Pembrolizumab as a promising intervention for advanced penile cancer

Abstract

Penile cancer (PeCa) as a rare neoplasm has an incidence of 0.1 to 0.9 per 100,000 men in Europe and the USA. Some factors related to this epidemiologic difference include HPV infection status, smoking history, poor hygiene, and lack of infant circumcision. Most patients show an initial period of local growth, followed by regional node compromise and, finally, distant spread. Unfortunately, patients who show at advanced stages have a grim prognosis. Studies have shown one-third of patients who have regional recurrences are alive at five years, and none with distant metastases live longer than two years (1, 2). Standard treatments used in penile cancer patients with recurrence and metastatic disease include schemes with paclitaxel, ifosfamide, and cisplatin (TIP). Disappointingly, the efficacy of these agents has been recently contested (3) and overall survival rates do not exceed twelve months (2). Since its approval in 2014 (4) and its further indication as salvage therapy in certain penile SCC (5), pembrolizumab has been considered as a relevant therapeutic option. Considering that there are no clinical trials to guide systemic therapy recommendations, we aimed to discuss the effectiveness and safety of pembrolizumab in patients with locally advanced or metastatic penile SCC. When searching the vast literature through most databases, we found scarce information regarding this topic. Only two studies accomplished this criteria: Hahn et al. (6) and Chahoud et al. (7). Regarding the general characteristics of people requiring immunotherapy, we might highlight that they are usually older patients with advanced stage penile cancer. Patients commonly show mass sensation, non-healing penile lesions, bloody discharge, and inguinal lymphadenopathies. Furthermore, they have T2-3 disease, N0-3, recurrent or even metastatic, squamous cell carcinoma (SCC) with a moderate to poor differentiation. Consequently, patients undergo a multimodal therapy. A partial or radical penectomy, and bilateral and pelvic lymph node dissection are their initial and stepped surgical approach. Consolidation surgery may comprise a wide hemipelvectomy resection with acetabular reconstruction. Among patients, commonly used chemotherapeutic schemas included cisplatin/gemcitabine/ifosfamide and paclitaxel/ifosfamide/cisplatin, and they also use radiation therapy. Although, patients may share interesting features regarding the biomarker expression, these are heterogeneous. PD-L1 expression and tumor Pembrolizumab as a promising intervention for advanced penile cancer _______________________________________________