiotherapy in patients with an intermediate risk of local recurrence. The addition of chemoradiotherapy is recommended in the majority of patients with transmural or node positive rectal cancer. However, some patients with favorable characteristics may have only a small incremental benefit from the addition of radiotherapy. The decision to treat or not to treat should take into consideration the patient and physician tolerance of risk of recurrence and risk of treatment related toxicity. The primary factors identified for determining low risk patients are circumferential radial margin (CRM), location within the rectum, and nodal status. Patients at lowest risk have widely negative CRM (>2mm), proximal lesions (>10cm from the anal verge), and no nodal disease. Patients with all three low risk factors have an absolute reduction in local recurrence that is <5% and may be eligible to forego radiotherapy. Additional factors identified which may impact local recurrence risk are elevated serum CEA level, lymphovascular space invasion, pathologic grade, and extramural space invasion.

5-fluorouracil, leucovorin and oxaliplatin (FOLFOX4) as postoperative adjuvant chemotherapy (CT) for node positive rectal cancer after radiochemotherapy (R-CT) and surgery

Aims: To evaluate the activity and safety of postoperative adjuvant CT of 8 cycles FOLFOX4 in patients with node-positive rectal cancer after neoadjuvant R-CT and surgery.

Importance of the Circumferential Extent of Tumors and Clinical Lymph Node Status as Prognostic Factors after Preoperative Chemoradiotherapy and Surgery in Patients with Rectal Cancer

To evaluate the clinical factors that influence pathological and clinical outcomes after preoperative concurrent chemoradiotherapy in patients with rectal cancer. Between 1999 and 2004, 121 patients with cT3-4 or node-positive rectal cancer received preoperative chemoradiotherapy and surgery. Preoperative radiation therapy with 45 Gy was delivered. Fluorouracil-based chemotherapy was administered to most of the patients. Pathological complete remission was 14.3% after preoperative chemoradiotherapy. More than 60% tumor circumferential extent was an independent adverse factor for complete remission (P = 0.011, HR 4.643, 95% CI 1.415-15.231). Local recurrence developed in 9.9% of the cases. Serum CEA level > 5 ng/ml (P = 0.057, HR 3.022, 95% CI 0.967-9.441) and > 60% circumferential extent of tumor (P = 0.064, HR 4.232, 95% CI 0.918-19.531) were marginal adverse factors for local recurrence. Five-year disease-free survival and overall survival were 72.2% and 86.6%, respectively. Disease-free survival was poor for patients with the lymph nodes > or = 1 cm in diameter (P = 0.028), cN2 stage disease (P = 0.047) and > 60% circumferential extent of tumor (P = 0.058). Multivariate analysis for disease-free survival showed that the lymph node size > or = 1 cm was an adverse factor (P = 0.019, HR 2.380, 95% CI 1.115-4.906). Patients with > 60% circumferential extent of tumor and cN2 stage had a more unfavorable survival than the other patients (disease-free survival, P = 0.018; overall survival, P = 0.015). Patients with > 60% circumferential extent of tumor and/or lymph node > or = 1 cm also had an unfavorable survival (disease-free survival, P = 0.016; overall survival, P = 0.049). In rectal cancer, circumferential extent of tumor and clinical lymph node status were important factors for preoperative chemoradiotherapy and surgery. A further prospective study is needed to confirm and expand these findings.

5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) as postoperative adjuvant chemotherapy (CT) for node-positive rectal cancer after radiochemotherapy (R-CT) and surgery.

e14125 Background: To evaluate the activity and safety of postoperative adjuvant CT of 8 cycles FOLFOX4 in patients with node-positive rectal cancer after neoadjuvant R-CT and surgery. Methods: We ...

683h: Prospective Evaluation of Clinical, Endoscopic and EUS FNA Peri-Iliac Lymph Node Status in Primary Rectal Cancer

Total mesorectal excision (TME) results in low local recurrence rates in lymph node (LN) positive rectal cancer. However, lymphatic flow from low-lying rectal cancers (distal 1/3 of rectum) passes beyond the boundaries of TME to LN's in close proximity to the iliac vessels in the lateral pelvic region. The low prognostic value of EUS nodal appearance mandates EUS guided fine needle aspiration (FNA). It is currently unknown, if iliac LN status confirmed by EUS FNA in primary rectal cancer is of potential clinical significance.

Preoperative Multimodality Therapy Improves Disease-Free Survival in Patients With Carcinoma of the Rectum: NSABP R-03

Although chemoradiotherapy plus resection is considered standard treatment for operable rectal carcinoma, the optimal time to administer this therapy is not clear. The NSABP R-03 (National Surgical Adjuvant Breast and Bowel Project R-03) trial compared neoadjuvant versus adjuvant chemoradiotherapy in the treatment of locally advanced rectal carcinoma. Patients with clinical T3 or T4 or node-positive rectal cancer were randomly assigned to preoperative or postoperative chemoradiotherapy. Chemotherapy consisted of fluorouracil and leucovorin with 45 Gy in 25 fractions with a 5.40-Gy boost within the original margins of treatment. In the preoperative group, surgery was performed within 8 weeks after completion of radiotherapy. In the postoperative group, chemotherapy began after recovery from surgery but no later than 4 weeks after surgery. The primary end points were disease-free survival (DFS) and overall survival (OS). From August 1993 to June 1999, 267 patients were randomly assigned to NSABP R-03. The intended sample size was 900 patients. Excluding 11 ineligible and two eligible patients without follow-up data, the analysis used data on 123 patients randomly assigned to preoperative and 131 to postoperative chemoradiotherapy. Surviving patients were observed for a median of 8.4 years. The 5-year DFS for preoperative patients was 64.7% v 53.4% for postoperative patients (P = .011). The 5-year OS for preoperative patients was 74.5% v 65.6% for postoperative patients (P = .065). A complete pathologic response was achieved in 15% of preoperative patients. No preoperative patient with a complete pathologic response has had a recurrence. Preoperative chemoradiotherapy, compared with postoperative chemoradiotherapy, significantly improved DFS and showed a trend toward improved OS.

Prognostic Significance of the Metastatic Lymph Node Ratio in Node-Positive Rectal Cancer

The purpose of the study was to evaluate the prognostic value of metastatic lymph node ratio (LNR) in node-positive rectal cancer. A retrospective review was performed in 318 rectal cancer patients who received curative anterior resection in a single institution. Clinicopathological variables including LNR were studied in univariate and multivariate analyses by Cox regression. LNR was further studied when stratified by quartiles. Survival analyses were performed using the Kaplan-Meier method and log-rank test. With median follow-up of 41 months, the 5-year disease-free survival (DFS) rate, overall survival (OS) rate, and local recurrence (LR) rate were 56.82%, 59.8%, and 11%, respectively. Multivariate analysis revealed that LNR as a continuous variable was the most significant prognostic factor for DFS, OS, and LR. On quartiles, LNR was stratified into three groups: <0.14, 0.14-0.49, and 0.5-1. The 5-year DFS rate was 72.57%, 58.54%, and 34.75% (P = 0.0001) and the 5-year OS rate was 72.19%, 61.92%, and 38.47% (P = 0.002) in the three groups, respectively. Five-year LR rate was significantly higher with LNR between 0.14 and 1 (3.6% in LNR<0.14 versus 15.6% in LNR 0.14-1, P = 0.019). LNR is an important prognostic factor for node-positive rectal cancers. With a cutoff of 0.14 and 0.5, node-positive rectal cancer patients could be categorized into three subsets with significant different outcomes.

Tumor Hypoxia Detected by Positron Emission Tomography with 60Cu-ATSM as a Predictor of Response and Survival in Patients Undergoing Neoadjuvant Chemoradiotherapy for Rectal Carcinoma: A Pilot Study

The response of rectal cancers to neoadjuvant chemoradiotherapy is variable. Tumor hypoxia reduces the effectiveness of both radiation therapy and chemotherapy and is a well-known risk factor for tumor radioresistence. We hypothesized that imaging with the novel hypoxia-detecting agent, (60)Cu-diacetyl-bis (N(4)-methylthiosemicarbazone) ((60)Cu-ATSM), previously validated in cervical and lung cancers, would predict the response of rectal cancers to neoadjuvant chemoradiotherapy and prognosis. Patients with locally invasive (T2-4) primary or node-positive rectal cancer located <12 cm from the anal verge were recruited for this pilot study. Pretreatment tumor size and stage were determined by endorectal ultrasonography, CT, and magnetic resonance imaging. Eleven patients also underwent clinical positron emission tomography with (18)F-fluorodeoxyglucose at the discretion of the treating clinician. The primary tumor was imaged by positron emission tomography with (60)Cu-ATSM, and accumulation of the tracer was measured semiquantitatively by determining the tumor-to-muscle activity ratio. Neoadjuvant chemoradiotherapy was then administered (within 2 weeks of (60)Cu-ATSM-positron emission tomography) and consisted of 45 Gy given in 25 fractions to the pelvis with continuous intravenous infusion of 5-fluorouracil (225 mg/m(2)/day). Proctectomy was performed six to eight weeks after neoadjuvant chemoradiotherapy and the tumor submitted to pathology for size measurement and staging. Tumor-to-muscle activity ratios were compared with tumor (18)F-fluorodeoxyglucose uptake, tumor response to neoadjuvant chemoradiotherapy, and with patient survival. Nineteen patients were enrolled in the study, two of whom were excluded from final analysis (1 death during neoadjuvant chemoradiotherapy and 1 tumor perforation during neoadjuvant chemoradiotherapy requiring emergent surgery). Of the 17 remaining patients, 14 had a reduction in tumor size and 13 were downstaged. The median tumor-to-muscle activity ratio of 2.6 discriminated those with worse prognosis from those with better prognosis. Both overall and progression-free survivals were worse with hypoxic tumors (tumor-to-muscle activity ratio >2.6) than with nonhypoxic tumors (tumor-to-muscle activity ratio <or=2.6; both P < 0.05). In addition, 2 of the 3 tumors with no change in size had tumor-to-muscle activity ratios >2.6 (positive predictive value 66 percent), whereas 6 of 14 with decreased size had tumor-to-muscle activity ratios >2.6 (negative predictive value 57 percent). Three of the 4 tumors not downstaged had tumor-to-muscle activity ratios >2.6 (positive predictive value 75 percent), whereas 5 of 13 downstaged tumors had tumor-to-muscle activity ratios >2.6 (negative predictive value 62 percent). The mean tumor-to-muscle activity ratio for downstaged tumors (2.2) was significantly lower than that of nondownstaged tumors (3.3) (P = 0.03). The difference in mean tumor-to-muscle activity ratio between downsized (2.3) and nondownsized (2.9) tumors did not reach statistical significance (P = 0.36). Tumor (18)F-fluorodeoxyglucose uptake (n = 11) did not correlate with (60)Cu-ATSM uptake (r = 0.4; P = 0.9) and there was no significant difference in mean tumor (18)F-fluorodeoxyglucose uptake between patients with hypoxic tumors and those with normoxic tumors (P = 0.3). The results of this small pilot study suggest that (60)Cu-ATSM-PET may be predictive of survival and, possibly, tumor response to neoadjuvant chemoradiotherapy in patients with rectal cancer. A larger Phase II study is warranted to validate these results.

Postoperative Radiotherapy for Stage IIIA Rectal Cancer: Is It Justified?

Adjuvant radiotherapy is currently recommended for all node-positive rectal cancers to reduce local recurrence. This study evaluated if an adequate mesorectal excision can obviate the need for radiotherapy in early node-positive cancer. Stage IIIA rectal cancer patients were identified in a prospectively maintained database. Patients who received postoperative radiotherapy (radiotherapy) and those who did not (no radiotherapy) were compared for recurrence, survival, bowel function, and quality of life. Quality of life was assessed using the Short Form-36 Medical Outcomes Survey. Eighty-six patients underwent proctectomy for T1-T2,N1 rectal cancers from 1978 to 2004. Patients receiving radiotherapy (n = 34) were younger and had a higher percentage of T1 tumors than patients who did not receive radiotherapy (n = 52). Other tumor characteristics, type of surgery, and number of involved lymph nodes were comparable. Estimated 5-year local recurrence was radiotherapy 3.4 percent and no radiotherapy 4.7 percent; distant recurrence was radiotherapy 13.5 percent and no radiotherapy 16.5 percent; and disease-specific mortality rates were similar 13.5 vs. 11.3 percent, for radiotherapy and no radiotherapy (all P > .05). Patients receiving radiotherapy had higher frequency of daytime bowel movements, urgency, and usage of pads and antidiarrheal medications. Age adjusted quality of life parameters were comparable between treatments. Postoperative radiotherapy did not reduce recurrence or mortality. Function but not quality of life was adversely affected. Routine postoperative radiotherapy for Stage IIIA rectal cancer should be reconsidered.

ACR Appropriateness Criteria on Resectable Rectal Cancer: Expert Panel on Radiation Oncology—Rectal/Anal Cancer

In what arguably may be the most pivotal recent trial in the area of resectable rectal cancer management, a randomized trial from Germany has established a regimen of preoperative chemoradiotherapy and surgery followed by additional cycles of chemotherapy alone as the standard of care for clinical stages T3 or T4, or for node-positive rectal cancer. Other clinical studies from the United States, Europe, and Asia have also influenced the treatment strategies of operable rectal cancer, as various approaches using preoperative or postoperative radiotherapy, with or without chemotherapy, have been examined. A summary of the major randomized clinical trials spanning the past several decades is provided.

Ratio of metastatic to examined lymph nodes is a powerful predictor of overall survival in rectal cancer: An analysis of Intergroup 0114

4006 Background: Lymph node (LN) metastasis is associated with decreased survival in rectal cancer. It has been suggested that at least 14 LN be evaluated for adequate staging. However, a large percentage of patients have fewer than the recommended number of LN examined. We hypothesized that LN ratio would be predictive of overall survival in rectal cancer. Methods: Data was analyzed from Intergroup 0114, a mature trial of postoperative adjuvant chemotherapy and radiation in T3/4 and/or LN positive rectal cancer. Survival was the same for all arms allowing the entire group to be considered as one. The primary endpoint evaluated was overall survival. A proportional hazards model was used to determine the relative prognostic impact of LN ratio compared to number of LN examined, number of positive LN, number of negative LN and AJCC nodal stage. LN ratio was defined as the number of positive LN divided by the total number of LN examined. Four groups were analyzed based on proportion of positive LN: =0.25, &gt;0.25–0.50, &gt;0.50–0.75 and &gt;0.75. Results: 1,648 patients were evaluable. There were 251 T1/2, 1,251 T3 and 146 T4 tumors. 513 patients were N0, 743 N1 and 392 N2. Median number of LN was 9. LN ratio was predictive of 5-year overall survival with rates of 0.71, 0.56, 0.50 and 0.43 respectively when analyzed by quartile (p&lt;0.0001). LN ratio remained significant when overall survival was analyzed by number of LN examined and grouped into &lt;10, &lt;15 and &gt;15 nodes evaluated (p&lt;0.0001 for all). LN ratio also predicted overall survival in N1 (p=0.04) and N2 (p=0.0002) disease. When comparing LN ratio (χ2=79.5, p&lt;0.0001) to number of LN examined (χ2=4.7, p=0.03), number of positive LN (χ2=38, p&lt;0.0001), number of negative LN (χ2=32, p&lt;0.0001) and AJCC nodal stage (χ2=55.5, p&lt;0.0001), LN ratio appears to be the strongest predictor of overall survival. Conclusion: LN ratio predicts overall survival in patients with resected rectal cancer. Importantly, this is true in patients who have had a small number of LN evaluated, in addition to those with a large number of LN examined. LN ratio also appears to be a stronger predictor of overall survival than other described LN prognostic factors. LN ratio may be a useful variable to stratify outcome in patients with node-positive rectal cancer. No significant financial relationships to disclose.

Prognostic Markers of Local Relapse in Rectal Cancer: Are We Any Further Forward?

Rectal cancer is a major health problem affecting more than 100,000 patients in the United States and Europe each year. 1 Although it is a highly treatable and often curable disease when localized to the bowel, the prognosis for locally advanced disease varies, with local recurrence rates ranging from 4% to 40%; local recurrenceoftenisthecauseofseveremorbidityandpoormortalityin this disease. 2 Therefore, clinical approaches to prevent early recurrence are one of the major goals in the treatment of rectal cancer. The treatment for patients with clinically resectable, locally invasive rectal cancer has begun to evolve away from more radical surgical approaches such as abdominoperitoneal resection toward attempts at preservation of the anal sphincter and maintenance of anorectal function. 3 In the postoperative setting, there is clear evidence that adjuvant fluorouracil (FU) -based chemotherapy combined with radiotherapy significantly improves disease-free survival and overall survival in patients with rectal cancer. 4 More recently, several groups clearly have shown the benefit in reducing local recurrence rates and toxicity using neoadjuvant preoperative chemotherapy/radiotherapy combinations as opposed to adjuvant treatment. 5,6 Onesuchstudy,theGermanCAO/ARO/AIO-94rectalcancer group trial, randomly assigned 823 patients with T3/4 and/or node-positive rectal cancer to receive preoperative versus postoperative combined-modality therapy consisting of FU on weeks 1 and 5 and 50.4 Gy of concurrent radiation therapy. 4 There was a significant improvement in local recurrence rates (6% in the preoperative group v 13% in the postoperative group) as well as improvements in acute and long-term toxicity. Moreover, in the preoperative group, 39% of the patients initially requiring an abdominoperitoneal resection were able to undergo a sphinctersparing operation, whereas in the postoperatively treated group only 19% were eligible for a sphincter-sparing procedure. Although there was no difference in overall survival between the two groups, the preoperative combined-modality approach significantlyimprovedthechancesofsphincterpreservationandalsoled

CT3N0 rectal cancer: Potential overtreatment with preoperative chemoradiation (CRT) is warranted

3568 Background: Although CRT has emerged as the preferred treatment for T3 and/or lymph node (LN) positive rectal cancer, Sauer et al (NEJM 2004) demonstrated that 18% of patients deemed suitable for preop CRT via endorectal ultrasound (ERUS) were overstaged and therefore received unnecessary preoperative CRT. Since data also suggest that LN negative rectal cancer s/p TME may not need adjuvant therapy, it is reasonable to consider the omission of radiotherapy for the cT3N0 subset. We therefore determined the accuracy of pre-CRT ERUS/MRI staging in order to explore the validity of a non-radiation approach for cT3N0 disease. Methods: 188 ERUS/MRI staged T3N0 rectal cancer patients from 6 insitutions in the US, Europe and Asia received preoperative CRT (5-FU based and 45–52.5 Gy) followed by radical resection. Rates of pathologic complete response (pCR) and mesorectal LN involvement were determined. Results: Tumors were located a median of 5 centimeters from the anal verge. Sphincter-preserving surgery was performed in 135 (81%) patients. Overall pCR was 19%. Median number of LN sampled was 9 (range 0–38). Rate of positive LN was significantly associated with T-stage: pT0: 3%, pT1: 7%, pT2: 20%, pT3–4: 36%(p=0.001). 41 patients (22%) had pathologically positive mesorectal LN. There was no significant difference in rate of positive LN between those staged by ERUS and MRI(25% vs 16%, p=0.19). Conclusions: Accuracy of preoperative ERUS/MRI for identifying mid to distal T3N0 rectal cancer is limited, as 22% will have undetected mesorectal LN involvement despite CRT. Therefore, ERUS/MRI staged T3N0 patients should continue to receive preoperative CRT. Although 19% are overstaged and therefore overtreated, our data suggest that an even larger number would be understaged and require postoperative CRT, which is associated with inferior local control, higher toxicity, and poor functional outcome. No significant financial relationships to disclose.

Combined modality therapy for rectal cancer

Combined modality therapy for rectal cancer

Chemoradiation for localized rectal cancer: Neoadjuvant versus adjuvant approaches

For many years, adjuvant postoperative chemotherapy and radiation has been the standard of care in the United States for patients with T3, T4, or node-positive rectal cancer. Preoperative chemoradiation has generally been reserved for situations in which a response to therapy would allow for sphincter-preserving surgery. Recent data support the use of chemoradiation in the preoperative setting, demonstrating improvements in tumor downstaging, treatment toxicity, rate of sphincter-preserving surgery, and pelvic recurrence.

Restorative proctocolectomy for ulcerative colitis complicated by colorectal cancer.

Restorative proctocolectomy with ileal pouch-anal anastomosis is widely accepted as the procedure of choice for patients requiring surgery for chronic ulcerative colitis. The role of restorative proctocolectomy in the setting of chronic ulcerative colitis complicated by colorectal carcinoma is not clear. This study was undertaken to explore the clinical outcomes of chronic ulcerative colitis patients with coexisting colorectal carcinoma who underwent restorative proctocolectomy. A total of 756 patients with chronic ulcerative colitis were followed prospectively after restorative proctocolectomy. Forty-five (5.9 percent) were found to have invasive carcinoma of the colon (n = 31) or rectum (n = 14). These patients were followed with special attention to cancer stage, adjuvant therapy, oncologic outcome, and functional results after restorative proctocolectomy. Twenty-one patients (45.6 percent) had staged surgery (colon, 14; rectum, 7). Twenty-seven patients received adjuvant chemotherapy (colon, 22; rectum, 5). Fourteen patients (51.8 percent) who received chemotherapy were not diverted during this treatment. Two node-positive rectal cancer patients had pelvic radiotherapy: one before restorative proctocolectomy and one after restorative proctocolectomy. Mean time to restoration of intestinal continuity among staged patients did not differ between cancer and noncancer patients. Six patients died of metastatic disease (colon, 3; rectum, 3). Five deaths occurred among patients with Stage III disease (colon, 3/13, 23.1 percent; rectum, 2/3, 66.7 percent). One patient with Stage I cancer at the time of restorative proctocolectomy died. Thirty-nine patients are alive without evidence of disease at a mean interval from surgery of 76.5 months. Thirty-six patients have functioning pelvic pouches. Bowel frequency, continence, and complication rates are similar among restorative proctocolectomy patients with and without cancer. Restorative proctocolectomy as a single or staged procedure is a viable therapeutic option for selected chronic ulcerative colitis patients with associated colorectal cancers. Prognosis seems to be related to cancer stage. Adjuvant chemotherapy can safely be given to nondiverted patients. Appropriate use of preoperative and postoperative radiotherapy for rectal cancer patients who are otherwise candidates for restorative proctocolectomy is unknown. Long-term functional results for cancer patients are similar to those seen in chronic ulcerative colitis patients without cancer.

Total mesorectal excision results in low local recurrence rates in lymph node-positive rectal cancer.

Most series report lymph node involvement as the main predictor for local recurrence. The principal lymphatic drainage of the rectum is to nodes in the mesorectum and then nodes along the superior rectal and inferior mesenteric arteries. If total mesorectal excision provides adequate block dissection of the lymphatics of the rectum, good local control with low rates of local recurrence should be achieved even in node-positive disease. Prospective data on all rectal cancers have been collected since 1978; 170 patients with Dukes C rectal cancer have undergone anterior resection and total mesorectal excision. We did not perform any internal iliac node dissections. Follow-up data were analyzed for local recurrence and distant recurrence. The local recurrence rate was 2 percent for Dukes A cases, 4 percent for Dukes B, and 7.5 percent for Dukes C ( P = 0.0127). The systemic recurrence rate was 8 percent for Dukes A, 18 percent for Dukes B, and 37 percent for Dukes C ( P = 0.0001). If surgical priority is given to the difficult task of excision of the whole mesorectum, anterior resection with total mesorectal excision in node-positive rectal cancer, local recurrence rates of < 10 percent can be achieved.

Total Mesorectal Excision Results in Low Local Recurrence Rates in Lymph Node-Positive Rectal Cancer

PURPOSE:: Most series report lymph node involvement as the main predictor for local recurrence. The principal lymphatic drainage of the rectum is to nodes in the mesorectum and then nodes along the superior rectal and inferior mesenteric arteries. If total mesorectal excision provides adequate block dissection of the lymphatics of the rectum, good local control with low rates of local recurrence should be achieved even in node-positive disease. METHODS:: Prospective data on all rectal cancers have been collected since 1978; 170 patients with Dukes C rectal cancer have undergone anterior resection and total mesorectal excision. We did not perform any internal iliac node dissections. Follow-up data were analyzed for local recurrence and distant recurrence. RESULTS:: The local recurrence rate was 2 percent for Dukes A cases, 4 percent for Dukes B, and 7.5 percent for Dukes C (P= 0.0127). The systemic recurrence rate was 8 percent for Dukes A, 18 percent for Dukes B, and 37 percent for Dukes C (P= 0.0001). CONCLUSIONS:: If surgical priority is given to the difficult task of excision of the whole mesorectum, anterior resection with total mesorectal excision in node-positive rectal cancer, local recurrence rates of < 10 percent can be achieved.

Long-term prognostic significance of extent of rectal cancer response to preoperative radiation and chemotherapy.

To determine whether selected clinicopathologic factors, including the extent of pathologic response to preoperative radiation and chemotherapy (RT +/- chemo), have an impact on long-term recurrence-free survival (RFS) in patients with locally advanced primary rectal cancer after optimal multimodality therapy. Although complete pathologic response to preoperative RT +/- chemo has been detected in up to 30% of rectal cancers, its significance on long-term outcome has not been widely reported. Previous retrospective studies evaluating clinical outcome in patients with complete or near-complete pathologic response documented good prognosis in this population but were limited by median follow-up in the range of 2 to 3 years. Sixty-nine patients with locally advanced (T(3-4) and/or N1) primary rectal cancer were prospectively identified. All were treated at one institution with preoperative RT to the pelvis (at least 4,500 cGy). Forty patients received concurrent preoperative 5-fluorouracil-based chemotherapy and 27 received both pre- and postoperative chemotherapy. Patients underwent resection 4 to 7 weeks after completion of RT. TNM stage, angiolymphatic or perineural invasion, and extent of response to preoperative RT +/- chemo were determined by pathologic evaluation. Adverse pathologic features were defined as the presence of angiolymphatic and/or perineural invasion. RFS at 5 years was determined by the Kaplan-Meier method. With a median follow-up of 69 months, 5-year RFS was 79%. RFS was significantly worse for patients with aggressive pathologic features and positive nodal status identified in the postirradiated surgical specimen. Risk ratios for RFS were 3.68 for the presence of aggressive pathologic features and 4.64 for node-positive rectal cancers. In patients with greater than 95% rectal cancer response to preoperative RT +/- chemo, only one patient has died as a consequence of cancer, another has died of an unrelated cause, and the remainder were free of disease with a minimum follow-up of 47 months. These data suggest that a marked response to preoperative RT +/- chemo may be associated with good long-term outcome but was not predictive of RFS. The presence of poor histopathologic features and positive nodal status are the most important prognostic indicators after neoadjuvant therapy.