"The days are numbered for axillary surgery" in breast cancer patients and, in the coming years, use of the commonplace procedure will be "very limited," write a pair of Italian surgeons in a viewpoint published in the November issue of JAMA Oncology.
This is great departure from history, say Oreste Gentilini, MD, and Umberto Veronesi, MD, from the European Institute of Oncology in Milan.
"Breast cancer and axillary surgery became almost indivisibly wed," they write, referring to the era before mammography (and the increased detection of early-stage disease) when almost all breast cancers spread to the axillary lymph nodes.
Nevertheless, multiple trials, such as National Surgical Adjuvant Breast and Bowel Project B-04 and the International Breast Cancer Study Group (IBCSG) 10-93, have failed to show that axillary surgery actually saves lives.
"We have to realize that removal of nodes — many or a few or just one — is not leading to an improvement of outcomes, regardless of nodal status," the pair write.
The two surgeons ask an obvious question: Why put patients through multiple axilla-related procedures, from lymphoscintigraphy to surgery, which all have risks and complications?
The "only possible benefit" might be to obtain prognostic information that, in turn, could influence the choice of adjuvant therapy. But even that value is diminishing; postsurgical treatment is "increasingly based on the biology" and not nodal status, they say.
Regardless of nodal status, "cytotoxic agents are recommended for patients with triple-negative cancer, chemotherapy plus trastuzumab for patients with HER2 overexpression, and endocrine treatment alone for patients with luminal A cancer," they point out.
"The only matter of debate [about the value of axillary surgery] is probably the [treatment] decision in patients with luminal B disease," they say.
Thus, axillary surgery is now really only a staging tool, the Italian experts suggest.
They argue that the staging purpose could be rendered obsolete by ultrasonography, the imaging procedure that identifies the presence or absence of disease in the lymph nodes. The ongoing SOUND (Sentinel Node vs Observation After Axillary Ultra-Sound) trial will shed light on the value of the tool. The trial compares sentinel lymph node biopsy with no surgery at all in the axilla when the axilla ultrasonography findings are negative. Patients with breast cancer lesions up to 2 cm who are receiving breast-conserving surgery are eligible for enrollment.
An American breast cancer surgeon does not argue with the pair. "I completely agree with what they say," said Kandace McGuire, MD, a surgical oncologist from the Lineberger Comprehensive Cancer Center at the University of North Carolina in Chapel Hill. "In the future, they may be right."But we still need sentinel lymph node surgery in 2015 to stage the axilla," she emphasized. "If more than two nodes are involved, then we do an axillary dissection."
This is data-driven practice, said Dr McGuire. The landmark American College of Surgeons Oncology Group (ACOSOG) Z0011 trial demonstrated that there is no survival disadvantage in leaving one or two positive nodes in place, compared with completion dissection. But no one knows if that holds true for three or more positive lymph nodes. In short, there are unknowns about managing the axilla, she explained.
She is not sure that ultrasound is a good enough staging tool to replace sentinel lymph node biopsy. "We use it to identify lymph node involvement preoperatively," she said. "But its accuracy is not that great yet."
Dr McGuire pointed out that ultrasound has an excellent positive predictive value. When it shows lymph node involvement, the nodes are indeed involved upon lymph node surgery, but the negative predictive value is not as good.
She said she agrees that axillary surgery will also continue to be of value in the future in a couple of specific circumstances: in patients presenting with "bulky" nodal involvement who might benefit from neoadjuvant treatment with a substantial downstaging of nodal involvement, and in the few patients who experience overt axillary recurrence after primary treatment.
Dr McGuire also agrees that the days of axillary surgery are numbered, and has heard Armando Giuliano, MD, principal investigator of the Z0011 trial, say "the same thing in multiple forums."
Before agreeing that the time is truly up for axillary surgery, Dr McGuire wants to see results from various trials investigating the management of positive lymph nodes. About axillary surgery she said, "its dying, but we need more data before it's dead."
Dr Gentilini, Dr Veronesi, and Dr McGuire have disclosed no relevant financial relationships.