RARE DISEASE
Malignant tumor of penis
Malignant tumor of penis
Malignant tumor of penis
Synonyms: Cancer of penis, Malignant penile tumor, Penile cancer
Synonyms: Cancer of penis, Malignant penile tumor, Penile cancer
Synonyms: Cancer of penis, Malignant penile tumor, Penile cancer
Drug discovery
0
drugs
With orphan designations
Overview
Malignant tumor of the penis is a rare malignancy primarily affecting older men, with >95% being squamous cell carcinoma (SCC). Risk factors include HPV infection, poor hygiene, phimosis, and lack of circumcision. Staging (TNM system) guides treatment, ranging from organ-preserving therapies for localized disease to radical surgery or multimodal approaches for advanced/metastatic cases [1][3][8][9].
Burden
Global incidence rising (+1.3% annual increase in 15 countries) [14]; 5-year survival drops from 95% (localized) to 35% (lymph node-positive) [4][9].
Treatment complications (sexual dysfunction, lymphedema) impair quality of life; 11.8% positive surgical margins reported in advanced cases [5][7][14].
Therapies
Early-stage: Topical chemotherapy (5-fluorouracil/imiquimod, 57% response), laser ablation, or glans-sparing surgery [1][3][7][11].
Locally advanced: Partial/total penectomy with inguinal lymph node dissection ± radiation (60 Gy) [1][11][13].
Metastatic: TIP chemotherapy (53% response) or immunotherapy (pembrolizumab/atezolizumab for PD-L1+/MSI-H cases) [4][7][15].
Categories: rare neoplastic diseases, rare urogenital diseases
Research Papers
1,591 drug discovery papers about Malignant tumor of penis, with 6 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,591 drug discovery papers about Malignant tumor of penis, with 6 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-07 | Intratumoral para-toluenesulfonamide as a tumor-ablative therapy for equine cutaneous tumors: a case series of three horses.
Equine neoplasia, including sarcoids, melanomas, and squamous cell carcinomas, presents therapeutic challenges due to recurrence and limitations of conventional treatments. Para-toluenesulfonamide (p-TLS) is a tumor-ablating agent that is associated with localized tumor necrosis and subsequent lesion resolution. It has been evaluated in human clinical settings as an intratumoral treatment of malignant airway obstruction caused by non-small cell lung cancer. This study aimed to describe the clinical outcomes and tolerability of intratumoral p-TLS in equine neoplasia. Three equine cases, including a fibroblastic sarcoid, perianal melanoma, and penile squamous cell carcinoma, were treated. The fibroblastic sarcoid and penile squamous cell carcinoma achieved complete response. The melanoma fulfilled the criteria for partial response at the protocol-defined clinical evaluation timepoint and subsequently demonstrated complete clinical resolution during follow-up. All cases demonstrated a consistent pattern of response characterized by tumor necrosis, sloughing, and subsequent wound healing with complete re-epithelialization. Local adverse effects were limited to transient inflammation and mild discomfort, which were effectively managed with supportive care. No severe adverse events or tumor recurrence were observed during the follow-up period ranging from 120 days to 15 months. These findings suggest that p-TLS may represent a feasible, highly minimally invasive intratumoral therapeutic approach for equine neoplasia and support further evaluation.
2026-07-31 | [Testicular Germ Cell Tumors and Penile Cancer: Molecular-Based Diagnosis and Treatment].
Molecular diagnostics and targeted therapies are increasingly evolving towards a personalized medicine approach. This review summarizes recent advances in testicular germ cell tumors (TGCTs) and penile cancer, with a focus on emerging biomarkers and targeted therapeutic strategies. Conventional serum tumor markers such as AFP, β-HCG, and LDH remain important but are limited by suboptimal sensitivity and specificity. Novel biomarkers, particularly microRNA miR-371a-3p, have demonstrated substantially higher diagnostic accuracy and may improve risk stratification, detection of disease recurrence, and treatment decision-making in TGCTs. In addition, the analysis of circulating tumor DNA (ctDNA) has emerged as a promising liquid biopsy procedure. In penile squamous cell carcinoma, molecular classification based on human papillomavirus (HPV) status and comprehensive genomic profiling are becoming increasingly relevant for prognosis and therapeutic selection. The identification of actionable molecular alterations has facilitated the development of immunotherapy, anti-EGFR strategies, and antibody-drug conjugates. Early clinical data also suggest that ctDNA may provide valuable information for treatment monitoring and early relapse detection. Despite these promising findings, further prospective studies and standardized methodologies are required before many of these approaches can be incorporated into routine clinical practice. Overall, these developments highlight the ongoing transition towards biomarker-driven precision oncology and the potential for more individualized management of patients with TGCTs and penile cancer.
2026-07-21 | Multi-Stage Surgical Treatment of Penile Squamous Cell Carcinoma: Primary Tumor and Nodal Management Outcomes in a Retrospective Cohort.
Background: Multi-stage surgical management of penile squamous cell carcinoma (PSCC) requires sequential decision-making from primary tumor treatment through extensive lymphadenectomy, the lack of adherence to treatment indications and prognostic stratification remaining clinical challenges. This study assessed outcomes and prognostic determinants in patients undergoing staged surgical treatment. Methods: This retrospective cohort study analyzed 49 patients with surgically treated PSCC with surgical indication for bilateral inguinal-femoral lymphadenectomy (ILND) following curative-intent primary tumor resection between October 2020 and December 2024 in a tertiary Romanian oncological surgery center. Primary endpoints included overall survival (OS), treatment completion rates, and prognostic factor identification through univariate and multivariate Cox regression analysis. Results: Among 49 patients (median age 64 years), 31 (63.3%) completed second-stage bilateral ILND, while 18 (36.7%) remained non-compliant. Pathological staging revealed pN0-N1 in 36.7%, pN2 in 42.9%, and pN3 in 20.4%. Eleven patients (22.4%) underwent third-stage pelvic lymphadenectomy (PLND). Overall mortality reached 55.1% (27/49) with median OS of 20 months. Patients requiring third-stage pelvic dissection demonstrated 90.9% mortality and median OS of only 12 months. Multivariate analysis identified three independent prognostic factors for OS: absence of lymphovascular invasion (LVI) (HR 0.43, 95% CI: 0.19-0.99, p = 0.048), absence of urethral invasion (HR 0.36, 95% CI: 0.12-1.03, p = 0.056), and pathological N stage. Each additional positive lymph node increased mortality hazard by 4% (HR 1.04, 95% CI: 1.01-1.06, p = 0.002). Conclusions: Multi-stage surgical management of PSCC faces a low level of patient compliance (63.3%) and identifies high-risk populations through staged progression. While LVI, urethral invasion, and nodal stage provide independent prognostic stratification, patients meeting third-stage pelvic dissection criteria exhibit poor outcomes despite complete surgical staging, suggesting these patients may benefit more from integrated systemic therapy approaches than from extended surgery alone.
2026-07-15 | The Relationship Between Neutrophil Extracellular Traps and CD8+ T Lymphocytes in Cancer: A Comprehensive Review of Current Data.
Neutrophil extracellular traps (NETs) are web-like structures composed of decondensed DNA, histones, and proteins released by activated neutrophils. Originally identified as an innate defense mechanism against pathogens, NETs have since been implicated in cancer progression and immune evasion. Within the tumor microenvironment (TME), NETs suppress anti-tumor immunity through multiple mechanisms, including the physical exclusion of CD8+ cytotoxic T lymphocytes from the tumor interior and upregulation of exhaustion markers via checkpoint ligands. This review synthesizes current preclinical and clinical evidence on the interplay between NETs and CD8+ T cells across multiple malignancies, including non-small cell lung cancer, pancreatic ductal adenocarcinoma, cholangiocarcinoma, colorectal cancer, bladder cancer, hepatocellular carcinoma, skin cancer, and penile cancer. Cancer-specific mechanisms of NET-mediated immune suppression are discussed, including IL-8, IL-17, CXCL6, and TGF-β-driven NETosis pathways. Clinical data consistently demonstrate that elevated NET levels correlate with reduced CD8+ T cell infiltration, T cell dysfunction, and worse patient outcomes. Emerging therapeutic strategies targeting this axis are reviewed, including DNase I-mediated NET degradation, Peptidyl arginine deiminase 4 (PAD4) inhibition, CXCR2 blockade, and combination approaches with immune checkpoint inhibitors. These interventions have shown promise in restoring CD8+ T cell cytotoxicity and overcoming immunotherapy resistance in preclinical models. Collectively, the evidence supports the NET-CD8+ T cell axis as a promising prognostic and therapeutic target warranting further clinical investigation.
2026-07-09 | Penile Metastasis as a First Manifestation of Metastatic Castrate Resistant Prostate Cancer: A Case Report and Review of Management Challenges
Introduction: Penis is a rare site of metastasis of prostate cancer, with an incidence of 0.3%. Penile metastasis is often detected incidentally via imaging modalities. Symptomatic cases may present with penile nodules, deformity, or urinary symptoms, and a biopsy is required for confirmation. Treatment varies based on disease extent and patient condition, ranging from tumour-directed approaches (penectomy, radiotherapy) to systemic therapies. Case Presentation: A 69-year-old man with high-risk non-metastatic prostate cancer (T3bN0M0) underwent pelvic radiotherapy and androgen deprivation therapy (ADT). Five months later, he presented with urinary difficulty and penile pain. Imaging revealed multiple nodules within corpora cavernosa, along with lung lesions suggesting metastatic disease. A biopsy confirmed penile metastasis from prostate adenocarcinoma (Gleason score 9). Following a multidisciplinary team discussion, penectomy was ruled out, and the patient underwent palliative radiotherapy (RT), 20 Gy in 5 fractions, followed by systemic chemotherapy with docetaxel and carboplatin. Despite four cycles of chemotherapy, the disease progressed into the lungs, and the patient’s performance status declined. The patient was transitioned to palliative care and passed away 12 months after the diagnosis of penile metastasis. Conclusion: Penile metastasis from prostate cancer is rare but an aggressive entity with a median survival ranging from 6 to 18 months. Penile metastasis shall be in the differentials when patients present with priapism, penile pain, and urinary difficulty. Tumour-directed approaches, including surgery and RT, could be curative. Emerging therapies such as stereotactic body radiotherapy (SBRT) and PSMA-targeted radioligand therapy may improve outcomes for this rare and aggressive manifestation.
2026-08-07 | Intratumoral para-toluenesulfonamide as a tumor-ablative therapy for equine cutaneous tumors: a case series of three horses.
Equine neoplasia, including sarcoids, melanomas, and squamous cell carcinomas, presents therapeutic challenges due to recurrence and limitations of conventional treatments. Para-toluenesulfonamide (p-TLS) is a tumor-ablating agent that is associated with localized tumor necrosis and subsequent lesion resolution. It has been evaluated in human clinical settings as an intratumoral treatment of malignant airway obstruction caused by non-small cell lung cancer. This study aimed to describe the clinical outcomes and tolerability of intratumoral p-TLS in equine neoplasia. Three equine cases, including a fibroblastic sarcoid, perianal melanoma, and penile squamous cell carcinoma, were treated. The fibroblastic sarcoid and penile squamous cell carcinoma achieved complete response. The melanoma fulfilled the criteria for partial response at the protocol-defined clinical evaluation timepoint and subsequently demonstrated complete clinical resolution during follow-up. All cases demonstrated a consistent pattern of response characterized by tumor necrosis, sloughing, and subsequent wound healing with complete re-epithelialization. Local adverse effects were limited to transient inflammation and mild discomfort, which were effectively managed with supportive care. No severe adverse events or tumor recurrence were observed during the follow-up period ranging from 120 days to 15 months. These findings suggest that p-TLS may represent a feasible, highly minimally invasive intratumoral therapeutic approach for equine neoplasia and support further evaluation.
2026-07-31 | [Testicular Germ Cell Tumors and Penile Cancer: Molecular-Based Diagnosis and Treatment].
Molecular diagnostics and targeted therapies are increasingly evolving towards a personalized medicine approach. This review summarizes recent advances in testicular germ cell tumors (TGCTs) and penile cancer, with a focus on emerging biomarkers and targeted therapeutic strategies. Conventional serum tumor markers such as AFP, β-HCG, and LDH remain important but are limited by suboptimal sensitivity and specificity. Novel biomarkers, particularly microRNA miR-371a-3p, have demonstrated substantially higher diagnostic accuracy and may improve risk stratification, detection of disease recurrence, and treatment decision-making in TGCTs. In addition, the analysis of circulating tumor DNA (ctDNA) has emerged as a promising liquid biopsy procedure. In penile squamous cell carcinoma, molecular classification based on human papillomavirus (HPV) status and comprehensive genomic profiling are becoming increasingly relevant for prognosis and therapeutic selection. The identification of actionable molecular alterations has facilitated the development of immunotherapy, anti-EGFR strategies, and antibody-drug conjugates. Early clinical data also suggest that ctDNA may provide valuable information for treatment monitoring and early relapse detection. Despite these promising findings, further prospective studies and standardized methodologies are required before many of these approaches can be incorporated into routine clinical practice. Overall, these developments highlight the ongoing transition towards biomarker-driven precision oncology and the potential for more individualized management of patients with TGCTs and penile cancer.
2026-07-21 | Multi-Stage Surgical Treatment of Penile Squamous Cell Carcinoma: Primary Tumor and Nodal Management Outcomes in a Retrospective Cohort.
Background: Multi-stage surgical management of penile squamous cell carcinoma (PSCC) requires sequential decision-making from primary tumor treatment through extensive lymphadenectomy, the lack of adherence to treatment indications and prognostic stratification remaining clinical challenges. This study assessed outcomes and prognostic determinants in patients undergoing staged surgical treatment. Methods: This retrospective cohort study analyzed 49 patients with surgically treated PSCC with surgical indication for bilateral inguinal-femoral lymphadenectomy (ILND) following curative-intent primary tumor resection between October 2020 and December 2024 in a tertiary Romanian oncological surgery center. Primary endpoints included overall survival (OS), treatment completion rates, and prognostic factor identification through univariate and multivariate Cox regression analysis. Results: Among 49 patients (median age 64 years), 31 (63.3%) completed second-stage bilateral ILND, while 18 (36.7%) remained non-compliant. Pathological staging revealed pN0-N1 in 36.7%, pN2 in 42.9%, and pN3 in 20.4%. Eleven patients (22.4%) underwent third-stage pelvic lymphadenectomy (PLND). Overall mortality reached 55.1% (27/49) with median OS of 20 months. Patients requiring third-stage pelvic dissection demonstrated 90.9% mortality and median OS of only 12 months. Multivariate analysis identified three independent prognostic factors for OS: absence of lymphovascular invasion (LVI) (HR 0.43, 95% CI: 0.19-0.99, p = 0.048), absence of urethral invasion (HR 0.36, 95% CI: 0.12-1.03, p = 0.056), and pathological N stage. Each additional positive lymph node increased mortality hazard by 4% (HR 1.04, 95% CI: 1.01-1.06, p = 0.002). Conclusions: Multi-stage surgical management of PSCC faces a low level of patient compliance (63.3%) and identifies high-risk populations through staged progression. While LVI, urethral invasion, and nodal stage provide independent prognostic stratification, patients meeting third-stage pelvic dissection criteria exhibit poor outcomes despite complete surgical staging, suggesting these patients may benefit more from integrated systemic therapy approaches than from extended surgery alone.
2026-07-15 | The Relationship Between Neutrophil Extracellular Traps and CD8+ T Lymphocytes in Cancer: A Comprehensive Review of Current Data.
Neutrophil extracellular traps (NETs) are web-like structures composed of decondensed DNA, histones, and proteins released by activated neutrophils. Originally identified as an innate defense mechanism against pathogens, NETs have since been implicated in cancer progression and immune evasion. Within the tumor microenvironment (TME), NETs suppress anti-tumor immunity through multiple mechanisms, including the physical exclusion of CD8+ cytotoxic T lymphocytes from the tumor interior and upregulation of exhaustion markers via checkpoint ligands. This review synthesizes current preclinical and clinical evidence on the interplay between NETs and CD8+ T cells across multiple malignancies, including non-small cell lung cancer, pancreatic ductal adenocarcinoma, cholangiocarcinoma, colorectal cancer, bladder cancer, hepatocellular carcinoma, skin cancer, and penile cancer. Cancer-specific mechanisms of NET-mediated immune suppression are discussed, including IL-8, IL-17, CXCL6, and TGF-β-driven NETosis pathways. Clinical data consistently demonstrate that elevated NET levels correlate with reduced CD8+ T cell infiltration, T cell dysfunction, and worse patient outcomes. Emerging therapeutic strategies targeting this axis are reviewed, including DNase I-mediated NET degradation, Peptidyl arginine deiminase 4 (PAD4) inhibition, CXCR2 blockade, and combination approaches with immune checkpoint inhibitors. These interventions have shown promise in restoring CD8+ T cell cytotoxicity and overcoming immunotherapy resistance in preclinical models. Collectively, the evidence supports the NET-CD8+ T cell axis as a promising prognostic and therapeutic target warranting further clinical investigation.
2026-07-09 | Penile Metastasis as a First Manifestation of Metastatic Castrate Resistant Prostate Cancer: A Case Report and Review of Management Challenges
Introduction: Penis is a rare site of metastasis of prostate cancer, with an incidence of 0.3%. Penile metastasis is often detected incidentally via imaging modalities. Symptomatic cases may present with penile nodules, deformity, or urinary symptoms, and a biopsy is required for confirmation. Treatment varies based on disease extent and patient condition, ranging from tumour-directed approaches (penectomy, radiotherapy) to systemic therapies. Case Presentation: A 69-year-old man with high-risk non-metastatic prostate cancer (T3bN0M0) underwent pelvic radiotherapy and androgen deprivation therapy (ADT). Five months later, he presented with urinary difficulty and penile pain. Imaging revealed multiple nodules within corpora cavernosa, along with lung lesions suggesting metastatic disease. A biopsy confirmed penile metastasis from prostate adenocarcinoma (Gleason score 9). Following a multidisciplinary team discussion, penectomy was ruled out, and the patient underwent palliative radiotherapy (RT), 20 Gy in 5 fractions, followed by systemic chemotherapy with docetaxel and carboplatin. Despite four cycles of chemotherapy, the disease progressed into the lungs, and the patient’s performance status declined. The patient was transitioned to palliative care and passed away 12 months after the diagnosis of penile metastasis. Conclusion: Penile metastasis from prostate cancer is rare but an aggressive entity with a median survival ranging from 6 to 18 months. Penile metastasis shall be in the differentials when patients present with priapism, penile pain, and urinary difficulty. Tumour-directed approaches, including surgery and RT, could be curative. Emerging therapies such as stereotactic body radiotherapy (SBRT) and PSMA-targeted radioligand therapy may improve outcomes for this rare and aggressive manifestation.
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Drug Discovery Landscape
0 orphan drug designations.
0 orphan drug designations.
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