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：阴茎癌是一种罕见且侵袭性强的恶性肿瘤，其发病率存在地域差异。其主要危险因素为人乳头瘤病毒（Human Papillomavirus, HPV）感染。鳞状细胞癌是最常见的组织学亚型，约占所有病例的95%。对于晚期阴茎癌患者，预后仍较差，IV期患者的5年生存率仅为16%。当前治疗主要以姑息性全身治疗为主。本综述概述了晚期阴茎癌姑息性全身治疗的相关证据，涵盖化疗、免疫治疗、靶向治疗以及新兴治疗策略。
总结：以顺铂为基础的化疗是晚期阴茎癌公认的一线治疗方案，但该疗法的疗效往往有限且持续时间较短。免疫检查点抑制剂在阴茎癌中展现出有限但具有前景的疗效，部分患者可获得持久应答，尤其是肿瘤突变负荷较高、HPV阳性或PD-L1高表达的患者，但仍需进一步研究以确定用于优化患者筛选的预测性生物标志物。靶向HPV癌蛋白的HPV疫苗疗法、过继性T细胞疗法以及binatrafusp alfa等药物在HPV相关癌症中显示出潜力，但其在阴茎癌中的治疗地位仍不明确。目前正在开展的临床试验正在探索具有协同潜力的联合治疗方案，例如HPV疫苗联合检查点抑制剂，或免疫疗法联合化疗或酪氨酸激酶抑制剂。
核心要点：以顺铂为基础的化疗仍是晚期阴茎癌的一线治疗方案，免疫治疗与靶向治疗虽展现出治疗潜力，但仍需开展更多研究。若条件允许，将患者纳入临床试验并尽早开展肿瘤分子测序，对于改善患者预后、明确有效治疗靶点至关重要。