Sentinel-Lymph-Node-Based Management or Routine Axillary Clearance? One-Year Outcomes of Sentinel Node Biopsy Versus Axillary Clearance (SNAC): A Randomized Controlled Surgical Trial

Abstract

We sought the extent to which arm morbidity could be reduced by using sentinel-lymph-node-based management in women with clinically node-negative early breast cancer. One thousand eighty-eight women were randomly allocated to sentinel-lymph-node biopsy followed by axillary clearance if the sentinel node was positive or not detected (SNBM) or routine axillary clearance (RAC, sentinel-lymph-node biopsy followed immediately by axillary clearance). Sentinel nodes were located using blue dye, alone or with technetium-labeled antimony sulfide colloid. The primary endpoint was increase in arm volume from baseline to the average of measurements at 6 and 12 months. Secondary endpoints were the proportions of women with at least 15% increase in arm volume or early axillary morbidity, and average scores for arm symptoms, dysfunctions, and disabilities assessed at 6 and 12 months by patients with the SNAC Study-Specific Scales and other quality-of-life instruments. Sensitivity, false-negative rates, and negative predictive values for sentinel-lymph-node biopsy were estimated in the RAC group. The average increase in arm volume was 2.8% in the SNBM group and 4.2% in the RAC group (P = 0.002). Patients in the SNBM group gave lower ratings for arm swelling (P < 0.001), symptoms (P < 0.001), and dysfunctions (P = 0.02), but not disabilities (P = 0.5). Sentinel nodes were found in 95% of the SNBM group (29% positive) and 93% of the RAC group (25% positive). SNB had sensitivity 94.5%, false-negative rate 5.5%, and negative predictive value 98%. SNBM was successfully undertaken in a wide range of surgical centers and caused significantly less morbidity than RAC.

Appendix

Volume of a Truncated Cone

Consider a segment of length h with a base circumference C _b and an apex circumference C _a. The area of the base and apex circles is given by A _b = C ²_b /4Π and A _a = C ²_a /4Π.

The volume of this segment is

$$ V = h \times {{\left\{ {A_{\text{a}} + A_{\text{b}} + \surd [A_{\text{a}} \times A_{\text{b}} ]} \right\}} \mathord{\left/ {\vphantom {{\left\{ {A_{\text{a}} + A_{\text{b}} + \surd [A_{\text{a}} \times A_{\text{b}} ]} \right\}} 3}} \right. \kern-\nulldelimiterspace} 3}; \quad h = 100 $$

The volume of each arm is then estimated as the sum of the six truncated cones.

Contributors to the SNAC Trial

Writing Committee

P. Grantley Gill (chair), Neil Wetzig, Val Gebski, Martin Stockler, Owen Ung, Ian Campbell, John Simes

Management Committee

P. Grantley Gill (study chair), N. Wetzig (deputy study chair), M. Bilous, I. Campbell, J. Collins, X. Coskinas, G. Farshid, V. Gebski, D. Gillett, W. Hague, R. Harman, J. Kollias, A. Macphee, R.J. Simes, M. Stockler, O. Ung, R. Uren, B. Vachan, L. Young

Safety and Data Monitoring Committee

B. Chatterton, M. Jones, W. Raymond, J. Simpson

Pathology Audit Committee

M. Bilous, G Farshid, X. Coskinas

NHMRC Clinical Trials Centre (Coordinating Centre)

X. Coskinas, A. Ray, K. Scott, B. Vachan (trial coordinators); C. Greig, A. Lucas, R. Tangunan, S. Wonders (data managers); C. Brown, V. Gebski, C. Hargreaves, C. Pardy, T. Sourjina (statisticians); C. Munro, A.-T. Nguyen (database administrators); R. Pike (writer-editor); R.J. Simes (director), M.R. Stockler (oncology co-director)

Sites Contributing Patients to the SNAC Trial and the Principal Investigators

Westmead Hospital, Sydney: Owen Ung, Dominic Moon, James French

Concord Hospital, Sydney: David Gillett, Gail Molland

Coffs Harbour Base Hospital, Coffs Harbour: Bill Ross

Lismore Base Public Hospital, Lismore: Rob Simon

Nepean Hospital, Sydney: Patrick Cregan, Deborah Cheung

Royal Prince Alfred Hospital, Sydney: Andrew Spillane

St Vincent’s Mater Health, Sydney: Margaret Pooley

Strathfield Breast Centre, Sydney: David Gillett, Gail Molland

St. Vincent’s Private Hospital, Lismore: Rob Simon

Baringa Private Hospital, Coffs Harbour: Bill Ross

Royal Melbourne Hospital, Melbourne: John Collins, Bruce Mann, Craig Murphy, Julie Miller

St Vincent’s Hospital, Melbourne: Michael Henderson, Suzanne Moore, Paul Kitchen

Geelong Hospital, Geelong: Gregory Mitchell

Royal Women’s Hospital, Melbourne: Bruce Mann

Princess Alexandra Hospital, Brisbane: Neil Wetzig, David Wilkinson, Ian Bennet

Mater Private Hospital, Brisbane: Neil Wetzig, David Wilkinson, Chris Pyke

Nambour General Hospital, Nambour: Justin D’Arcy, Michael Donovan, Lisa Creighton

Gold Coast Hospital, Southport: Daniel DeVianna

Wesley Medical Centre, Brisbane: Neil Wetzig

Mater Adult Hospital, Brisbane: Chris Pyke

Royal Adelaide Hospital, Adelaide: Grantley Gill, James Kollias, Melissa Bochner, Robert Kennedy

St Andrew’s Hospital, Adelaide: Grantley Gill, James Kollias, Melissa Bochner

Queen Elizabeth Hospital, Adelaide: Vladamir Humeniuk, David Walsh

Western Breast Clinic, Adelaide: Vladamir Humeniuk, David Walsh

Sir Charles Gairdner Hospital, Perth: David Oliver, Diana Hastrich

St John of God Murdoch, Perth: David Oliver

Auckland Hospital, Auckland: Alex Ng

Middlemore Hospital, Auckland: Garth Poole

North Shore Hospital, Auckland: Richard Harman, Sharon Cacala, Eva Juhasz

Palmerston North Hospital, Palmerston North: Colin Wilson, Pravin Kumar, Bruce Rhind

Waikato Hospital, Waikato: Ian Campbell

Principal Site Coordinators

V. Arriola, A. Bell, A. Brown, D. Dash, A. Davis, K. Devantier, A. Dowd, J. Goad, S. Govenlock, J. Hargan, C. Kennedy, K. Latimer, C. MacDonald, C. McBride, L. Neave, M. Osinski, C. Paine, A. Power, C. Preston, J. Scarlet, J. Silbereisen, M. Stanley, P. Whitfield, R. Wicks, R. Winter