An update on the pharmacotherapy of penile cancer

A cancer so rare its "standard" chemo regimen has never been tested against newer immunotherapy in a randomized trial

Journal: Journal of Oncology Pharmacy Practice | Published: 2025-10-01 | Type: Journal Article, Review | PMID: 41032682 Authors: Samperio Victor M, Ike Ifeoma, Hamoud Moza, Dasanu Constantin A (Department of Medicine, Eisenhower Health, Rancho Mirage, CA; Lucy Curci Cancer Center) Funding/COI: No funding listed. Authors declared no conflicts of interest.

Summary

This is a narrative review of drug treatment for penile squamous cell carcinoma (PSCC), covering the period from January 2000 to June 2025. The authors describe platinum-based chemotherapy, specifically the paclitaxel-ifosfamide-cisplatin (TIP) regimen, as the current first-line standard for fit patients with advanced disease, while immune checkpoint inhibitors like cemiplimab and pembrolizumab are presented as emerging alternatives with better tolerability. No new patient data is generated here; the paper synthesizes existing literature.

Claims

• TIP chemotherapy remains the standard first-line option for fit patients with advanced PSCC, with "reasonable response rates" but significant toxicity.
• Cemiplimab and pembrolizumab have shown durable responses in biomarker-selected patients with advanced PSCC, with improved tolerability and quality of life compared to chemotherapy.
• No randomized controlled trials of immune checkpoint inhibitors in PSCC currently exist; the authors describe them as "awaited."
• The authors call for trials testing checkpoint inhibitors added to platinum-based chemotherapy, rather than as chemo replacements.

Study Quality

This is a narrative review, not a systematic review or meta-analysis, despite searching three databases (Medline, Embase, Cochrane). No PRISMA methodology, inclusion/exclusion criteria, or quality-scoring framework for the underlying studies is reported in the abstract. That matters here specifically because the evidence base for PSCC pharmacotherapy is thin by nature of the disease's rarity, so the review is largely built on small single-arm studies and case series rather than large trials, and the paper doesn't quantify how sparse that evidence actually is.

Because it's a review of reviews and small studies rather than a primary trial, there is no sample size, effect size, or p-value to report for the paper itself. The strength of a piece like this rests entirely on the transparency of its literature selection, which isn't detailed in the available abstract.

Red Flags

• Narrative rather than systematic review methodology, despite a multi-database search — no stated inclusion criteria or risk-of-bias assessment for the underlying studies.
• The abstract's own conclusion acknowledges the central gap: no randomized trial data exists for the checkpoint inhibitors it highlights as promising.
• "Durable responses" for cemiplimab and pembrolizumab is a claim carried over from the primary studies being reviewed, not something this paper independently verifies; no numbers accompany it in the abstract.

Strengths

• Covers a genuinely underserved area — PSCC is rare enough that consolidated pharmacotherapy reviews are uncommon.
• No funding or conflicts of interest declared.
• 25-year search window gives broad historical coverage of the treatment landscape.
• Explicitly flags the absence of randomized evidence rather than overstating what's known, and calls for combination trials rather than declaring a winner.

Verdict

Useful as an orientation piece for a rare cancer with a thin evidence base, but it's a summary of other people's small studies, not new evidence. The most important finding is really an absence: nobody has run a randomized trial comparing chemotherapy to checkpoint inhibitors in PSCC, so "TIP remains standard" is more a statement about trial infrastructure than proven superiority. Worth a skim if you're tracking the field, not a paper that moves any needle.