The core of Demircan’s critique rests on a principle familiar to every epidemiologist: treatment effect and treatment selection are two very different things. When patients are not randomized, the group that receives one therapy is often systematically different from the group that receives another, and any difference in outcomes may reflect those baseline differences rather than the therapy itself. In the study under scrutiny, patients who underwent microsurgical resection had greater baseline motor impairment than those allocated to stereotactic radiotherapy. That detail matters enormously, because a patient who enters treatment with a weakened arm or leg has far more room to demonstrate measurable improvement than a patient whose motor function is already intact. Improvement in the surgical cohort and stability in the radiotherapy cohort may therefore describe the same underlying quality of care, even though the numbers appear to favor one arm over the other.

This asymmetry in scoring is more than a statistical quirk. Functional outcome scales typically capture change from baseline, so a patient who regains the ability to walk after tumor decompression registers a dramatic gain, while a patient who never lost the ability to walk and remains unchanged after focused radiation registers only stability. Yet clinically, preserving intact neurological function is precisely the goal of treating a metastasis in eloquent motor cortex without opening the brain. Demircan points out that categorizing preserved near-intact function after stereotactic radiotherapy as mere stability understates what is, for those patients, a meaningful and desirable result. The apparent superiority of surgery may, in part, be an artifact of the yardstick rather than a genuine therapeutic advantage.

The second major concern involves what statisticians call informative crossover, and here the numbers are striking. Of the 41 patients initially allocated to stereotactic radiotherapy, 17 ultimately required salvage surgery, either because their tumors progressed or because they developed a new neurological deficit despite irradiation. That is a crossover rate of roughly 41 percent, and all of those patients were excluded from the comparative radiotherapy cohort. What remains in the analyzed group is, by construction, the subset of patients for whom radiotherapy succeeded. This is a form of survivorship bias built directly into the study design: the radiotherapy arm is pre-selected for good outcomes, while the failures are silently transferred out of view. Any comparison between the trimmed radiotherapy cohort and the surgical cohort will therefore flatter radiotherapy less than an intention-to-treat analysis would, or, depending on how the comparison is framed, obscure the clinically important fact that a substantial minority of radiotherapy patients fared poorly and needed rescue operations.

Demircan emphasizes that this 41 percent crossover does double duty. It simultaneously selects the analyzed radiotherapy cohort for patients in whom the treatment worked, and it identifies a subgroup with genuinely poor outcomes after initial radiotherapy, patients who progressed or deteriorated neurologically and required surgery anyway. For clinicians counseling a patient, that subgroup is not a footnote; it is central to the decision. A patient with a metastasis in the motor cortex wants to know not only the average outcome of each strategy but also the risk that the first choice will fail and leave them worse off. When more than four in ten patients initially assigned to radiotherapy end up needing surgery, the effective comparison is no longer surgery versus radiotherapy but surgery versus radiotherapy followed, in many cases, by surgery after all.

A third layer of complexity concerns what the surgical arm actually received. Postoperative radiotherapy was administered to 95 percent of surgically treated patients with available data. This means the study did not compare surgery alone with radiotherapy alone; it compared a multimodality package, microsurgical resection followed by adjuvant irradiation, against definitive stereotactic radiotherapy. The distinction is far from academic. Landmark randomized trials, including the phase 3 studies by Mahajan and colleagues and Brown and colleagues published in Lancet Oncology in 2017, established that postoperative stereotactic radiosurgery reduces local recurrence after resection but carries its own considerations regarding toxicity and cognitive outcomes. Attributing the combined strategy’s results to surgery alone would misrepresent the intervention patients actually underwent and could mislead centers that lack the full multidisciplinary apparatus the combined approach presumes.

Compounding all of this, the extent of resection was not reported. In neurosurgical oncology, the degree to which a tumor is removed is one of the strongest determinants of local control, particularly when adjuvant radiation is planned. A gross-total resection followed by cavity radiosurgery behaves very differently biologically from a subtotal decompression, both in terms of residual tumor cells and in the dose constraints that nearby motor pathways impose on the radiation plan. Without knowing how complete the resections were, readers cannot disentangle how much of the local control in the surgical arm came from the operation itself and how much from the postoperative irradiation that nearly all of those patients received. Demircan argues that this missing variable further complicates any interpretation of the study’s local control data and its functional outcomes.

None of this means the study is without value. Demircan is explicit that the findings do support microsurgical resection for appropriately selected patients, particularly those with large, symptomatic lesions that require rapid decompression. When a tumor is exerting mass effect on motor pathways and a patient is losing function hour by hour, focused radiation cannot act quickly enough, and surgical relief is the only option that restores room for the brain to recover. The critique is narrower and more precise: the data do not establish that surgery produces better functional outcomes than stereotactic radiotherapy once treatment selection is properly accounted for. Those are two very different claims, and conflating them could push clinical practice toward aggressive intervention in patients who would do just as well, with less risk, under a radiation-first strategy.

The path forward, according to the correspondence, lies in how future studies are designed and reported. Outcomes should be tracked from the initial treatment allocation all the way through salvage therapy, so that the true cost of each starting strategy, including its failure rate, is visible rather than hidden by cohort trimming. Analyses should incorporate the variables that actually drive decisions and outcomes in this population: lesion volume, baseline neurological status, involvement of the corticospinal tract as mapped by diffusion tensor imaging and navigated transcranial magnetic stimulation, the extent of resection achieved, the burden of systemic disease, and the urgency of decompression. Advanced imaging and tractography techniques, already being used to spare motor structures in adjuvant radiotherapy planning, offer a way to individualize these decisions with far greater anatomical precision than was possible a decade ago.

For patients and clinicians, the takeaway is a familiar lesson in modern oncology delivered in an unfamiliar setting. Observational comparisons, however carefully assembled, are hostage to the forces that determine who receives which treatment. In motor cortex metastases, those forces, performance status, motor function, tumor size, and disease burden, are precisely the factors that also shape functional outcomes, making confounding especially potent. The study by Kraus and colleagues adds real evidence that surgery can serve selected patients well, and the correspondence by Demircan sharpens that evidence into something clinically usable: a reminder that preserved function after radiation is a success worth counting, that crossover is a result worth reporting, and that the question is not simply which treatment works, but which treatment works for which patient, under which circumstances, measured from the moment the first decision is made.

Subject of Research: Interpreting functional outcomes and treatment selection bias in managing brain metastases of the primary motor cortex

Article Title: Treatment selection or treatment effect? Interpreting functional outcomes in motor cortex metastases

Article References: Demircan, V. (2026). Treatment selection or treatment effect? Interpreting functional outcomes in motor cortex metastases. Journal of Neuro-Oncology, 179(2), Article 72. https://doi.org/10.1007/s11060-026-05787-x

Image Credits: AI Generated

DOI: 10.1007/s11060-026-05787-x

Keywords: brain metastases, motor cortex, microsurgical resection, stereotactic radiotherapy, treatment selection bias, functional outcomes, crossover, postoperative radiotherapy, extent of resection, corticospinal tract, neuro-oncology, salvage surgery