TROP-2: Prognostic Significance for Penile Squamous Cell Carcinoma?

Richard Weiten, MD, and colleagues designed a study to determine the potential utility of antibody-drug conjugates (ADCs) targeting TROP-2 in both localized penile squamous cell carcinoma (PSCC) and patient-matched distant metastases.

Their results were presented at the 2024 American Urological Association Annual Meeting.

Despite recent advancements in the management of patients with locally advanced or metastatic PSCC, systemic treatment options are still limited, and effective salvage therapies are needed. Research in other solid tumors (eg, breast and bladder) has demonstrated the clinical efficacy of ADCs.

To assess TROP-2-targeted ADCs in PSCC, Dr. Weiten and colleagues performed an immunohistochemical analysis of TROP-2 expression in patients with localized disease (n=40) and their corresponding distant metastases (n=9, including lymph node and lung metastases). Overall survival (OS) was evaluated by stratifying patients into subgroups based on TROP-2 expression: weak (H-score, 15-99) versus moderate/strong (H-score, 100-300).

Researchers also explored the relationship between TROP-2 expression and human papillomavirus (HPV)-dependency, and they designed an enzyme-linked immunosorbent assay to measure TROP-2 serum samples derived from localized PSCC (n=40) and a healthy control group (n=10).

Results of the analysis showed a statistically significant increase in TROP-2 messenger RNA expression levels in patients with PSCC compared with healthy individuals (P<.0001).

A “notable” elevation in TROP-2 protein expression was observed in the serum specimens obtained from the PSCC cohort (P<.01), and the majority of patients reportedly exhibited moderate/strong TROP-2 expression, indicative of a robust median H-score of 280.

Upon subgroup analysis, researchers discovered a correlation between TROP-2 expression and HPV status (P<.01), which led to discernible associations with more favorable clinical outcomes (P<.05).

“TROP-2 protein expression in PSCC holds prognostic significance,” Dr. Weiten concluded, adding that “TROP-2-targeted ADCs, [including] sacituzumab govitecan or datopotamab deruxtecan, may emerge as promising novel therapeutic interventions for these patients.”