Messaggi chiave

• INSEMA è uno studio di non inferiorità, prospettico, randomizzato, che si è proposto di valutare gli esiti associati all’omissione della resezione ascellare rispetto alla biopsia del linfonodo sentinella (sLN) in pazienti affette da carcinoma mammario (BC) in stadio T1 o T2 con linfonodi clinicamente negativi candidate a chirurgia mammaria conservativa.
• La popolazione per protocollo ha incluso un totale di 4858 pazienti (gruppo con omissione della chirurgia ascellare, n = 962; gruppo con biopsia sLN, n = 3896). Dopo un follow-up mediano di 73,6 mesi, il tasso stimato di sopravvivenza libera da malattia invasiva a 5 anni è risultato pari al 91,9 vs 91,7%, rispettivamente, con un hazard ratio di 0,91 (IC 95%, 0,73-1,14), al di sotto del margine predefinito di non inferiorità. L’incidenza di recidiva ascellare è stata lievemente più alta nel gruppo sperimentale (1,0 vs 0,3%), senza effetti sulla sopravvivenza globale (OS) (tasso stimato di OS a 5 anni, 98,2 vs 96,9%).
• In termini di sicurezza, le pazienti non sottoposte a resezione ascellare hanno presentato una minor incidenza di linfedema (1,8 vs 5,7%), limitazione della mobilità del braccio o della spalla (2,0 vs 3,5%) e dolore al movimento (2,0 vs 4.2%). Nel complesso, i risultati dello studio supportano la possibilità di evitare la biopsia del linfonodo sentinella, senza effetti negativi sugli esiti di sopravvivenza, in donne con BC precoce cN0, soprattutto in presenza di fattori clinico-patologici di basso rischio.

Abstract

Background

• Whether surgical axillary staging as part of breast-conserving therapy can be omitted without compromising survival has remained unclear.

Methods

• In this prospective, randomized, noninferiority trial, we investigated the omission of axillary surgery as compared with sentinel-lymph-node biopsy in patients with clinically node-negative invasive breast cancer staged as T1 or T2 (tumor size, ≤5 cm) who were scheduled to undergo breast-conserving surgery.
• We report here the per-protocol analysis of invasive disease-free survival (the primary efficacy outcome). To show the noninferiority of the omission of axillary surgery, the 5-year invasive disease-free survival rate had to be at least 85%, and the upper limit of the confidence interval for the hazard ratio for invasive disease or death had to be below 1.271.

Results

• A total of 5502 eligible patients (90% with clinical T1 cancer and 79% with pathological T1 cancer) underwent randomization in a 1:4 ratio.
• The per-protocol population included 4858 patients; 962 were assigned to undergo treatment without axillary surgery (the surgery-omission group), and 3896 to undergo sentinel-lymph-node biopsy (the surgery group).
• The median follow-up was 73.6 months.
• The estimated 5-year invasive disease-free survival rate was 91.9% (95% confidence interval [CI], 89.9 to 93.5) among patients in the surgery-omission group and 91.7% (95% CI, 90.8 to 92.6) among patients in the surgery group, with a hazard ratio of 0.91 (95% CI, 0.73 to 1.14), which was below the prespecified noninferiority margin.
• The analysis of the first primary-outcome events (occurrence or recurrence of invasive disease or death from any cause), which occurred in a total of 525 patients (10.8%), showed apparent differences between the surgery-omission group and the surgery group in the incidence of axillary recurrence (1.0% vs. 0.3%) and death (1.4% vs. 2.4%).
• The safety analysis indicates that patients in the surgery-omission group had a lower incidence of lymphedema, greater arm mobility, and less pain with movement of the arm or shoulder than patients who underwent sentinel-lymph-node biopsy.

Conclusions

• In this trial involving patients with clinically node-negative, T1 or T2 invasive breast cancer (90% with clinical T1 cancer and 79% with pathological T1 cancer), omission of surgical axillary staging was noninferior to sentinel-lymph-node biopsy after a median follow-up of 6 years.