Advanced Penile Cancer Research Articles

Impact of treatment approaches in patients with advance penile cancer: An analysis from a nationwide study.

e17024 Background: Advance penile cancer (APC) is a rare and aggressive malignancy, characterized by the presence of metastases to lymph nodes and/or distant organs. The rarity of patients with APC poses challenges in conducting comprehensive studies, with most existing evidence being small-scale, retrospective analyses from single institutions. Additionally, the absence of large clinical trials limits the evidence to compare the survival rates with different treatment approaches in patients with APC. Methods: Our study utilized the national cancer database (NCDB) from 2004 to 2021. Our primary analytic cohort included patients diagnosed with advance penile cancer based on the AJCC 8 th classification (T4 or N3 or M1). Treatment modalities comprised perioperative systemic therapy combined with definitive surgery (PST), concurrent chemoradiation (CCR), surgery only (S), and systemic therapy only (ST). We used Kaplan-Meier analysis and the cox proportional regression to evaluate the impact of these treatment modalities on survival outcomes. Results: We identified 1342 patients with advance penile cancer. The median overall survival (OS) was 22.24 months (CI: 15.87-27.86, P <0.001) for patients who received PST, 16.99 months (CI: 13.86-27.4) for those who underwent CCR, 11.99 months (CI: 9.2-15.01) for patients managed with surgery only, and 10.94 months (CI: 9.95-14.09) for those who received only ST. Our multivariate analysis revealed combining PST with surgery was associated with 27% reduction in the risk of death (HR: 0.73, P = 0.037) compared to systemic therapy after adjusting for age, race, tumor grade, comorbidities, distant metastasis and socioeconomic factors. Conclusions: Treatment approach with systemic therapy along with definitive penile surgery is associated with improved survival in patients with advanced penile cancer compared to other treatment modalities. Whenever feasible, this treatment approach should be considered as a management strategy in patients with APC. Further prospective studies are needed to validate our observations. [Table: see text]

A phase II trial of pembrolizumab plus platinum-based chemotherapy as first-line systemic therapy in advanced penile cancer: HERCULES (LACOG 0218) trial.

A phase II trial of pembrolizumab plus platinum-based chemotherapy as first-line systemic therapy in advanced penile cancer: HERCULES (LACOG 0218) trial.

SAVE: A prospective, single-arm, single-center clinical study of disitamab vedotin in combination with toripalimab in patients with advanced penile cancer that has progressed or is intolerant to cisplatin chemotherapy.

SAVE: A prospective, single-arm, single-center clinical study of disitamab vedotin in combination with toripalimab in patients with advanced penile cancer that has progressed or is intolerant to cisplatin chemotherapy.

Therapeutic Targets in Advanced Penile Cancer: From Bench to Bedside.

Discovery of effective systemic therapies for patients with advanced penile cancer has been slow to occur. Comprehensive genomic profiling from several studies shed light on the molecular oncogenesis of penile squamous cell carcinoma (PSCC) and differences between HPV-related and unrelated tumors. While these two subsets of PSCC appear distinct in their biology, there are not yet specific treatment strategies recommended on that basis. Cell surface proteins have been identified that may potentially serve as drug targets for monoclonal antibodies or small molecule inhibitors. Here, we review some of the new biological insights regarding PSCC that could lead to improved therapies, as well as the related clinical trials recently completed or in progress. We conclude that antibody-drug conjugates are especially promising, as are the combinations of immune checkpoint inhibitors with other types of drugs.

Abstract 2488: The penile cancer tumor microenvironment and immunotherapy response: Results from the PERICLES trial

Abstract Introduction: The phase II PERICLES trial investigated the efficacy of atezolizumab (anti-PD-L1) for advanced penile cancer, with or without radiotherapy. As previously published, durable responses (progression-free at 12 months) were observed in 4 out of 32 enrolled patients. Here, we present the final overall survival (OS) results and an analysis of potential biomarkers for immunotherapy response. Methods: Preplanned analysis projected that at 27/32 events, the study would have 80% power (2-sided α=0.05) to assess whether the OS for the entire cohort significantly differed from the hypothesized historical median for stage IV patients. Baseline tumor tissue samples were subjected to bulk-RNA sequencing (n=31), fluorescent (n=28) and chromogenic (n=30) multiplex immunohistochemistry. We quantified the densities of CD3+CD8+ cytotoxic T-cells, CD3+CD8−FoxP3− T-helper cells, CD3+CD8−FoxP3+ regulatory T-cells, CD68+ macrophages and CD20+ B-cells in both the tumor and stromal compartments and assessed spatial relationships. We also quantified CD8+PD1+ (potentially enriched for tumor reactivity) and CD8+PD1− T-cells. Differential expression and gene set enrichment analysis (GSEA) were performed using the hallmarks gene sets. Results: The median OS for the entire study cohort was 11.3 months (95% CI, 5.5-16.7), which is an improvement compared to the hypothesized historical median of 7.8 months for stage IV patients (one sample log-rank p=0.033). Biomarker analyses showed an increased density of stromal macrophages (p<0.001) and intratumoral cytotoxic T-cells (p=0.035) in durable responders compared to non-responders. Additionally, we observed an increased density of intratumoral CD8+PD1+ in durable responders (p<0.001). In contrast, intratumoral CD8+PD1− densities were comparable between durable and non-responders (p=0.057). Patients with a high density of intratumoral CD8+PD1+ also had an improved progression-free survival (PFS) (log-rank, p<0.001) and OS (log-rank, p=0.002). Analysis of the spatial relationships in the tumor microenvironment (TME) showed that durable responders had larger distances between cytotoxic T-cells and T-helper cells (p=0.034). GSEA revealed significant (FDR≤5%) up-regulation of IFN-α/γ responses in durable responders. In contrast, non-responders showed up-regulation of epithelial-mesenchymal transition, KRAS signaling and angiogenesis, suggesting potential barriers to an anti-tumor response. Conclusion: In the final clinical analysis, OS was improved with atezolizumab compared to the historical population of stage IV patients. CD8+PD1+ T-cells, a common proxy for tumor-reactive T-cells, and spatial relationships in the TME might serve as biomarkers of durable response to immunotherapy in advanced penile cancer. Citation Format: Tynisha S. Rafael, Alberto Gil-Jimenez, Hielke M. de Vries, Iris M. Seignette, Elise Bekers, Marta Lopez-Yurda, Dennis Peters, Erik Hooijberg, Annegien Broeks, Oscar R. Brouwer, Eva Schaake, Daniel J. Vis, Tanja D. de Gruijl, Lodewyk F.A. Wessels, Michiel S. van der Heijden. The penile cancer tumor microenvironment and immunotherapy response: Results from the PERICLES trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2488.

Safety and efficacy of immune checkpoint inhibitors in advanced penile cancer: report from the Global Society of Rare Genitourinary Tumors.

Treatment options for penile squamous cell carcinoma are limited. We sought to investigate clinical outcomes and safety profiles of patients with penile squamous cell carcinoma receiving immune checkpoint inhibitors. This retrospective study included patients with locally advanced or metastatic penile squamous cell carcinoma receiving immune checkpoint inhibitors between 2015 and 2022 across 24 centers in the United States, Europe, and Asia. Overall survival and progression-free survival were estimated using the Kaplan-Meier method. Objective response rates were determined per Response Evaluation Criteria in Solid Tumours 1.1 criteria. Treatment-related adverse events were graded per the Common Terminology Criteria for Adverse Events, version 5.0. Two-sided statistical tests were used for comparisons. Among 92 patients, 8 (8.7%) were Asian, 6 (6.5%) were Black, and 24 (29%) were Hispanic and/or Latinx. Median (interquartile range) age was 62 (53-70) years. In all, 83 (90%) had metastatic penile squamous cell carcinoma, and 74 (80%) had received at least second-line treatment. Most patients received pembrolizumab monotherapy (n = 26 [28%]), combination nivolumab-ipilimumab with or without multitargeted tyrosine kinase inhibitors (n = 23 [25%]), or nivolumab (n = 16 [17%]) or cemiplimab (n = 15 [16%]) monotherapies. Median overall and progression-free survival were 9.8 months (95% confidence interval = 7.7 to 12.8 months) and 3.2 months (95% confidence interval = 2.5 to 4.2 months), respectively. The objective response rate was 13% (n = 11/85) in the overall cohort and 35% (n = 7/20) in patients with lymph node-only metastases. Visceral metastases, Eastern Cooperative Oncology Group (ECOG) performance status of 1 or higher, and a higher neutrophil/lymphocyte ratio were associated with worse overall survival. Treatment-related adverse events occurred in 27 (29%) patients, and 9.8% (n = 9) of the events were grade 3 or higher. Immune checkpoint inhibitors are active in a subset of patients with penile squamous cell carcinoma. Future translational studies are warranted to identify patients more likely to derive clinical benefit from immune checkpoint inhibitors.

Atezolizumab With or Without Radiotherapy for Advanced Squamous Cell Carcinoma of the Penis (The PERICLES Study): A Phase II Trial.

Patients with advanced penile squamous cell carcinoma have a poor prognosis (21% 2-year overall survival [OS] from diagnosis). We assessed the activity of atezolizumab (anti-PD-L1) in patients with advanced penile cancer, with or without radiotherapy (RT). A single-center, nonrandomized phase II study with two treatment arms was conducted in 32 patients with histologically confirmed advanced penile cancer. All patients received atezolizumab (1,200 mg) once every 3 weeks. Twenty patients, who were expected to benefit from RT for locoregional disease control, received additional irradiation. The primary end point was 1-year progression-free survival (PFS) for the complete cohort and was reached if the actual 1-year PFS was at least 35%. Secondary end points included OS, objective response rate (ORR), and tolerability. Exploratory biomarker analyses were conducted in pretreatment specimens. Median follow-up was 29.1 months (IQR, 18.1-33.5). Grade 3-4 adverse events related to atezolizumab or RT were observed in 3/32 (9.4%) and 13/20 (65%) patients, respectively. One-year PFS was 12.5% (95% CI, 5.0 to 31.3), which did not meet the study's primary end point. Median OS was 11.3 months (95% CI, 5.5 to 18.7). In the objective response-evaluable population (n = 30; 93.8%), the ORR was 16.7% (95% CI, 6 to 35), including 2 (6.7%) complete responders and 3 (10%) partial responders. Improved PFS was observed in patients with high-risk human papillomavirus (hrHPV)-positive tumors (P = .003) and those with high infiltration of intratumoral CD3+CD8+ T cells (P = .037). Although the primary end point of 1-year PFS was not met, durable antitumor activity to atezolizumab was observed in a subset of patients. Biomarkers, such as hrHPV and intratumoral CD3+CD8+ T-cell infiltration, may help to better select responders.

Predicting Limited Survival Following Inguinal Lymph Node Dissection in Penile Cancer: Should We Revisit the Goals of Care?

Patients with advanced penile squamous cell cancer have a poor prognosis and can benefit from early palliative care consultation. We built a model to identify those patients most likely to benefit. Patients with penile squamous cell cancer undergoing inguinal lymph node dissection were identified from the National Cancer Database (NCDB) and a multi-institutional international dataset (INT). A multivariable Cox proportional hazards model for overall survival (OS) was developed using the NCDB and applied to the INT dataset. Parameters were used to make receiver operating characteristic (ROC) curves. ROC-related criteria were optimized to identify a predictive probability cut point and dichotomize patients from INT into risk groups for limited OS of <6 and <12 months. NCDB had 860 deaths; 105 (5%) at 6 months and 296 (15%) at 12 months. INT had 257 deaths; 56 (8%) at 6 months and 124 (18%) at 12 months. Limited OS was associated with older age, greater T and N stage, and fewer lymph nodes removed. Optimized ROC criteria using the OS <6 months curve best dichotomized INT patients into high-risk group with median OS of 24 months (95% CI 18-34) and low-risk group with median OS of 174 months (95% CI 120-NE). We developed a simple model that could be used as a screening tool for early palliative care referral.

Therapeutic Approaches to Penile Cancer: Standards of Care and Recent Developments.

Penile cancer is a rare malignancy, most commonly diagnosed in older men, associated with poor outcomes, dramatic decline in quality of life and sexual function. Squamous cell carcinoma is the most common histopathology of penile cancer, accounting for 95% of all cases. Localized, early-stage penile cancer can be effectively managed through penile-sparing techniques in many cases, though advanced stages of penile cancer carry a poor prognosis. Current innovative treatments are exploring the role of targeted therapy, HPV-directed therapy, immune checkpoint inhibitors and adoptive T-cell therapies in treatment and prevention of relapse of penile cancer. Clinical trials are investigating the potential of targeted therapies and immune checkpoint inhibitors in advanced penile cancer. This review examines the current management of penile cancer and highlights future directions in research and treatment.

MP33-05 NEOADJUVANT PLATINUM-BASED CHEMOTHERAPY FOR CLINICALLY NODE-POSITIVE PENILE SQUAMOUS CELL CARCINOMA: AN INTERNATIONAL, MULTICENTER, REAL-WORLD STUDY

You have accessJournal of UrologyCME1 Apr 2023MP33-05 NEOADJUVANT PLATINUM-BASED CHEMOTHERAPY FOR CLINICALLY NODE-POSITIVE PENILE SQUAMOUS CELL CARCINOMA: AN INTERNATIONAL, MULTICENTER, REAL-WORLD STUDY Kyle Rose, Darren Sanchez, Arfa Mustasam, Kathryn Marchetti, Reagan Sandstrom, Lance Pagliaro, Niki Millward, Constantine Alifrangis, Kelvin Moses, Maarten Albersen, Eduard Roussel, Viraj Master, Bahzel Nazha, Tony Zhuang, Jeffrey Montgomery, Chris Protzel, Marcos Tobias-Machado, Philippe Spiess, Curtis Pettaway, and Jad Chahoud Kyle RoseKyle Rose More articles by this author , Darren SanchezDarren Sanchez More articles by this author , Arfa MustasamArfa Mustasam More articles by this author , Kathryn MarchettiKathryn Marchetti More articles by this author , Reagan SandstromReagan Sandstrom More articles by this author , Lance PagliaroLance Pagliaro More articles by this author , Niki MillwardNiki Millward More articles by this author , Constantine AlifrangisConstantine Alifrangis More articles by this author , Kelvin MosesKelvin Moses More articles by this author , Maarten AlbersenMaarten Albersen More articles by this author , Eduard RousselEduard Roussel More articles by this author , Viraj MasterViraj Master More articles by this author , Bahzel NazhaBahzel Nazha More articles by this author , Tony ZhuangTony Zhuang More articles by this author , Jeffrey MontgomeryJeffrey Montgomery More articles by this author , Chris ProtzelChris Protzel More articles by this author , Marcos Tobias-MachadoMarcos Tobias-Machado More articles by this author , Philippe SpiessPhilippe Spiess More articles by this author , Curtis PettawayCurtis Pettaway More articles by this author , and Jad ChahoudJad Chahoud More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003266.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The efficacy of neoadjuvant platinum-based chemotherapy (NAPC) in locally advanced Penile Squamous Cell Carcinoma (PSCC) has been demonstrated in prior small studies, leaving clinicians with scant evidence-based guidance. Thus, we aimed to provide evidence on real-world outcomes of patients with PSCC who received NAPC prior to surgical resection. METHODS: Patients who had undergone NAPC prior to surgical resection for PSCC were included from ten centers. Patients had locally advanced (cTany, cN+), non-metastatic (M0) disease. Clinicopathologic data, chemotherapeutic agents utilized including TIP (Paclitaxel - Ifosfamide - Cisplatin), surgical modalities, and clinicopathologic outcomes were assessed. The primary outcome was overall survival (OS), analyzed using Kaplan-Meier Method and compared using Cox Proportional Hazard Modelling. The secondary outcome was progression-free survival (PFS). Response was determined via best overall response measured with RECIST 1.1 criteria following completion of NAPC. RESULTS: 167 patients with PSCC treated with NAPC were included, 137 (84%) of whom received TIP. 92 (55%) patients died during follow up, and the median follow up for survivors was 57 months. The median OS was 42.0 months, while the median PFS was 17.0 months. After NAC, 22% had progressive disease (PD), 20% had stable disease, 47% had partial response, and 11% had complete response, with median OS of 16 months, 51 months, 56 months, and 119 months, respectively (p<0.01). Predictors for OS and RFS included lymphovascular invasion, positive number of lymph nodes, extranodal extension, downstaging after chemotherapy, best overall response, and ypN status. Figure 1 demonstrates OS outcomes by RECIST best response after chemotherapy, presence of downstaging after NAPC, ypN stage, and presence of extranodal extension. CONCLUSIONS: NAPC is effective in patients with lymph node metastases from PSCC. This study represents the largest conglomeration of multi-institutional penile carcinoma patients treated with upfront cisplatin based therapy, and provides further supportive data for multimodal therapy for advanced penile cancer patients while prospective clinical trials complete accrual . Source of Funding: NA © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e451 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kyle Rose More articles by this author Darren Sanchez More articles by this author Arfa Mustasam More articles by this author Kathryn Marchetti More articles by this author Reagan Sandstrom More articles by this author Lance Pagliaro More articles by this author Niki Millward More articles by this author Constantine Alifrangis More articles by this author Kelvin Moses More articles by this author Maarten Albersen More articles by this author Eduard Roussel More articles by this author Viraj Master More articles by this author Bahzel Nazha More articles by this author Tony Zhuang More articles by this author Jeffrey Montgomery More articles by this author Chris Protzel More articles by this author Marcos Tobias-Machado More articles by this author Philippe Spiess More articles by this author Curtis Pettaway More articles by this author Jad Chahoud More articles by this author Expand All Advertisement PDF downloadLoading ...

Video endoscopic inguinofemoral lymphadenectomy in penile cancer

Background. Dissection of inguinal lymph nodes is an important method of treatment of invasive and locally advanced penile cancer. Unfortunately, the procedure is associated with very high complication rate exceeding 50 %.Aim. To perform retrospective comparative analysis of oncological outcomes, intraoperative and early postoperative complications of open and endoscopic inguinofemoral lymphadenectomy in treatment of patients with penile cancer.Materials and methods. Treatment outcomes of 64 patients with penile cancer who underwent open or video endoscopic lymphadenectomy were analyzed. Primary and secondary surgical treatment outcomes were evaluated.Results. Open inguinofemoral lymphadenectomy was performed in 54 patients, video endoscopic in 10. Analysis of primary surgical results showed a significant (3-fold) reduction of the duration of lymphorrhea and the duration of hospitalization (2-fold) in patients of the video endoscopic lymphadenectomy group. There was no difference in the number of removed lymph nodes in the two types of surgeries. Average operative time for video endoscopic lymphadenectomy was 15–20 % longer than operative time of open intervention. Analysis of safety indicators showed that during open surgery, the frequency of wound infection was 24 %, skin flap necrosis – 55.5 %, wound dehiscence – 52 %, lymphedema – 15 %. No such complications were observed in lateral video endoscopic inguinofemoral lymphadenectomy.Conclusion. Video endoscopic inguinofemoral lymphadenectomy has significant advantages compared to open method in terms of reduction of the rate of surgical complications and duration of hospitalization.

A phase II trial of pembrolizumab combined with platinum-based chemotherapy as first-line systemic therapy in advanced penile cancer: HERCULES (LACOG 0218) trial.

TPS14 Background: Penile squamous cell carcinoma (PSCC) is an uncommon malignancy which accounts for 2,300 new cases and 400 deaths annually worldwide. However, in low-income countries from South America, Asia and Africa, incidence corresponds to 10-20% of all malignancies in men. Approximately 4% of PSCC patients present with metastatic disease at diagnosis. Also, even if diagnosed in early stages (localized disease), around 30% of patients will recur. No improvements have been achieved over the last three decades in platinum-based chemotherapy, which remains the standard-of-care; objective response rate (ORR), median progression-free survival (PFS) and overall survival (OS) are currently at 20-30%, 3-4 months and 7-15 months, respectively. HPV16 is the most important known risk factor for PSCC. Favorable results have been achieved with Pembrolizumab in other HPV-associated cancers, such as cervical and oropharyngeal cancer. HERCULES (LACOG 0218) aims to evaluate the efficacy of pembrolizumab combined with platinum-based chemotherapy as first-line treatment in advanced PSCC. Methods: HERCULES is a phase 2, single-arm, multicentric trial evaluating patients with histologically proven PSCC and metastatic disease (de novo or recurrent); or recurrent locally advanced disease not amenable to curative-intent therapy; or TanyN3M0 or T4NanyM0 (stage IV – AJCC 8th ed) not amenable to curative-intent therapy. Additional inclusion criteria were ECOG PS 0–1; measurable disease by RECIST 1.1; no prior systemic therapy for recurrent or metastatic disease (however, patients progressing after 12 months of neo/adjuvant chemotherapy completion are allowed). The primary endpoint is ORR up to week 24. Secondary endpoints are OS, PFS, clinical benefit rate, immune related response criteria, quality of life, safety, and predictive biomarkers of response/survival. Eligible subjects receive 5-FU 1000mg/m²/day IV D1-D4, cisplatin 70mg/m² or carboplatin AUC 5 IV D1 plus pembrolizumab 200mg IV D1 at each 3-week (Q3W) dosing cycle for 6 cycles, followed by Pembrolizumab 200mg IV Q3W maintenance. Patients without disease progression are allowed to continue pembrolizumab monotherapy until completing 34 cycles, disease progression or unacceptable toxicity, whichever comes first. Tumor evaluations are performed every 6 weeks until week 24. Sample size was calculated as 33 patients to detect an increase in ORR from 20% to 40% up to week 24 with 78.5% power and considering 10% drop-out. From Aug 2020 to Jul 2022, 33 patients were enrolled in 11 Brazilian research sites. Results are expected in 2023. NCT04224740. Clinical trial information: NCT04224740 .

Neoadjuvant platinum-based chemotherapy for clinically node-positive penile squamous cell carcinoma: An international, multicenter, real-world study.

9 Background: The efficacy of neoadjuvant platinum-based chemotherapy (NAPC) in penile squamous cell carcinoma (PSCC) was provided by small clinical trials, leaving clinicians with scant evidence-based guidance. Thus, we aimed to analyze real-world outcomes of patients with PSCC who received NAPC prior to surgical resection. Methods: Patients from 9 tertiary care centers who had undergone NAPC prior surgical resection for PSCC were included with locally advanced (cTany, cN+), non-metastatic (M0) disease. The primary and secondary outcomes were overall survival (OS) and progression-free survival (PFS), Response was determined via best overall response measured with RECIST 1.1 criteria. Results: 167 patients were included, 137 (84%), of which received TIP prior to surgical resection. Ninety-two (55%) patients died during follow up, and the mean follow up for survivors was 57 months. The median OS was 42 months, while the median PFS was 17 months. The table details the response rates to NAPC, the associated survival, and Cox Proportional Hazards Modelling of OS and PFS. Predictors for OS and RFS included lymphovascular invasion, positive number of lymph nodes, extranodal extension, downstaging, best overall response, and ypN status. Figure 1 demonstrates OS outcomes by RECIST best response after chemotherapy, presence of downstaging after NAPC, ypN stage, and presence of extranodal extension. Conclusions: Upfront NAPC is effective in patients with lymph node metastases from penile carcinoma. Unsurprisingly, patients who demonstrated a robust response to therapy had improved survival outcomes compared to those who had not—as measured by RECIST criteria, tumor downstaging, pN staging, and presence of extranodal extension. This study represents the largest conglomeration of multi-institutional penile carcinoma patients treated with NAPC, and provides further supportive data for multimodal therapy for advanced penile cancer patients while prospective clinical trials complete accrual. [Table: see text]

Subtotal penectomy and perineostomy configuration in locally advanced penile cancer

Subtotal penectomy and perineostomy configuration in locally advanced penile cancer

Venous thrombosis, multiple carcinomatous foci and differences in metastatic pathways of penile carcinoma.

The aim of the present study was to explore the life-threatening complications and metastatic pathways of penile squamous cell carcinoma (SCC), as numerous patients with penile cancer are relatively young, are of good general health and have no visceral metastasis, yet have poor survival rates. A total of 94 patients with SCC of the penis who were surgically treated were included in the current study. The coagulation parameters, including prothrombin time (PT), fibrinogen and D-dimer, were analyzed. The patients' age ranged from 25 to 95 years (mean ± standard deviation, 53.3±1.4 years). A total of 77 patients (81.9%) underwent partial penectomy and 17 (18.1%) underwent radical penectomy. The PT was significantly different between patients whose tumour invaded the corpora cavenosum and those whose tumour had not invaded, and between patients with and without pelvic lymph node metastasis. A negative correlation was obtained between PT and pelvic lymph node metastasis. In addition, six typical SCC cases and one metastatic penile carcinoma case manifested with multiple carcinomatous foci, embolisms and evidence of a metastatic pathway occurring simultaneously with tumour progression were presented. The present study indicated that venous thrombosis is one of the life-threatening complications of advanced penile cancer. Furthermore, multiple carcinomatous foci were detected in histological images. Of note, direct clinical evidence for different metastatic pathways of primary and secondary penile carcinoma was provided.

Role of radiotherapy in the treatment of locally advanced penile cancer

Penile cancer is a rare but aggressive tumor, most commonly squamous cell carcinoma. Treatment modalities depend on the stage of the disease, but the backbone of treatment is surgical resection of the primary tumor and regional lymph nodes with the use of neoadjuvant/adjuvant chemotherapy and radiotherapy. Our case report is about a 59-year-old patient which was presented with bilateral inguinal lymphadenitis, scrotal and penile edema. A biopsy of the change in the penis confirmed squamous cell carcinoma. Partial amputation of the penis and an excisional biopsy of the inguinal lymph nodes was performed, which confirmed the metastasis to the lymph nodes. Diagnostic imaging revealed bilateral enlarged inguinal lymph nodes which were later surgically removed. Postoperative CT scan showed three suspected lung metastases. The patient was then treated with polychemotherapy. Follow-up CT scan showed complete regression of metastatic changes in the lungs but also showed local recurrence in the area of the penile root. Radiotherapy with concomitant administration of cisplatin was conducted. Penile cancer is an aggressive disease that can be cured at an early stage if adequate treatment is applied. We highlight the importance of a multimodal and multidisciplinary approach consisting of polychemotherapy, surgical treatment, and radiotherapy.

Patterns of Recurrence and Survival After Pelvic Treatment for Locally Advanced Penile Cancer

BackgroundPenile cancer (PeCa) is rare, and the survival of patients with advanced disease remains poor. A better understanding of where treatment fails could aid the development of new treatment strategies. ObjectiveTo describe the disease course after pelvic lymph node (LN) treatment for PeCa. Design, setting, and participantsWe retrospectively analysed 228 patients who underwent pelvic LN treatment with curative intent from 1969 to 2016. The main treatment modalities were neoadjuvant chemotherapy, chemoradiation, and pelvic LN dissection. Outcome measurements and statistical analysisIn the case of multiple recurrence locations, the most distant location was taken and recorded as follows: local (penis), regional (inguinal and pelvic LN), and distant (any other location). A competing risk analysis was used to calculate the time to recurrence per location, and a Kaplan-Meier analysis was used for overall survival (OS). Results and limitationsThe median follow-up of the surviving patients was 79 mo. The reason for pelvic treatment was pelvic involvement on imaging (29%), two or more tumour-positive inguinal LNs (61%), or inguinal extranodal extension (52%). More than half of the patients (61%) developed a recurrence. The median recurrence-free survival was 11 mo. The distribution was local in 9%, regional in 27%, and distant in 64% of patients. The infield control rate of nonsystemically treated patients was 61% (113/184). From the start of pelvic treatment, the median OS was 17 mo (95% confidence interval 12–22). After regional or distant recurrence, all but one patient died of PeCa with median OS after a recurrence of 4.4 (regional) and 3.1 (distant) mo. This study is limited by its retrospective nature. ConclusionsThe prognosis of PeCa patients treated on their pelvis who recur despite locoregional treatment is poor. The tendency for systemic spread emphasises the need for more effective systemic treatment strategies. Patient summaryIn this report, we looked at the outcomes of penile cancer patients in an expert centre undergoing various treatments on their pelvis. We found that survival is poor after recurrence despite locoregional treatment. Therefore, better systemic treatments are necessary.

Immune landscape and immunotherapy for penile cancer.

Penile cancer is a rare malignancy and usually refers to penile squamous cell carcinoma (PSCC), which accounts for more than 95% of all penile malignancies. Although organ-sparing surgery is an effective treatment for early-stage PSCC, surgical intervention alone is often not curative for advanced PSCC with metastases to the inguinal and/or pelvic lymph nodes; thus, systemic therapy is required (usually platinum-based chemotherapy and surgery combined). However, chemotherapy for PSCC has proven to be of limited efficacy and is often accompanied by high toxicity, and patients with advanced PSCC usually have poor prognosis. The limited treatment options and poor prognosis indicate the unmet need for advanced PSCC. Immune-based therapies have been approved for a variety of genitourinary and squamous cell carcinomas but are rarely reported in PSCC. To date, several studies have reported high expression of PDL1 in PSCC, supporting the potential application of immune checkpoint inhibitors in PSCC. In addition, human papillomavirus (HPV) infection is highly prevalent in PSCC and plays a key role in the carcinogenesis of HPV-positive PSCC, suggesting that therapeutic HPV vaccine may also be a potential treatment modality. Moreover, adoptive T cell therapy (ATC) has also shown efficacy in treating advanced penile cancer in some early clinical trials. The development of new therapeutics relies on understanding the underlying biological mechanisms and processes of tumor initiation, progression and metastasis. Therefore, based on the interest, we reviewed the tumor immune microenvironment and the emerging immunotherapy for penile cancer.

Patient reported outcomes in advanced penile cancer.

Patient reports of their symptom burden (i.e., patient-reported outcomes or PROs) have been shown to direct clinicians' ability to personalize care and improve outcomes. A disciplined assessment of PRO in the population of patients with advanced penile cancer (PeCa) has not previously been undertaken. Our center leveraged a significant cadre of patients with PeCa and a significant experience with a well-established PRO: the Edmonton Symptom Assessment Scale (ESAS). After IRB approval, we screened ESAS surveys of 14,781 patients completed between February 2017 and February 2021; these were collected in the Supportive Care and Radiation Oncology clinics. Of these, those with PeCa were divided into 3 cohorts: (A) Those after any partial penectomy procedure without lymph node dissection (LND); (B) Those after partial penectomy procedure with LND; and (C) Those after total penectomy and LND. Patients with recurrent disease were analyzed separately (D). ESAS scores were collated and compared both by individual symptom and cumulatively. Twenty-two PeCa patients completed 122 ESAS surveys in this time and are included in this analysis: a median of 4 ESAS surveys (mean = 5, range = 1-19) were completed by each patient. The symptom with the highest median ESAS score was Tiredness (3.00). Patients with recurrent disease had the highest cumulative symptom score (median score = 30). Patients after total penectomy with LND had a higher cumulative symptom score (14.4) than those with partial penectomy and LND (7.9). Patients with partial penectomy without LND had a cumulative score of 22. PROs provide an insight into the morbidity of therapies for advanced PeCa, and the most symptoms are reported by patients with recurrent disease.

Video 8 - Phallus Preservation and reconstruction in a young male with advanced penile cancer

Video 8 - Phallus Preservation and reconstruction in a young male with advanced penile cancer