Predictive factors for residual disease in re-excision specimens after breast-conserving surgery

Local recurrence is an issue of concern after breast-conserving therapy and removing the primary tumor with negative surgical margins is the most important determinant of local recurrence. However, some patients with positive margins after initial surgery will have no residual tumor in the re-excision specimen. To avoid unnecessary re-excisions, factors predicting residual disease in re-excision material should be determined. This study aimed to determine the predictive factors for residual disease in the re-excision material in a homogeneous group of patients with positive margins and only invasive ductal carcinoma. Breast cancer patients treated between 2005 and 2008 with breast-conserving surgery and subsequent re-excisions due to positive surgical margins after initial surgery were included in the study. Patients were divided into two groups as those with and without residual disease in the re-excision material. One hundred and four breast cancer patients were included in the study. Forty-seven patients (45.2%) had residual tumor in re-excision specimen. Patient characteristics such as age (p = 0.42) and physical findings (p = 1.0) and specimen volume (p = 0.24), tumor grade (p = 0.33), estrogen (p = 1.0), and progesterone (p = 0.37) receptor status, axillary lymph node metastases (p = 0.16), extensive intraductal component (p = 0.8), and lymphovascular invasion (p = 0.064) were found as insignificant factors for predicting residual tumor. Large tumor size (>3 cm) (p = 0.026), human epidermal growth factor receptor2 (HER2) positivity (p = 0.013), and tumor to specimen volume ratio of >70% (p = 0.002) significantly increased the probability of finding residual disease after re-excision. In multivariate analysis, HER2 positivity (p = 0.046) and tumor to specimen volume ratio of >70% (p = 0.006) independently predicted the presence of residual disease. As a result, in patients with HER2 positive tumors larger than 3 cm, larger volume of breast tissue around the tumor should be removed to decrease the number of re-excisions due to positive surgical margins.     

Close surgical margins after radical prostatectomy mimic biochemical recurrence rates of positive margins

IntroductionThe significance of a “close” but negative surgical margin after radical prostatectomy (RP) is controversial. We evaluated the effect of a close surgical margin (CSM) on biochemical recurrence (BCR) compared to a negative margin after RP.Materials and methodsPathologic records of men who underwent RP from 2005-2011 were retrospectively reviewed. Margin status was classified as “positive” (PSM), “negative” (NSM), or “close” (<1 mm from margin). BCR was defined as 2 consecutive postoperative prostate specific antigen measurements >0.2 ng/ml. Probability of BCR was estimated using the Kaplan-Meier method and stratified by margin status. Univariable and multivariable Cox proportional hazards models were used to determine whether close margin status was associated with an increased rate of BCR.ResultsA total of 609 consecutive patients underwent RP (93% robotic) and had complete pathologic data. A total of 126 (20.7%) had PSM, 453 (74.4%) had NSM, and 30 (4.9%) had CSM (mean<0.44 mm). The 3-year BCR-free survival for patients with CSM was similar to those with PSM (70.4% vs. 74.5%, log rank P = 0.66) and significantly worse than those with NSM (90%, log rank P<0.001). On multivariable regression, positive margin status (HR = 3.26, P<0.001) was significantly associated with a higher risk of BCR, along with close margins (HR = 2.7, P = 0.04).ConclusionsBCR for patients with CSM at RP is tantamount to PSM patients. CSM <1 mm should be explicitly noted on pathology reports. Patients with this finding should be followed up closely and offered adjuvant therapy.     

Tumour involvement of the re-excision specimen following clear local excision of breast cancer with positive margins

Background: Breast conservation surgery and subsequent radiotherapy is an acceptable method of treating breast cancer. Complete excision of the primary tumour is important to minimize the risk of local recurrence. Re‐excision is usually carried out if the initial primary tumour excision shows positive margins. However, a significant proportion of re‐excision specimens are negative for tumour. The aim of the present study was to identify factors predicting a histologically positive re‐excision specimen. Methods: The case records of all patients with invasive and in situ breast cancer referred to the William Buckland Radiotherapy Centre between January 1996 and December 2001 were reviewed. The factors evaluated were patient age, whether or not tumours were detected by screening mammography, use of hook‐wire needle localization, whether tumours were marked with orientating sutures, histopathological characteristics of the tumour and involvement of axillary nodes. Univariate analysis was performed. Results: In the study period, a total of 1128 patients were reviewed. Of these, 742 underwent breast conservation surgery. Twenty‐nine (3.9%) of the 742 had positive surgical margins and underwent re‐excision. Data were insufficient for six, leaving 23 patients eligible for the study. The number of patients entering the study was small, limiting the statistical analysis. Of these, 21 patients had invasive cancer and two patients had ductal carcinoma in situ only. Of 23 re‐excisions, 11(48%) contained residual tumour. Univariate analysis of the data revealed no significant factors that were likely to predict tumour in the re‐excision specimen. The local recurrence after re‐excision in patients with positive margins was 4.3%. Conclusion: The results suggest that it is not possible to predict which patients will have tumour in the re‐excision specimen. However, approximately 50% of re‐excision specimens showed residual cancer. Therefore it is recommended that all excisions with positive margins need further surgery.     

Positive surgical margins are a risk factor for significant biochemical recurrence only in intermediate-risk disease

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Positive surgical margins (PSMs) after radical prostatectomy are common, although their impact on the risk of disease recurrence is unknown. We examined the impact of PSMs on the risk of ‘significant’ biochemical recurrence stratified by their risk of occult metastatic disease. We find that only in intermediate‐risk disease does the presence of a PSM have a significant impact on the risk of recurrence, and this represents a failure of technique. By contrast, for high‐ and low‐risk disease, the risk of recurrence is driven by intrinsic tumour biology, and the presence of a PSM has little impact on outcome.

OBJECTIVE

• ? To determine the impact of surgical margin status on the risk of significant biochemical recurrence (prostate‐specific antigen [PSA] doubling time <3, <6 or <9 months) after prostatectomy.

MATERIALS AND METHODS

• ? Patients undergoing radical prostatectomy with complete clinical and pathological data and detailed PSA follow‐up were identified from two prospectively recorded databases.
• ? Patients were stratified according to their risk of occult systemic disease (low risk: PSA < 10 ng/dL, pT2 stage and Gleason score ≤6; intermediate risk: PSA 10–20 ng/dL, pT2 stage and/or Gleason score 7; high: PSA > 20 ng/dL or pT3‐4 stage or Gleason score 8–10) and the impact of a positive surgical margin (PSM) within each stratum determined by univariable and multivariable analysis.

RESULTS

• ? Of 1514 patients identified, 276 (18.2%), 761 (50.3%) and 477 (31.5%) were classified as having low‐, intermediate‐ and high‐risk disease respectively.
• ? A total of 370 (24.4%) patients had a PSM and with a median follow‐up of 22.2 months, and 165 (7%) patients had a biochemical recurrence.
• ? Sufficient PSA data was available to calculate PSA doubling times in 151/165 patients (91.5%).
• ? The PSM rate rose significantly, from 11% in low‐risk to 43% in high‐risk disease (P < 0.001), with similar positive associations noted with tumour grade, stage and serum PSA (P < 0.001).
• ? Patients with low‐risk disease had essentially identical risks of significant biochemical recurrence over the study period, regardless of surgical margin status. By contrast, in patients with both intermediate‐ and high‐risk disease, a PSM was a strong predictor of significant biochemical recurrence on univariable analysis. On multivariable analysis, howver, PSM predicted significant disease recurrence in intermediate‐risk disease only.

CONCLUSIONS

• ? PSM is a risk factor for significant biochemical recurrence only in intermediate risk disease.

     

Role of re-excision for positive and close resection margins in patients treated with breast-conserving surgery

PurposeTo evaluate the incidence of residual disease after additional surgery for positive/close margins and the impact on the rate of local and distant recurrence.MethodsA retrospective analysis on 1339 patients treated for breast cancer with breast conserving-surgery and radiotherapy at a single Institution between 2000 and 2009 was performed.ResultsDuring primary surgery 526 patients (39.3%) underwent intraoperative re-excision. At the final pathological report, the margins were positive in 132 patients (9.9%) and close in 85 (6.3%). To obtain clear margins, 142 of these women underwent a second surgery; 35 patients with positive margins (27%) and 40 with close margins (47%) did not receive additional surgery because of different reasons (patients refusal, old age, comorbidity or for focal margin involvement). At second surgery, residual disease was found in 62.9% of patients with positive margins and in 55.5% of those with close margins. At a median follow-up time of 4 years, local recurrence (LR) rate was 2.9% for patients with clear margins, 5.2% (p = 0.67) for patients with unresected close margins and 11.7% (p = 0.003) for those with unresected positive margins. The HER-2 and the basal-like subtypes had the higher rate of LR and the luminal A the lowest.ConclusionsA significantly higher LR rate was found only among patients with positive margins not receiving additional surgery, but not in those with unresected close margins. Positive margins are a strong predictor for LR and need re-excision that can be avoided for close margins.     

The oncologic safety of breast-conserving surgery for breast ductal carcinoma in situ

Objective To evaluate the safety of breast-conserving surgery for ductal carcinoma in situ( DCIS) . Methods One hundred and nineteen patients with pathologically confirmed DCIS were analyzed retrospectively.     

The rate of breast-conserving surgery for early breast cancer is not influenced by the surgical strategy of excisional biopsy followed by the definitive procedure

Increased emphasis on breast conservation and the primacy of the patient's preferences has led to the promotion and increased use of a two-step surgical strategy (definitive operation only after a final tissue diagnosis from a biopsy done on a previous visit) in the treatment of early breast cancer, with the assumption being that this is more conducive to the performance of breast-conserving surgery (BCS). We sought to test this by examining the effect of the surgical strategy (one-step versus two-step) on the operation performed (BCS versus mastectomy). A random sample of women with node-negative breast cancer diagnosed in 1991 in Ontario was drawn from the Ontario Cancer Registry database and matched to the Canadian Institute of Health Information and Ontario Health Insurance Plan databases (n = 643). This provided information on the timing and nature of all surgical procedures performed as well as patient, tumor, hospital, and surgeon characteristics. The surgical strategy was defined as either a one-step procedure (biopsy and definitive surgery performed at the same time) or a two-step procedure (surgical biopsy and pathologic diagnosis, followed by definitive surgery at a later date). The axillary lymph node dissection was used to define the definitive procedure. BCS was employed in 68% of patients, and this did not differ significantly between the one-step and two-step groups (66% versus 70%). Patients with palpable lesions had a significantly lower rate of breast conservation than those with nonpalpable lesions. Other variables associated with a lower rate of BCS were larger tumor size, presence of extensive ductal carcinoma in situ (DCIS), and central or multifocal tumors. The use of a one-step procedure was associated with a patient age of more than 50 years, a palpable mass, tumor size larger than 1 cm, previous fine needle aspiration (FNA) biopsy, absence of extensive DCIS, and surgery in an academic setting. Breast conservation was not affected by the surgical strategy used or the timing of the decision, but was associated with several accepted tumor factors. This study shows that, contrary to the opinion of some, there is a group of breast cancer patients in whom treatment in a one-step manner is appropriate.     

Breast reconstruction by local flaps after conserving surgery for breast cancer: an added asset to oncoplastic techniques

Abstract:  This study describes and evaluates the results of a proposed simple technique of volume replacement by local flaps to reconstruct the breast after conserving surgery for breast cancer. Twenty-five patients with breast cancer were enrolled in the study between 1998 and 2004. All patients were surgically treated by wide local excision and axillary dissection of level I & II. The primary closure was not feasible because of resulting large defect in proportion to the breast size. The defect was constructed by local flap raised from adjacent skin and subcutaneous tissue with or without glandular breast tissue. Data analyzed includes: age, tumor location, tumor size, histopathology results, operative techniques, complications, long-term oncological events, and cosmetic outcome. The mean follow-up was 48 months. The mean age was 45.3 years. The mean tumor size was 3.1 cm. All tumors had upper outer or upper central location. Fourteen tumors were in left breast. Histopathological analysis had revealed 84% infiltrating ductal carcinoma of no otherwise specified type, 12% medullary type, and 4% tubulo-lobular carcinoma. Additional ductal carcinoma in situ was found in three patients. One patient had focally positive deep margin. One hematoma and one fat necrosis during radiotherapy were documented. During follow-up, one patient developed local recurrence after 4 years and required mastectomy, another patient developed concomitant local recurrence and distant metastasis in the lung and brain after 18 months of the primary treatment and died 1 year later. In this study, 84% of women were satisfied with their cosmetic outcome. This study demonstrated the value of local flaps to reconstruct breast defects after wide local excision of tumors in upper outer or upper central location as simple alternative to latissimus dorsi flap and other volume displacement techniques.     

Impact of initial surgical margins and residual cancer upon re-excision on outcome of patients with localized breast cancer

Background

A significant proportion of patients undergoing breast conservation therapy require additional operations to obtain clear margins. The aim of this study was to assess the impact of initial margins and residual carcinoma found on second surgery on the outcomes of breast cancer patients.

Methods

In this retrospective study, Cox proportional-hazard regression analysis was performed to evaluate data from 437 patients with stage I to IIIA breast cancer who underwent initial breast-conserving surgery between 1994 and 2004.

Results

The distant recurrence rate was higher among patients with initial positive margins than among those with initial negative margins (15.5% vs 4.9%; hazard ratio, 3.6; 95% confidence interval 1.5-8.7; P = .003). For patients who had underwent second surgery, the finding of a residual invasive carcinoma was associated with increased risk for distant recurrence (22.8% vs 6.6%; hazard ratio, 3.5; 95% confidence interval, 1.8-7.4; P = .0001).

Conclusion

Invasive residual carcinoma found during subsequent surgery after initial compromised margins is an important prognostic marker for distant recurrence.     

A prospective, randomized, controlled, multicenter study of a real-time, intraoperative probe for positive margin detection in breast-conserving surgery

BACKGROUND: This randomized, double-arm trial was designed to study the benefit of a novel device (MarginProbe, Dune Medical Devices, Caesarea, Israel) in intraoperative margin assessment for breast-conserving surgery (BCS) and the associated reduction in reoperations. METHODS: In the device group, the probe was applied to the lumpectomy specimen and additional tissue was excised according to device readings. Study arms were compared by reoperation rates and by correct surgical reaction confirmed by histology. RESULTS: Three hundred patients were enrolled. Device use was associated with improved correct surgical reaction, defined as additional re-excision in all histologically detected positive margins, with tumor within 1 mm of inked margin. The repeat lumpectomy rate was significantly reduced by 56% in the device arm: 5.6% versus 12.7% in the control arm. There were no differences in excised tissue volume or cosmetic outcome. CONCLUSIONS: Intraoperative use of the MarginProbe for positive margin detection is safe and effective in BCS and decreases the rate of repeat operations.     

The influence of additional surgical margins on the total specimen volume excised and the reoperative rate after breast-conserving surgery

BACKGROUND: It is unclear whether the additional removal of breast tissue during breast-conserving therapy (BCT) for breast cancer beyond the standard lumpectomy reduces the incidence of inadequate microscopic margins found at pathological examination and subsequent reoperation. This study compares the reoperative rates after initial BCT in 3 groups of patients who underwent lumpectomy with complete resection of 4 to 6 additional margins, lumpectomy with selective resection of 1 to 3 additional margins, or standard lumpectomy. METHODS: Retrospective data were reviewed from 171 selected cases of BCT, from May 2000 to February 2006. Forty-five cases involved lumpectomy with complete resection of 4 to 6 additional margins; 77 involved lumpectomy with selective resection of 1 to 3 additional margins, whereas 49 involved standard lumpectomy. All samples underwent pathologic analysis of inked resection margins by permanent section. The 3 groups were compared for patient demographics, tumor size and histologic subtype, tumor stage, margin status, excised specimen volume, and eventual subsequent reoperation. Adequate surgical margin was defined as any negative margin greater than 2 mm. RESULTS: The group with complete resection of 4 to 6 additional margins had a subsequent reoperation rate of 17.7%, whereas the group with selective resection of 1 to 3 additional margins and the standard lumpectomy group had a subsequent reoperation rate of 32.5% and 38.7%, respectively, because of inadequate margins. The mean total excised specimen volume in the 3 groups was 129.19, 46.04, and 37.44 cm3, respectively. CONCLUSIONS: The complete resection of 4 to 6 additional margins during the initial BCT resulted in the lowest subsequent reoperation rate, and the largest total volume specimen excised among the 3 techniques studied.     

The impact of nerve sparing on incidence and location of positive surgical margins in radical prostatectomy

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Nerve sparing radical prostatectomy has been associated with increased risk of positive surgical margins due to the close anatomical relationship of the neurovascular bundle to the posterolateral aspect of the prostatic fascia. Our study of 945 men who underwent radical prostatectomy be one experienced surgeon found no increased risk of positive surgical margins, whether the cancer was organ confined or extracapsular extension was present.

OBJECTIVE

• ? To examine whether nerve‐sparing surgery (NSS) is a risk factor for positive surgical margins (PSMs) in patients with either organ‐confined prostate cancer or extracapsular extension (ECE).

PATIENTS AND METHODS

• ? Clinicopathological outcome data on 945 consecutive patients treated with radical prostatectomy (RP) were prospectively collected.
• ? All patients underwent RP (bilateral, unilateral or non‐NSS) by one surgeon between 2002 and 2007.
• ? Risk of PSMs and their locations with respect to NSS was determined by multivariate logistic regression analysis adjusting for preoperative risk factors for PSMs within pT2, pT3a and pT3b tumours.

RESULTS

• ? Overall a PSM was identified in 19.6% of patients in an unscreened population with mean prostate‐specific antigen (PSA) level of 8.1 ng/mL.
• ? There was no significant difference in rates of PSMs between NSS groups on multivariate analysis (P= 0.147).
• ? There was no significant difference in pT2 (P= 0.880), pT3a (P= 0.175) or pT3b (P= 0.354) tumours.
• ? The only significant predictor of PSMs was preoperative PSA level (risk ratio 1.289, P= 0.006).
• ? There was no significant difference in the location of PSMs except for the pT3a group, where the patients that had bilateral NSS were at higher risk of a posterolateral PSM (P= 0.028).

CONCLUSIONS

• ? With appropriate selection of patients, NSS does not increase the risk of PSMs, whether the cancer is organ confined or ECE is present.
• ? The adverse impact of the NSS procedure in the hands of an experienced surgeon is minimal and is a realistic compromise to obtain the increase in health‐related quality of life offered by NSS.

     

The impact of positive soft tissue surgical margins following radical cystectomy for high-grade,invasive bladder cancer

Introduction  We evaluate the incidence and risk factors associated with positive soft tissue surgical margins (STSM) and determine the association with various surgical and pathological characteristics and clinical outcomes in patients undergoing radical cystectomy (RC) for bladder cancer. Patients and methods  From November 1971 to December 2005, 1,591 patients with primary transitional cell carcinoma (TCC) of the bladder underwent RC, with an extended bilateral pelvic lymphadenectomy and urinary diversion. A positive STSM was defined as tumor identified at the inked perivesical soft tissue surrounding the cystectomy specimen. Data were analyzed according to various clinical and pathologic variables, and survival analysis was performed. Results  A total of 18 patients (1%) demonstrated pathologic evidence of a positive STSM following RC. Positive STSM were significantly associated with lymphovascular invasion, advanced pathologic stage, lymph node involvement, extent of nodal involvement and lymph node density. No patient with an organ-confined primary bladder tumor had a positive STSM, while 3% with extravesical tumor extension demonstrated a positive STSM. Recurrence-free and overall survival at 5 and 10 years for patients with a positive STSM was 29 and 22%, and 29 and 11%, respectively (p < 0.001). A positive STSM increased the risk of recurrence by threefold and the overall risk of death by 2.6 times. Only nine patients (1%) without evidence of nodal involvement had a positive STSM with a worse survival compared to those same pathologic subgroup and negative STSM. Nine patients (2%) with lymph node tumor involvement had positive STSM and also demonstrated significantly worse survival. Conclusion  Although a positive STSM was present in only 1% of patients undergoing a RC for TCC of the bladder, it was found to be an independent risk factor for advanced disease, lymph node involvement and tumor progression with worse survival. A dedicated effort should be made to avoid a positive STSM at the time of RC.     

Influence of breast cancer margin assessment method on the rates of positive margins and residual carcinoma

BACKGROUND: We hypothesized that the method of breast cancer margin assessment may be associated with different rates of positive margins and residual carcinoma. METHODS: A total of 178 breast cancer specimens were divided into 2 groups (A and B) based on the margin assessment method used. Rates of positive margins, re-excision, and residual carcinoma at re-excision were compared and analyzed statistically. RESULTS: At least 1 margin was positive in 64.7% in group A and in 65.2% in group B. At directed re-excision 54% in group A and 51% in group B had residual carcinoma. The lateral margin was positive in 44% in group A compared with 26% in group B (P = .06). The posterior margin was positive in 19% in group A and in 51% in group B (P = .001). CONCLUSIONS: Two different breast cancer specimen margin assessment methods had comparable rates of positive margins and residual carcinoma at re-excision. Different patterns of specific margin positivity suggest that the method of margin assessment may alter results.     

Positive margins after nephron‐sparing surgery for renal cell carcinoma: long‐term follow‐up of patients on active surveillance

Study Type – Therapy (case series)
Level of Evidence 4

OBJECTIVE

To analyse our long‐term oncological outcomes with active surveillance in patients with positive surgical margins (PSMs) after nephron‐sparing surgery (NSS) for renal cell carcinoma (RCC), as this situation is a difficult therapeutic dilemma.

PATIENTS AND METHODS

We performed open NSS for renal masses with frozen‐section analysis of any suspicious zone of the surgical bed, followed by extensive argon‐beam coagulation. In patients where the final histopathological examination of the renal mass revealed PSMs, follow‐up consisted of computed tomography (CT) every 6 months in the first 2 years and then annually up to 5 years, and thereafter we alternated ultrasonography with CT.

RESULTS

From 1995 to 2003 we had 11 cases of microscopic definitive PSMs after NSS for RCC. Two patients required nephrectomy (one for postoperative bleeding and another as an elective procedure), so nine were followed. These patients were either operated under elective (seven) or imperative (two) conditions. The histological subtype was clear cell carcinoma in three, papillary in two, chromophobe in two and hybrid oncocytic RCC in two, with a Furhman grade of 2 in six and 3 in three. The mean size was 31.4 mm, and the stage was pT1a in six, pT1b in one and pT3a in two. After a median follow‐up of 80.5 months, there was no local recurrence or distant progression.

CONCLUSIONS

In our experience, microscopic PSMs in NSS specimens can be managed conservatively with active surveillance, achieving excellent results and avoiding extensive reoperation without compromising long‐term oncological outcomes.     

影响乳腺癌患者保乳手术边缘阳性因素的临床研究

目的探讨乳腺癌的临床病理学特征对保乳手术边缘阳性的影响。方法189例预行保乳手术术(BCT)的原发性乳腺癌患者,分析她们的临床特征(年龄,活检类型)和病理学特征(肿瘤大小,组织学类型,激素受体状态,HER2状态,和腋窝淋巴结状态)与阳性手术边缘的关系。结果189例患者中本组室心针肿脾物案例活检确诊79例,门诊或手术中切除活检确诊128例。61例手术边缘阳性(32.3%)。结论本研究的结果揭示:肿瘤直径大于2cm,腋窝淋巴结阳性PR阳性和年龄小于50岁是乳癌保乳手术边缘阳性的高危因素对1999年1月～2004年7月189例乳腺癌患者按受保乳手术进行回顾性分析,并总结手术切口边保阳性与临床特征病理案组但表现及激素受体状态的关系。