Optimal Margin Width Research Articles

Impact of Margin Status on Local Recurrence in Patients with Breast Cancer Undergoing Breast-Conserving Surgery After Neoadjuvant Chemotherapy: A Retrospective Multi-Institutional Cohort Study.

Questions have been raised as to an increased risk of local recurrence with breast-conserving surgery (BCS) post NAC highlighting the uncertainty around optimal margin width in this patient population. We examined the association between margin status and local recurrence-free survival (LRFS) in patients who underwent BCS following NAC. We performed a retrospective cohort study of adult female patients with stage I-III breast cancer who underwent NAC followed by BCS between 2012 and 2021 at two cancer centers. Margins were categorized as "close" if they were < 1 mm. The full cohort included 544 patients with a median age of 53 years (interquartile range [IQR] 44-64). Pathologic complete response (pCR) was achieved in 41.2% of the overall cohort (n = 224). Of the 320 with residual disease, 29.4% (n = 94) had at least one close margin, and 10.9% (n = 35) had ≥2 close margins. Median follow-up was 55 months (IQR 32-83); 4.8% had an ipsilateral breast recurrence (n = 26). Patients with pCR had a higher 5-year LRFS than those with residual disease (98.0% vs. 91.6%, p = 0.02). There was no difference in 5-year LRFS between the margin categories (clear vs. 1 close margin vs. ≥2 close margins) in those with residual disease (92.2% vs. 88.9% vs. 92.9%) (p = 0.78). In patients undergoing BCS post-NAC, those who achieved pCR had a significantly higher LRFS compared with those with residual disease at the time of surgery, but LRFS was not associated with margin width nor the number of close margins.

Surgical De-Escalation for Re-Excision in Patients with a Margin Less Than 2 mm and a Diagnosis of DCIS.

The current surgical guidelines recommend an optimal margin width of 2 mm for the management of patients diagnosed with ductal carcinoma in situ (DCIS). However, there are still many controversies regarding re-excision when the optimal margin criteria are not met in the first resection. The purpose of this study is to understand the importance of surgical margin width, re-excision, and treatments to avoid additional surgery on locoregional recurrence (LRR). The study is retrospective and analyzed surgical margins, adjuvant treatments, re-excision, and LRR in patients with DCIS who underwent breast-conserving surgery (BCS). A total of 197 patients were enrolled. Re-operation for a close margin rate was 13.5%, and the 3-year recurrence was 7.6%. No difference in the LRR was reported among the patients subjected to BCS regardless of the margin width (p = 0.295). The recurrence rate according to margin status was not significant (p = 0.484). Approximately 36.9% (n: 79) patients had resection margins < 2 mm. A sub-analysis of patients with margins < 2 mm showed no difference in the recurrence between the patients treated with a second surgery and those treated with radiation (p = 0.091). The recurrence rate according to margin status in patients with margins < 2 mm was not significant (p = 0.161). The margin was not a predictive factor of LRR p = 0.999. Surgical re-excision should be avoided in patients with a focally positive margin and no evidence of the disease at post-surgical imaging.

ASO Visual Abstract: The Application of Artificial Intelligence to Investigate Long-Term Outcomes and Assess Optimal Margin Width in Hepatectomy for Intrahepatic Cholangiocarcinoma.

ASO Visual Abstract: The Application of Artificial Intelligence to Investigate Long-Term Outcomes and Assess Optimal Margin Width in Hepatectomy for Intrahepatic Cholangiocarcinoma.

ASO Author Reflections: Long-Term Outcomes and Optimal Margin Width Among Patients Undergoing Hepatectomy for Intrahepatic Cholangiocarcinoma.

ASO Author Reflections: Long-Term Outcomes and Optimal Margin Width Among Patients Undergoing Hepatectomy for Intrahepatic Cholangiocarcinoma.

The Application of Artificial Intelligence to Investigate Long-Term Outcomes and Assess Optimal Margin Width in Hepatectomy for Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is associated with poor long-term outcomes, and limited evidence exists on optimal resection margin width. This study used artificial intelligence to investigate long-term outcomes and optimal margin width in hepatectomy for ICC. The study enrolled patients who underwent curative-intent resection for ICC between 1990 and 2020. The optimal survival tree (OST) was used to investigate overall (OS) and recurrence-free survival (RFS). An optimal policy tree (OPT) assigned treatment recommendations based on random forest (RF) counterfactual survival probabilities associated with each possible margin width between 0 and 20 mm. Among 600 patients, the median resection margin was 4 mm (interquartile range [IQR], 2-10). Overall, 379 (63.2 %) patients experienced recurrence with a 5-year RFS of 28.3 % and a 5-year OS of 38.7 %. The OST identified five subgroups of patients with different OS rates based on tumor size, a carbohydrate antigen 19-9 [CA19-9] level higher than 200 U/mL, nodal status, margin width, and age (area under the curve [AUC]: training, 0.81; testing, 0.69). The patients with tumors smaller than 4.8 cm and a margin width of 2.5 mm or greater had a relative increase in 5-year OS of 37 % compared with the entire cohort. The OST for RFS estimated a 46 % improvement in the 5-year RFS for the patients younger than 60 years who had small (<4.8 cm) well- or moderately differentiated tumors without microvascular invasion. The OPT suggested five optimal margin widths to maximize the 5-year OS for the subgroups of patients based on age, tumor size, extent of hepatectomy, and CA19-9 levels. Artificial intelligence OST identified subgroups within ICC relative to long-term outcomes. Although tumor biology dictated prognosis, the OPT suggested that different margin widths based on patient and disease characteristics may optimize ICC long-term survival.

Margin Status and Local Recurrence in Phyllodes Tumours of the Breast: A Canadian Series.

Phyllodes tumours of the breast are rare fibroepithelial neoplasms with a propensity for recurrence. While surgical excision remains the standard of care, the optimal margin width is an area of active investigation. Recent studies have questioned the necessity for wide, local excision. We conducted a retrospective, cohort study of patients with phyllodes tumours treated at our institution between 2003 and 2021. Demographic, histopathological, and recurrence data were captured; malignant phyllodes were excluded. Cox proportional hazard models were used to identify covariates associated with local recurrence. Of 187 patients with phyllodes tumours, 82.9% (n = 155) were classified as benign while 17.1% (n = 32) were borderline. Initial surgical margins were positive in 26.2% (n = 49), < 2 mm in 50.8% (n = 95), and ≥ 2 mm in 23% (n = 43) patients. Among patients with positive margins, 61.2% (n = 30) underwent margin revision. At a median follow-up of 2.9 years, the recurrence rate was 3.7%. On univariate analysis, only a positive margin at the time of initial surgery and not margin width was significantly associated with a higher rate of disease recurrence (hazard ratio [HR] 9.52, 95% confidence interval [CI] 1.85-49.2), as was a size greater than 4 cm on preoperative imaging (HR 10.78, 95% CI 0.97-120.1). Revision of an initially positive margin was not significantly associated with decreased local recurrence (p = 1). In this large cohort of benign and borderline phyllodes tumours, positive resection margins and not margin width at the initial surgery were associated with a increased recurrence. Individualization of decisions regarding margin reexcision is important.

Using Artificial Intelligence to Find the Optimal Margin Width in Hepatectomy for Colorectal Cancer Liver Metastases

In patients with resectable colorectal cancer liver metastases (CRLM), the choice of surgical technique and resection margin are the only variables that are under the surgeon's direct control and may influence oncologic outcomes. There is currently no consensus on the optimal margin width. To determine the optimal margin width in CRLM by using artificial intelligence-based techniques developed by the Massachusetts Institute of Technology and to assess whether optimal margin width should be individualized based on patient characteristics. The internal cohort of the study included patients who underwent curative-intent surgery for KRAS-variant CRLM between January 1, 2000, and December 31, 2017, at Johns Hopkins Hospital, Baltimore, Maryland, Memorial Sloan Kettering Cancer Center, New York, New York, and Charité-University of Berlin, Berlin, Germany. Patients from institutions in France, Norway, the US, Austria, Argentina, and Japan were retrospectively identified from institutional databases and formed the external cohort of the study. Data were analyzed from April 15, 2019, to November 11, 2021. Hepatectomy. Patients with KRAS-variant CRLM who underwent surgery between 2000 and 2017 at 3 tertiary centers formed the internal cohort (training and testing). In the training cohort, an artificial intelligence-based technique called optimal policy trees (OPTs) was used by building on random forest (RF) predictive models to infer the margin width associated with the maximal decrease in death probability for a given patient (ie, optimal margin width). The RF component was validated by calculating its area under the curve (AUC) in the testing cohort, whereas the OPT component was validated by a game theory-based approach called Shapley additive explanations (SHAP). Patients from international institutions formed an external validation cohort, and a new RF model was trained to externally validate the OPT-based optimal margin values. This cohort study included a total of 1843 patients (internal cohort, 965; external cohort, 878). The internal cohort included 386 patients (median [IQR] age, 58.3 [49.0-68.7] years; 200 men [51.8%]) with KRAS-variant tumors. The AUC of the RF counterfactual model was 0.76 in both the internal training and testing cohorts, which is the highest ever reported. The recommended optimal margin widths for patient subgroups A, B, C, and D were 6, 7, 12, and 7 mm, respectively. The SHAP analysis largely confirmed this by suggesting 6 to 7 mm for subgroup A, 7 mm for subgroup B, 7 to 8 mm for subgroup C, and 7 mm for subgroup D. The external cohort included 375 patients (median [IQR] age, 61.0 [53.0-70.0] years; 218 men [58.1%]) with KRAS-variant tumors. The new RF model had an AUC of 0.78, which allowed for a reliable external validation of the OPT-based optimal margin. The external validation was successful as it confirmed the association of the optimal margin width of 7 mm with a considerable prolongation of survival in the external cohort. This cohort study used artificial intelligence-based methodologies to provide a possible resolution to the long-standing debate on optimal margin width in CRLM.

Does margin width impact breast cancer recurrence rates in women with breast conserving surgery for ductal carcinoma in situ?

Controversy remains regarding the optimal margin width for patients with ductal carcinoma in situ (DCIS) who undergo breast conserving surgery (BCS). Women with a primary DCIS diagnosis were enrolled in a statewide population-based cohort from 1997 to 2006. Patients were surveyed every two years with follow-up data available through 2016. Surgical pathology reports were collected for 559 participants following breast conserving surgery. Multivariable Cox proportional hazard models evaluated relationships between locoregional recurrence (LRR) and margin width in the presence or absence of adjuvant radiation therapy while controlling for age, menopausal status and duration of endocrine therapy use. The majority of women in this study were over 50yo (74%), 34% had high grade disease, and 77% underwent radiation. The overall LRR rate was 12%. A LRR occurred in 46 women who had radiation (11%) and 23 women who did not undergo radiation (19%). Univariate analysis identified smaller margin width, younger age, premenopausal status, no radiotherapy, and shorter endocrine therapy use associated with LRR. Multivariable models demonstrated that close margins (< 2mm) were associated with an increased risk of recurrence when compared to margins ≥ 2mm in width whether women received radiation (HR 1.98 CI 0.87-4.54) or not (HR 1.32 CI 0.27-6.49), but confidence intervals were wide. In this study, patients with DCIS and close margins were less likely to experience recurrence after routine re-excision to margins greater than 2mm.

Is the Rationale of Anatomical Liver Resection for Hepatocellular Carcinoma Universally Adoptable? A Hypothesis-Driven Review.

Surgical resection is the first-line curative treatment modality for resectable hepatocellular carcinoma (HCC). Anatomical resection (AR), described as systematic removal of a liver segment confined by tumor-bearing portal tributaries, may improve survival by reducing the risk of tumor recurrence compared with non-AR. In this article, we propose the rationale for AR and its universal adoption by providing supporting evidence from the advanced understanding of a tumor microenvironment and accumulating clinical experiences of locoregional tumor ablation therapeutics. AR may be advantageous because it completely removes the en-bloc by interrupting tumor vascular supply and thus extirpates the spreading of tumor microthrombi, if they ever exist, within the supplying portal vein. However, HCC is a hypervascular tumor that can promote neoangiogenesis in the local tumor microenvironment, which in itself can break through the anatomical boundary within the liver and even retrieve nourishment from extrahepatic vessels, such as inferior phrenic or omental arteries. Additionally, increasing clinical evidence for locoregional tumor ablation therapies, such as radiofrequency ablation, predominantly performed as a non-anatomical approach, suggests comparable outcomes for surgical resection, particularly in small HCC and colorectal, hepatic metastases. Moreover, liver transplantation for HCC, which can be considered as AR of the whole liver followed by implantation of a new graft, is not universally free from post-transplant tumor recurrence. Overall, AR should not be considered the gold standard among all surgical resection methods. Surgical resection is fundamentally reliant on choosing the optimal margin width to achieve en-bloc tumor niche removal while balancing between oncological radicality and the preservation of postoperative liver function. The importance of this is to liberate surgical resilience in hepatocellular carcinoma. The overall success of HCC treatment is determined by the clearance of the theoretical niche. Developing biomolecular-guided navigation device/technologies may provide surgical guidance toward the total removal of microscopic tumor niche to achieve superior oncological outcomes.

Narrow resection margins are not associated with mortality or recurrence in patients with Merkel cell carcinoma: A retrospective study

Wide local excision constitutes the standard of care for Merkel cell carcinoma, but the optimal margin width remains controversial. To assess whether narrow margins (0.5-1cm) were associated with outcome. Patients were recruited from a retrospective French multicentric cohort and included if they had had excision of primary tumor with minimum lateral margins of 0.5cm. Factors associated with mortality and recurrence were assessed by multivariate regression. Among the 214 patients included, 58 (27.1%) had undergone excision with narrow margins (0.5-1cm) versus 156 (72.9%) with wide margins (>1cm). During a median follow-up of 50.7months, cancer-specific survival did not differ between groups (5-year specific survival rate 76.8% [95% confidence interval 61.7%-91.9%] and 76.2% [95% confidence interval 68.8%-83.6%], respectively). Overall survival, any recurrence-free survival, and local recurrence-free survival did not significantly differ between groups. Cancer-specific mortality was associated with age, male sex, American Joint Committee on Cancer stage III, and presence of positive margins. Retrospective design, heterogenous baseline characteristics between groups. Excision with narrow margins was not associated with outcome in this cohort, in which most patients had clear margins and postoperative radiation therapy. Residual tumor, mostly found on deep surgical margins, was independently associated with prognosis.

Ductal Carcinoma In Situ and Margins

To determine the relationship between negative margin width and locoregional recurrence (LRR) in a contemporary cohort of ductal carcinoma in situ (DCIS) patients. Recent national consensus guidelines recommend an optimal margin width of 2 mm or greater for the management of DCIS; however, controversy regarding re-excision remains when managing negative margins <2 mm. One thousand four hundred ninety-one patients with DCIS who underwent breast-conserving surgery from 1996 to 2010 were identified from a prospectively managed cancer center database and analyzed using univariate and multivariate Cox proportional hazard models to determine the relationship between negative margin width and LRR with or without adjuvant radiation therapy (RT). A univariate analysis revealed that age <40 years (n = 89; P = 0.02), no RT (n = 298; P = 0.01), and negative margin width <2 mm (n = 120; P = 0.005) were associated with LRR. The association between margin width and LRR differed by adjuvant RT status (interaction P = 0.02). There was no statistical significant difference in LRR between patients with <2 mm and ≥2 mm negative margins who underwent RT (10-yr LRR rate, 4.8% vs 3.3%, respectively; hazard ratio, 0.8; 95% CI, 0.2-3.2; P = 0.72). For patients who did not undergo RT, those with margins <2 mm were significantly more likely to develop a LRR than were those with margins ≥2 mm (10-yr LRR rate, 30.9% vs 5.4%, respectively; hazard ratio, 5.5; 95% CI, 1.8-16.8, P = 0.003). Routine additional surgery may not be justified for patients with negative margins <2 mm who undergo RT but should be performed in patients who forego RT.

Margins in Breast-Conserving Surgery After Neoadjuvant Therapy.

Optimal margin width for breast-conserving therapy (BCT) after neoadjuvant chemotherapy (NAC) is unknown. We sought to determine the impact of margin width on local recurrence and survival after NAC and BCT. Patients treated with NAC and BCT for stage I-III breast cancer from 2002 to 2014 were identified. Multivariate Cox regression was performed to determine the relationship between margin width and local recurrence free-survival (LRFS), disease-free survival (DFS), and overall survival (OS). A total of 382 patients were included. Median age was 51years [range 22-79], median tumor size 3.0cm [range 0.6-11.0], and receptor subtypes included 144 (37.7%) HR-/HER2-, 47 (12.3%) HR-/HER2+, 118 (30.9%) HR+/HER2-, and 70 (18.3%) HR+/HER2+. Breast pathologic complete response (pCR) was achieved in 105 (27.5%) patients. Final margin status was positive in 8 (2.1%) patients, ≤ 1mm in 65 (17.0%), 1.1-2mm in 30 (7.9%), and > 2mm in 174 (45.5%). The 5-year LRFS was 96.3% (95% CI 94.0-98.6), DFS was 85.5% (95% CI 81.8-90.7), and OS was 90.8% (95% CI 87.4-94.2). There was no difference in LRFS, DFS, or OS for margins ≤ 2 versus > 2mm, and no difference in DFS or OS for margins ≤ 1 versus > 1mm. HR+ subtype (p = 0.04) and pCR (p = 0.03) were correlated with favorable DFS and node negativity (p < 0.001) with favorable DFS and OS. In this cohort treated with NAC and BCT, there was no association between margin width and LRFS, DFS, or OS. Although further studies are needed, the excellent long-term outcomes demonstrated in patients with close (≤ 2mm) margins following NAC suggest that a margin of "no-ink-on-tumor" may be acceptable in appropriately selected patients.

Contemporary breast conservation patient outcomes for ductal carcinoma in situ and margins &lt; 2 mm.

559 Background: Recent national consensus guidelines regarding optimal margin width for the management of DCIS have been published; however, controversy remains for managing margins &lt;2mm. The relationship between margin width and locoregional recurrence (LRR) was determined in a contemporary cohort of patients. Methods: 1504 patients with DCIS undergoing definitive breast conserving surgery from 1996 to 2010 were analyzed for clinical and pathologic characteristics from a prospectively managed comprehensive academic cancer center database. Cox proportional hazard models were used to examine the relationship between margin width (&lt;2mm or ≥2mm) and LRR by adjuvant radiation therapy (RT). Patients with positive margins (n=11) were excluded. Results: Overall, 3.4% of patients had a LRR at a median follow-up of 8.7 years. Univariate analysis of age, family history, grade, tumor size, comedonecrosis, RT, adjuvant hormonal therapy, ER status, and margin width found younger age (&lt; 40 yr, p=0.02), no RT (n=299, p=0.005), and margin width &lt;2mm(n=138, p=0.005) to be associated with LRR. The association between margin width and LRR differed by adjuvant radiation therapy status (p=0.02 for the interaction). There was no statistical significant difference in LRR for patients with margins &lt;2mm vs ≥2 mm who received RT, (10-year LRR 6.0% vs 3.2%, respectively; HR 1.5, 95% CI 0.5-4.2, p=0.48). For patients who did not receive RT (n=299), those with margins &lt; 2 mm were significantly more likely to develop a LRR than those with margins ≥2mm (10-year LRR 35.7% vs. 4.6%, respectively; HR 7.2, 95%CI 2.6-19.4, p=0.0001). Conclusions: In patients with &lt;2mm margins receiving adjuvant radiation therapy, there is no difference in locoregional recurrence when compared to patients with ≥2mm margins. Additional surgery for wider margins of resection are not routinely justified in this group of patients but should be obtained for patients with &lt;2mm margins who forego radiotherapy.

Optimal Margin Width in Breast Conservation Therapy: a Review of the Current Guidelines and Literature

Randomized trials have clearly established breast conservation therapy (BCT) as appropriate treatment for early-stage invasive breast cancer. Current evidence shows that positive margins confer a greater than twofold risk of ipsilateral breast tumor recurrence. Thus, patients who have positive margins after BCT warrant re-excision. With regard to negative margins, however, the optimal negative margin width remains unclear. This article reviews the recent guidelines set forth by the Society of Surgical Oncology and the American Society of Radiation Oncology regarding the margin width in stage I and II invasive breast cancer. We also discuss the controversies related to implementation of these guidelines.

Society of Surgical Oncology–American Society for Radiation Oncology Consensus Guideline on Margins for Breast-Conserving Surgery With Whole-Breast Irradiation in Stages I and II Invasive Breast Cancer

Controversy exists regarding the optimal margin width in breast-conserving surgery for invasive breast cancer. A multidisciplinary consensus panel used a meta-analysis of margin width and ipsilateral breast tumor recurrence (IBTR) from a systematic review of 33 studies including 28,162 patients as the primary evidence base for consensus. Positive margins (ink on invasive carcinoma or ductal carcinoma in situ) are associated with a two-fold increase in the risk of IBTR compared with negative margins. This increased risk is not mitigated by favorable biology, endocrine therapy, or a radiation boost. More widely clear margins than no ink on tumor do not significantly decrease the rate of IBTR compared with no ink on tumor. There is no evidence that more widely clear margins reduce IBTR for young patients or for those with unfavorable biology, lobular cancers, or cancers with an extensive intraductal component. The use of no ink on tumor as the standard for an adequate margin in invasive cancer in the era of multidisciplinary therapy is associated with low rates of IBTR and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease health care costs.

Society of Surgical Oncology–American Society for Radiation Oncology Consensus Guideline on Margins for Breast-Conserving Surgery With Whole-Breast Irradiation in Stages I and II Invasive Breast Cancer

Controversy exists regarding the optimal margin width in breast-conserving surgery for invasive breast cancer. A multidisciplinary consensus panel used a meta-analysis of margin width and ipsilateral breast tumor recurrence (IBTR) from a systematic review of 33 studies including 28,162 patients as the primary evidence base for consensus. Positive margins (ink on invasive carcinoma or ductal carcinoma in situ) are associated with a two-fold increase in the risk of IBTR compared with negative margins. This increased risk is not mitigated by favorable biology, endocrine therapy, or a radiation boost. More widely clear margins do not significantly decrease the rate of IBTR compared with no ink on tumor. There is no evidence that more widely clear margins reduce IBTR for young patients or for those with unfavorable biology, lobular cancers, or cancers with an extensive intraductal component. The use of no ink on tumor as the standard for an adequate margin in invasive cancer in the era of multidisciplinary therapy is associated with low rates of IBTR and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease health care costs. J Clin Oncol 32. 2014 American Society of Clinical Oncology®, American Society for Radiation Oncology®, and Society of Surgical Oncology®. All rights reserved. No part of this document may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without written permission by the American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology.

Impact of subcentimeter margin on outcome after hepatic resection for colorectal metastases: A meta-regression approach

The optimal margin width and its influence on outcomes after hepatic resection for colorectal liver metastases is still controversial: a meta-analysis was conducted to analyze the impact of subcentimeter margin width on patient and disease-free survival after resection. A systematic search was performed, covering the last decade, following the Meta-analysis Of Observational Studies in Epidemiology guidelines. Relative risks (RRs) for patient and disease-free survival (DFS) were calculated after resection in relationship to a margin width >1 cm (R0 > 1 cm) and between 1 mm and 1 cm (R0 < 1 cm) using the DerSimonian and Laird random-effects model. Meta-regression was applied for covariate adjustment. Eleven observational studies were identified involving 2823 patients. Overall, 59.1% of patients were R0 < 1 cm and 40.9% were R0 > 1 cm. Meta-analysis showed that compared with patients with margins R0 > 1 cm, a R0 < 1 cm margin lead to decreased 1-, 3-, and 5-year DFS with a RR of 1.17 (95% confidence interval [CI] 1.07-1.27), 1.38 (95% CI 1.16-1.65), and 1.55 (95% CI 1.25-1.91), respectively, but patient survival was obviously affected (P > .05 in all cases). Patients with margins of R0 < 1 cm differ from those with R0 > 1 cm for greater proportions of multiple metastases (RR 1.43; 95% CI 0.25-1.61) and synchronous bowel disease (RR 1.42; 95% CI 0.8-1.92). Meta-regression showed that these two covariates had a significant impact on DFS but not on patient survival. A resection margin width >1 cm is desirable even if patient survival is at best only slightly affected by subcentimeter margin as a consequence of a decreased DFS. The presence of multiple metastases and synchronous bowel neoplasm represent potential study selection biases that significantly decrease DFS; well-conducted, matched analyses consequently are essential to clarify the issue.

Resection Margin and Recurrence-Free Survival After Liver Resection of Colorectal Metastases

Optimal margin width is uncertain because of conflicting results from recent studies using overall survival as the end-point. After recurrence, re-resection and aggressive chemotherapy heavily affect survival time; the potential confounding effect of such factors has not been investigated. Use of recurrence-free survival (RFS) may overcome this limitation. The aim of this study is to evaluate the impact of width of resection margin on RFS and site of recurrence after hepatic resection for colorectal metastases (CRM). From a prospectively maintained institutional database (1/1999-12/2007) we identified 314 patients undergone hepatectomy for CRM (1/1999-12/2007) with detailed pathologic analysis of the surgical margin and complete follow-up imaging studies documenting disease status and site of recurrence, which was categorized as: resection margin (M(arg)), other intra-hepatic ((other)IH), lung (L) or other extra-hepatic ((other)EH). Recurrence-free estimation was the survival end-point. Median follow-up was 56.5 months. Two hundred and fifteen patients (68.8%) recurred at 288 sites after a mean of 15.5 months. A positive resection margin was associated with an increased risk of M(arg) recurrence (P < 0.001). The presence of >or=2 metastases was the only factor increasing the risk of positive margins (P < 0.05). The width of the negative resection margin (>or=1 cm versus >1 cm) was not a prognostic factor of worse RFS (30.2% versus 37.3%, P = 0.6). Node status of the primary tumour, and size and number of CRM were independent predictors of RFS. Tumour biology and not the width of the negative resection margin affect RFS.

The Impact of Margins on Outcome After Hepatic Resection for Colorectal Metastasis

To analyze the impact of margin width on long-term outcome after hepatic resection for colorectal metastasis. The optimal margin width and its influence on long-term outcome after hepatic resection for colorectal metastasis are unclear. All patients undergoing hepatic resection for colorectal metastasis from 1991 to 2003 were identified, and the prognostic influence of margin width and other clinicopathologic factors were analyzed. A total of 1019 patients with a clear description of margin width were included. Analysis of margin width as a continuous variable suggested the following grouping: group I, involved (n = 112, 11%); group II, <1-10 mm (n = 563, 55%); and group III, >10 mm (n = 344, 33.7%). On univariate analysis, there was a statistically significant difference in median survival between all 3 groups: group II versus group I (42 vs. 30 months, P < 0.01) and group III versus group II (55 vs. 42 months, P < 0.01). Margin width >1 cm retained statistical significance (P < 0.01) on multivariate analysis after adjusting for established risk factors. After adjustment, survival in group III was significantly better than either group I or II (P < 0.01), but there was no difference between groups I and II (P = 0.31). This study provides evidence that margin width of >1 cm is optimal and is an independent predictor of survival after hepatic resection for colorectal metastasis. However, subcentimeter resections are also associated with favorable outcome and should not preclude patients from undergoing resection.