Node-positive Colon Cancer Research Articles

Role of Repeated Hepatectomy in the Multimodal Treatment of Hepatic Colorectal Metastases

Multimodal treatment consisting of repeated hepatectomy and adjuvant systemic chemotherapy for liver-confined recurrence of colorectal cancer can yield long-term survival comparable with that associated with primary hepatectomy. Retrospective analysis. A prospective database at a tertiary referral cancer center. Review of 274 consecutive liver resections identified 64 patients who underwent resection of hepatic colorectal metastases without ablation followed by adjuvant irinotecan hydrochloride- or oxaliplatin-based systemic chemotherapy. Median and 5-year overall and disease-free survival after primary and repeated hepatectomy. At median follow-up of 40 months, median and 5-year overall survival after hepatectomy were 60 months and 53%, respectively; median and 5-year disease-free survival were 33 months and 25%, respectively. Multivariate analysis showed that less than 1 year between colectomy and liver resection (P = .001), more than 3 metastases (P = .001), no repeated hepatectomy (P = .01), and lymph node-positive primary colon cancer (P = .02) were independently predictive of worse survival. Of 28 patients (44%) with liver-confined recurrence, 19 (30%) underwent repeated hepatectomy; at median follow-up of 38 months, median and 5-year overall survival after repeated hepatectomy were 48 months and 44%, respectively. No risk factors were identified in multivariate analysis. In patients with recurrence, median and 5-year overall survival measured from primary hepatectomy were 70 months and 73%, respectively, with repeated hepatectomy vs 43 months and 43%, respectively, without repeated hepatectomy (P = .03). Multimodal treatment of recurrent colorectal cancer confined to the liver should begin with consideration of repeated hepatectomy.

Concordance with national guidelines for colorectal cancer care in New South Wales: a population‐based patterns of care study

To investigate predictors of evidence-based surgical care in a population-based sample of patients with newly diagnosed colorectal cancer. Prospective audit of all new patients with colorectal cancer reported to the New South Wales Central Cancer Registry between 1 February 2000 and 31 January 2001. Concordance with seven guidelines from the 1999 Australian evidence-based guidelines for colorectal cancer; predictors of guideline concordance; the mean proportion of relevant guidelines followed for individual patients. Questionnaires were received for 3095 patients (91.6%). Between 0 and 100% of relevant guidelines were followed for individual patients (median, 67%). Concordance with individual guidelines varied considerably. Patient age independently predicted non-concordance with guidelines for adjuvant therapy and preoperative radiotherapy. Adjuvant chemotherapy was more likely if a patient with node-positive colon cancer was treated in a metropolitan hospital or by a general surgeon. Surgeons with a high caseload or specialty in colorectal cancer were more likely to perform colonic pouch reconstruction, prescribe thromboembolism or antibiotic prophylaxis, and were less likely to refer patients with high-risk rectal cancer for adjuvant radiotherapy. Bowel preparation was less likely among older patients and in high-caseload hospitals. Effective strategies to fully implement national colorectal cancer guidelines are needed. In particular, increasing the use of appropriate adjuvant therapy should be a priority, especially among older people.

The role of the surgeon in whether patients with lymph node‐positive colon cancer see a medical oncologist

Chemotherapy improves survival for patients with stage III colon cancer, but some older patients with lymph node-positive colon cancer do not see a medical oncologist and, thus, do not receive adjuvant chemotherapy. To evaluate the role of the surgeon in determining referrals to medical oncology among patients with stage III colon cancer, the authors conducted a retrospective cohort study of 6158 patients aged >or=66 years who were diagnosed with stage III colon cancer from 1992 through 1999 by using the Surveillance, Epidemiology, and End Results-Medicare linked database. Multilevel analysis was used to simultaneously model variations in patients' seeing a medical oncologist at the patient and surgeon levels. Twenty-one percent of the total variance in seeing a medical oncologist was attributable to the surgeon after adjusting for available patient, tumor, and surgeon characteristics. The individual surgeon characteristics that significantly predicted whether the patient saw a medical oncologist were year since graduation (<or=10 years vs >20 years; hazard ratio [HR], 1.60; 95% confidence interval [95% CI], 1.19-2.16), practicing in a teaching hospital (yes vs. no: HR; 1.30; 95% CI, 1.07-1.58), and volume of patients with colon cancer (<30 patients vs >or=121 patients; HR, 0.66; 95% CI, 0.46-0.94). Surgeon sex, race, board certification, and type of practice were not independent predictors of medical oncology referral. Surgeons accounted for approximately 20% of the variation in patients seeing a medical oncologist. Interventions at the level of the surgeon may be appropriate to improve the care of patients with colon cancer.

Does shorter duration of chemotherapy worsen survival for elderly patients with colon cancer?

BACKGROUND: Fluorouracil (FU)-based chemotherapy has been the standard of care for the adjuvant treatment of node-positive colon cancer for over 10 years. Randomized clinical trials have demonstrated improved survival in patients who receive 6 months of FU-based chemotherapy relative to those who do not. Little is known, however, about the prevalence of early termination of treatment, and possible predictors of, or the survival associated with, the duration of chemotherapy in the community.

Timing of adjuvant chemotherapy initiation after surgery for stage III colon cancer

An important advance in medical oncology has been the use of adjuvant chemotherapy for lymph node-positive colon cancer. However, to the authors' knowledge, the effect of the interval between surgery and the initiation of chemotherapy on survival has not been investigated. The authors analyzed predictors and outcomes of time intervals to treatment after surgery among patients older than 65 years who were diagnosed with stage III colon cancer between 1992 and 1999 using Surveillance, Epidemiology, and End Results (SEER)-Medicare data. Linear and logistic regression analyses were used to model predictors of delay, and Cox proportional hazards models were used to analyze the impact of treatment timing on survival. Among 4382 patients with colon cancer, 1122 patients (26%) began adjuvant chemotherapy within 1 month, 2391 patients (55%) began adjuvant chemotherapy in 1 to 2 months, 454 patients (10%) began adjuvant chemotherapy in 2 to 3 months, and 415 patients (9%) began adjuvant chemotherapy >/=3 months after surgery. Intervals of >/=3 months (delay) were associated with older age, increased comorbid conditions, well/moderately differentiated grade, and being unmarried. Colon cancer-specific mortality was associated with a delay in the initiation of chemotherapy (hazards ratio [HR], 1.48; 95% confidence interval [95% CI], 1.15-1.92), advanced age, increased comorbidity, poorly differentiated tumor grade, the presence of >/=4 positive lymph nodes, and undergoing surgery in a nonteaching hospital. All-cause mortality was associated with intervals >2 months between surgery and chemotherapy (2 to 3 months: HR, 1.41; 95% CI, 1.15-1.74; >/=3 months: HR, 1.62; 95% CI, 1.31-1.99) compared with <1 month. In the older population that was studied, only 9% of patients initiated adjuvant chemotherapy >3 months after the date of curative surgery. However, delay in initiation was associated with both cancer-specific and all-cause mortality. Determining whether these results were because of chemotherapy timing or other associated factors will require further study.

Number of Lymph Node Metastases Is Better Predictor of Prognosis Than Level of Lymph Node Metastasis in Patients with Node-Positive Colon Cancer

Lymph node metastasis is the most important prognostic factor for colon cancer patients. Survival is also related to the number and level of positive lymph nodes (PLNs). Definitions of degree of PLNs for colon cancer differ greatly between the number and level of PLNs. The aim of this study is to compare number and level of PLNs to see which is a better predictor of prognosis for node-positive colon cancer. One hundred eighteen patients underwent histologically curative resection for node-positive colon cancer. We calculated the cumulative 5-year survival rates and examined prognostic factors for multivariate analysis based on the number and level of PLNs and additional factors. The number of PLNs was classified as either one to three PLNs or more than four PLNs, and level of PLNs was classified as either Level I (pericolic lymph node metastasis) or Level II (lymph node metastasis along the major named vessel supplying the tumor, and that around the origin of a main artery). Cumulative 5-year survival rates were statistically different between the 1 to 3 PLNs group and the more than 4 PLNs group, but not significantly different between Level I group and Level II group. Multivariate analysis showed that number, not level, of PLNs was an independent prognostic factor. In node-positive colon cancer, number of PLNs predicted prognosis better than level of PLNs.

Adjuvant Chemotherapy in Elderly Patients (≥75 yr) Completely Resected for Colon Cancer Stage III Compared to Younger Patients: Toxicity and Prognosis

To compare benefits and risks to adjuvant chemotherapy following complete resection of node-positive colon cancer stage III for patients aged >or=75 yr and younger. A retrospective study compared recurrence-free and overall survival, toxicity, and dose intensity of adjuvant bolus 5-FU according to the Mayo regimen chemotherapy in consecutive patients aged 19-74 (n=203) and >or=75 yr (n=24). The estimated 5-yr proportional survival rates were 0.65 for patients age less than 75 yr compared to 0.65 (p=0.96) for elderly. The frequencies of anemia (0%), thrombocytopenia (0%), leukopenia (4%), infection (8%), vomiting (0%), mucositis (17%), diarrhea (13%) CTC grade 3 or 4 toxicity in elderly patients were not significantly different from that in younger patients (p > 0.05). Significantly more elderly (8%) had a decline in performance status to grade 3 or 4, as compared to younger patients (4%) (p=0.002). 5-FU dose reduction was necessary for significantly more elderly (51%) as compared to younger patients (28%) (p=0.02), and fewer elderly (54%) completed the scheduled six treatment courses as compared to younger patients (82%) (p=0.05). Adjuvant 5-FU chemotherapy should be considered for elderly patients aged >or=75 yr in good performance at high risk of recurrence of colon carcinoma after resection.

Increase of Survival Benefit in Advanced Resectable Colon Cancer by Extent of Adjuvant Treatment

The benefit of adjuvant therapy in curatively resected lymph node-positive colon cancer was established using 5-fluorouracil (5-FU) and levamisole (LEV) for 12 months. 5-FU cytotoxicity can be modulated by folinic acid (FA) or interferon-alpha (INF-alpha). The aim of this study was to investigate the efficacy of modulating 5-FU+ LEV by either FA or IFN-alpha in the adjuvant treatment of high-risk colon cancer. Patients with curatively resected colon cancer (stages UICC IIb and III) were stratified according to T, N, and participating center and randomized to receive a 12-month treatment using 5-FU + LEV alone or in combination with FA or IFN-alpha. A total of 855 of 904 entered patients (94.6%) were eligible. The median follow-up of all eligible patients was 4.6 years. Addition of FA to 5-FU + LEV improved recurrence-free and overall survival in comparison with 5-FU + LEV alone (P = 0.007 and P = 0.004, respectively, 1-sided). The 5-year overall survival rates were 60.5% (95% confidence interval, 54.3-66.7) and 72.0% (95% confidence interval, 66.5-77.5) for 5-FU + LEV and 5-FU + LEV + FA, respectively. Addition of INF-alpha showed a tendency to improve recurrence-free survival, however, without altering overall survival. Toxicities (WHO III + IV) were generally tolerable except one toxic death in the control arm and were observed in 9.9% of the patients receiving 5-FU + LEV alone and in 13.3% and in 30.7% of patients receiving additional FA and IFN-alpha, respectively. Addition of IFN-alpha was associated with increased toxicity without markedly influencing the outcome and should therefore not be recommended for adjuvant treatment. Addition of FA increased the 5-year recurrence-free and overall survival rate by 9.3 and 11.5 percentage points, respectively. 5-FU + LEV + FA for 12 months may be an effective adjuvant treatment option for locally advanced high-risk colon cancer.

Optimizing adjuvant therapy for colon cancer: Ongoing investigations

In 2004, oxaliplatin plus 5-fluorouracil (5FU) and leucovorin (LV) supplanted 5FU/LV as the standard of care for adjuvant therapy of node-positive colon cancer. Data from recently presented phase III clinical trials fail to show a similar benefit for adjuvant irinotecan-5FU/LV over 5FU/LV alone. Current investigations focus on further refining the optimal combination chemotherapy regimen, and incorporating biologic agents into adjuvant therapy of stage II and III colon cancer. In the future, stage-independent prognosticators and markers predictive of chemotherapy response and toxicity may allow for patient-specific selection of more effective and less toxic adjuvant therapy.

Sentinel node staging of resectable colon cancer: Results of CALGB 80001

3506 The most important outcome predictor for resectable colon cancer (RCC) is the status of locoregional lymph nodes. This information is critical, as patients with positive nodes may benefit from post-operative adjuvant therapy. A subset of patients with node-negative RCC experiences a poor outcome, suggesting that improved staging would benefit this population by identifying patients who should receive additional treatment. CALGB 80001, a study conducted by 25 surgery-pathology teams at 12 institutions, was designed to determine whether sentinel lymph node sampling (SLNS) could identify a subset of lymph nodes that predict the status of the nodal basin for RCC, and therefore could be extensively evaluated for the presence of metastases. SLNS was performed on 79 of 91 patients enrolled, followed by multilevel sectioning (MLS) of the nodes, and examination by H&E as well as IHC to identify cells positive for cytokeratin (CK) and carcinoembryonic antigen (CEA). Sentinel nodes (SN) were successfully located in 66 of 72 colon cancer cases (92%), with an average of 2.0 sentinel nodes per patient. SNs were negative in 14 of 25 node-positive cases (56%). MLS revealed tumor in a SN in one of these cases, bringing the sensitivity of SN examination by H&E and MLS to 48%. Results of further sentinel node studies are as follows: The addition of IHC for CK and CEA doubled the total number of node positive colon cancer cases from 25 to 50 of 62 (40 to 81%). Conclusion: These results show that SN examined by H&E and MLS failed to predict nodal status in 52% of cases. Analysis of SNs from colon cancer is unlikely to predict the nodal status of the patient, and studies to examine micrometastatic disease should involve all draining nodes removed. No significant financial relationships to disclose.

Sentinel node staging of resectable colon cancer: Results of CALGB 80001

3506 The most important outcome predictor for resectable colon cancer (RCC) is the status of locoregional lymph nodes. This information is critical, as patients with positive nodes may benefit from post-operative adjuvant therapy. A subset of patients with node-negative RCC experiences a poor outcome, suggesting that improved staging would benefit this population by identifying patients who should receive additional treatment. CALGB 80001, a study conducted by 25 surgery-pathology teams at 12 institutions, was designed to determine whether sentinel lymph node sampling (SLNS) could identify a subset of lymph nodes that predict the status of the nodal basin for RCC, and therefore could be extensively evaluated for the presence of metastases. SLNS was performed on 79 of 91 patients enrolled, followed by multilevel sectioning (MLS) of the nodes, and examination by H&E as well as IHC to identify cells positive for cytokeratin (CK) and carcinoembryonic antigen (CEA). Sentinel nodes (SN) were successfully located in 66 of 72 colon cancer cases (92%), with an average of 2.0 sentinel nodes per patient. SNs were negative in 14 of 25 node-positive cases (56%). MLS revealed tumor in a SN in one of these cases, bringing the sensitivity of SN examination by H&E and MLS to 48%. Results of further sentinel node studies are as follows: The addition of IHC for CK and CEA doubled the total number of node positive colon cancer cases from 25 to 50 of 62 (40 to 81%). Conclusion: These results show that SN examined by H&E and MLS failed to predict nodal status in 52% of cases. Analysis of SNs from colon cancer is unlikely to predict the nodal status of the patient, and studies to examine micrometastatic disease should involve all draining nodes removed. No significant financial relationships to disclose.

Adverse histopathological findings as a guide to patient management after curative resection of node-positive colonic cancer.

The aim of this study was to identify patient and tumour characteristics that might assist in developing an improved approach to patient selection for chemotherapy after resection of clinicopathological stage C colonic cancer. Clinical, pathological and follow-up data have been collected prospectively for all patients undergoing resection for colorectal cancer at Concord Hospital since 1971. From an initial 2980 patients, after exclusions 378 remained who had a potentially curative operation for colonic cancer with nodal metastases and did not receive adjuvant chemotherapy. Associations between several pathological features and survival were examined by proportional hazards regression. In a multivariate model, both overall and colonic cancer-specific survival rates were negatively associated with serosal surface involvement, apical node metastasis, high histological grade and venous invasion. The survival of patients with stage C disease who had none of these adverse features was not significantly different from that of patients with stage B lesions. However, survival diminished significantly when one or more of the adverse features were present. Patients with a stage C tumour but with none of the identified adverse features experience relatively good survival and are unlikely to benefit from adjuvant chemotherapy. In this series such patients accounted for 40.5 per cent of patients with stage C disease.

The role of chemotherapy in the management of resectable colorectal cancer

Adjuvant chemotherapy has been established as the standard of care for patients with node-positive resected colon cancer. 5-fluorouracil modulated with leucovorin given for six months is currently the most widely accepted "standard" regimen. The role of adjuvant chemotherapy in stage II remain investigational and some prognostic indicators that correlate with higher risk for subsequent recurrence may be used for these patients when consider adjuvant chemotherapy. Other investigational approaches include regional portal vein infusion and intraperitoneal therapy, immunotherapy, and new drugs, with proven activity in metastatic disease. Patients older than 70 years are also candidate for adjuvant therapy of colorectal cancer. Adjuvant chemotherapy of rectal cancer is often associated with radiotherapy and enhances local control seen with radiotherapy and improves survival of these patients.

Adjuvant therapy in lymph node–positive colon cancer: Current standards and future perspectives

Abstract The significant survival benefit for adjuvant chemotherapy after a curative resection for node-positive colon cancer has been established for over a decade. The first major step in progression, from randomized trials that failed to demonstrate benefit for postoperative single-agent fluorinated pyrimidines, came with intensive immunobiochemical modulation of 5-fluorouracil for a 1-year course. Subsequent trials confirmed equivalent benefit for a shorter course of therapy, and additional improvement in disease-free and overall survival has been sought through employment of alternative modulatory agents or drug administration schedule changes. Newer cytotoxic agents, whose mechanisms of action differ from that of the fluorinated pyrimidines, have been examined in combination with 5-FU, and changes in recommendations for standard of care, based on results of these maturing data sets, are awaited. The impact of tumor molecular profiles on therapeutic prediction and rational design of new agents is expected to inform the design of future generations of clinical trials. Copyright 2002, Elsevier Science (USA). All rights reserved.

Adjuvant therapy for node-negative colon cancer

Abstract While randomized trials have proven the benefits of adjuvant therapy in node-positive colon cancer, the role of chemotherapy after curative resection of node-negative colon cancer is still debated. Individually, these trials have failed to conclusively demonstrate that 5-fluorouracil (5FU)-based chemotherapy significantly improves on the 80% 5-year survival of patients with stage II colon cancer. The debate has been further fueled by the publication of 2 conflicting meta-analyses: IMPACT B2 and the NSABP series. Based on their analysis of 5 adjuvant trials, the IMPACT investigators conclude that adjuvant therapy in stage II colon cancer is not routinely justified, whereas the pooled analysis of 4 trials by the NSABP recommends adjuvant therapy in this setting, citing similar proportional reductions in mortality for both stage II and stage III disease. Considered in total, current evidence does not support adjuvant therapy for all patients with stage II disease. However, the careful evaluation of node-negative patients for high-risk prognostic features may identify a cohort of patients for whom adjuvant therapy warrants consideration. Whenever available, patients with stage II colon cancer should continue to be encouraged to participate in clinical trials of adjuvant therapy. Copyright 2002, Elsevier Science (USA). All rights reserved.

A new TNM staging strategy for node-positive (stage III) colon cancer: an analysis of 50,042 patients.

To analyze a large cohort of patients with stage III colon cancer to determine whether subgroup stratification better defines outcome. The Tumor (T), Node (N), Metastasis (M) system is based on depth of tumor invasion into the colonic wall, the number of regional lymph nodes involved, and distant metastasis. Traditionally, colon cancer has been designated as stage III based on nodal involvement regardless of the depth (T1-4) of tumor penetration. Treatment decisions have been based on nodal involvement with less emphasis on colonic wall penetration in stage III patients. Patients (n = 50,042) with stage III colon cancer reported to the National Cancer Data Base from 1987 through 1993 were analyzed. Observed survival was calculated by actuarial life table methods for three new node-positive subgroups (IIIA: T1/2, N1; IIIB: T3/4, N1; IIIC: any T, N2). The Cox proportional hazards model was used to test the prognostic strength of selected covariates. Three distinct subcategories within a traditional stage III cohort of colonic cancer were identified. Five-year observed survival rates for these three subcategories were 59.8%, IIIA; 42.0%, IIIB; and 27.3%, IIIC. Differences between subgroups were significant ( <.0001). Similar differences were calculated after stratification for treatment. A multivariate proportional hazards model identified the new stage III subgroups, modality of the first course of therapy, patient age, and tumor grade as significant independent prognostic covariates. The current stage III designation of colon cancer excludes prognostic subgroups stratified for mural penetration (T1-4) or nodal involvement (N1 vs. N2). Analysis of a large data set supports stratification into three subsets, confirming the benefit of adjuvant chemotherapy in each subgroup. This strategy should be used in the reporting and staging of node-positive colon cancers.

Survival Associated with 5-Fluorouracil–Based Adjuvant Chemotherapy among Elderly Patients with Node-Positive Colon Cancer

Randomized clinical trials have demonstrated the efficacy of adjuvant 5-fluorouracil (5-FU)-based chemotherapy after surgical resection of node-positive colon cancer. Although this treatment became the standard in 1990 following a National Institutes of Health Consensus Conference, among those at least 65 years of age it is less likely to be offered to older or nonwhite patients. To determine the association between 5-fu-based chemotherapy and survival in older patients. Retrospective cohort study. Combined database of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program and Medicare. 4768 patients 65 years of age or older who received a diagnosis of node-positive colon cancer from 1992 to 1996, were covered by Medicare Parts A and B, and resided in the population covered by the SEER program. Propensity scores to control for known predictors of receiving treatment, Cox proportional hazards models to assess the association of 5-FU therapy with survival, and sensitivity analyses to estimate the possible effects of unknown confounders. Fifty-two percent of patients received 5-FU therapy. For this sample, the hazard ratio for death associated with 5-FU therapy was 0.66 (95% CI, 0.60 to 0.73). Confounding could have accounted for this association only if an unmeasured confounder were extremely unequally distributed between the treated and untreated groups or increased mortality by at least 50%. 5-Fluorouracil adjuvant therapy is significantly associated with reduced mortality in older patients, similar to the association found in randomized, controlled trials among younger patients. More frequent use of 5-FU therapy in older patients would probably reduce death from colon cancer.

Identifying patients with T3-T4 node-negative colon cancer at high risk of recurrence.

Adjuvant chemotherapy is effective for node-positive colon cancer patients. In node-negative patients, it could be justified in high-risk patients. The purpose of this study was to determine clinical and pathological findings associated with tumor recurrence in T3-T4 node-negative colon cancer patients. From 1974 to 1993, 108 patients undergoing colectomy for T3-4N0M0 colon cancer, without adjuvant chemotherapy, followed until death or for a minimum of five years, were divided into two groups: patients without recurrence (n = 74) and those dead from colon cancer or alive with recurrence (n = 34). Thirty-three clinical and pathological findings were studied. In univariate analysis, the following were significantly associated with a high risk of tumor recurrence: male patients (P = 0.006), bowel obstruction (P < 0.001), weight loss >5 Kg (P = 0.03), circumferential tumor (P = 0.02), macroscopic or microscopic pericolic organ invasion (T4 stage; P < 0.001), perineural invasion (P = 0.02), vascular invasion (P = 0.045), poor tumor differentiation (P = 0.005), mesocolic invasion >1 cm (P = 0.009), less than 14 uninvolved nodes on the specimen (P = 0.03), and visceral peritoneal invasion (T4; P < 0.001). In multivariate analysis, the following were independent prognostic factors of recurrence: male patients (P = 0.005), bowel obstruction (P = 0.002), pericolic organ invasion (i.e., T4 tumor; P = 0.02), and less than 14 uninvolved nodes on a specimen (P = 0.01). On the other hand, preoperative carcinoembryonic antigen serum level, size and tumor location, blood transfusion, and mucin production were not associated with higher risk of tumor recurrence. Our study identifies a subgroup of patients with node-negative colon cancer at high risk of recurrence, who could be included in priority trials of adjuvant chemotherapy.

Vascular endothelial growth factor expression, S-phase fraction and thymidylate synthase quantitation in node-positive colon cancer: Relationships with tumor recurrence and resistance to adjuvant chemotherapy

The behaviour of colorectal carcinomas may depend on molecular properties of tumors. In node-positive colon cancer, we assessed the S-phase fraction (SPF) index, the vascular endothelial growth factor (VEGF) expression and the TS levels. The combined analysis of SPF/VEGF was studied for predictivity of recurrent disease, the TS quantitation was related to the efficacy of fluorouracil-based adjuvant chemotherapy. Consecutive patients with surgically-resected, node-positive colon cancer were studied. Flow cytometry for the SPF and immunohistochemistries for the TS and the VEGF expression were carried out on the primary tumor. Recurrences had to be proven by biopsy or surgery, and they were categorized as early, if occurred within 12 months after surgery, or late if occured 13 months or more. Of 150 evaluable patients, 100 had received fluorouracil-based adjuvant chemotherapy and 50 control patients were untreated. The combined analysis of the VEGF and the SPF showed a strong association between the two markers; 48 patients (32%) had high SPF/VEGF positive tumors and 69 patients (46%) had low SPF/VEGF negative tumors (P < 0.0001). The majority of disease-free patients (73.4%) showed VEGF negative/low SPF tumors (P < 0.0001). Early recurrences occurred more frequently in patients with VEGF positive/high SPF tumors (P < 0.001). In the 100 patients treated with adjuvant chemotherapy, 86% of relapsed patients had TS overexpressing tumors and 69% of disease-free patients had TS negative tumors (P < 0.001). Also, early recurrences occurred more frequently in TS overexpressing tumors (P < 0.0001). Evidence is supported that node-positive colon cancer constitutes a heterogenous disease. Patients with VEGF positive/high SPF tumors showed an unfavourable outcome compared to patients with VEGF negative/low SPF tumors. The efficacy of fluorouracil-based adjuvant chemotherapy may depend on the TS status.

Colorectal cancer: evolving concepts in diagnosis, treatment, and prevention

Colorectal cancer: evolving concepts in diagnosis, treatment, and prevention