You have accessJournal of UrologyPenile & Testicular Cancer II (MP61)1 May 2024MP61-08 TROP-2—A PROMISING NEW THERAPEUTIC TARGET IN PENILE SQUAMOUS CELL CARCINOMA Richard Weiten, Carolina Kessler, Christina Meisl, Hanna Elisa Spohn, Enno Storz, David Pfister, Tim Nestler, Yuri Tolkach, Friederike Linden, Ralph Wirtz, Melanie von Brandenstein, Philipp Krausewitz, and Axel Heidenreich Richard WeitenRichard Weiten , Carolina KesslerCarolina Kessler , Christina MeislChristina Meisl , Hanna Elisa SpohnHanna Elisa Spohn , Enno StorzEnno Storz , David PfisterDavid Pfister , Tim NestlerTim Nestler , Yuri TolkachYuri Tolkach , Friederike LindenFriederike Linden , Ralph WirtzRalph Wirtz , Melanie von BrandensteinMelanie von Brandenstein , Philipp KrausewitzPhilipp Krausewitz , and Axel HeidenreichAxel Heidenreich View All Author Informationhttps://doi.org/10.1097/01.JU.0001009536.58867.87.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Penile squamous cell carcinoma (PSCC) is an infrequent yet progressively prevalent malignancy. Despite ongoing advancements in patients with the diagnosis of locally advanced or metastasized PSCC especially systemic treatment options are limited. Therefore, there is an urgent need for efficient salvage therapies. Recently in other solid tumor entities, e.g., breast and urothelial cancer, antibody-drug-conjugates (ADCs) demonstrated significant clinical efficacy. Our aim was to ascertain the potential utility of ADCs targeting TROP-2 in both localized PSCC (PRIM) and patient-matched distant metastases (MET). METHODS: Immunohistochemical analysis of TROP-2 expression was conducted in PRIM (n=40) and their corresponding METs (n=9, including lymph node and lung metastases). We assessed overall survival (OS) by stratifying patients into subgroups based on TROP-2 expression: weak (H-score 15–99) versus moderate/strong (H-score 100–300). Additionally, we explored the relationship between TROP-2 and HPV-dependency. Furthermore, TROP-2 mRNA expression levels were quantified via qRT-PCR, and an enzyme-linked immunosorbent assay was employed to measure TROP-2 in serum samples derived from PRIM (n=40) and a healthy control group (n=10). RESULTS: We found a statistically significant increase in TROP-2 mRNA expression levels in individuals afflicted with PSCC compared to healthy controls (p<0.0001). Moreover, a notable elevation in TROP-2 protein expression was observed in the serum specimens obtained from PSCC patients (p<0.01). The majority of patients exhibited moderate to strong TROP-2 expression, indicative of a robust median H-score of 280 (interquartile range: 210–300). Subgroup analysis revealed a correlation between TROP-2 expression and HPV status (p<0.01), demonstrating discernible associations with more favorable clinical outcomes, as evidenced by the log-rank (Mantel-Cox) test (p<0.05). CONCLUSIONS: TROP-2 protein expression in PSCC holds prognostic significance. Furthermore, the elevated TROP-2 levels in both PRIM and PSCC metastases suggest that the TROP-2-targeted ADC, Sacituzumab govitecan or Datopotamab deruxtecan, may emerge as a promising novel therapeutic intervention for these patients. Download PPT Source of Funding: N/A © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e1013 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Richard Weiten More articles by this author Carolina Kessler More articles by this author Christina Meisl More articles by this author Hanna Elisa Spohn More articles by this author Enno Storz More articles by this author David Pfister More articles by this author Tim Nestler More articles by this author Yuri Tolkach More articles by this author Friederike Linden More articles by this author Ralph Wirtz More articles by this author Melanie von Brandenstein More articles by this author Philipp Krausewitz More articles by this author Axel Heidenreich More articles by this author Expand All Advertisement PDF downloadLoading ...

12 Background: Penile squamous cell carcinoma (PSCC) is an infrequent yet progressively prevalent malignancy. Despite ongoing advancements in personalized and immunotherapeutic approaches, patients grappling with the diagnosis of locally advanced or metastasized PSCC still confront a limited therapeutic arsenal, leading to an unfavorable prognosis. Consequently, an imperative mandate arises to explore alternative therapeutic modalities, particularly antibody-drug-conjugates (ADCs), which have demonstrated significant clinical efficacy in the context of metastatic solid tumor pathologies. Our aim was to ascertain the potential utility of ADCs targeting Trop-2 in both localized PSCC (PRIM) and patient-matched distant metastases (MET). Methods: Immunohistochemical analysis of Trop-2 expression was conducted in PRIM ( N=40) and their corresponding METs ( N=9, including lymph node and lung metastases). We assessed overall survival (OS) by stratifying patients into subgroups based on Trop-2 expression: weak (H-score 15-99) versus moderate/strong (H-score 100-300). Additionally, we explored the relationship between Trop-2 and HPV-dependency. Furthermore, Trop-2 mRNA expression levels were quantified via qRT-PCR, and an enzyme-linked immunosorbent assay was employed to measure Trop-2 in serum samples derived from PRIM ( N=40) and a healthy control group ( N=10). Results: We found a statistically significant increase in Trop-2 mRNA expression levels in individuals afflicted with PSCC compared to healthy controls ( p<0.0001). Moreover, a notable elevation in Trop-2 protein expression was observed in the serum specimens obtained from PSCC patients ( p<0.01). The majority of patients exhibited moderate to strong Trop-2 expression, indicative of a robust median H-score of 280 (interquartile range: 210-300). Subgroup analysis revealed a correlation between Trop-2 expression and HPV status ( p<0.01), demonstrating discernible associations with more favorable clinical outcomes, as evidenced by the log-rank (Mantel-Cox) test ( p<0.05). Conclusions: Trop-2 protein expression in PSCC holds prognostic significance. Furthermore, the elevated Trop-2 levels in both PRIM and PSCC metastases suggest that the Trop-2-targeted ADC, Sacituzumab govitecan, may emerge as a promising novel therapeutic intervention for these patients.