Dissections OBSERVATIONAL

29 June 2009
Evidence-based Medicine for Surgeons

The relationship between surgical factors and margin status after breast-conservation surgery
for early stage breast cancer
Authors: Lovrics PJ, Cornacchi SD, Farrokhyar F, et al
Journal: The American Journal of Surgery 2009; 197: 740-746
Centre: McMaster University, Hamilton,Ontario, Canada
Early-stage breast cancers may be managed with breast-conserving surgery (BCS) followed by
radiation therapy. The goal of BCS is to completely remove the identified cancer while preserving
adequate breast tissue for an acceptable cosmetic result. The presence of a microscopically clear
BACKGROUND surgical margin is vital; a positive surgical margin (reported in 4-31% of BCS) is a major
predictor of local recurrence. Identification of controllable factors that are associated with the
margin status would be a valuable aid in the management of patients by BCS.

RESEARCH QUESTION IN SUMMARY

Population Likelihood of negative margins
A cohort of patients with early- 489 patients studied Odds ratio 95% confidence interval
stage breast cancer (clinical stage
I and II) who underwent breast Tumour biological factors (not in surgeon's control)
conserving surgery (BCS) for
Absence of multifocality 6.4 2.5–16.5
invasive breast carcinoma.
Lobular cancer 2.7 1.4–5.2
Indicator variable
Ductal histology 2.5 1.1–5.8
A wide range of data abstracted
from clinical, pathological, and Smaller cancer 2 1.0–4.3
operative reports. Controllable (modifiable) factors
Outcome variable Confirmed preoperative diagnosis 2.7 1.5–4.7
Primary: the proportion of positive Resection of separate cavity margins 2.7 1.5–4.8
margins.
Increased volume of excision 2.3 1.3–4.2
Comparison
The rate of positive margins was 26% for the entire sample (127 patients)
-

Authors' claim(s): “...The analysis also confirms the importance of specific surgical factors. A confirmed
preoperative diagnosis is essential for optimal operative planning, and ensuring a preoperative diagnosis led to
fewer reoperations. The resection of separate cavity margins and greater volume of excision were also found to
be independent predictors of margin status.”

THE TISSUE REPORT

Yet another tedious example of taking a large database that was already there, throwing it into a statistical package for
multivariate analysis and coming up with conclusions of dubious value. These kind of papers are always difficult to analyse
and apply in practice. How does one use the information obtained in an advantageous fashion? Looking closely at the
factors that are within a surgeon's control, none of the three are of practical value. The odds ratios only show marginally
favourable values. The only strong odds ratio is for the absence of multifocality (no surprise there): a feature that can be
demonstrated only after excision. Moreover, unless confirmed in a prospective trial, this paper does not qualify as evidence-
based Medicine. (Interestingly, the report comes from McMaster University, the Mecca of EBM.)

EBM-O-METER
Evidence level Overall rating Bias levels
Double blind RCT Sampling
Randomized controlled trial (RCT) Comparison
Trash Swiss Safe News-
Prospective cohort study - not randomized cheese worthy Measurement
Life's too Holds water
short for this Full of holes “Just do it”
Case controlled study
Interesting l | Novel l | Feasible l
Case series - retrospective  Ethical l | Resource saving l

The devil is in the details (more on the paper) ... 

© Dr Arjun Rajagopalan
 SAMPLING
Sample type Inclusion criteria Exclusion criteria Final score card
Simple random Patients with early- Patients who AA
stage breast cancer underwent initial
Stratified random Target 2249
(clinical stage I and mastectomy 
Cluster II) who underwent Ductal carcinoma in Accessible 654
breast conserving situ only 
Consecutive surgery (BCS) for Recurrent disease  Intended 489
Convenience invasive breast T3/T4 disease  Drop outs -
carcinoma. 
Judgmental Study 489

= Reasonable | ? = Arguable |  = Questionable


Duration of the study: January 2000 to December 2002
Assuming a prevalence of 30%, it was estimated that 329 patients would be required to produce a 95% confidence
interval (CI) +/-5%, with alpha 0.05.

Sampling bias: The study is a retrospective analysis of patients randomly selected from a database of all patients
from hospitals in the regional health network in Canada who were referred for consideration of radiation or systemic
therapy an existing database of patients. There was no a priori statement of intent at the time of accrual.

COMPARISON
Randomized Case-control Non-random Historical None

Controls - details
Allocation details Relevant data were abstracted from clinical, pathological, and operative reports. The primary
outcome variable assessed was the proportion of positive margins.
Comparability -
Disparity -

Comparison bias: There was no comparison attempted in this study.

MEASUREMENT
Measurement error
Device used Device error Observer error
Gold std.

Device suited to task

Training

Scoring

Blinding
Repetition

Protocols

Y ? N

1.Positive margins Y N Y N N N N

A positive margin was defined as microscopically confirmed disease (invasive or in situ) at the inked margin.
Preoperative diagnosis was considered confirmed if malignant cells were identified by either fine needle aspiration or
core biopsy.
Tissue was considered a cavity margin if labeled specimens distinct from the main surgical specimen were identified in
the pathology report.
The volume of lumpectomy specimens was defined as the product of the 3-dimensional lengths of the surgical specimen
as documented in the pathology report. For the analysis, the volume of lumpectomy specimen was classified as greater
or less than the mean for the whole sample (167 cm3).

Measurement bias: The study was a chart review of already recorded data. No attempt was made to control
measurement error.

© Dr Arjun Rajagopalan