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Multicenter Study
. 2025 Mar;39(3):576-585.
doi: 10.1111/jdv.20093. Epub 2024 Jun 6.

Factors predictive of recurrence, metastasis and death in node-negative penile squamous cell carcinoma: A retrospective multicentre cohort study

Affiliations
Multicenter Study

Factors predictive of recurrence, metastasis and death in node-negative penile squamous cell carcinoma: A retrospective multicentre cohort study

Katie A O'Connell et al. J Eur Acad Dermatol Venereol. 2025 Mar.

Abstract

Background: Penile squamous cell carcinoma (PSCC) carries significant morbidity and mortality. Literature is limited regarding prognostic factors, especially prognostic factors for development of metastasis.

Objectives: To identify independent prognostic factors associated with poor outcomes, defined as local recurrence (LR), metastasis and disease-specific death (DSD) in clinically node-negative PSCC undergoing local therapy.

Methods: Thirty-two-year Retrospective Multicenter Cohort Study of 265 patients with histologically diagnosed PSCC at three tertiary care centres. Predictive models based on patient or tumour characteristics were developed.

Results: Local recurrence occurred in 56 patients, metastasis in 52 patients and DSD in 40 patients. In multivariable models, the following five factors were independent prognostic factors based on subhazard ratio (SHR): history of balanitis (LR SHR: 2.3; 95% CI 1.2-4.2), poor differentiation (metastasis SHR 1.9; 95% CI 1.0-3.6), invasion into the corpora (metastasis SHR: 3.0; 95% CI 1.5-5.8 and DSD SHR: 4.5; 95% CI 1.7-12.1), perineural invasion (PNI) (metastasis SHR: 2.8; 95% CI 1.4-5.5 and DSD SHR: 3.5; 95% CI, 1.6-7.8) and a history of phimosis (DSD SHR: 2.5; 95% CI 1.2-5.3). The 5-year cumulative incidence of metastasis was higher for tumours with PNI [cumulative incidence function (CIF) = 55%, 95% CI 38-75 vs. CIF 15%, 95% CI 11-22], corporal invasion (CIF: 35%, 95% CI 26-47 vs. 12%, 95% CI 7-19) and poorly differentiated tumours (CIF = 46%, 95% CI 31-64 vs. CIF 15%, 95% CI 11-22).

Conclusions: History of balanitis, history of phimosis, PNI, corporal invasion and poor differentiation are independent risk factors associated with poor outcomes. Since poor differentiation and PNI currently constitute only T1b disease, prognostic staging can likely be improved.

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Conflict of interest statement

Conflicts of Interests: KAO, JLT, FM, GZ, AJX, TNM have no conflicts of interest to declare. CDS is a steering committee member for Castle Biosciences; a steering committee member and consultant for Regeneron Pharmaceuticals; has received research funding from Castle Biosciences, Regeneron Pharmaceuticals, Novartis, Genentech, and Merck, and is the chair of the NCCN non-melanoma skin cancer panel. PES is Vice-chair of NCCN bladder and penile cancer panel, President of the Global Society of Rare Genitourinary Tumors and on the ASCO/EAU Penile cancer panel. MM: Speaker, AstraZeneca.

AMR disclosures: Almirall: Consultant; Mavig: Travel; Merz: Consultant; Dynamed: Consultant; Canfield Scientific: Consultant; Allergan Inc: Advisory Board; Evolus: Consultant; Biofrontera: Consulatant; Quantia MD: Consultant; Lam Therapeutics; Consultant; Regeneron; consultant; Cutera, consultant; Skinfix, advisor; L’oreal, travel, DAR companies: Founder

ASLMS: A Ward Memorial Research Grant; Skin Cancer Foundation: Research Grant; Regen: Research / Study Funding; LeoPharma: Research / Study Funding; Biofrontera: Research Study Funding

Editorial Board: Lasers in Surgery and Medicine; CUTIS

Editorial Board: Journal of the American Academy of Dermatology (JAAD); Dermatologic Surgery

Board Member: ASDS

Committee Member and / or Chair: AAD; ASDS; ASLMS

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