Stelmach Ramona, Giannatempo Patrizia, Nicolai Nicola, Garcia Del Muro Xavier
Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg, Germany.
Department of Genito-Urinary Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Oncol Res Treat. 2025 May 5:1-13. doi: 10.1159/000546246.
Penile cancer is a rare, aggressive malignancy, with incidence varying geographically. The primary risk factor is human papillomavirus (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 centred 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.
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.
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.
阴茎癌是一种罕见的侵袭性恶性肿瘤，发病率在不同地区有所差异。主要危险因素是人乳头瘤病毒（HPV）感染。鳞状细胞癌是最常见的组织学亚型，约占病例的95%。对于晚期阴茎癌，预后仍然很差，IV期疾病的5年生存率为16%。治疗主要集中在姑息性全身治疗。本综述概述了晚期阴茎癌姑息性全身治疗的证据，包括化疗、免疫治疗和靶向治疗，以及新兴的治疗策略。
基于顺铂的化疗是晚期阴茎癌既定的一线治疗方法，但其疗效往往有限且持续时间短。免疫检查点抑制剂在阴茎癌中显示出有限但有前景的疗效，一些患者出现持久反应，特别是那些肿瘤突变负荷高、HPV阳性或PD-L1表达高的患者，不过需要进一步研究以确定最佳患者选择的预测生物标志物。基于HPV疫苗的针对HPV癌蛋白的疗法、过继性T细胞疗法以及双特异性抗体（如阿法双靶点抗体）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确定。正在进行的临床试验正在研究潜在的协同联合疗法，如HPV疫苗与检查点抑制剂联合，或免疫疗法与化疗或酪氨酸激酶抑制剂联合。
基于顺铂的化疗仍然是晚期阴茎癌的一线治疗方法，而免疫治疗和靶向治疗显示出前景，但需要进一步研究。将患者纳入临床试验并尽可能进行早期肿瘤分子测序，对于改善预后和确定有效的治疗靶点至关重要。
