Supplementary Material for: Management of Advanced Penile Cancer

Background: Penile cancer is a rare, aggressive malignancy, with incidence varying geographically. The primary risk factor is HPV infection. Squamous cell carcinoma represents the most common histological subtype, accounting for around 95% of cases. For advanced penile carcinoma, prognosis remains poor with a 5-year survival rate of 16% in stage IV disease. Treatment is largely centered on palliative systemic therapy. This review provides an overview of the evidence on palliative systemic treatment for advanced penile cancer, including chemotherapy, immunotherapy, and targeted therapy, as well as emerging treatment strategies.

Summary: Cisplatin-based chemotherapy is the established first-line treatment for advanced penile cancer, but its efficacy is often limited and short-lived. Immune checkpoint inhibitors showed limited but promising efficacy in penile carcinoma, with some patients experiencing durable responses, particularly those with high tumour mutational burden, HPV positivity, or high PD-L1 expression, though further research is needed to identify predictive biomarkers for optimal patient selection. HPV vaccine-based therapies targeting HPV oncoproteins, adoptive T-cell therapies and agents like binatrafusp alfa are showing potential in HPV-associated cancers, though their role in penile cancer remains uncertain. Ongoing clinical trials are investigating potentially synergistic combination therapies, such as HPV vaccines with checkpoint inhibitors or immune therapies combined with chemotherapy or tyrosine kinase inhibitors.

Key Messages: Cisplatin-based chemotherapy remains the first-line treatment for advanced penile cancer, while immunotherapy and targeted therapies show promise but require further investigation. Enrolling patients in clinical trials and conducting early tumour molecular sequencing, if possible, are crucial for improving outcomes and identifying effective treatment targets.

背景：阴茎癌是一种罕见的侵袭性恶性肿瘤，发病率存在地域差异。主要危险因素是人乳头瘤病毒（HPV）感染。鳞状细胞癌（Squamous Cell Carcinoma）是最常见的组织学亚型，约占病例的95%。对于晚期阴茎癌，预后仍然较差，IV期患者的5年生存率仅为16%。治疗主要集中在姑息性系统治疗。本综述概述了晚期阴茎癌姑息性系统治疗的证据，包括化疗、免疫治疗和靶向治疗，以及新兴治疗策略。

摘要：顺铂为基础的化疗是晚期阴茎癌公认的一线治疗方案，但其疗效往往有限且持续时间短。免疫检查点抑制剂（Immune Checkpoint Inhibitors）在阴茎癌中显示出有限但有前景的疗效，部分患者出现持久应答，尤其是那些肿瘤突变负荷（Tumour Mutational Burden）高、HPV阳性或程序性死亡配体1（PD-L1）表达高的患者，不过仍需进一步研究以确定最佳患者选择的预测性生物标志物。针对HPV癌蛋白的HPV疫苗疗法、过继性T细胞疗法（Adoptive T-cell Therapy）以及binatrafusp alfa等药物在HPV相关癌症中显示出潜力，但其在阴茎癌中的作用仍不明确。正在进行的临床试验正在研究潜在的协同联合疗法，例如HPV疫苗与检查点抑制剂联用，或免疫疗法与化疗或酪氨酸激酶抑制剂（Tyrosine Kinase Inhibitors）联用。

核心信息：顺铂为基础的化疗仍是晚期阴茎癌的一线治疗方案，而免疫治疗和靶向治疗虽显示出前景，但仍需进一步研究。让患者参与临床试验，并在可能的情况下进行早期肿瘤分子测序，对于改善预后和确定有效治疗靶点至关重要。