Neoadjuvant Chemotherapy in Patients with Stage IV Colorectal Cancer: A Comparison of Histological Response in Liver Metastases, Primary Tumors, and Regional Lymph Nodes

Background  

We report the histopathological results of a novel “inversed” strategy designed to manage patients with colorectal cancer (CRC) who have synchronous liver metastases by using chemotherapy first, liver surgery second, and resection of the primary tumor as a final step. This study was designed to compare the response to chemotherapy in liver metastases, primary tumors, and locoregional lymph nodes.     

Prognostic Impact of Positive Surgical Margins After Resection of Colorectal Cancer Liver Metastases: Reappraisal in the Era of Modern Chemotherapy

Background

The purpose of the present study was to assess the prognostic impact of positive surgical margins (R1) after liver resection (LR) of colorectal liver metastases (CRLM) in the era of modern chemotherapy regimens. R1 resection is a negative prognostic factor after LR of CRLM. The significance of R1 margins in the era of effective chemotherapy is unknown.

Methods

From January 2000 to December 2009, 215 patients (177 men: 62 %; median age 60 years; range 30–84 years) underwent LR of CRLM. The LR was considered R1 (margin <1 mm) in 49 patients (23 %) and R0 in 166 patients (77 %). Overall, 108 (50 %) patients received preoperative chemotherapy and 156 (72 %) patients received postoperative chemotherapy.

Results

With a median follow-up of 36 months (range 1–141 months), the 5-year overall survival (OS) rate (47 vs 40 %; p = 0.05) and the disease-free survival (DFS) rate (36 vs 23 %; p = 0.006) were significantly lower in the R1 group. Recurrence developed in 152 patients (71 %) and the rate of recurrence was significantly higher (84 vs 67 %; p = 0.02) in the R1 group. On multivariate analysis, N+ status of the colorectal primary tumor (p = 0.008), presence of radiologically occult disease (p = 0.04), and R1 resection (p = 0.03) were independent adverse predictors of OS. The N+ status of the primary tumor (p = 0.003) and R1 resection (p = 0.02) were independent adverse predictors of DFS. On multivariate analysis use of postoperative chemotherapy was the only independent predictor of improved DFS (p = 0.02) in the R1 group.

Conclusions

A positive resection margin remains a significant poor prognostic factor after LR of CRLM in the era of modern chemotherapy. Postoperative chemotherapy reduces recurrence rates after R1 resection of CRLM.     

Impact of Palliative Chemotherapy and Surgery on Management of Stage IV Incurable Colorectal Cancer

Background  

Recent trials proposed chemotherapy (CHT) as the treatment of choice for patients affected by incurable colorectal cancer (ICRC). Nevertheless, surgery is still commonly offered to these patients. On the other hand, CHT is offered to ICRC patients regardless of the pattern of spread of the disease, local or distant, despite some evidence suggesting that metastatic pattern may influence the response to treatment.     

A Meta-Analysis to Determine the Effect of Primary Tumor Resection for Stage IV Colorectal Cancer with Unresectable Metastases on Patient Survival

Background

Approximately 20 % of patients diagnosed with colorectal cancer will have distant metastases at first presentation (stage IV disease). The effect of removing the primary tumor on survival for patients with stage IV disease with unresectable metastases remains unclear. To address this a meta-analysis of all studies comparing primary tumor resection with chemotherapy alone in cases of stage IV colorectal cancer with unresectable metastases was performed.

Methods

A comprehensive search for published studies examining the effect of primary tumor resection in the setting of colorectal cancer with unresectable metastases was performed. Each study was reviewed and data extracted. Random-effects methods were used to combine data.

Results

There were 21 studies including a total of 44,226 patients that met the inclusion criteria. Resection of the primary tumor in patients with unresectable metastases compared with chemotherapy alone was associated with a lower mortality risk (OR 0.28; 95 % CI 0.165–0.474; P < 0.001), translating into a difference in mean survival of 6.4 months in favor of resection (95 % CI 5.025–7.858, P < 0.001). Patients who underwent resection of the primary tumor were more likely to have liver metastasis only (OR 1.551; 95 % CI 1.247–1.929; P < 0.001), were less likely to have ≥2 metastasis (OR 0.653; 95 % CI 0.508–0.839; P = 0.001), and were less likely to have rectal cancer (OR 0.495; 95 % CI 0.390–0.629; P < 0.001). There was significant cross-study heterogeneity.

Conclusions

Resection of the primary tumor may confer a survival advantage in stage IV colorectal cancer with unresectable metastases but significant selection bias exists in current studies. Randomized controlled trials are essential to validate these findings.     

结直肠癌肝转移的术前化疗

结直肠癌是最常见的恶性肿瘤之一,结直肠癌的肝脏转移是造成结直肠癌患者死亡的最主要原因之一。超过50%的结直肠癌患者会发生肝脏转移,其治疗的疗效直接影响着结直肠癌患者的预后。对于结直肠癌肝转移的患者行最佳支持治疗,患者的中位生存时间大约为6个月;行甲酰四氢叶酸钙(CF)+5-FU化疗,患者的中位生存时间为8～12个月;应用奥沙利铂或伊立替康的联合化疗(FOLFOX或FOLFIRI),其中位生存时间可延长至20～24个月。     

Microsatellite Instability as a Prognostic Factor in Resected Colorectal Cancer Liver Metastases

Background: Two distinct genetic mutational pathways characterized by either chromosomal instability or high-frequency microsatellite instability (MSI-H) are currently recognized in the pathogenesis of colorectal cancer (CRC). Recently, it has been shown that patients with primary CRC that displays MSI-H have a significant, stage-independent, multivariate survival advantage. Untreated CRC hepatic metastases are incurable and are associated with a median survival of 4 to 12 months. Conversely, surgical resection in selected patients results in a 20% to 50% cure rate. The aim of this study was to investigate the prognostic importance of MSI-H in patients undergoing resection of hepatic CRC metastases.Methods: DNA was extracted from paraffin-embedded, resected metastatic CRC liver lesions and corresponding normal liver parenchyma from 190 patients. MSI-H status was determined by polymerase chain reaction–based evaluation of the noncoding mononucleotide repeats BAT-25 and BAT-26.Results: MSI was detected in tumors from 5 (2.7%) of the 190 CRC patients. All MSI-H tumors were in patients with node-positive CRC primary tumors. The median survival after hepatic resection of MSI-H and non–MSI-H tumors was 67 and 61 months, respectively (P = .9).Conclusions: These data suggest that MSI-H is not a common feature in resected CRC liver metastases and do not suggest a role for MSI in stratifying good versus poor prognosis in these patients.the Annual Meeting of the Society of Surgical Oncology, Los Angeles, California, March 5–9, 2003.     

Surgical Resection of Stage IV Colorectal Cancer and Prognosis

BACKGROUND: Colorectal cancer (CRC) harbors accumulated genetic alterations with cancer progression, which results in uncontrollable disease. To regulate the most malignant CRC, we have to know the most dismal phenotype of stage IV disease. METHODS: A retrospective review of the Kitasato University Hospital was performed (from 1990 to 2001) to extract the 162 resected stage IV CRC. Clinical variables were tested for their relationship to survival in a multivariate prognostic analysis and revealed the interaction of the prognostic factors. RESULTS: In stage IV CRC with noncurable resection, the most robust univariate predictors for poor prognosis were preoperative high value of CA19-9, peritoneal dissemination, depth of invasion, age, extent of liver metastases, pathologic lymph node metastasis status, and gender as tumor factors, and postoperative therapy, perioperative transfusion, and lymph node dissection extent as treatment factors. Among these factors, postoperative therapy (p < 0.0001), perioperative transfusion (0.0002), CA19-9 (0.001), extent of liver metastases (0.004), and peritoneal dissemination (0.02) were identified as independent prognostic factors by multivariate analysis. Interestingly, among the independent prognostic factors, treatment factors did not depend upon tumor factors and the combination of the three tumor factors (CA19-9, extent of liver metastases, and peritoneal dissemination) can clearly classify the patients into the definite prognostic groups. CONCLUSION: Our results suggested that the most dismal CRC harbors three definite vectors that may represent the strongest phenotype of putative systemic immune (CA19-9), distant metastasis (extent of liver metastases), and local progression (peritoneal dissemination).     

Comparison of Prognostic Scores for Patients with Colorectal Cancer Peritoneal Metastases Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

Background

There are three prognostic scores for the cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) treatment of colorectal cancer peritoneal metastases: the newly introduced COREP (colorectal peritoneal) score, the peritoneal surface disease severity score (PSDS), and the prognostic score (PS). The aim was to determine which prognostic score had the best prognostic value.

Methods

Between 2006 and 2010, a total of 77 patients with peritoneal metastases from colorectal cancer underwent CRS/HIPEC treatment. The COREP, PSDS, and PS scores were successfully applied to 56 patients (73 %) having sufficient data. The end points were prediction of open-and-close cases (n = 9), R1 resections (n = 41), and survival of <12 months (n = 18). Area under the receiver operating characteristic curves (accuracy) was compared. Subgroup analysis was performed on patients not previously used for the development of the COREP score (n = 24). Multivariable logistic regressions of the three end points were performed as well as Cox regression for overall survival. Furthermore, COREP and peritoneal cancer index were compared.

Results

For open-and-close case prediction, accuracy for the whole group (n = 56) and subgroup (n = 24) was 87 and 88 %, respectively for COREP; 66 and 77 % for PSDS; and 68 and 78 % for PS. For R1 resection prediction, accuracy was 81 and 81 %, 76 and 78 %, and 75 and 77 %, respectively. For prediction of survival of <12 months, accuracy was 83 and 84, 54 and 67 %, and 55 and 56 %, respectively. The COREP score was the only independent prognostic factor in all four multivariable analyses. A COREP score of ≥6 identified patients with poor survival more accurately than a PCI of >20.

Conclusions

The COREP score predicted open-and-close cases, R1 resections, and poor survival better than PSDS and PS. COREP better identifies patients with poor survival than intraoperative PCI.     

Meta-Analysis of Survival of Patients with Stage IV Colorectal Cancer Managed with Surgical Resection Versus Chemotherapy Alone

Background  

There is no consensus regarding the appropriate management of asymptomatic and minimally symptomatic patients with stage IV colorectal cancer and irresectable metastases.     

Outcome and Natural History of Patients with Stage IV Colorectal Cancer Receiving Chemotherapy Without Primary Tumor Resection

Background  

There is a trend toward nonsurgical management of patients with nonobstructing metastatic (stage IV) colorectal cancer (CRC), although some will eventually undergo surgery. We examined patients with metastatic CRC who were managed with an intact primary tumor.     

Prognostic Significance of Preoperative Bowel Obstruction in Stage III Colorectal Cancer

Background  

Previous studies have suggested a detrimental prognostic effect of preoperative obstruction proximal to colorectal cancer (CRC). If such a detrimental effect is preserved in each stage of advanced (stage II or III) CRC, we can identify high-risk patients.