Recurrence After Partial Hepatectomy for Metastatic Colorectal Cancer: Potentially Curative Role of Salvage Repeat Resection

Annals of Surgical Oncology - Patients with recurrence after complete resection of colorectal liver metastases (CLM) are considered for repeat resection as a potential salvage therapy (PST)....     

Repeat Hepatectomy for Metastatic Colorectal Cancer Is Safe but Marginally Effective

Background

Although hepatectomy for metastatic colorectal cancer (mCRC) offers prolonged survival in up to 40% of people, recurrence rates are high, approaching 70%. Many patients experience recurrent disease in the liver after initial hepatectomy. We examined our experience with repeat hepatectomy for mCRC.

Methods

After Institutional Review Board approval, we reviewed the records of all patients at a single institution who underwent hepatectomy for mCRC. Repeat hepatectomy was defined as partial liver resection any time after the initial hepatectomy for recurrent mCRC. We estimated time to recurrence and survival by using the Kaplan?CMeier method and compared outcomes between groups by using the log-rank test.

Results

From 1998 to 2008, 405 patients underwent hepatectomy for mCRC, and 215 (53%) experienced disease recurrence at a median of 13?months. Of 150 patients with liver-only or liver-predominant recurrence, 52 (35%) underwent repeat hepatectomy. The median time to recurrence after repeat hepatectomy was 10?months, and median overall survival was 19?months. There was one (1.9%) perioperative death, and there were 14 (27%) major complications. The median overall survival in the repeat hepatectomy group from the time of recurrence after initial hepatectomy was 22?months, compared with 15?months in the 98 patients with liver recurrence who were not selected for repeat hepatectomy (P?=?0.02).

Conclusions

Repeat hepatectomy for mCRC is feasible in highly selected patients, with acceptable perioperative morbidity and mortality. Although repeat hepatectomy should be considered, recurrence rates are high. Although the initial hepatectomy for mCRC is potentially curative, recurrence of metastatic disease in the liver is unlikely to be cured.     

Determinants of Survival following Hepatic Resection for Metastatic Colorectal Cancer

p = 0.0001), resected versus nonresected ( p < 0.0001), and tumor-free surgical margins versus positive margins ( p = 0.001). Surprisingly, the disease-free interval and the original stage of the primary tumor did not predict survival ( p = not significant). Other factors that had no influence on survival were type of resection, size and number of liver metastases, ABO blood group, and the number of perioperative blood transfusions. For those patients who underwent resection of unilobar metastases with tumor-free margins, the 5-year survival rate was 29% with a median survival of 35 months and eight survivors > 7 years. In addition, one patient with bilobar disease had survival > 7 years and five patients who had resection of hepatic metastases and extrahepatic cancer simultaneously had survival > 3 years. Our data support the concept that patients with unilobar metastatic disease who undergo surgical resection with tumor-free surgical margins can be afforded a significant opportunity at long-term survival with acceptable morbidity, mortality, and hospital stay. Also, certain patients with bilobar or extrahepatic disease (or both) who undergo complete resection can enjoy a long-term survival. In these subgroups of patients resection should be considered on an individual basis.     

Ninety-Six Five-Year Survivors After Liver Resection for Metastatic Colorectal Cancer

Background: Studies have consistently confirmed the benefit of liver resection for metastatic colorectal cancer. Few reports, however, have a long enough followup or sufficient 5-year survivors to study the clinical course of patients beyond 5 years.

Study Design: From July 1985 through December 1991, 456 patients underwent liver resection for colorectal metastases. Ninety-six actual 5-year survivors (21%) were identified and their clinical course retrospectively reviewed.

Results: Five-year survivors (n = 96) were more likely to have a Duke’s B primary colorectal carcinoma, fewer than four metastatic lesions, unilobar disease, and a negative histologic margin when compared with patients not surviving 5 years (n = 298). Forty-four (46%) of the 96 five-year survivors had a recurrence after hepatectomy. Of these 44, 19 (43%) were rendered disease free after further treatment. Overall, 71 of the 96 five-year survivors were free of disease at last followup. The actuarial 10-year survival of this group was 78%.

Conclusions: Patients that are disease free 5 years after liver resection are likely to have been cured by liver resection. Patients should be aggressively followed for recurrence because of the potential for further treatment and longterm survival.     

Resection Margin with Anatomic or Nonanatomic Hepatectomy for Liver Metastasis from Colorectal Cancer

Background

When hepatectomy is used as a primary treatment for liver metastasis from colorectal cancer (CRCLM), the balance between surgical curability and functional preservation of the remnant liver is of great importance.

Methods

A total of 108 patients who underwent initial hepatectomy for CRCLM were retrospectively analyzed with respect to tumor extent, operative method, and prognosis, including recurrence.

Results

The 1-, 2-, 3-, and 5-year overall survival rates (OS) for all patients were 90.5%, 77.8%, 63.2%, and 51.6%, respectively. Multivariate analysis indicated serum carbohydrate antigen 19-9 (CA 19-9) level after hepatectomy (<36 or ??36?mAU/mL) and presence of recurrence as independent prognostic factors of OS (P?=?0.0458 and 0.0249, respectively), and tumor depth of colorectal cancer (P?=?0.0025 and 0.00138, respectively). Neither resection margin nor type of hepatectomy (anatomic or nonanatomic) for CRCLM was a significant prognostic factor for OS or DFS or CRCLM recurrence, including intrahepatic recurrence.

Conclusions

In CRCLM, we believe that nonanatomic hepatectomy with narrow margin is indicated, and optimal treatment would include functional preservation of as much of the remnant liver as possible.     

Laparoscopic Bowel Resection in the Setting of Metastatic Colorectal Cancer

Background This study aimed to review the outcomes of laparoscopic colorectal resection for patients with stage IV colorectal cancer. Methods From the prospectively collected database for patients who underwent surgery for colorectal cancer in our institution, those with stage IV colorectal cancer who underwent elective resection of tumor during the period from January 2000 to June 2006 were included. The outcomes of those with laparoscopic resection were reviewed and comparison was made between patients with laparoscopic and open resection. Results A total of 200 patients (127 men) with median age of 69 years (range: 25–91 years) were included, and 77 underwent laparoscopic resection. Conversion was required in ten patients (13.0%) and all except one conversion were due to fixed or bulky tumors. There was no operative mortality in the laparoscopic group. The complication rate was 14% and the median postoperative hospital stay was 7 days. When patients with laparoscopic resection were compared with those with open operations, there was no difference in age, gender, comorbidity, or tumor size between the two groups. However, the complication rate was significantly lower in those with laparoscopic resection (14% versus 32%, P = 0.007) and the median hospital stay was significantly shorter (7 days versus 8 days, P = 0.005).The operative mortalities and the survivals were similar in the two groups. Conclusions Colorectal resection can be performed safely in patients with stage IV colorectal cancer. The operative outcomes in terms of complication rate and hospital stay compare favorably with patients with open resection. Presented in the Scientific Meeting of the Society of American Gastrointestinal and Endoscopic Surgeons on 18–22 April 2007 in Las Vegas, Nevada, USA.     

Liver Resection for Metastatic Colorectal Cancer in the Presence of Extrahepatic Disease

Background  Hepatic resection for metastatic colorectal cancer (CRC) with concomitant extrahepatic disease (EHD) is controversial. Earlier reports of the results of liver resection for metastatic CRC identified patients with EHD as a group with poor outcomes, suggesting that the presence of EHD was an absolute contraindication to resection. This has recently been challenged in several reports due to advances in systemic chemotherapy, surgical technique, and patient selection. Methods  This review was restricted to published data in the English language identified by searches of MEDLINE and Pubmed databases as well as reference lists of recent review articles on subjects of surgery for metastatic colorectal cancer. Results  Five-year survival after resection is worse than patients with liver-only disease but approximates the survival rates seen in patients with resected liver-only metastases in the era prior to the use of modern chemotherapy. Recurrence occurs in the great majority of patients. Conclusions  At this time, there appears to be a role for surgery in highly selected patients with a single site of EHD amenable to complete resection. Unlike patients with liver-only disease, however, the goals of surgery must not be viewed as potentially curative.     

Up-front Hepatic Resection for Metastatic Colorectal Cancer Results in Favorable Long-term Survival

Background

Hepatic metastasis from colorectal cancer (CRC) is best managed with a multimodal approach; however, the optimal timing of liver resection in relation to administration of perioperative chemotherapy remains unclear. Our strategy has been to offer up-front liver resection for patients with resectable hepatic metastases, followed by post–liver resection chemotherapy. We report the outcomes of patients based on this surgical approach.

Methods

A retrospective review of all patients undergoing liver resection for CRC metastases over a 5-year period (2002–2007) was performed. Associations between clinicopathologic factors and survival were evaluated by the Cox proportional hazard method.

Results

A total of 320 patients underwent 336 liver resections. Median follow-up was 40 (range 8–80) months. The majority (n = 195, 60.9 %) had metachronous disease, and most patients (n = 286, 85 %) had a major hepatectomy (>3 segments). Thirty-six patients (11 %) received preoperative chemotherapy, predominantly for downstaging unresectable disease. Ninety-day mortality was 2.1 %, and perioperative morbidity occurred in 68 patients (20.2 %). Actual disease-free survival at 3 and 5 years was 46.2 % and 42 %, respectively. Actual overall survival (OS) at 3 and 5 years was 63.7 % and 55 %, respectively. Multivariate analysis identified four factors that were independently associated with differences in OS (hazard ratio; 95 % confidence interval): size of metastasis >6 cm (2.2; 1.3–3.5), positive lymph node status of the primary CRC (N1 (2.0; 1.0–3.8), N2 (2.4; 1.2–4.9)), synchronous disease (2.1; 1.3–3.5), and treatment with chemotherapy after liver resection (0.42; 0.23–0.75).

Conclusions

Up-front surgery for patients with resectable CRC liver metastases, followed by chemotherapy, can lead to favorable OS.     

Aggressive Multimodal Treatment and Metastatic Colorectal Cancer Survival

1. Download : Download high-res image (265KB)
2. Download : Download full-size image

     

Analysis of Prognostic Factors Influencing Long-term Survival After Hepatic Resection for Metastatic Colorectal Cancer

Background The aim of this study was to analyze the prognostic factors associated with long-term outcome after liver resection for colorectal metastases. The retrospective analysis included 297 liver resections for colorectal metastases. Methods The variables considered included disease stage, differentiation grade, site and nodal metastasis of the primary tumor, number and diameter of the lesions, time from primary cancer to metastasis, preoperative carcinoembryonic antigen (CEA) level, adjuvant chemotherapy, type of resection, intraoperative ultrasonography and portal clamping use, blood loss, transfusions, complications, hospitalization, surgical margins status, and a clinical risk score (MSKCC-CRS). Results The univariate analysis revealed a significant difference (p < 0.05) in overall 5-year survival rates depending on the differentiation grade, preoperative CEA >5 and >200 ng/ml, diameter of the lesion >5 cm, time from primary tumor to metastases >12 months, MSKCC-CRS >2. The multivariate analysis showed three independent negative prognostic factors: G3 or G4 grade, CEA >5 ng/ml, and high MSKCC-CRS. Conclusions No single prognostic factor proved to be associated with a sufficiently disappointing outcome to exclude patients from liver resection. However, in the presence of some prognostic factors (G3–G4 differentiation, preoperative CEA >5 ng/ml, high MSKCC-CRS), enrollment of patients in trials exploring new adjuvant treatments is suggested to improve the outcome after surgery.     

Bevacizumab Efficacy in Metastatic Colorectal Cancer is Dependent on Primary Tumor Resection

Purpose

Bevacizumab plus fluoropyrimidine-based chemotherapy is standard treatment for first-line and second-line metastatic colorectal cancer (mCRC). However, to date, there is no current biomarker predictive for the benefit of bevacizumab use for these patients. Preclinical data suggest that the presence of the primary tumor could be involved in less efficient antitumor activity of antiangiogenic agents, but no clinical data currently support this hypothesis.

Methods

We performed a retrospective analysis of factors associated with overall survival (OS) in a study cohort of 409 mCRC patients. Univariate and multivariate Cox proportional hazard regression models were used to assess the influence of primary tumor resection and bevacizumab use on OS. We evaluated associations linking bevacizumab use and OS among patients who previously underwent or did not undergo primary tumor resection. Results were externally validated in a second independent cohort of 328 mCRC patients.

Results

In the study cohort, bevacizumab use and resection of the primary tumor were associated with improved OS. However, subgroup analyses indicate that bevacizumab did not influence survival of patients bearing a primary colorectal tumor (hazard ratio (HR) 0.98, 95 % confidence interval (CI) 0.60–1.61, log-rank test P = 0.6). By contrast, the survival benefit of bevacizumab was restricted to patients who previously underwent primary tumor resection (HR 0.71, 95 % CI 0.55–0.92, P = 0.009). Similar results were observed in the validation cohort.

Conclusions

Addition of bevacizumab to chemotherapy is associated with improvement of OS only in patients with primary tumor resection. These data support the rationale to validate prospectively the influence of primary tumor resection on bevacizumab antitumor effect in synchronous mCRC.     

伊立替康联合氟尿嘧啶/亚叶酸钙治疗转移性结直肠癌

目的观察伊立替康联合亚叶酸钙及氟尿嘧啶方案治疗FOLFOX4方案失败的晚期结直肠癌的临床疗效及毒副反应。方法用CPT-11联合5-FU/CF方案治疗晚期结直肠癌患者28例,采用2周方案化疗,至少2个周期,即CPT-11180mg/m2静脉滴注,第1天;四氢叶酸200mg/m2静脉滴注,第1、2天;5-FU400mg/m2静脉推注,第1、2天;5-FU600mg/m2静脉滴注22h,第1、2天。按照WHO实体瘤近期客观疗效评定标准进行评价。结果全组28例患者均可评价疗效及不良反应。其中完全缓解0例,部分缓解10例,稳定9例,进展9例,有效率为35.7%。中位肿瘤进展时间TTP6.5个月,中位生存时间MST为12.5个月。不良反应主要是骨髓抑制,恶心、呕吐,脱发及延迟性腹泻。结论伊立替康联合5-FU/CF为二线治疗晚期结直肠癌安全有效的方案。     

External Validation of Two Nomograms for Predicting Patient Survival After Hepatic Resection for Metastatic Colorectal Cancer

Background  

Two nomograms are available for predicting patient survival after hepatic resection for metastatic colorectal cancer (CRC). However, they have not been externally validated using other databases, and so their universal applicability has not been established. We aimed to examine the validity of these nomograms for predicting patient survival after hepatic resection for metastatic CRC in different institutions.     

Regeneration After Two-Stage Hepatectomy vs Repeat Resection for Colorectal Metastasis Recurrence

Background Two-stage hepatectomy aims to minimize liver failure risk by performing a second resection after regeneration, assuming that remnant liver hypertrophy after the second resection is similar to that seen in repeat hepatectomy, yet the impact of a two-stage strategy on liver volume and function remains to be demonstrated. Patients and Methods Twenty patients undergoing two-stage hepatectomy for multiple colorectal cancer metastases and 21 patients with more than two sections of liver parenchyma totally removed by repeat liver resections for recurrence were enrolled. Liver volumes after final hepatectomy and postoperative liver function were compared. Results Median total liver volumes before initial hepatectomy and after final hepatectomy of multiple resections were 942 and 863 ml in patients with repeat hepatectomy, whereas volumes at corresponding time points were 957 and 777 ml in patients with two-stage hepatectomy. The ratio of total liver volume after both hepatectomies to preoperative volume in the two-stage group (81.7%) was lower than that in the repeat resection group (92.0%, P = 0.027). Greater aspartate aminotransferase and prothrombin time and lower platelet count 1 month postoperatively and lower albumin at 6 months were evident after two-stage hepatectomy compared with repeat hepatectomy. Conclusions Two-stage hepatectomy is characterized by diminished hepatic regenerative capacity and postoperative liver function.     

Preventing Futile Liver Resection: A Risk-Based Approach to Surgical Selection in Major Hepatectomy for Colorectal Cancer

Annals of Surgical Oncology - Early recurrence following liver resection for metastatic colorectal cancer generally portends poor survival. We sought to identify factors associated with early...     

Impact of Resection for Primary Colorectal Cancer on Outcomes in Patients with Synchronous Colorectal Liver Metastases

Purpose  

This study was designed to evaluate the impact of resection for primary colorectal cancer on oncologic outcomes in patients with synchronous colorectal liver metastases.