Insights into the management of penile squamous cell carcinoma: from conventional approaches to emerging novel therapies

ABSTRACT

Introduction

Penile squamous cell carcinoma (PSCC), a rare genitourinary cancer, is associated with poor outcomes due to limited treatment effectiveness, especially in advanced stages.

Areas covered

While chemotherapy and/or surgery remain the standard of care, emerging therapies like immunotherapy, targeted therapy, and human papillomavirus (HPV) directed therapies show promise. Key to advancing treatment is understanding the immune microenvironment to gain insights into tumor resistance mechanisms and potential therapeutic targets. The scarcity of data on PSCC is a major obstacle in advancing research for this rare cancer.

Expert opinion

Future research should prioritize collaborative efforts across various research centers and countries. Enhancing data sharing and pooling resources can lead to a more comprehensive understanding of PSCC, ultimately supporting the development of precision medicine strategies tailored to this specific cancer type. This collaborative approach is essential for making significant strides in PSCC treatment and care.

KEYWORDS:

• Penile squamous cell carcinoma
• tumor microenvironment
• human papillomavirus
• pharmacotherapy
• novel therapies

Article highlights

• Current mainstay treatments for penile squamous cell carcinoma (PSCC) include chemotherapy and surgery, with emerging potential in immunotherapy, targeted therapy, and human papillomavirus (HPV) directed therapies.

• Approximately half of PSCC cases are HPV-positive, presenting distinct genetic and biological characteristics, highlighting the potential of HPV-directed vaccines and therapies.

• New treatments focusing on target molecules like Nectin-4 and heat shock proteins (HSPs) are being explored, emphasizing the importance of understanding the pathophysiology in order to design novel treatment modalities.

• The rarity of PSCC and limited research funding present challenges to advancing this treatment landscape, highlighting the need for international collaboration and the Global Society for Rare Genitourinary Tumors’ role in advancing research and treatment.

Declaration of interest

A Necchi reports the following: honoraria: Roche, MSD, AstraZeneca, Janssen, Foundation Medicine, BMS, Astellas. Consulting or Advisory role: MSD, Roche, Bayer, AstraZeneca, Clovis Oncology, Janssen, Incyte, Seattle Genetics/Astellas, Bristol-Myers Squibb, Rainier Therapeutics, Bycicle Therapeutics, GlaxoSmithKline, Basilea Pharmaceutica, Catalym. Research Funding (Institution): MSD, AstraZeneca, Ipsen, Gilead. Travel, Accommodations, Expenses: Roche, MSD, AstraZeneca, Janssen, Rainer Therapeutics, Pfizer.

P E Spiess reports the following leadership positions: President of Global Society of Rare GU Tumors, NCCN bladder and penile cancer panel, vice-chair, Member of ASCO/EAU Penile Cancer Panel.

J Chahoud received consultation fees from Pfizer, aveo, exelisis and mycaregorythm.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Acknowledgments

We would like to thank the R.S Evans foundation for their generous support of the penile cancer research program at Moffitt Cancer Center.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.