Predictors Of Positive Margins Research Articles

Clinicopathological Predictors of Positive Resection Margins in Breast-Conserving Surgery.

Ductal carcinoma in situ (DCIS) is associated with risk of positive resection margins following breast-conserving surgery (BCS) and subsequent reoperation. Prior reports grossly underestimate the risk of margin positivity with IBC containing a DCIS component (IBC + DCIS) due to patient-level rather than margin-level analysis. The aim of this study was to delineate the relative risk of IBC + DCIS compared with pure IBC (without a DCIS component) on margin positivity through detailed margin-level interrogation. A single institution, retrospective, observational cohort study was conducted in which pathology databases were evaluated to identify patients who underwent BCS over 5years (2014-2019). Margin-level interrogation included granular detail into the extent, pathological subtype and grade of disease at each resection margin. Predictors of a positive margin were computed using multivariate regression analysis. Clinicopathological details were examined from 5454 margins from 909 women. The relative risk of a positive margin with IBC + DCIS versus pure IBC was 8.76 (95% confidence interval [CI] 6.64-11.56) applying UK Association of Breast Surgery guidelines, and 8.44 (95% CI 6.57-10.84) applying the Society of Surgical Oncology/American Society for Radiation Oncology guidelines. Independent predictors of margin positivity included younger patient age (0.033, 95% CI 0.006-0.060), lower specimen weight (0.045, 95% CI 0.020-0.069), multifocality (0.256, 95% CI 0.137-0.376), lymphovascular invasion (0.138, 95% CI 0.068-0.208) and comedonecrosis (0.113, 95% CI 0.040-0.185). Compared with pure IBC, the relative risk of a positive margin with IBC + DCIS is approximately ninefold, significantly higher than prior estimates. This margin-level methodology is believed to represent the impact of DCIS more accurately on margin positivity in IBC.

Breast-Conserving Therapy in Patients with cT3 Breast Cancer with Good Response to Neoadjuvant Systemic Therapy Results in Excellent Local Control: A Comprehensive Cancer Center Experience.

Many cT3 breast cancer patients are treated with mastectomy, regardless of response to neoadjuvant systemic therapy (NST). We evaluated local control of cT3 patients undergoing breast-conserving therapy (BCT) based on magnetic resonance imaging (MRI) evaluation post-NST. In addition, we analyzed predictive characteristics for positive margins after breast-conserving surgery (BCS). All cT3 breast cancer patients who underwent BCS after NST between 2002 and 2015 at the Netherlands Cancer Institute were included. Local recurrence-free interval (LRFI) was estimated using the Kaplan-Meier method, and predictors for positive margins were analyzed using univariable analysis and multivariable logistic regression. Of 114 patients undergoing BCS post-NST, 75 had negative margins, 16 had focally positive margins, and 23 had positive margins. Of those with (focally) positive margins, 12 underwent radiotherapy, 6 underwent re-excision, and 21 underwent mastectomy. Finally, 93/114 patients were treated with BCT (82%), with an LRFI of 95.9% (95% confidence interval [CI] 91.5-100%) after a median follow-up of 7 years. Predictors for positive margins in univariable analysis were hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) subtype, lobular carcinoma, and non-mass enhancement (NME) on pre-NST MRI. MRI response was not correlated to positive margins. In multivariable regression, the odds of positive margins were decreased in patients with HER2-positive (HER2+; odds ratio [OR] 0.27, 95% CI 0.10-0.73; p=0.01) and TN tumors (OR 0.17, 95% CI 0.03-0.82; p=0.028). A trend toward positive margins was observed in patients with NME (OR 2.38, 95% CI 0.98-5.77; p=0.055). BCT could be performed in 82% of cT3 patients in whom BCT appeared feasible on post-NST MRI. Local control in these patients was excellent. In those patients with HR+/HER2- tumors, NME on MRI, or invasive lobular carcinoma, the risk of positive margins should be considered preoperatively.

Necessity for subsequent surgery in women of child-bearing age with positive margins after conization

Background20–25% of women with high-grade cervical intraepithelial neoplasias (HSIL) have residual lesions after conization. The state of the margin is generally considered to be a risk factor for recurrence or persistent lesions. Predictors of positive margins and residual lesions need to be identified. A design for postoperative management and avoidance of overtreatment needs to be provided, especially for women of child-bearing age.MethodsThis study was a retrospective analysis of 1309 women of child-bearing age with HSIL, who underwent cold knife conization (CKC). Age, gravidity, parity, human papillomavirus (HPV) species, cytology, transformation zone type, results of endocervical curettage (ECC), quadrant involvement, glandular involvement, and Cervical Intraepithelial Neoplasia (CIN) grade were analyzed. Among those with positive margins, 245 patients underwent secondary surgery within three months, including CKC, a loop electrosurgical excision procedure, and total hysterectomy. Risk factors for positive margins and residual lesions were assessed.ResultsThere was no significant difference in age, gravidity, parity, glandular involvement, and CIN grade between the two groups (P > 0.3). There was a significant difference in HPV species, cytology, ECC results, and quadrant involvement (P < 0.002). Multivariate analysis showed a major cytology abnormality, high-risk HPV infection, type III transformation zone, positive ECC result, and multiple quadrant involvement were independent risk factors for positive margins and residual lesions (P < 0.02). Age > 35 years was also a risk factor for residual lesions (P < 0.03).ConclusionHigh-risk women should be treated appropriately considering fertility. Patients with positive margins should be managed uniquely. Surgery for women without fertility may be appropriate. Close follow-up is necessary for women who have fertility requirements or are unwilling to undergo subsequent surgery if they have no risk factors, especially women < 35 years.

Association of menopause, aging and treatment procedures with positive margins after therapeutic cervical conization for CIN 3: a retrospective study of 8,856 patients by the Japan Society of Obstetrics and Gynecology.

ObjectiveThe Japan Society of Obstetrics and Gynecology conducted a retrospective multi-institutional survey of patients who underwent cervical conization in Japan. This study aimed to determine the predictive factors for positive surgical margins in cervical intraepithelial neoplasia grade 3 (CIN 3) patients after therapeutic cervical conization and those for positive margins in patients who did not experience recurrence and did not undergo additional treatment.MethodsIn 2009 and 2013, 14,832 patients underwent cervical conization at 205 institutions in Japan. Of these, 8856 patients who underwent therapeutic conization fulfilled the inclusion criteria. Their histologic findings and clinical outcomes were evaluated based on standard statistical procedures and clinical and demographic characteristics.ResultsNegative and positive margins were observed in 7,585 and 1,271 (14.4%) patients, respectively. The predictors of positive margins were menopausal status (p<0.001), loop electrosurgical excision procedure (p<0.001), and Shimodaira-Taniguchi (S-T) conization (p<0.001). Of 1,271 patients with positive margins, 1,060 underwent no additional treatment; among those 1,060 patients, 129 (12.2%) experienced recurrence. The predictors of positive margins in patients who did not undergo additional treatment and did not experience recurrence were age, parity, gravidity, S-T conization, and laser scalpel conization.ConclusionMenopausal status and treatment procedures were associated with positive margins after therapeutic conization of CIN 3. It is important to understand the characteristics of treatment procedures and select an appropriate procedure for each case. For elderly or menopausal patients with positive margins, immediate additional treatment is recommended.

Predicting Positive Margins in Pancreatic Head Adenocarcinoma After Neoadjuvant Therapy: Investigating Disparities in Quality Care Using the National Cancer Database.

In pancreatic cancer, surgical resection with neoadjuvant therapy improves survival, but survival relies significantly on the margin status of the resected tissue. This study aimed to develop a model that predicts margin positivity, and then to identify facility-specific factors that influence the observed-to-expected (O/E) ratio for positive margins among facilities. This retrospective review analyzed patients in the National Cancer Database (2004-2016) with pancreatic head adenocarcinoma [tumor-node-metastasis (TNM) stage 1 or 2] who received neoadjuvant therapy for a pancreaticoduodenectomy. Logistic regression was used to develop a model that predicts margin positivity. This model then was used to identify outlier facilities with regard to the O/E ratio. Hospital volume was defined as the total number of pancreaticoduodenectomies per year. The study enrolled 4085 patients, and 16.8% of these patients had positive margins. Most of the patients (64%) had a tumor size of 2 to 4cm, and approximately 51% of the patients did not have positive lymph nodes at resection. A logistic regression model showed that the predictors of positive margins after resection with neoadjuvant therapy were male sex, larger tumor size, and positive lymph nodes. This model was validated to yield a bootstrap-corrected concordance index of 0.632. The study calculated O/E ratios with the model, identifying 12 low- and 17 high O/E-ratio outlier facilities among 401 studied hospitals. The outlier hospitals did not differ in facility type (i.e., academic vs integrated network), but did differ significantly in terms of yearly hospital volume (low outlier of 20.6 vs high outlier of 10.7; p = 0.008). An association of lower-volume facilities with higher than expected rates of positive margins was found to indicate a disparity in care. This disparity was identified via an O/E ratio as a quality indicator for facilities. Facilities can gauge the efficiency of their own practices by referencing their O/E ratios, and they also can improve their practices by analyzing the framework of low O/E-ratio facilities.

P063: Predictors of positive resection margins - Results of a four-year evaluation

Introduction: Re-operative intervention due to close positive margins (PM) following Breast Conserving Surgery (BCS) carries human and economic burden. The mean rate of re-operation in England is 20%, impalpable tumours, such as ductal carcinoma in situ (DCIS) pose a greater threat (29.5%). We aimed to examine the predictors of PM at our institution to determine clinicopathological factors that influence re-operation.

Establishment and validation of nomogram for positive surgical margin of prostate cancer

Objective To establish a nomogram model for predicting positive resection margins after prostate cancer surgery, and to perform the corresponding verification, in order to predict the risk of positive resection margins after surgery. Methods A total of 2 215 prostate cancer patients from The First Affiliated Hospital of Naval Medical University, Hospital, Peking University First Hospital, Peking University Third Hospital, Peking University, and First Affiliated Hospital of Xi′an Jiaotong University were included in the PC-follow database from 2015 to 2018, and a simple random sampling method was used. They were divided into 1 770 patients in the modeling group and 445 patients in the verification group. In the modeling group, the age ( 70 years), PSA ( 20 ng/ml), pelvic MRI (negative, suspicious, positive), clinical stage of the tumor (T1-T2, ≥T3), percentage of positive needles (≤33%, 34%-66%, >66%), Gleason score of biopsy pathology (≤6 points, 7 points, ≥8 points). Univariate and multivariate logistic analysis were performed to screen meaningful indicators to construct a nomogram model. The model was used for validation in the validation group. Results The results of multivariate analysis showed that preoperative PSA level (OR=2.046, 95%CI 1.022 to 4.251, P=0.009), percentage of puncture positive needles (OR=1.502, 95%CI 1.136 to 1.978, P=0.002), Gleason score of puncture pathology (OR=1.568, 95%CI 1.063 to 2.313, P=0.028), pelvic MRI were correlated (OR=1.525, 95%CI 1.160 to 2.005, P=0.033). Establish a nomogram model for independent predictors of positive margin of prostate cancer. The area under the receiver operating characteristic (ROC) curve of the validation group is 0.776. The area under the ROC curve of the preoperative PSA level, percentage of puncture positive needles, puncture pathology Gleason score, pelvic MRI, postoperative pathology Gleason score were 0.554, 0.615, 0.556, 0.522, and 0.560, respectively. The difference between the nomogram model and other indicators was statistically significant (P<0.05). Conclusions The constructed nomogram model has higher diagnostic value than the preoperative PSA level, percentage of puncture positive needles, Gleason score of puncturing pathology, pelvic MRI, and postoperative pathological Gleason score in predicting positive margin. Key words: Prostatic neoplasms; Prostate cancer; Positive surgical margin; Models statistical

Predictors of Positive Margins After Definitive Resection for Gastric Adenocarcinoma and Impact of Adjuvant Therapies

Positivemargins after definitive resection in gastric adenocarcinoma are associated with inferior outcomes. There are few randomized data to guide optimal adjuvant therapy after positive margins. Using the National Cancer Database, we identified 24,619 nonmetastatic gastric adenocarcinoma patients who received diagnoses from 2004 to 2013 and underwent definitive resection to analyze for predictors of positive surgical margins. Of these patients, 2754 had positive margins (11.2%). Multivariate prevalence ratios were used to determine predictors. Survival analyses were performed with a Cox proportional hazards model by use of several methods of propensity score analysis. Increasing T and/or N category, high grade, and lymphovascular invasion predicted higher rates of positive margins. Asian race, treatment at an academic center, and robotic surgery predicted lower rates of positive margins. Among positive-margin patients with adjuvant treatment (n=1021), with a median follow-up period of 55months, age, comorbidity score, nodal disease, and T4 disease predicted for worse overall survival (OS). Treatment at an academic center was associated with improved OS. Use of adjuvant concurrent chemoradiation therapy (CCRT) was associated with higher OS compared with chemotherapy alone after positive margins (hazard ratio, 0.72; 95% confidence interval, 0.58-0.91; P=.005) after propensity matching adjusting for predictors of OS. The 2-year and 3-year OS for positive-margin patients with chemotherapy alone was 43% and 29%, respectively, compared with 53% and 38%, respectively, with adjuvant CCRT. The log-rank P value for survival was .0015. Stage, race, treatment center, and surgery approach predict for margin status after resection. Adjuvant CCRT after positive margins is associated with improved OS after accounting for available clinical variables.

Index lesion tumor volume on MRI to predict adverse pathologic outcomes following radical prostatectomy.

43 Background: Tumor volume measured on postoperative pathology has been shown to be associated with adverse pathologic and oncologic outcomes. Advances in imaging technology may facilitate the prediction of these outcomes prior to surgery. In this study, we evaluated the predictive value of tumor volume of the index lesion (ILTV) calculated from prostate MRI in analyzing adverse pathologic outcomes following radical prostatectomy (RARP). Methods: Clinical and pathologic data from a prospectively maintained, single-institution database was analyzed for patients who underwent 3T MRI prior to RARP (without prior therapy) between 2007 and 2016. ILTV was calculated from T2W MRI by multiplying length by width by depth by 0.52. Adverse pathologic outcomes were determined on whole mount prostatectomy specimens, and defined as positive margins (PM), extracapsular extension (ECE), positive lymph nodes (LNI), and seminal vesicle invasion (SVI). Logistic regression was used to assess associations of clinical, imaging, and histopathological variables with adverse pathologic features. Results: From the 501 patients who underwent RARP, 490 received MRI prior to surgery. The median age of our cohort of was 60 years (IQR 10), and median PSA was 6.21 ng/ml (IQR 6). There were 74/480 patients (15.4%) with PM, 112/474 (23.6%) with ECE, 30/478 (6.4%) with LNI, and 32/482 (6.7%) with SVI. Patients with adverse outcomes had larger ILTV compared to those without (PM: 1.038cc vs 0.807cc, p=0.041; ECE: 1.388cc vs 0.765cc, p&lt;0.001; LNI: 2.970cc vs 0.797cc, p&lt;0.001; SVI: 2.269cc vs 0.798cc, p&lt;0.001). On multivariate analysis, ILTV was found to be an independent predictor of PM (OR: 1.149, p=0.036), ECE (OR: 1.269, p=0.001), LNI (OR: 1.387, p&lt;0.001), and SVI (OR: 1.341, p&lt;0.001). Conclusions: We demonstrate that Index Lesion Tumor Volume measured on T2W MRI is an independent predictor of PM, ECE, LNI, and SVI following RARP, and serves as a preoperative marker that may facilitate and inform patient counseling and decision making.

Predictors of Positive Margins at Time of Loop Electrosurgical Excision Procedure.

The aim of the study was to identify factors associated with the presence of high-grade squamous intraepithelial lesion (HSIL) at surgical margins of loop electrosurgical excision procedure (LEEP) pathology specimens. All women evaluated for lower genital tract disease at a single academic institution were prospectively entered into a database. The database was queried for all women who had a LEEP performed for indications within contemporary American Society of Colposcopy and Cervical Pathology guidelines between April 1, 2013, and April 30, 2015. Factors extracted from the database included demographics, contraception, weight, tobacco use, provider volume, resident participation, history of cervical procedure, and pathology features including preceding Pap test category. A positive margin was defined as HSIL on either the endocervical or ectocervical margin of the LEEP specimen or in endocervical curettage specimen after LEEP. We performed univariable statistics to identify factors associated with positive margins and then logistic regression modeling on significant factors for the outcome of positive margins. Two hundred sixty-nine women were identified. Seventy five (27.8%) of these women had positive margins. Only tobacco use, gravity, parity, and preceding Pap category were significant on univariable analysis. After multivariable analysis, smokers remained more likely to have positive margins (odds ratio = 2.01; CI = 1.12-3.6; p < .01) as did those with preceding HSIL Pap tests (odds ratio = 1.96; CI = 1.13-3.41; p < .01). In our population, of all the factors assessed, only tobacco use and preceding high-grade Pap tests were associated with positive margins at time of LEEP. This information may be helpful in preprocedural planning to optimize treatment.

Reexamining the Association Between Positive Surgical Margins and Survival After Partial Nephrectomy in a Large American Cohort.

To investigate the impact of positive surgical margins (PSM) on overall survival (OS) in a large American cohort with intermediate-term follow-up. Using the National Cancer Data Base, we identified 6038 cases of pathological T1-T3a, nonmetastatic renal-cell carcinoma managed with partial nephrectomy (PN) from 2003 to 2006. Patients were stratified into two groups based on margin status. Predictors of positive margins were evaluated using multivariable logistic regression analysis. OS by margin status was evaluated using Kaplan-Meier analysis and the log-rank test. A multivariable Cox proportional hazards model was used to evaluate the adjusted association between margin status and survival. Overall, 302 (5.3%) patients had positive margins. On multivariable analysis, higher pathological T stage and higher comorbidity score were the only factors significantly associated with positive margins (p < 0.001 and p = 0.015, respectively). At 71-month median follow-up, the unadjusted 5-year OS for the entire cohort was 92%. Positive margins were significantly associated with decreased 5-year OS (89% vs 92%, p = 0.002), and this association remained significant in healthy patients (p = 0.027). On multivariable survival analysis, positive margins significantly predicted hastened time to all-cause death (hazards ratio 1.34; 95% CI 1.01, 1.78; p = 0.038). In the largest observational study to date, PSM were associated with worse OS after PN. Further study on cancer-specific outcomes with long-term follow-up is needed.

Effect on postoperative survival of the status of distal ureteral margin: The necessity to achieve negative margins at the time of radical cystectomy

BackgroundDespite several studies, the adequate management of positive distal ureter margins at the time of radical cystectomy (RC) remains controversial. Particularly, it is not clear whether the achievement of negative distal ureter margins at the intraoperative frozen sections (IFS) affects postoperative cancer-specific mortality (CSM). MethodsIn all, 1,447 consecutive patients treated with RC at a single center between January 1987 and August 2014 were considered. Multivariable (MVA) logistic regression analyses were used to determine predictors of positive IFS. MVA Cox regression analyses were used to test the effect on CSM of intraoperative conversion to negative margins. ResultsAt IFS, 368 patients (25%) experienced at least 1 positive margin. Of these, a negative conversion of the margin at IFS occurred in 178 (48%) whereas 190 (52%) had a positive final ureteral margin. The mean follow-up was 95 months (median = 102). At MVA, history of carcinoma in situ (odds ratio = 6.40, P<0.001) was predictors of positive margin at IFS. At MVA, ureteral margins that were not converted to negative (hazard ratio = 1.92, P = 0.01) were associated with CSM but only in patients with negative soft tissue margin and without node metastases. ConclusionsAchieving negative IFS margins may be associated with survival benefit in patients without residual bladder cancer after RC. Patients who recorded a history of carcinoma in situ before RC are at higher risk to incur positive ureteral margin at IFS and should be investigated during RC.

Do screen-detected breast cancers have positive margins less often than clinically detected breast cancers?

Positive tumour margins after breast-conserving surgery (BCS) have been selected as one of the major quality criteria for the surgical treatment of localized primary breast cancer. The national guideline states that the rate of positive margins should not exceed 30% in ductal carcinoma in situ and 20% in invasive cancers. We aimed to determine whether BCS in women with screen-detected breast cancer (SDBC) will have positive margins less often compared with women with clinically detected breast cancer (CDBC). Furthermore, the choice of subsequent therapy is studied when margins were positive after initial BCS. Women 50-75 years of age who underwent BCS for invasive breast cancer between July 2008 and December 2009 were selected from the Netherlands Cancer Registry. Data were merged with the National Cancer Screening Program, regions North and East, to identify women with SDBC. The relation to screening history, clinical and pathological factors was evaluated for correlation with margin status using multilevel analysis. Of 1537 women with an invasive breast cancer, 873 (57%) were diagnosed through the screening programme. SDBCs were significantly smaller (87 vs. 69% T1 tumours, i.e. ≤2 cm), more often well differentiated (33 vs. 26%), preoperatively confirmed (98 vs. 96%), diagnosed in a nonteaching hospital (60 vs. 66%) and more often had negative lymph nodes (LNs) (80 vs. 68%). In 170 out of 1537 women, the resection margins were positive. Multivariable analysis showed that hospital, tumour size, multifocality, positive LNs and absent preoperative confirmation were predictors of positive margins. No difference was found between women with SDBC and CDBC. Of women with positive margins, 90% underwent additional surgery. Women diagnosed with SDBC do not have a lower risk of having positive margins after BCS than women with CDBC. Although positive margins may occur in 11% of women with invasive tumours, well below the percentage recommended by the national guideline, the presence of encouraging factors by SDBC such as a smaller tumour size, unifocality, negative LNs and the presence of preoperative confirmation should not lead to performing a more sparing excision than is considered usual for comparable CDBC.

Invited commentary on “A prospective study of tumor and technical factors associated with positive margins in breast-conservation therapy for nonpalpable malignancy” by Reedijk et al

This commentary accompanies the article by Reedijk et al in which the authors analyzed prospectively collected data from a randomized trial of radioactive iodine seed versus wire localization to determine factors predictive of positive margins after breast-conserving procedures for nonpalpable breast cancers. Margins were considered positive when disease was found at,1 mm from the inked margin. Given this definition, the rate of positive margins was 20%. Multivariable analysis of pooled data from the 2 arms of the trial revealed that localizations performed using stereotactic guidance, the presence of ductal carcinoma in situ, tumors .2 cm, and multifocal disease were predictive of positive margins. These data confirmed prior retrospective studies from these same and other authors, who identified young age, the presence of calcifications on mammography, lobular histology, and lymphovascular invasion as predictors of positive margins, in addition to the factors identified earlier in the current article. The relatively high rate of margin positivity begs 2 questions. The first relates to methods for lowering the risk of positive margins in breast-conserving operations. Pathologic touch preparation cytology and frozen section analyses are used in some centers for intraoperative margin assessment but have not gained wide popularity because of

DCIS in pre-operative core biopsy is a predictor of positive margins after breast conserving surgery.

DCIS in pre-operative core biopsy is a predictor of positive margins after breast conserving surgery.

Preoperative Predictors of Positive Margins after Loop Electrosurgical Excisional Procedure-Cone

Preoperative Predictors of Positive Margins after Loop Electrosurgical Excisional Procedure-Cone

Predictors of positive margins after local excision of ductal carcinoma in situ

Background: This study aimed to examine the association between clinicopathologic parameters and positive margins in women with ductal carcinoma in situ (DCIS) treated by breast-conserving surgery (BCS). Methods: We retrospectively reviewed the clinical, radiologic, and pathologic data of 100 women who had undergone BCS for DCIS in our center. Results: Sixty-seven percent of patients presented via breast screening and 55% of all cases were diagnosed preoperatively on fine needle aspiration cytology ([FNAC] ie, C5). Overall, 45% of patients had clear margins after initial local excision. Positive margins showed a nonsignificant trend of association with distribution of microcalcifications (MCC), nonconsultant operating surgeon, inconclusive preoperative FNAC, presence of necrosis, and low specimen weight. There was a highly significant association between low grade DCIS ( P = 0.003) and incomplete excision. There was no significant association with age, associated invasive focus, morphology of MCC, or with mode of presentation. Conclusion: Positive margins after local excision of DCIS are significantly associated with low nuclear grade, and preoperative determination of nuclear grade by core biopsy may have surgical implications.

Site specific predictors of positive margins at radical prostatectomy: an argument for risk based modification of technique

Correspondence to Mr Christopher R. Chapple, Urology Research Department, Royal Hallamshire Hospital, Glossop Road, Sheffield S10 2JF, UK. Tel: +44 114 271 2791; fax: +44 114 279 8318 Royal Hallamshire Hospital, Glossop Road, Sheffield, UK