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Abstract. Leptomeningeal metastasis/leptomeningeal carcinomatosis (LMC; terms used interchangeably) is an inflammatory complication of primary tumors that involves the spread of the disease to the meninges (specifically the arachnoid and pia maters) and spinal cord. In the United States, approximately 110,000 new cases are diagnosed each year, and the prognosis is usually poor. Complications of LMC include cognitive impairment, cranial nerve dysfunction, ischemic stroke, and mortality. The survival times of untreated and treated LMC are approximately 4–6 weeks and 2–4 months, respectively. Leptomeningeal carcinomatoses are usually metastatic cancers that spread to the central nervous system. Although lung and breast cancers have a clearly defined relationship with LMC, it remains unclear whether prostate cancer (PC) is also directly associated with LMC. To determine whether such association exists, we conducted a PubMed review of the literature on patients with PC with coexisting LMCs. Our search yielded 23 case reports of patients with preexisting PC who developed LMC. In addition, 2 retrospective cohort studies were examined. Various findings were identified in the revised cases and studies. The first 3 findings were related to the progression of the disease: patients presenting with neurological disease symptoms were in remission from PC for 7 years on average, LMCs tended to occur after other cancer diagnoses, and the disease had already rapidly progressed by the time the symptoms were present. Regarding diagnosis, the major finding was that most LMCs were detected by magnetic resonance imaging (which does not detect early dissemination), and it was suggested that single-photon emission computed tomography or positron emission tomography imaging could be used for earlier detection. Finally, in terms of treatment, the main finding was that treatment was palliative rather than curative and that prognosis remained poor despite treatment. On the basis of these results, we recommend for individuals with risk factors, such as high-grade PC and hormonal PC, to be evaluated on a case-by-case basis for increased surveillance of LMC development.

Abstract. Between 2.6 and 3.8 million veterans served in Vietnam while the US military dispersed Agent Orange (AO), although the exact number of exposed individuals is unknown. Agent Orange, an herbicide, is a known risk factor for various cancers, including sarcoma and leukemia, but less is known about its link with prostate cancer (PC). Prostate cancer is the most commonly diagnosed malignancy in men and the fifth most common cause of cancer-related death in men worldwide. In 2023, approximately 288,300 patients will be given a diagnosis of PC, and an estimated 34,700 fatalities will occur in the United States. However, whether the pathologic characteristics of PC among those exposed to AO differ from those in the general population remains unclear. Our review synthesizes the literature regarding the impact of AO exposure on PC incidence and disease course. A comprehensive PubMed literature search of articles published beginning in 1950 was performed using the primary search terms “Agent Orange,” “TCDD,” and “tetrachlorodibenzodioxin” and the secondary search terms “prostate cancer” or “prostate neoplasm.” The search was limited to studies that focused on human participants and were published in English. Four authors thoroughly reviewed the retrieved articles for relevancy to the study aims: discussion of PC diagnosis, prognosis, or management among patients exposed to AO. Of 108 studies identified in our search, 13 were included in this systematic review. Findings within studies concerning AO exposure with relation to PC incidence, age at diagnosis or treatment initiation, and PC severity seemed to be mixed and generally conflicting. However, the literature seems to indicate that there are no significant differences in survivorship between exposed and unexposed veterans who are given a diagnosis of PC. Given these heterogeneous outcomes, the evidence does not encourage a significantly different approach to the diagnosis and management of PC for veterans exposed to AO. Clinicians should make case-by-case decisions regarding PC screening and potential treatment options for this patient group, weighing clinical suspicion against the harms of diagnostic workup and treatment.