|Year : 2018 | Volume
| Issue : 4 | Page : 361-365
Comparison of resection margins and cosmetic outcome following intraoperative ultrasound-guided excision versus conventional palpation-guided breast conservation surgery in breast cancer: A randomized controlled trial
Tejas Vispute1, Suhani2, V Seenu2, Rajinder Parshad2, Smriti Hari3, Sanjay Thulkar3, Sandeep Mathur4
1 Department of Surgical Oncology, BRA-IRCH; Department of Surgical Disciplines, All India Institute of Medical Sciences, New Delhi, India
2 Department of Surgical Disciplines, All India Institute of Medical Sciences, New Delhi, India
3 Department of Radio Diagnosis, All India Institute of Medical Sciences, New Delhi, India
4 Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
|Date of Web Publication||28-Feb-2019|
Department of Surgical Disciplines, All India Institute of Medical Sciences, New Delhi
Source of Support: None, Conflict of Interest: None
INTRODUCTION: Use of intraoperative ultrasound (IOUS) has been shown to help achieve satisfactory cosmesis and negative margins in breast conserving surgery (BCS). This study has been done to compare the oncological and cosmetic outcomes following BCS using conventional palpatory method and IOUS. MATERIALS AND METHODS: This is a prospective randomized controlled trial conducted at a tertiary care teaching and research institute in India. Patients with early operable breast cancer willing for BCS were included. Tumors were excised with 1 cm margin. In palpatory group, tumor was palpated and 1 cm margin was taken with a measuring scale while in the second group, IOUS was used to mark the margins. Histopathological evaluation was done to assess margins and cosmesis was assessed by patient, resident doctor, and nurse independently. RESULTS: Sixty patients were included, 32 in the ultrasonography-guided and 28 in palpation-guided wide local excision. The mean age of patients was 48.78 years. In both groups, mean tumor size was 3.18 cm. Margin thickness and positivity was higher in palpatory group (though P > 0.05). Most patients were satisfied with cosmesis. There was no significant difference in complications and specimen volume in both groups. Presence of ductal carcinoma in situ component and expression of Her2neu by tumor cells had a significant impact on margin positivity. CONCLUSIONS: Intraoperative use of ultrasound offers a real-time assessment of margin status and may reduce the margin positivity rate compared to conventional palpation-guided method.
Keywords: Breast cancer, breast conservation surgery, ultrasonography-guided WLE, wide local excision
|How to cite this article:|
Vispute T, Suhani, Seenu V, Parshad R, Hari S, Thulkar S, Mathur S. Comparison of resection margins and cosmetic outcome following intraoperative ultrasound-guided excision versus conventional palpation-guided breast conservation surgery in breast cancer: A randomized controlled trial. Indian J Cancer 2018;55:361-5
|How to cite this URL:|
Vispute T, Suhani, Seenu V, Parshad R, Hari S, Thulkar S, Mathur S. Comparison of resection margins and cosmetic outcome following intraoperative ultrasound-guided excision versus conventional palpation-guided breast conservation surgery in breast cancer: A randomized controlled trial. Indian J Cancer [serial online] 2018 [cited 2019 Jul 15];55:361-5. Available from: http://www.indianjcancer.com/text.asp?2018/55/4/361/253285
| » Introduction|| |
Breast conserving surgery (BCS) is the standard of care for early breast cancer. The term BCS comprises wide local excision (WLE) of primary tumor, sentinel node biopsy (SLNB) ± axillary lymph node dissection (ALND), and radiotherapy to breast. The two cardinal principles of WLE are tumor-free margin at the primary tumor site and good cosmesis. Excising too much or too little margin has its own advantages and pitfalls. While inadequate surgical margins represent a high risk for adverse clinical outcome requiring additional treatment in the form of repeat surgery or radiation boost, excision of large amounts of breast tissue to achieve tumor-free margin may give poor cosmetic results. Surgeons, hence, have to strike a balance between these two ends. Conventional technique of WLE entails intraoperative palpation of the edge of the tumor and resection of breast tissue of at least 1 cm from the palpable edge in all planes. However, reported positive resection margins in patients undergoing WLE by palpatory technique vary from 20% to 40%. To reduce the presence of tumor at margin, some investigators advocated use of cavity shavings. However, routine use of cavity shavings to decrease margin positivity is also not a universally accepted norm. Use of intraoperative ultrasound (IOUS) has been shown to aid in giving a near accurate “real-time” estimate of the tumor size as well as the margin, leading to decrease in margin positivity as well as improved cosmesis. This randomized trial has been designed to compare the oncological and cosmetic outcomes following WLE of primary breast tumor using conventional palpatory method and IOUS.
| » Materials and Methods|| |
This study was a prospective randomized controlled trial conducted at a tertiary care teaching and research institute in India after obtaining approval from the institutional ethics committee. The trial was registered with the clinical trials registry – India (CTRI/2017/11/010576). It was carried out with the aim to compare the oncological and cosmetic outcomes following WLE of primary breast tumor using conventional palpatory method and IOUS. The assessment of margin status and cosmetic satisfaction was taken as primary outcome variables to be studied while study of factors associated with margin positivity was taken as secondary outcome. Patients with early operable breast cancer (T1/T2 lesions amenable to breast conservation primarily or downstaged by neo adjuvant chemotherapy) willing for breast conservation were included in the study. Patients not desirous of breast conservation, poor tumor-to-breast ratio, multicentric tumors, pregnant/lactating patients, and patients with severe comorbidities precluding fitness for general anesthesia were excluded. Patients were randomized into two groups by “block randomization.” One group was allocated to undergo WLE with IOUS-guided technique (mentioned in this study as group I) and the other to undergo WLE with conventional tumor palpation technique (mentioned in this study as group II).
All procedures were performed under general anesthesia. While the essential surgical procedure was same in both groups, technique of taking 1 cm margin was different. In palpatory method, tumor was palpated and 1 cm margin was taken with a measuring scale in three dimensions and WLE was performed. The margins of the cavity were palpated for suspicious areas and cavity shavings were sent for histopathology in cases of suspicious margins. In ultrasonography (USG)- guided method, 1 cm margins were marked (superior, inferior, medial, and lateral) with the help of ultrasound and WLE was performed under US guidance. MicroMaxx SonoSite® with HFL38X linear array transducer (probe) with frequency range 6–13 MHz was used for IOUS. Ex vivo US of the excised specimen was performed. In either group, cavity shavings were sent for histopathology from suspicious margins only. Level 1 oncoplastic closure was done in all cases. Margins of the specimen were marked with sutures for orientation and the volume of whole resected specimen was measured by volume displacement method and/or by ellipsoid formula [V = abc × (π/6), where a, b, and c are three dimensions of specimen]. All specimens were sent for detailed histopathological evaluation. In patients showing positive margins, margin re-excision or mastectomy was done. Patients in each group received axillary treatment and adjuvant treatment as per standard protocol.
Cosmesis was assessed by patient, a resident doctor, and a breast care nurse independently on postoperative day 7 and at 3 months. Patients rated their cosmesis using visual analogue scale as not satisfied, satisfied, or extremely satisfied. Resident doctor and nurse rated cosmesis as fair, good, or excellent.
All data were pooled into a Microsoft Office Excel worksheet for analysis. Chi-square test and Fisher's exact test were used for categorical data, whereas Student's t-test and Mann–Whitney test were used for quantitative data. Agreement between two assessors was calculated by Kappa analysis.
Sample size calculation
A sample size of 84 in each group was calculated using expected margin positivity as 17% and 4% in palpation- guided and USG- guided WLE, respectively, α error of 5% (considering 95% confidence interval), and β = 20% (taking power of study as 80%). However due to logistic reasons, a sample size of convenience of 60 patients was taken.
| » Results|| |
Between May 2014 and April 2016, 68 patients as per the eligibility were suitable for inclusion and willing to be involved in the study. However, six patients opted to undergo mastectomy and two patients refused to participate in the study. Out of the 60 patients included in the study, 32 underwent USG-guided WLE and 28 underwent palpation-guided WLE. [Figure 1] represents the CONSORT diagram.
The mean age of patients was 48.78 years (SD 11.02) – 48.18 years in group I and 49.75 years in group II. Twenty-five patients were premenopausal (14 in group I and 11 in group II). One patient in each group was nulliparous. Tumor was right sided in 30 patients (16 in group I and 14 in group II). Mean tumor size was 3.18 cm (range – 1.5–5 cm in palpation-guided and 2–5 cm in USG-guided group) in both groups. Thus, demographic and tumor characteristics of each group were similar in both the groups.
Majority of the patients had tumor in upper outer quadrant – 41 out of 60 (68%) followed by lower outer quadrant and upper inner quadrant – 9 patients each (15%). Seven out of 60 patients (12%) received neoadjuvant chemotherapy prior to WLE – 2 in group I and 5 in group II. Thirty-nine (65%) patients underwent WLE + SLNB; 13 (22%) patients underwent WLE + SLNB + ALND; and 8 (13%) patients underwent WLE + ALND. Cavity shavings were sent in 23 patients (38.3%).
Out of these 23 patients, 4 (17.4%) showed presence of tumor – 1 patient in group I and 3 in group II.
Mean thickness of the excised margin was 1.67 cm in group I and 1.92 in group II. Five patients out of 60 patients had positive margin (8.33%) at final histopathology – 1 patient out of 32 patients in group I (3.22%) and 4 out of 28 patients in group II (14.28%) [Table 1]. Though the margin thickness and margin positivity were higher in group II, there was no statistical difference among the two groups.
Out of five margin-positive patients, three patients underwent margin re-excision whereas two opted for completion mastectomy. Among the patients undergoing mastectomy, residual ductal carcinoma in situ (DCIS) focus was found in one case while no tumor could be identified in the other. Amongst the patients undergoing margin re-excision, in histopathology of re-excised tissue, invasive ductal carcinoma (IDC) was found in first case, DCIS in second one, and no tumor could be identified in third one. The final histopathology revealed tumor-free margins in all these cases. All these five margin-positive patients were seen to have DCIS component in their original HPE.
Median specimen volume in whole group was 71 cm 3 (range – 6–350 cm 3, mean 86.45 cm 3), 78 cm 3 (range – 6–275 cm 3, mean 92.3 cm 3) in group I, and 67 cm 3 (range – 43–350 cm 3, mean 80.6 cm 3) in group II. However, difference in volume was not statistically significant (P = 0.101) among the two groups.
Assessment of cosmesis
Two patients who underwent revision mastectomy were excluded from the cosmetic assessment. Thirty patients in group I [30/32 (93.75%) cases in group I and 24/26 (92.31%) cases in group II] were happy with the cosmetic outcome. Results of cosmetic outcome as assessed by patient, doctor, and nurse are given in [Table 2].
There was 65% agreement between doctor and nurse with a Kappa value of 0.4395, which is significant. Thus, there was strong agreement between doctor and nurse. There was 60.34% agreement between doctor and patient with a Kappa value of 0.3252, which is significant. Thus, there was strong agreement between patient and doctor.
Association of margin positivity with various tumor characteristics
Tumor characteristics like size, nodal status, presence of DCIS component in tumor, presence of lymphovascular emboli, hormone receptor and Her2neu status, and their association with margin positivity was assessed. Presence of DCIS component and expression of Her2neu by tumor cells had a significant impact on margin positivity. The results are shown in [Table 3].
Postoperative complications were seen in 13 out of 60 (22%) patients – 8 out of 32 (28.8%) in group I and 5 out of 28 patients in group II (17.85%) – seroma: 3 in group I and 2 in group II; hematoma: 1 in each group; wound infection: 4 in group I and 2 in group II. However, difference in complication rate in two groups was not statistically significant (Fisher's exact = 0.507). Seroma subsided with repeated aspirations. Hematoma was managed successfully with cold compresses and analgesics. Wound infection responded to drainage of fluid and five-day course of broad spectrum oral antibiotics.
| » Discussion|| |
The increased breast health awareness, improved screening, earlier detection of disease, and more effective systemic therapy have resulted in detection of smaller tumors as well as considerable decline in breast cancer mortality. The longer postsurgery life expectancy has led to adverse psychological impact on the women, especially when the surgery was a mastectomy. These factors along with an understanding that BCS as well as mastectomy offer similar overall survival to the women have resulted in more women opting for breast conservation surgery. In a quest to decrease the margin positivity rates without compromising on cosmesis in breast conservation surgeries, IOUS is being used increasingly. IOUS helps the surgeon real time to evaluate the tumor margin status while the specimen is in vivo as well as ex vivo.
In our study evaluating the usefulness of IOUS in breast conservation surgeries, the peak prevalence of breast cancer was seen in 40–50 years with the mean age of 48.9 years. This is similar to the peak prevalence seen in most Indian studies wherein breast cancer is reported to occur a decade earlier as seen in western countries. The average tumor size of our study group was 3.18 cm for whole group as well as USG-guided and palpation- guided group, which is considerably higher than other study groups reporting the use of IOUS.
In this study, there were four patients (04/28) in the palpatory group who had margin positivity while only one in the USG group who had positive margin. Though the positive margins were lesser with the use of USG, this was not statistically significant (3% vs. 14%). However, it might not be appropriate to deem that USG does not add to the advantage, as the sample size was small. Krekel et al. (2013) reported that tumor-free resection margins could be seen in additional 15% cases with the use of IOUS. Similarly, Moore et al. in 2001 conducted a prospective study and reported the reduction in incidence of positive margins from 29% to 3% with the use of IOUS in patients with palpable breast cancer undergoing BCS. In another retrospective study done by Eggeman et al., analysis of positive margins and re-excision rates was done in patients who underwent BCS with either palpation or IOUS- guided method. In their study, 198 patients underwent USG- guided BCS from which 24 showed positive margin (12.1%), whereas 28.5% of all patients who underwent palpation- guided BCS showed positive margins. They also showed that after surgery, the reconfirmation of margin status by performing specimen ultrasonography identified close margins (less than 5 mm) and helped in excising the cavity shave in correct direction (as confirmed by histopathology) in 81% of cases requiring re-excision, as compared to 18% of cases where re-excision was done by palpation guidance. This has also been seen by Karanlik et al.
In our study, all patients who had positive margins underwent re-surgery. Three patients underwent re-excision (one was USG guided and two palpation guided) of involved margin and two patients underwent completion mastectomy. Although not statistically significant, use of IOUS did decrease the margin positivity rate and hence rates of a second surgery.
Of the various parameters studied in this study, presence of additional DCIS component and Her2neu receptor positivity were seen to result in significantly higher positive excision margins. Eggeman et al. found that the negativity of surgical margins was significantly influenced by age, menopausal status, presence or absence of an intraductal component surrounding the invasive breast cancer, histologic grade, and type of tumor with elderly postmenopausal status, higher tumor grade, and presence of intra ductal component surrounding invasive cancer to be associated with higher positive margin status. Moore et al. found that four out of seven patients undergoing re-excision for positive margins had DCIS at the margin. Out of these four cases, only one had associated invasive component also at the margin.
Minor complications following surgery like hematoma, seroma, and wound infection did not differ significantly in two groups as described in results. None of these required any surgical intervention. Complications were seen in eight patients in USG- guided WLE and five palpation- guided WLE group. Complications were seen in a total of 7 patients out of 134 patients (5.2%) in the COBALT trial. In their study, four patients underwent USG- guided WLE and three palpation guided, with the difference being statistically insignificant. [Table 4] summarizes various studies done so far on this subject.
Our study did not show any significant difference in cosmesis between two groups neither in terms of patient satisfaction nor assessment by a doctor and a nurse as shown in results. This can be explained by the fact that there was no statistically significant difference in volume of specimen excised in two groups. The median volume was 78 versus 67 cm 3 in the USG- and palpation- guided group, respectively. Other such trials show a better cosmesis with the USG group mainly because the specimen volume is significantly less than in the palpation- guided group. As seen in our study, the average volume of specimen excised was 91 cm 3 which is more when compared to western studies. This is due to the fact that the average tumor size was more than most western studies due to late presentation, a fact seen almost uniformly in most Indian studies.
| » Conclusions|| |
Margin negativity and good cosmesis are the most important concerns of breast conservation surgery. Intraoperative use of ultrasound offers a real-time assessment of margin status and may reduce the margin positivity rate compared to conventional palpation- guided method.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]