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Penile Cancer and Rare Urogenital Malignancies: From Biology to Clinical Management

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: 15 July 2026 | Viewed by 3718

Special Issue Editors

Dr. Mateusz Czajkowski

E-Mail Website
Guest Editor
Department of Urology, Medical University of Gdańsk, Mariana Smoluchowskiego 17 Street, 80-214 Gdańsk, Poland
Interests: urology; urologic cancers; kidney cancer; penile cancer; reconstructive urology; lichen sclerosus; penile diseases
Prof. Dr. Marcin Matuszewski

E-Mail Website
Guest Editor
Department of Urology, Medical University of Gdańsk, Mariana Smoluchowskiego 17 Street, 80-214 Gdańsk, Poland
Interests: urology; urologic cancers; prostate cancer; bladder cancer; kidney cancer; penile cancer; robotic surgery

Special Issue Information

Dear Colleagues,

Rare urogenital malignancies, such as penile cancer, upper tract urothelial carcinoma (UTUC), primary urethral carcinoma, and tumors of the penile skin or scrotum, present significant diagnostic and therapeutic challenges for clinicians. Their low prevalence has resulted in a scarcity of comprehensive data, which has impeded the establishment of standardized care protocols. This Special Issue will consolidate the current evidence on molecular biology, inflammation-driven mechanisms, microbial influences, and clinical outcomes. We invite the submission of original research, narrative or systematic reviews that address surgical management, systemic therapies, epidemiology, and prognostic biomarkers in this disease. By fostering interdisciplinary insights, we aim to enhance clinical decision-making and advance effective individualized treatment approaches in these uncommon but impactful genitourinary cancers.

Dr. Mateusz Czajkowski
Prof. Dr. Marcin Matuszewski
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Publisher’s Notice

The Special Issue, together with its publications, has been removed from Section "Methods and Technologies Development" on 6th November 2025. The publications remain available in the regular issues in which they were originally published. The Editorial Office confirms that these articles adhered to MDPI's standard editorial process (https://www.mdpi.com/editorial_process).

Keywords

  • penile cancer
  • urethral carcinoma
  • upper tract urothelial carcinoma
  • rare urogenital tumors
  • surgical management
  • systemic therapy
  • epidemiology

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Published Papers (3 papers)

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Research

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28 pages, 1284 KB  
Article
Prognostic Factors of Survival in Patients with Surgically Treated Penile Squamous Cell Carcinoma: A Retrospective Cohort Analysis
by Andrei Andreșanu, Constantin Gîngu, Dragoș Eugen Georgescu, Mihaela Roxana Oliță, Mihai Adrian Dobra, Cristian Mirvald, Bogdan Obrișcă, Mihai-Adrian Eftimie and Ioanel Sinescu
Cancers 2026, 18(6), 952; https://doi.org/10.3390/cancers18060952 - 14 Mar 2026
Viewed by 605
Abstract
Background/Objectives: Penile squamous cell carcinoma (PSCC) is a rare malignancy with a potential major impact on survival. Prognostic assessment remains challenging, particularly in underrepresented eastern European populations, where region-specific evidence is lacking. This paper aimed to identify independent predictors of overall survival [...] Read more.
Background/Objectives: Penile squamous cell carcinoma (PSCC) is a rare malignancy with a potential major impact on survival. Prognostic assessment remains challenging, particularly in underrepresented eastern European populations, where region-specific evidence is lacking. This paper aimed to identify independent predictors of overall survival in surgically treated patients with PSCC from a Romanian high-volume tertiary center. Methods: This retrospective cohort study analyzed 60 patients who were surgically treated for PSCC between October 2020 and December 2024. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify independent prognostic factors. Results: The mean patient age was 62 ± 12 years. T-stage distribution showed 30% pT1, 35% pT2, 31.67% pT3, and 3.33% pT4, with 55% of patients presenting with nodal metastases. Univariate analyses demonstrated significant associations between lymphovascular invasion (p < 0.001), perineural invasion (p = 0.022), and positive surgical margins (p = 0.030) and risk of death. Multivariate analysis identified three independent prognostic factors: absence of histologically documented urethral invasion (HR 0.32; p = 0.027), T3–T4 disease (HR 8.26; p = 0.005 vs. T1), and N3 stage (HR 3.53; p = 0.030 vs. N0–N1). Patients without urethral invasion demonstrated significantly longer median overall survival (63 months vs. 11 months). The final three-variable prognostic model demonstrated good discrimination (C-index 0.78), providing a potential practical risk stratification tool. Conclusions: Urethral invasion, advanced T-stage, and N3 disease independently predict poor survival in surgically treated PSCC. The identification of urethral invasion as an independent prognostic factor warrants consideration in clinical practice. This is the first study of a Romanian cohort to provide critical data for risk-adapted treatment strategies in underrepresented eastern European populations. Full article
(This article belongs to the Special Issue Penile Cancer and Rare Urogenital Malignancies: From Biology to Clinical Management)
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14 pages, 1301 KB  
Article
Tissue Factor Expression in Penile Squamous Cell Carcinoma: A Potential Marker of HPV-Independent Disease
by Jamaal C. Jackson, Andrew C. Johns, Leticia Campos Clemente, Christopher M. Manuel, Wei Qiao, Wei Lu, Khaja Khan, Luisa M. Solis Soto, Jad Chahoud, Priya Rao, Matthew T. Campbell, Curtis A. Pettaway and Niki M. Zacharias
Cancers 2025, 17(21), 3410; https://doi.org/10.3390/cancers17213410 - 23 Oct 2025
Viewed by 1160
Abstract
Background/Objectives: In a series of 33 patients with advanced penile squamous cell carcinoma (PSCC), we evaluated tissue factor (TF), TROP2, and nectin-4 protein expression as potential therapeutic targets. Expression levels of these proteins were also correlated to clinicopathological characteristics, including high-risk human [...] Read more.
Background/Objectives: In a series of 33 patients with advanced penile squamous cell carcinoma (PSCC), we evaluated tissue factor (TF), TROP2, and nectin-4 protein expression as potential therapeutic targets. Expression levels of these proteins were also correlated to clinicopathological characteristics, including high-risk human papillomavirus (HPV), CDKN2A (p16) status, and aberrant p53 expression. Methods: A tissue microarray (TMA) was constructed with three cores per patient tumor (99 total cores). Anti-TF antibody staining was performed by immunohistochemistry, and H-scores for membrane and cytoplasm staining were assessed (range 0–300). The percentage of cores and patient tumors staining positive for TF (≥10% of tumor cells with at least 1+ intensity in cytoplasm and/or membrane) and H-scores were described and compared with HPV and p16 status. The association of TF expression with tumor grade, presence of metastatic disease, lymphovascular invasion (LVI), perineural invasion (PNI), aberrant p53 expression, recurrence-free survival (RFS), and cancer-specific survival (CSS) was assessed. Nectin-4 and TROP2 staining and their association with clinical/pathological data were determined in a similar manner. Results: TF staining was evident in 26 (81.3%) of the cohort and was more prominent in HPV-negative tumors in both the membrane (H-score 69.6 vs. 18.8; p = 0.003) and cytoplasm (H-score 59.2 vs. 17.7, p = 0.007). Cytoplasmic (H-score 61.7 vs. 11.7, p < 0.001) and membrane TF staining (H-score 71.7 vs. 15.0, p < 0.001) favored p16-negative tumors. The p53 status was more likely to be aberrant in the higher TF staining samples (cytoplasm H-score 61.7 vs. 18.3, p = 0.012; membrane H-score 67.5 vs. 20.3, p = 0.006). We observed an association with TROP2 staining and positive p16 status (membrane H-score 120.3 vs. 85, p = 0.052; cytoplasmic H-score 135 vs. 107.5, p = 0.041). We observed an association of TROP2 staining with positive LVI (membrane H-score 136.7 vs. 66.7, p = 0.014; cytoplasmic H-score 110 vs. 93.3, p = 0.04). We found no association between TF, TROP2, or nectin-4 staining with CSS or RFS; however, we suspect that this was due to our small sample size. Conclusions: Our results indicate that TF was expressed in the majority of advanced PSCC with enhanced expression among HPV-independent, p53-aberrant tumors and may represent a novel therapy target in advanced PSCC. Full article
(This article belongs to the Special Issue Penile Cancer and Rare Urogenital Malignancies: From Biology to Clinical Management)
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Review

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36 pages, 905 KB  
Review
Systemic Chemotherapy in Penile Squamous Cell Carcinoma: Mechanisms, Clinical Applications, and Evidence-Based Regimens
by Michalina Grudzińska, Mateusz Czajkowski, Maciej Dolny, Marcin Matuszewski, Piotr Mieczysław Wierzbicki, Agnieszka Rybarczyk and Oliver Walther Hakenberg
Cancers 2026, 18(1), 46; https://doi.org/10.3390/cancers18010046 - 23 Dec 2025
Cited by 2 | Viewed by 1442
Abstract
Background/Objectives: Penile squamous cell carcinoma (PSCC) is rare but aggressive. Systemic chemotherapy plays a crucial role in the management of node-positive or metastatic cases; however, the supporting evidence predominantly originates from small, non-randomized studies. This review provides a narrative analysis of the cytotoxic [...] Read more.
Background/Objectives: Penile squamous cell carcinoma (PSCC) is rare but aggressive. Systemic chemotherapy plays a crucial role in the management of node-positive or metastatic cases; however, the supporting evidence predominantly originates from small, non-randomized studies. This review provides a narrative analysis of the cytotoxic classes and regimens employed in PSCC and compares major clinical guidelines to facilitate informed decision-making in practice. Methods: English-language reports were identified in PubMed/Scopus/Google Scholar without date limits. Selection prioritized objective response, survival and toxicity outcomes, and guidance statements across neoadjuvant, adjuvant, and palliative settings. Results: Bleomycin-containing triplet regimens demonstrated efficacy but were associated with unacceptable pulmonary toxicity, leading to their discontinuation in clinical recommendations. Currently, cisplatin/taxane-based combinations remain fundamental in treatment protocols. The paclitaxel–ifosfamide–cisplatin (TIP) regimen achieves approximately 40–50% objective responses in phase II studies and may enable curative surgery, while taxane–cisplatin–5-fluorouracil (TPF) shows comparable efficacy with higher toxicity. For less fit patients, cisplatin–5-fluorouracil (PF) or carboplatin–taxane doublets are pragmatic alternatives. Single-agent taxanes or vinflunine offer modest second-line benefits. Although EAU–ASCO 2023, ESMO–EURACAN 2024, and NCCN v2.2025 are broadly in consensus, recommendations differ regarding eligibility thresholds and regimen preferences. Overall, the quality of the evidence remains low. Conclusions: TIP remains the reference neoadjuvant option for chemotherapy-fit patients with bulky nodal disease; doublets are reasonable when cisplatin fitness is limited; and bleomycin should be avoided. Harmonized eligibility criteria, biomarker-enriched studies, and coordinated multicenter trials are needed to improve outcomes in this rare malignancy. Full article
(This article belongs to the Special Issue Penile Cancer and Rare Urogenital Malignancies: From Biology to Clinical Management)
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