small molecules

2026-09-07 | Apatinib monotherapy for pretreated advanced squamous cell carcinoma of the penis: a phase 2 trial.

Treatment options for patients with advanced penile squamous cell carcinoma who have disease progression on systemic chemotherapy are scarce. Antiangiogenic drugs have shown antitumor effects in case series. This phase 2 trial evaluated the activity and safety of apatinib (a Vascular Endothelial Growth Factor (VEGF) receptor inhibitor) in such patients. This investigator-initiated, single-arm, phase 2 trial was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN000021849) and performed at a tertiary cancer center in Shanghai, China. Eligible patients had histologically confirmed penile squamous cell carcinoma, were not candidates for surgery with curative intent, had measurable disease, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, pretreated with one or more kinds of systemic treatment. Patients were prescribed oral apatinib 500 mg daily with the option of dose reduction to manage adverse events. The primary endpoint was the investigator-assessed overall response rate (ORR) assessed in all patients who received at least one dose of study drug. Between 2016 and 2023, we enrolled 23 patients, all of whom received at least one dose of study treatment. Of the 23 patients, 16 had an ECOG performance status of 2. Only 6 patients had human papillomavirus-positive tumors. Five patients had a partial response (ORR = 22% [95% CI, 10%-42%]). The median progression-free survival was 3.8 months, and median overall survival was 7.2 months. Treatment-related adverse events of grade 3 or worse occurred in 7 (30%) of 23 patients. The most common grade 3 or 4 treatment-related adverse events were hand-foot syndrome (13%), hypertension (9%), and increase in serum alanine aminotransferase (9%). Apatinib in pretreated advanced penile cancer showed limited efficacy with a manageable safety profile. UMIN000021849.

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2026-08-24 | Randomized trial of adjuvant 5-FU-platinum vs paclitaxel-platinum for high-risk penile cancer.

Adjuvant chemotherapy is recommended for high-risk penile squamous cell carcinoma (SCC) metastatic to lymph nodes based on retrospective data, but no randomized trials have been conducted. We compared 5-fluorouracil (5-FU)-platinum with paclitaxel-platinum in this setting. In this open-label, randomized trial at an Indian tertiary cancer center, men <70 years with resected node-positive penile SCC and ≥1 high-risk feature (perinodal extension, pelvic node involvement, >1 inguinal nodes, or ≥ 4 cm node) were assigned 1:1 to four 3-weekly cycles of 5-FU-platinum or paclitaxel-platinum, followed by cisplatin-based chemoradiotherapy. Primary endpoint was disease-free survival (DFS). Secondary endpoints were overall survival (OS), toxicity, and quality-of-life (QoL). Between 2017 and 2024, 49 patients were randomized (5-FU-platinum: 25, paclitaxel-platinum: 24). At a median follow-up of 69 months, median DFS was 12.4 months (95% CI, 3.38-NR) vs 19.6 months (95% CI, 5.82-NR) (HR, 1.16; 95% CI, 0.55-2.45; P = 0.686) and median OS was 21.3 vs 36.7 months (HR, 1.13; 95% CI, 0.52-2.44; P = 0.754) for 5-FU-platinum and paclitaxel-platinum, respectively. Grade ≥3 toxicities occurred in 77.3% vs 40.9% (P = 0.014), grade ≥3 hematologic toxicities in 54.5% vs 4.5% (P < 0.001), and hospitalization for toxicity in 45.5% vs 9.1% (P = 0.016). Completion of all planned cycles was higher with paclitaxel-platinum (83.3% vs 48%; P = 0.009). QoL and sexual health were similar between the two treatment arms. Adjuvant paclitaxel-platinum was associated with improved tolerability compared with fluorouracil-platinum in high-risk node positive penile cancer and warrants further evaluation in larger multicenter studies. Early termination precluded definitive efficacy comparisons. Clinical Trials Registry of India (CTRI/2016/12/007567). This work was supported by Indian Cooperative Oncology Network and Tata Memorial Center.

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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.

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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.

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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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cell therapies

2026-05-28 | Transcriptomic profiling to identify cancer–immune meta-programs in penile squamous cell carcinoma.

e17035 Background: Penile squamous cell carcinoma (PSCC) is a rare malignancy with substantial heterogeneity in tumor-intrinsic biology & the immune microenvironment. While genomic studies have identified recurrent alterations, how cancer & immune programs jointly shape PSCC ecosystems & outcomes remain poorly defined. Methods: We profiled 67 PSCC tumors using the nCounter PanCancer Immune Profiling Panel, interrogating cancer-relevant genes & curated immune-response pathways. The cohort included 29 HPV-positive tumors (43.3%) & was balanced across stage (33 stage I–II; 34 stage III–IV). Highly variable genes (HVGs) were identified, followed by unsupervised clustering, pathway-based analyses using 61 curated canonical gene sets, & survival analyses for recurrence-free survival (RFS) & overall survival (OS). To model joint cancer–immune ecosystems, non-negative matrix factorization (NMF) was applied to derive cancer–immune meta-programs with program-level signals interpreted using independent single-cell RNA sequencing data. Results: HVG analysis revealed transcriptional variability spanning inflammatory & myeloid-associated genes, interferon & antigen-presentation genes, tumor-intrinsic epithelial & cancer-testis antigens. Unsupervised expression-based clustering identified four major transcriptional clusters that were not strongly associated with any clinical covariates. Pathway-level analyses demonstrated distinct transcriptional programs associated with stage, HPV status and smoking history. Survival analyses identified Th17 signaling & canonical PI3K signaling associated with RFS in univariable analyses, canonical PI3K signaling & cytotoxic cell signatures remaining associated with RFS in multivariable models. NMF resolved this heterogeneous landscape into three orthogonal cancer–immune meta-programs that captured coordinated transcriptional structure across tumors. Program 1 was enriched for interferon-α & complement pathways, Program 2 for interferon-γ signaling, & Program 3 for E2F targets & epithelial–mesenchymal transition. These meta-programs showed clear prognostic stratification with Program 2 associated with favorable RFS and OS, whereas Program 3 associated with adverse outcomes. Integration with single-cell PSCC data demonstrated preferential enrichment of Program 1 in myeloid compartments, Program 2 across B cells, myeloid cells, and subsets of T cells, & Program 3 predominantly within epithelial, fibroblast, and endothelial compartments. Conclusions: Transcriptomic analysis in PSCC identifies coordinated cancer–immune meta-programs that define biologically distinct tumor ecosystems & stratify clinical outcomes beyond conventional clinical features supporting a promising framework for understanding penile cancer molecular heterogeneity, motivating ecosystem-informed biomarker & therapeutic strategies.

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2025-11-25 | Molecular characterisation of human penile carcinoma and generation of paired epithelial primary cell lines.

Penile carcinoma is a rare malignancy in developed countries but is more common in South America and East Africa. The small number of cases means there are limited resources to investigate disease pathogenesis. This report describes a method of generating primary cell lines from freshly isolated human penile tissue using a clonal expansion approach on mitotically inactivated fibroblasts. Matched normal and penile cancer cell lines from two patients were generated and characterised. Molecular karyotyping and targeted sequencing were performed to compare their genomic landscape. Gains in 8q13.3, 10q23.2, 10q25.1, 10q26.13,12p13.33, 20q13.33, Xq21.1 or losses in Yq11.23 were consistent in both tumour cell lines. Gains in 8q13.3 and Xq21.1 cytobands positively correlated with changes in the expression of nearby genes. The top 20 differentially expressed genes are involved in immune responses like interferon alpha/beta signalling. Additionally, there was an increase in integrin β1, transglutaminase 1, keratins 5, 10, 14 and 16, and a decrease in involucrin protein expression. The cell lines described in this study can provide an invaluable platform for new insights and testing of therapies for penile carcinoma.

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2024-09-28 | HPV and Penile Cancer: Epidemiology, Risk Factors, and Clinical Insights.

Penile cancer (PC) is a rare malignancy predominantly of squamous cell origin. Approximately 40% of penile tumors are associated with human papillomavirus (HPV) infection. Diagnosing PC remains challenging due to its rarity and variety of clinical presentations. Furthermore, the impact of HPV on the tumor immune microenvironment complicates clinical management, although recent advancements in immune checkpoint inhibitors (ICIs) have shown some efficacy in treating HPV-associated PC. Ongoing research efforts aim to develop oncologic treatments that target HPV-induced cellular modifications. Additionally, novel therapeutic vaccines and adoptive T-cell therapies targeting HPV oncoproteins represent emerging treatment modalities. Our review highlights the complex interplay between HPV and penile carcinogenesis, emphasizing its epidemiology, etiology, clinicopathological characteristics, and potential therapeutic implications.

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2024-07-01 | Immunotherapy in Penile Cancer

Summary Penile cancer is a rare and aggressive malignancy, with higher incidence rates seen in regions such as India, Africa, and South America. Treatment options for advanced and metastatic disease, particularly in platinum-refractory cases, remain limited, resulting in poor prognosis. Immunotherapy, including immune checkpoint inhibitors, human papillomavirus (HPV)-targeted vaccines, and adoptive T-cell therapies, is a focus of ongoing research and demonstrates encouraging results, both as monotherapy and in combination with chemotherapy, radiotherapy, or targeted agents. Ongoing research aims to identify predictive biomarkers like tumor mutational burden, PD-L1 expression, and HPV status to improve patient selection. Collaborative global effort is essential to optimize treatments and improve patient outcomes.

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2023-11-06 | Male infertility and urological tumors: Pathogenesis and therapeutical implications.

Most genitourinary tract cancers have a negative impact on male fertility. Although testicular cancers have the worst impact, other tumors such as prostate, bladder, and penis are diagnosed early and treated in relatively younger patients in which couple fertility can be an important concern. The purpose of this review is to highlight both the pathogenetic mechanisms of damage to male fertility in the context of the main urological cancers and the methods of preserving male fertility in an oncological setting, in light of the most recent scientific evidence. A systematic review of available literature was carried out on the main scientific search engines, such as PubMed, Clinicaltrials.Gov, and Google scholar. Three hundred twenty-five relevant articles on this subject were identified, 98 of which were selected being the most relevant to the purpose of this review. There is a strong evidence in literature that all of the genitourinary oncological therapies have a deep negative impact on male fertility: orchiectomy, partial orchiectomy, retroperitoneal lymphadenectomy (RPLND), radical cystectomy, prostatectomy, penectomy, as well as radiotherapy, chemotherapy, and hormonal androgen suppression. Preservation of fertility is possible and includes cryopreservation, hormonal manipulation with GnRH analogs before chemotherapy, androgen replacement. Germ cell auto transplantation is an intriguing strategy with future perspectives. Careful evaluation of male fertility must be a key point before treating genitourinary tumors, taking into account patients' age and couples' perspectives. Informed consent should provide adequate information to the patient about the current state of his fertility and about the balance between risks and benefits in oncological terms. Standard approaches to genitourinary tumors should include a multidisciplinary team with urologists, oncologists, radiotherapists, psycho-sexologists, andrologists, gynecologists, and reproductive endocrinologists.

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vaccines

2026-07-06 | Vaccine Therapy for the Management of Penile Cancer: Evidence, Opportunities and Challenges

Penile squamous cell carcinoma (PSCC) is a rare malignancy with limited therapeutic options in advanced and recurrent diseases. Advanced PSCC is typically managed with multimodal therapy, including neoadjuvant chemotherapy or chemoradiation followed by surgery; however, durable responses remain uncommon, and outcomes after recurrence are poor. Cancer vaccines represent a promising immunotherapeutic strategy, as these treatments induce tumor-specific immunity and heightened immune surveillance against penile cancer cells. While therapeutic cancer vaccines have not yet demonstrated consistent clinical efficacy as monotherapy in PSCC, their integration with complementary immune-modulating approaches, particularly immune checkpoint blockade, represents a rational strategy to enhance antitumor immunity. This review summarizes the rationale for vaccine development in PSCC, with emphasis on HPV-derived antigens, neoantigens, and emerging tumor-associated targets. We examine major vaccine platforms, including viral-vector, peptide-based, nucleic acid, and dendritic cell-based approaches. We also discuss how spatial transcriptomics, single-cell RNA sequencing, artificial intelligence-assisted antigen prediction, and nanotechnology-enhanced delivery systems may support future personalized vaccine development. Overall, therapeutic vaccines remain investigational in PSCC but may become relevant within biomarker-driven, combination-based immunotherapy strategies.

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2026-06-12 | Burden of HPV-associated cancers in Peruvian men: Evidence from national health data.

HPV-associated cancers in men represent a growing public health concern in Latin America, yet evidence on burden remains limited. We analyzed national data in Peru (2015-2019) to estimate outpatient consultations, hospitalization, and death rates for HPV-associated cancers and applied site-specific attributable fractions to derive HPV-attributable burden. Rates were age-standardized (ASR) to the WHO World Standard Population. Sensitivity analysis excluded mortality data for 2015-2016 to account for improvements in cause‑of‑death completeness. Between 2015 and 2019, 5,996 outpatient consultations for HPV-associated cancers in men were recorded (ASR: 8.2 per 100,000), mainly due to head and neck (56.3%) and penile (30.4%) cancers. A total of 1,136 hospitalizations were identified (ASR: 1.6 per 100,000), with head and neck and penile cancers accounting for 46.3% and 45.9% of total hospitalizations, respectively. Rates increased with age, reaching 38.0 outpatient consultations and 7.5 hospitalizations per 100,000 among men ≥60 years, but were also present among younger (<30 years) and middle-aged (30-59 years) men. Applying attributable fractions, 2,056 outpatient consultations (ASR: 2.8) and 402 hospitalizations (ASR: 0.6) were HPV-attributable, with penile cancer contributing the largest share. A total of 859 deaths from HPV-associated cancers were recorded (ASR: 1.2), of which 208 were HPV-attributable (ASR: 0.3), predominantly among men aged ≥60 years (77.2%). Sensitivity analysis had minimal impact on mortality estimates. HPV‑attributable cancers impose a substantial and preventable burden on Peruvian men. Strengthening universal HPV vaccination, ensuring high coverage, expanding multi‑age catch‑up strategies, and improving access to early diagnosis and treatment are essential to reduce future burden.

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2025-12-28 | Etiologic fraction of HPV-attributed anal and penile squamous cell carcinoma: study in specialized hospitals, Sri Lanka.

BACKGROUND: The Human Papillomavirus (HPV) infection is known to cause anogenital cancers. Male HPV prevalence and Population Attributable Risk (PAR) are important to plan future HPV preventive strategies for HPV-driven anogenital cancers in males. METHODS: A hospital-based case-control study was carried out to determine the etiologic fraction attributed to HPV-driven anal and penile(anogenital) cancers among male patients presenting to specialised hospitals in Gampaha district and Apeksha Hospital (cancer specialised) in Sri Lanka and to calculate the PAR percentage on anogenital Squamous Cell Cancer (SCC) among the study population where HPV prevalence was 5.7%. New or recently diagnosed anal and penile SCC patients (August 2022–June 2023) were included as cases. For each case, four controls were selected from sexually active, clinically normal men aged 20–70 years residing in Gampaha district. Additional etiological factors that were checked included the presence of sexually transmitted infections, phimosis, anogenital injury, and the use of tobacco, alcohol or illegal drugs. The Chi-square test was used at the significant level of p < 0.05 and the Fisher’s exact test was applied when expected cell counts were low. Bivariate and multivariable binary logistic regression analyses were used to calculate Odds Ratios (ORs). RESULTS: A significantly associated factor for getting anal or penile SCC was HPV infection (Adjusted OR(AOR) = 27.7; 95% CI: 4.3-177.8; P < 0.001). For any HPV genotype & High-Risk (HR) HPV genotype, the prevalence was 55% & 50% among cases, and 5% & 2.5% among controls, respectively. Assuming prevalence among controls as the population prevalence, the calculated PAR% was 60.3% for any HPV genotype and 39.4% for the HPV 16 h genotype. CONCLUSIONS: 60% of the anal and penile SCCs were attributed to any HPV genotype and a significant proportion (more than one-third) of anal and penile SCCs could potentially be prevented by introducing the HPV 16 genotype-containing vaccine to males. CLINICAL TRIAL: Not applicable.

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2025-12-18 | Prevalence and time trends of human papillomavirus in penile cancer over 26 years-A comprehensive study of 1040 penile cancer cases from Denmark.

Penile cancer is rare. It has been suggested that approximately half are human papillomavirus (HPV) associated, but large-scale studies on HPV prevalence and time trends are limited. We aimed to examine the high-risk HPV (hrHPV) prevalence in a large single-country study of penile squamous cell carcinomas (SCC) during a 26-year period. From the nationwide Danish Pathology Register, we identified all penile SCCs diagnosed during the period 1995-2020 at hospitals covering most regions in Denmark. Histologic slides were evaluated by expert pathologists, and archived tumor tissue was tested for the presence of HPV DNA using the INNO-LiPA assay. We assessed the overall and type-specific HPV prevalence according to calendar period, age, and histology, and estimated the annual percentage change (EAPC) of hrHPV positivity over the entire study period. We included 1040 penile SCCs. The overall HPV prevalence was 54.5% and the hrHPV prevalence was 50.4%. We observed no change in the prevalence of hrHPV over time (EAPC = -0.03% [95% confidence interval: -0.91; 0.85]). HPV16 was the most prevalent genotype (41.1%), and 50.0% of the penile SCCs had an HPV type that would be covered by the nine-valent HPV vaccine (HPV6/11/16/18/31/33/45/52/58). Penile SCCs with HPV-associated histological features had the highest hrHPV prevalence, particularly tumors exhibiting basaloid features (81.8%-87.7%). In this large population-based study, covering most regions in Denmark, we found no substantial change in hrHPV prevalence during 1995-2020. Our findings suggest that prophylactic vaccination with the nine-valent HPV vaccine could prevent a considerable part of penile SCCs in Denmark.

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2025-12-11 | Public health impact and cost-effectiveness of implementing gender-neutral immunization with the nonavalent human papillomavirus vaccine in South Korea.

This study assessed the impact and cost-effectiveness of gender-neutral immunization with the nonavalent human papillomavirus (HPV) vaccine in South Korea. An established dynamic transmission model of HPV epidemiology was adapted to the South Korean population. Vaccinating both girls and boys with the nonavalent HPV vaccine was compared to the currently administered program of vaccinating girls only with the quadrivalent vaccine. Compared to vaccination of girls only with the quadrivalent HPV vaccine, gender-neutral vaccination with the nonavalent HPV vaccine was projected to prevent 1,282,415 cases of cervical intraepithelial neoplasia grade 1 (CIN1), 918,384 cases of CIN2/3, 36,248 cases of cervical cancer, and 9,313 cervical cancer deaths in females over 100 years. Gender-neutral vaccination was projected to reduce HPV-related vaginal, vulvar, anal, and head & neck cancers in females by 4.8-8.2%, in addition to reductions of 14.6% and 15.8% in genital warts and recurrent respiratory papillomatosis, respectively. In males, gender-neutral vaccination was projected to prevent 666,182 cases of genital warts, 7,422 cases of RRP, 995 cases of anal cancer, 2,441 cases of head & neck cancer, and 122 cases of penile cancer. The incremental cost-effectiveness ratio (ICER) was ₩38.9 million per quality-adjusted life year (QALY), which is below the accepted cost-effectiveness threshold in South Korea. These findings suggest that gender-neutral vaccination with the nonavalent HPV vaccine would reduce the public health burden of HPV disease in both females and males in South Korea and would be cost-effective under base case assumptions about vaccine price and coverage of boys.

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antibodies

2026-09-20 | Current Management and Investigational Therapeutic Strategies in Penile Squamous Cell Carcinoma: A Narrative Review.

Penile squamous cell carcinoma (PSCC) is a rare and aggressive genitourinary malignancy requiring integrated multidisciplinary management. This narrative review provides an updated overview of the diagnostic and therapeutic pathway of PSCC from localized disease, where surgery remains the cornerstone of treatment, to locally advanced disease, where multimodal strategies integrating chemotherapy and radiotherapy with surgery are required, and finally to metastatic disease, where systemic therapy becomes the mainstay of treatment. Platinum-based chemotherapy remains the established systemic backbone for advanced PSCC, whereas immune checkpoint inhibitors, chemo-immunotherapy combinations, targeted therapies, antibody-drug conjugates, vaccines, and adoptive cellular therapies represent investigational strategies supported by preliminary evidence. Although these approaches have shown early signals of activity, their routine integration into clinical practice remains limited by small and heterogeneous studies, the lack of definitive randomized evidence, and the need for prospective validation in well-defined clinical and molecular subgroups. The aim of this review is therefore to provide a stage-adapted and multidisciplinary overview of therapeutic strategies for the contemporary management of PSCC.

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2026-09-18 | MH-Penile-002: a phase II, prospective, single-arm trial of neoadjuvant anti-EGFR antibody-drug conjugate plus PD-1 inhibitor in penile cancer with challenging penile preservation or regional lymph node metastasis.

Emerging evidence suggests that combinations of antibody-drug conjugates (ADCs) and immune checkpoint inhibitors (ICIs) may be effective for advanced penile squamous cell carcinoma (PSCC). These findings support the translation of this strategy into the neoadjuvant setting, offering a novel approach for patients with locally advanced or regionally metastatic disease who have limited treatment options. This single-center, prospective, single-arm, phase II trial evaluates the efficacy and safety of neoadjuvant Becotatug Vedotin plus Pucotenlimab in EGFR-expressing PSCC patients with challenging penile preservation or regional lymph node metastasis. Utilizing a Simon's two-stage design, the primary endpoint is the investigator-assessed R0 resection rate. Secondary endpoints include the downstaging rate, objective response rate (ORR), pathological complete response (pCR) rate, major pathological response (MPR) rate, tumor regression grade (TRG), event-free survival (EFS), disease-free survival (DFS), and organ‑sparing rate. The study plans to enroll 60 patients with EGFR-expressing PSCC. Clinical trial registration: www.clinicaltrials.gov identifier is NCT07518979.

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2026-09-17 | Pre-existing immunity and hrHPV status determine immunotherapy response in advanced penile cancer: biomarkers and overall survival in the PERICLES trial.

Penile squamous cell carcinoma (PeSCC) is a rare malignancy with limited treatment options in advanced stages. The phase II PERICLES trial (NCT03686332) investigated atezolizumab with or without radiotherapy in advanced penile cancer. Here, we report mature overall survival (OS) and updated progression-free survival (PFS) outcomes and an in-depth biomarker analysis. Patients were treated with atezolizumab monotherapy (n=12) or atezolizumab in combination with radiotherapy (n=20, 33 fractions of 1.5-1.8 Gy) for locoregional disease control. Comprehensive analysis of baseline tumor tissue (n=28/31) was performed using bulk RNA sequencing, immunohistochemistry and multiplex immunofluorescence. Additionally, spatial transcriptomics (n=9) was conducted to further explore functionality and (co-)localization of immune cell subsets. With extended follow-up (median: 38 months), landmark 2-year OS and PFS in the full study cohort was 18.8% (95% CI, 9.1-38.6) and 12.5% (95% CI, 5.0-31.3), respectively. High-risk human papillomavirus (hrHPV)-positive tumors were enriched for IFN-γ and IFN-α signatures, potentially explaining the improved PFS and OS observed in this subgroup. Both stromal CD68+ myeloid cell density and intratumoral CD8+PD1+ T-cell density were associated with non-progression at 1 year. Increased intratumoral CD8+PD1+ T-cell density was also associated with improved PFS and OS, with consistent findings in the hrHPV-positive subgroup. Spatial transcriptomics identified these CD8+ T cells as tissue-resident cytotoxic effector cells co-expressing checkpoint molecules (LAG3 and TIGIT), chemokines (CCL4 and CXCL13), and cytotoxic molecules (PRF1 and GZMB). Interrogation of the penile cancer immune microenvironment highlights CD8+PD1+ T-cells as candidate biomarkers in relation to clinical benefit from immune checkpoint blockade in advanced PeSCC.

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2026-08-26 | Assessment of EGFR and HER2 expression in penile cancer as potential therapeutic targets.

Penile cancer (PC) is a rare but aggressive malignancy with limited systemic treatment options, particularly in advanced stages. Targeted therapies against receptor tyrosine kinases such as EGFR and HER2 have demonstrated clinical benefit in other cancer types, yet their role in PC remains poorly defined. Understanding their expression patterns in primary tumors and metastases is essential for identifying new therapeutic avenues. In this study, we aimed to systematically assess the expression of EGFR and HER2 in a large multicenter PSCC cohort and evaluate their potential relevance not only as therapeutic targets but also as prognostic biomarkers. In addition, we analyzed possible correlations with key clinicopathological features, including HPV status, tumor stage and histological subtype. Among 208 patients, moderate to strong EGFR expression was detected in 27.0% of primary tumors and 29.0% of metastases, with HER2 overexpression observed in 7.0% and 21.4%, respectively. EGFR expression was significantly higher in HPV-negative tumors and associated with reduced overall survival. In contrast, HER2 was more frequently overexpressed in HPV-positive and basaloid tumors without prognostic significance. Expression patterns of both markers were largely homogeneous within primary tumors but showed partial discordance between primary and metastatic lesions. EGFR and HER2 are variably expressed in PC, with EGFR displaying potential as a prognostic marker. These findings suggest that both receptors may serve as therapeutic targets in certain patients, particularly if confirmed in metastases. Future research should integrate molecular profiling to refine biomarker-based stratification and guide the use of targeted therapies in this rare but challenging cancer.

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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.

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other

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.

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2026-06-01 | Editorial Comment on “Prognostic Significance of Pretreatment Blood‐Based Biomarkers in Penile Cancer: A Multicenter Retrospective Study in Japan”

The author declares no conflicts of interest. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

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2026-06-01 | Blood‐Based Biomarkers in Penile Cancer

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

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2026-05-13 | Trends in age-standardized incidence rates of cancers of HPV-related cancer sites in Osaka, Japan: 1977-2019.

The trends in cancers of Human papillomavirus (HPV)-related cancer sites in Japan are insufficiently reported. We evaluated the long-term trends of them as a baseline before the effects of HPV vaccine introduction became apparent in Japan. This retrospective, population-based study used data from the Osaka Cancer Registry to analyze 39,349 cases between 1977 and 2019. For women, the ASIRs were particularly high for cervical cancer. For squamous cell carcinoma, the ASIR changed from a decrease (from high to low) to an increase (from low to high) around 2000, although the trend for females aged 40-59 has recently showed no significant change. The trend in ASIR for adenocarcinoma also shifted from an increase to no significant change in the 40-59 age group, but increased consistently in the ≤ 39 age group. Vaginal cancer exhibited no significant change, while cancers of the oropharynx, anus, and vulva have increased. For men, cancers of the oropharynx and anus consistently increased. Squamous cell carcinoma of the anus decreased from 1997 to 2004, but then increased thereafter. Similarly, penile cancer decreased from 1977 to 1995, but then increased. Future studies will observe how this trend changes as groups with high HPV vaccination rates reach cancer-susceptible ages.

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2026-03-17 | Association of CCL21+ CAFs with B-cell recruitment and TLS maturation in penile squamous cell carcinoma.

Penile squamous cell carcinoma (PSCC) is an aggressive malignancy with a poor prognosis and limited therapeutic options. Tertiary lymphoid structures (TLSs) can support antitumour immunity, yet TLS maturation and maturation-associated stromal determinants in PSCC remain unclear. Here, we integrated hematoxylin and eosin (H&E) staining, multiplex immunohistochemical (mIHC) colocalization, spatial transcriptomics, single-cell RNA sequencing (scRNA-seq), and bulk RNA sequencing (bulk RNA-seq) to profile TLS maturity and TLS-associated stromal-immune features in PSCC. TLS maturity was quantified using an AUCell germinal centre-like signature, and the presence of mature TLSs (mTLSs) coincided with improved survival. We identified a CCL21+ CAF subset that was preferentially enriched in mTLSs, spatially concentrated in the mTLS-core and adjacent to B-cell-rich areas; mIHC further confirmed dense CCL21+ACTA2+ CAFs near CD20+ aggregates. Along an inferred iTLS-to-mTLS continuum, the abundance of CCL21+ CAFs increased, and the expression of chemokines increased. Spatial and transcriptomic analyses further linked B-cell chemotaxis- and activation-related signatures to the CCL21-CCR7 axis, accompanied by germinal centre-like B-cell features. Clinically, higher CCL21 expression, elevated CCL21+ CAF signature scores, and stronger CCL21-CCR7 signatures in B cells were associated with favourable outcomes. Together, these data suggest that CCL21+ CAFs or CCL21 are potential prognostic biomarkers for risk stratification and immune microenvironment profiling and highlight the CCL21-CCR7 axis as a candidate pathway for therapeutic modulation of TLS maturity in PSCC.

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