Neurosurgery 99:519–529, 2026
Targeted therapy and immunotherapy have complicated the traditional decision of which antineoplastic drugs to stop before neurosurgery. This systematic review organizes the relevant agents around wound healing, bleeding and immune dysfunction. Anti-VEGF antibodies and mTOR inhibitors require particular caution because of impaired healing, while VEGF-receptor and Bruton’s tyrosine kinase inhibitors raise hemorrhagic concerns. Several immunomodulators increase infection risk, but the evidence is sparse for other widely used classes. The resulting framework is useful for multidisciplinary planning, although many intervals still rest on indirect evidence and expert consensus.
Objective
To provide a clinically actionable framework for perioperative interruption and resumption of targeted and biologic therapies in patients undergoing neurosurgical procedures.
Methods
The authors systematically reviewed pivotal trials, US Food and Drug Administration safety information, meta-analyses and society guidance. Drug classes were assessed by mechanism, pharmacokinetics and adverse effects relevant to wound healing, hemostasis and immune regulation. Recommendations were stratified by risk and combined the available evidence with expert consensus.
Main results
Anti-VEGF monoclonal antibodies carried the greatest wound-healing concern; the review recommends a preoperative interruption of at least 4 weeks and generally delaying postoperative treatment for 2–4 weeks. For mTOR inhibitors, the proposed preoperative interval was at least 1 week.
VEGF-receptor tyrosine kinase inhibitors and Bruton’s tyrosine kinase inhibitors were most concerning for bleeding and may require holds of up to 1 week, with resumption after 3–7 days once hemostasis is secure. CDK4/6 inhibitors, Janus kinase inhibitors and biologics directed at TNF, IL-6 or CD20 were linked to immunosuppression and infection risk; interruptions of 2–7 days and postoperative delays of 1–2 weeks were often proposed. Evidence remained limited for BRAF/MEK and immune-checkpoint inhibitors.
Interpretation
A single “stop all systemic therapy” rule is neither safe nor oncologically neutral. Timing should reflect the drug’s biological effect, half-life, operative magnitude, wound requirements and the consequences of delaying cancer control. The review is best used as a structured starting point for joint decisions among neurosurgery, oncology, anesthesia and pharmacy—not as a rigid calendar.
Limitations
Much of the evidence comes from non-neurosurgical populations, safety reports and expert interpretation rather than prospective perioperative trials. Recommendations within a class may not apply equally to every agent. The review cannot quantify the competing risk of oncological progression during interruption for an individual patient.
Clinical takeaway
At the preoperative visit, record the exact agent, last dose, half-life and principal surgical risk. Agree on stop and restart dates with the treating oncologist, verify wound healing and hemostasis before resumption, and document explicitly when limited evidence makes the plan individualized.