Abstract BACKGROUND Surveillance of patients with medulloblastoma includes magnetic resonance imaging of the brain and spine and cerebrospinal fluid (CSF) cytology evaluation. Certain protocols require frequent CSF cytology evaluations off-therapy while others perform CSF cytology only at the time of radiographic relapse. We wanted to determine the incidence of isolated CSF positivity at the time of recurrence and the outcome of these patients. METHODS We performed a retrospective analysis of patients with relapsed medulloblastoma treated at Texas Children’s Hospital between 1997 and 2023. RESULTS Out of 223 patients with medulloblastoma, 45 patients developed recurrences. Twenty-five (55.5%) patients underwent lumbar puncture for CSF cytology at the time of relapse. The radiographic distribution of recurrences was focal (n=7), focal and disseminated (n=6), disseminated (n=11), and negative imaging (n=1). Seven out of the 25 (28%) patients had positive CSF cytology for malignant cells at initial relapse. All seven patients succumbed secondary to disease progression. Among 18 patients who had negative CSF cytology at recurrence, three infant patients at initial diagnosis were disease-free following craniospinal radiation at recurrence. Only one among 25 patients had positive CSF cytology without radiographic evidence of relapse. Among ten patients with focal disease at the time of relapse, seven had negative CSF cytology for malignant cells, and three did not have CSF cytology evaluated at the time of relapse. DISCUSSION Frequent evaluation of CSF cytology to detect recurrence may not be necessary in addition to imaging studies. In our study, it did not influence the outcome of patients with recurrence. Prospective studies are necessary to support periodic CSF surveillance to detect ctDNA, which may allow for early interventions that may influence outcomes in patients with recurrent medulloblastoma who have poor outcomes.