Multidisciplinary care for brain metastases: Tracking a rapidly moving target

Multidisciplinary care for brain metastases is one of the most rapidly evolving fields in neuro-oncology, as well as one of the most common global causes of morbidity and mortality. Amidst this evolution with advances in neurosurgical, radiation, systemic therapies, and molecular oncology, Junger et al. retrospectively reviewed the outcomes of 2751 people who underwent neurosurgical resection of newly diagnosed brain metastases from solid tumors at 10 (mostly German) institutions from 2012 to 2022.1 Their observations confirm prior knowledge that resection can be beneficial for survival and local disease control, especially within the evolving context of effective systemic therapies (especially targeted treatments and immunotherapies) and increasing use of stereotactic radiosurgery over whole brain radiation. While most prior studies in this field have emphasized survival, few have rigorously addressed how surgical resection of brain metastases can improve and preserve function, and presumably quality of life. Indeed, they found that performance status improved in 37.8% of patients, and only worsened in 15.9% of patients, with age over 65 and extent of resection correlating with risk of worsening performance status postoperatively. Serious surgical adverse events were quite rare (grade 4 in 1.6% and death in 1.0%), but 7.4% of patients died within 30 days of surgery, and men, people over the age of 65, and performance status <70 correlated with 30-day mortality. As the authors acknowledge, corticosteroids alone sometimes improve performance status, so we cannot know how many patients would have improved without surgical intervention, and whether either approach achieves more durable symptom relief. However, what may be most interesting within their observations is what is missing. This study looked only at first interventions for brain metastases, but with prolonged survival, many patients undergo multiple serial interventions with surgery and radiosurgery. Numerous large studies have now confirmed that prognostic predictors for outcomes and treatment approaches for brain metastases differ substantially based on histologic and molecular subtype, and these authors indeed found that time to local recurrence was much longer for renal cancers and that age and performance status associations with outcomes differed between melanoma, breast, and lung cancers.2 Unexplored were the many advances in assessments of frailty and “geriatric” fitness that correlate with surgical complications and survival outcomes (Charlson Comorbidity Index, serum albumin, prognostic nutritional index, temporalis muscle wasting or its velocity, etc.), which are well established for patients with brain metastases.3–6 In addition, the diagnostic benefit of surgical interventions has also been confirmed, with ∼10% of intracranial pathology finding a different pathology than predicted or a molecular change with relevance for systemic therapy (eg, HER2 expression).7