Clinical outcomes of Kaposi's sarcoma in a cohort of HIV-negative men who have sex with men: An observational study (2000–2024).
Authors: Alberto Giovanni Leone, Jesal Gohil, Alessia Dalla Pria, Claudia A.M. Fulgenzi, Mark Lythgoe, Mark Bower, Monica Sebastian, Pascal Migaud, David James Pinato, Marta Boffito, John Forni
Journal: Journal of Clinical Oncology (2025)

e23538 Background: Kaposi's sarcoma (KS) is a multifocal vascular neoplasm associated with human herpesvirus-8 (HHV-8) infection. Historically, four main forms have been described: classic, endemic, iatrogenic, and HIV-related KS. Recently, in countries with low HHV-8 sero-prevalence, a distinct form has been identified in men who have sex with men (MSM), occurring independently of immunosuppression (MSM-KS). Limited data are available on its clinical presentation, management and outcomes. Methods: This is an observational study conducted at the National Centre for HIV Malignancy at the Chelsea and Westminster Hospital in London, UK. Prospectively collected records of MSM living without HIV diagnosed with histologically confirmed non-iatrogenic KS between 2000-2024 were reviewed. Statistical analyses were performed using multivariate regression models, and survival data were summarized. All analyses were conducted with JMP Pro 18. Results: A total of 58 patients with a median age at KS diagnosis of 52 years (range 25-85) were evaluated. The median follow up was 7.4 years (maximum 24). At KS diagnosis, the skin was the only site involved in 93%, whereas the remaining 7% (4 patients) presented with a single lymph node involvement. Blood HHV-8 DNA was undetectable in 69% of patients. Most patients (59%) had localized disease ( &lt; 5 skin lesions), of whom 89% received local treatment (surgical excision, radiotherapy or intralesional vinblastine) and 29% recurred with a median time to first recurrence of 22 months (range 4-144). At KS diagnosis, 34% had disseminated disease (≥5 skin lesions), of whom 37% received upfront systemic chemotherapy (liposomal anthracycline) and 63% had a subsequent recurrence (median time to first recurrence = 12 months, range 1-132). Two of these patients developed pathologically confirmed bone lesions. All patients with a single node involvement underwent surgical excision and none relapsed. The overall mortality rate was 7% (4 deaths, none related to KS). No other HHV-8-related malignancies were diagnosed during follow-up. For the whole cohort, 1-year progression free survival (PFS) was 80% [95% confidence interval (CI) = 68%-89%], 5-year PFS was 59% (95% CI: 45%-72%), and 5-year overall survival (OS) was 95% (95% CI: 82%-99%). When comparing patients with skin-localized versus skin-disseminated disease, 1-year PFS significantly differed in the two groups (87% vs 62% p = 0.011). There were no significant differences in OS between the two groups. Conclusions: KS in MSM without HIV most commonly presents as an indolent disease, with a clinical course and outcomes resembling the classic form of KS. These findings highlight the uniqueness of MSM-KS and its overlap with other forms and contribute to a better understanding of its clinical course. However, the epidemiology and pathogenesis of this specific form remain open questions for future research to address.