Wider margins in breast cancer surgery are associated with a reduced risk of local and distant recurrence, suggesting the need for a revision of international guidelines.
A systematic review and meta-analysis of the literature [link here] has found surgeons should aim to remove at least a 1mm width of healthy tissue around a breast tumour to reduce the risk of recurrence and improve breast cancer survival.
The meta-analysis included 68 observational studies published between 1980 and 2021 comprising 112,140 patients undergoing breast-conserving surgery for stages I-III breast cancer and followed for a minimum of five years.
It found that 9.4% of patient samples had involved “tumour on ink” margin, 14.7% had tumour within 1 mm of the inked margin, 17.8% had tumour within 2 mm, and 24.4% had tumour within 5 mm of the inked margin.
The study, published in The BMJ, found the rate of distant recurrence was 25.4% in patients with tumour on ink margins, 8.4% in patients with tumour on ink or close to inked margins, and 7.4% in patients with negative margins.
Rates of local recurrence were 15.9%, 8.8% and 3.9%, respectively.
Compared with negative margins, tumour on ink margins were associated with a two-fold increased risk of distant recurrence (HR 2.1) and local recurrence (HR 1.98).
Tumours within 1 mm of margins were associated with an increased risk of distant recurrence (HR 1.53) and local recurrence (HR 1.86) compared with tumours >1 mm from the margin.
Tumours between 0.1 mm and 2.0 mm were associated with an increased risk of distant recurrence (HR 1.38) and local recurrence (HR 2.09) compared with tumours >2 mm from margins.
“Where tumours were at, or close to, the margin, risk of distant recurrence (and local recurrence) was increased, even in patients treated with adjuvant chemotherapy; a finding consistent across all the margin width comparisons.”
Two studies which reported on overall survival found tumour on ink margins were associated with an increased rate of mortality (HR 1.61; P<0.001) as were positive or close margins (tumour on ink or <2 mm) versus wider ≥2 mm margins (HR 1.32; P=0.05).
“Positive or close margins were associated with increased distant recurrence, local recurrence, and lower overall survival compared with negative or wide margins and, importantly, close margins without tumour at ink were also associated with increased distant and local recurrence,” the study said.
The study called for a revision of the 2014 ASCO guidelines [link here] which suggest that “tumour margins (invasive cancer or ductal carcinoma in situ) not touching ink at the specimen edge are acceptable…”
“Our study does not support the overall conclusion expressed in these guidelines,” the investigators said.
“A minimum margin of at least more than 1 mm was the margin required to minimise both distant recurrence and local recurrence in this analysis, taking into account the wider confidence intervals in our analyses of close versus negative margins.”
“Recognising that wider margins require further surgery, decisions about re-excision should be the product of an informed discussion between clinicians and patients with full disclosure of the risks of increased distant recurrence associated with close margins.”
Communicating cancer surgery results
Meanwhile, surgeons who try to reassure cancer patients that “we got it all” are actually misleading their patients which can have negative clinical consequences.
A Viewpoint article in JAMA Oncology [link here] said the surgeon may mean to say they removed all the visible or palpable tumour but patients simply hear “we got it all” and interpret that as now being cancer-free.
The article, based on focus groups with stage III colorectal cancer patients, urged caution around using the common phrase.
“Immediately after surgery, there is no way to know whether all the cancer has been removed because the pathologist has not yet examined the lymph nodes.”
““We got it all,” said with the intention of providing reassurance and hope, can lead to misunderstanding and mistrust in subsequent clinical care and to tension between clinical specialists.”
“If a patient believes that all the cancer has been removed, they may be frustrated and confused when advised to undergo chemotherapy by the medical oncologist. If all the cancer is gone, why would chemotherapy be necessary?”
“Among communities with historical mistrust of medical institutions, conflicting information from different clinicians may exacerbate that mistrust. It may even do harm if it leads to refusal of chemotherapy, which conveys substantial survival benefit for stage III cancer.”