For patients who meet EMBARK criteria but also show oligometastatic disease on PSMA PET, clinicians are adopting a pragmatic approach. They combine the evidence-backed systemic hormone therapy from the trial with targeted radiation of metastatic sites, aiming to prolong the time until therapy needs to be restarted.

Experts assert that chemotherapy should not be used as first-line treatment for HR-positive metastatic breast cancer. Clinical trials show a CDK4/6 inhibitor with endocrine therapy provides better outcomes and tolerability than multi-agent chemotherapy, even for patients with aggressive, symptomatic visceral metastases, challenging the traditional use of chemo for rapid response.

Unlike the standard chemotherapy regimen TCHP, the newer drug T-DXd can cross the blood-brain barrier. This is a crucial advantage for high-risk HER2-positive breast cancer patients, as it offers the potential to prevent brain metastases, a common and devastating site of recurrence for this cancer subtype.

With new CNS-active drugs dramatically improving survival after a brain metastasis diagnosis, some experts are now advocating for routine screening brain MRIs in high-risk patients. The goal is to detect asymptomatic lesions early, potentially preventing catastrophic neurologic events like seizures.

For HER2+ gastric cancer patients with a single brain metastasis that is fully resected and radiated, experts may opt for close monitoring. This watch-and-wait approach is preferred over immediate systemic adjuvant therapy, even in this high-risk scenario.

For patients with otherwise well-controlled disease who develop isolated oligoprogression in the brain, evidence suggests a better survival outcome from adding local therapy (like SRS) and continuing the current effective systemic therapy, rather than switching the systemic regimen entirely.

Contrary to common belief, HER2 can be expressed or amplified in prostate cancer, particularly in subtypes with neuroendocrine features. This creates a rare but actionable target, with reported complete responses to HER2-directed therapies like TDXD, highlighting the need for broader genomic testing.

The COMPEL trial provides strong evidence for a "treat through progression" strategy. For patients progressing on osimertinib monotherapy, continuing the TKI while adding chemotherapy significantly reduces the probability of CNS progression, highlighting its role as a CNS protectant even when systemic efficacy is waning.

For EGFR-mutated NSCLC patients with brain metastases, even numerous ones (>30), potent systemic therapy like osimertinib plus chemotherapy is often initiated first. This can achieve high rates of complete intracranial response, allowing clinicians to delay or entirely avoid whole-brain radiation and its long-term toxicities.