ASSERT Trial: Antibiotics and surgical site infection in expander-based breast reconstruction

Authors: Kaur S, Gastman B, Broderick KP, Momoh AO, Phillips BT, Schwarz G, Hanson SE, Hespe GE, Cooney CM, Sommers K, Leu CS, Rohde CH; ASSERT Group 

Affiliation: The Plastic Surgery Foundation; Cleveland Clinic; Johns Hopkins University; University of Michigan; Duke University; University of Chicago; Columbia University 

Journal: Annals of Surgical Oncology, April 2026 

PMID: 41085801 (primary article), ASO Author Reflections

Key takeaways

• ASSERT did not establish noninferiority: 30-day SSI was 17% with single-dose prophylaxis versus 11% with 7 postoperative days. 

• The trial was severely underpowered: only 214 patients were analyzed versus 922 required; enrollment stopped when funding ended. 

• The 6% noninferiority (i.e. clinically meaningful) margin allowed an assumed SSI increase from 12% to 18%, a 50% relative increase. 

• Despite the failed noninferiority test, the authors suggest the findings support CDC-limited prophylaxis; the data are more appropriately considered inconclusive. 

Background

Prophylactic antibiotic duration after immediate tissue expander breast reconstruction (TE-BR) varies widely. CDC guidance recommends no postoperative prophylactic antibiotics after incision closure for clean or clean-contaminated surgery, even with drains, but implant-based reconstruction has unique infection and device-loss consequences.

Objective

Determine whether a single preoperative antibiotic dose is noninferior to the same perioperative regimen plus 7 days of postoperative oral antibiotics for preventing 30-day surgical site infection (SSI) after immediate TE-BR.

Methods

• Design: Prospective, open-label, multicenter randomized noninferiority trial at five US academic reconstructive centers. 

• Enrollment: 499 patients approached from May 2021-May 2023; 235 randomized; 21 were withdrawn after randomization and 214 were analyzed (102 single-dose, 112 week-postoperative). 

• Population: Women ≥18 undergoing unilateral or bilateral mastectomy for cancer or prophylaxis with immediate prepectoral or submuscular TE-BR, with or without acellular dermal matrix (ADM). 

• Key exclusions: Direct-to-implant, delayed or autologous reconstruction; prior chest wall radiation; prior reconstruction on the expander side. 

• Intervention: Weight-based cefazolin within 60 minutes before incision with indicated intraoperative redosing; allergy alternatives permitted. The comparator received the same plus 7 days of oral antibiotics. 

• Primary endpoint: CDC-defined SSI within 30 days. Secondary outcomes included later infection, hospitalization, expander/implant loss, cultures, and antibiotic-related adverse events. 

• Statistics: Investigators assumed 12% SSI with 7 postoperative days versus 18% with single-dose prophylaxis and set a 6% absolute noninferiority margin—equivalent to allowing a 50% relative increase in SSI. With one-sided α=0.025 and 80% power, 922 evaluable patients were required; only 235 were randomized before funding ended. 

Results

• Baseline/operative profile: Mean age ~49 years; 70% bilateral mastectomy; approximately 50% prophylactic mastectomy; ADM used in 75%; 90% of expanders were prepectoral. 

• Primary endpoint: 30-day SSI occurred in 17/102 (17%) vs 12/112 (11%)—a 6-percentage-point absolute difference and approximately 55% relative difference. Noninferiority was not established (p=0.496). 

• 180-day infection: 24% vs 18% (p=0.476); median onset 21 vs 29 days. 

• Expander removal for infection: Within 30 days, 6% vs 2% (p=0.232); any infection-related TE removal was 18% vs 12% (p=0.503). 

• Other outcomes: Thirty-day hospitalization was 9% vs 6%; return to OR 11% vs 10%. 

• Adverse events: Three patients receiving 7 postoperative days developed antibiotic-related rash or nausea/vomiting; none were reported in the single-dose group. 

• Higher BMI (p=0.048) and mastectomy weight (p=0.033) were associated with SSI within 180 days. 

Conclusion

The authors conclude that ASSERT did not definitively demonstrate noninferiority of a single preoperative dose versus 7 postoperative days and found no statistically significant evidence that the 7-day regimen was superior. Despite the failed noninferiority test, they state that the findings support limiting prophylactic antibiotics in accordance with CDC guidance.

Strengths

• Randomized, geographically diverse multicenter design. 

• Standardized CDC SSI definition with investigator review of uncertain cases and follow-up beyond 30 days. 

• Contemporary population: 90% prepectoral reconstruction and 75% ADM use. 

Limitations

• Severely underpowered and prematurely stopped: 214 patients were analyzed versus 922 required. Funding ended before accrual was complete; COVID-related interruptions and increasing use of excluded direct-to-implant reconstruction also impaired enrollment. 

• The authors’ 6% noninferiority margin allowed an assumed SSI increase from 12% to 18%, a 50% relative increase, without a justification for why that degree of excess infection should be deemed noninfeiror. 

• Open-label design, surgeon-level variation in technique, and underpowered subgroup analyses add uncertainty; 21 randomized patients were not analyzed, making the reported ITT approach effectively modified ITT. 

Clinical relevance

ASSERT does not establish that single-dose prophylaxis is noninferior or equivalent to 7 postoperative days. With SSI 17% versus 11% and a trial far short of its required sample, these data should not justify reducing prophylaxis; the principal finding is continued uncertainty.

Editorial notes

While we applaud the authors for their efforts with the ASSERT trial, it simply does not answer its primary question. The trial was severely underpowered and failed to establish noninferiority, yet the authors characterize the outcomes as comparable and argue that the findings support limited antibiotic prophylaxis; that interpretation is at best overreaching and at worst a misrepresentation. More importantly, the authors' chosen 6% clinically meaningful margin would accept an increase from 12% to 18% SSI, a 50% relative increase, as noninferior, without a clear justification for why that degree of added infection is acceptable. A potential increase of that magnitude is not trivial in tissue expander reconstruction; SSI can lead to IV antibiotics, hospitalization, reoperation, expander loss, and delay of reconstruction or oncologic care, as the authors clearly note. That potential harm is clinically far more consequential than the three minor antibiotic-related reactions reported in the 7-day group. With observed SSI of 17% versus 11% and infection-related expander removal also numerically favoring 7 days, the defensible conclusion is uncertainty, not equivalence and not evidence sufficient to reduce prophylaxis. Antibiotic stewardship is a valid goal, but ASSERT is not adequately powered to make any substantiated claims to reduce antibiotic prophylaxis.

Lastly, the authors’ description of ASSERT as Level I evidence is difficult to reconcile with the ASPS evidence hierarchy, which specifically requires adequate power for a therapeutic RCT to qualify as Level I. The study achieved only 23% of its required sample and failed its primary noninferiority analysis. Calling this Level I evidence risks overstating the certainty of a fundamentally inconclusive trial.