Blake Cady, Roger L. Jenkins, Glenn D. Steele, Jr., W. David Lewis, Michael D. Stone, William V. McDermott, John M. Jessup,. Albert Bothe, Peter Lalor, E. J. ...
ANNALS OF SURGERY Vol. 227, No. 4, 566-571 C) 1998 Lippincott-Raven Publishers
Surgical Margin in Hepatic Resection for Colorectal Metastasis A Critical and Improvable Determinant of Outcome Blake Cady, Roger L. Jenkins, Glenn D. Steele, Jr., W. David Lewis, Michael D. Stone, William V. McDermott, John M. Jessup, Albert Bothe, Peter Lalor, E. J. Lovett, Phillip Lavin, David C. Linehan From the Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
Objective
Results
To update the analysis of technical and biologic factors related to hepatic resection for colorectal metastasis in a large single-institution series to identify important prognostic indicators and patterns of failure.
Surgical margin, number of lesions, and carcinoembryonic antigen (CEA) levels significantly control prognosis. Patients with only one or two liver lesions, a 1 -cm surgical margin, and low CEA levels have a 5-year disease-free survival rate of more than 30%. Disease-free interval, original stage, bilobar involvement, size of metastasis, differentiation, and ploidy were not significant predictors of recurrence. The pattern of failure correlates with surgical margin. Routine use of intraoperative ultrasound resulted in an increased incidence of negative surgical margin during the period examined.
Summary Background Data Surgical therapy for colorectal carcinoma metastatic to the liver is the only potentially curable treatment. Careful patient selection of those with resectable liver-only metastatic disease is crucial to the success of surgical therapy.
Methods Two hundred forty-four consecutive patients undergoing curative hepatic resection for metastatic colorectal carcinoma were analyzed retrospectively. Variables examined included sex, stage of primary lesion, size of liver lesion(s), number of lesions, disease-free interval, ploidy, differentiation, preoperative carcinoembryonic antigen level, and operative factors such as resection margin, use of cryotherapy, intraoperative ultrasound, and blood loss.
Surgical therapy for isolated hepatic metastasis from colorectal cancer has gained acceptance as a safe and potentially curable treatment. Despite no prospective, randomized trials comparing surgery to medical therapy, many case-controlled and retrospective studies have shown a distinct survival advantage to surgical resection in carefully selected patients.1-15 Several large series have reported a 25% to 35% long-term survival rate after curative resection of hepatic metastasis, whereas the long-term survival rate Address correspondence and reprint requests to Blake Cady, MD, Breast Health Center; Woman and Infants Hospital, 101 Dudley St., Providence, RI 02905.
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Conclusions Surgical resection or cryotherapy of hepatic metastasis from colorectal cancer is safe and curable in appropriately selected patients. Biologic factors, such as number of lesions and carcinoembryonic antigen levels, determine potential curability, and surgical margin governs the patterns of failure and outcome in potentially curable patients. Optimization of selection criteria and surgical resection margins will improve outcome.
after medical therapy or no therapy is no more than 2%. 16 Nonetheless, some authors have questioned the value of surgery for hepatic metastasis, suggesting that careful selection of patients with biologically indolent tumors is the sole reason for improved survival rates after resection.17 Despite substantial evidence supporting the efficacy of surgical therapy for a small subset of patients with metastatic colorectal cancer, the majority of patients treated with hepatic resection have recurrences and die. Ideally, prognostic indicators available to the clinician at the time of recurrence could predict the pattem and likelihood of treatment failure associated with hepatic resection to optimize patient selection and to identify those who may benefit from adjuvant therapy after curative resection.
Hepatic Resection for Colorectal Metastasis
Vol. 227 * No. 4
Which technical and biologic factors predict survival after hepatic resection for colorectal metastasis continue to be debated. Data published by our group and others have confirmed the dominant effect of biologic factors such as metastatic pattern, number of lesions, and CEA level on outcome after liver resection 1-1,18 and have demonstrated that a 1-cm surgical margin is necessary to optimize survival.'9 Conflicting data exist with respect to the prognostic significance of disease-free interval, number of lesions, CEA level, size of lesion(s), bilobar distribution, and even surgical margin. This study adds another 140 patients to our previously published series and represents one of the largest single-institution series in the literature regarding long-term follow-up.
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Biologic factors analyzed included prehepatic resection serum CEA (ng/mL), stage and location of primary colorectal cancer, maximum diameter of the largest nodule, number of satellites, differentiation, and ploidy as determined by flow cytometry. Ploidy data were available for 184 of the 244 patients in the series. The number of metastases, excluding satellite metastases, also was analyzed. Satellite lesions were defined as metastases 1 cm or less in maximum diameter within 1 cm of a primary mass. Because the presence of a satellite lesion using this definition did not act as an independent prognostic indicator, they were not counted as separate nodules when this variable was analyzed. Thirteen percent of patients had one or more satellite lesions, and the maximum number of satellites was eight. Of the primary colorectal cancers, 209 were located in the colon and 35 were located in the rectum.
METHODS All curative hepatic resections for colorectal cancer metastasis at the Deaconess Hospital in Boston were analyzed. By October 1996, 244 patients had undergone curative resection, survived the surgery, and were available for analysis. There was a 100% follow-up. Median length of follow-up was 37 months (range = 2 months to 15 years). Follow-up was conducted through office examinations, chart reviews, and telephone conversations with patients, families, and referring physicians. Statistical analysis was performed using Kaplan-Meier Actuarial Survivor curves and covariate Cox models (BMPD Statistical Software, Los Angeles, CA). A diseasefree survival rate was determined by censoring patients free of disease at the time of the last follow-up. The first evidence of recurrent disease as demonstrated by physical examinations, radiologic findings, or elevated CEA levels ended the disease-free state. All results were given for disease-free survival. Correlation of surgical margin with site of recurrence was determined using the Kruskal-Wallis test.
Technical factors examined included resection margin, specimen weight, use of intraoperative ultrasound (IOUS), use of cryotherapy, type of hepatic resection, and blood loss. Histologic margin to the nearest metastasis was characterized as negative (.1 cm) close, (200 ng/mL. A statistically significant survival advantage also could be demonstrated between patients with low CEA levels (e.g.,
