Characterization of T cell receptor repertoire in penile cancer.

Tumor-infiltrating lymphocytes (TILs) play a key role in regulating the host immune response and shaping tumor microenvironment. It has been previously shown that T cell infiltration in penile tumors was associated with clinical outcomes. However, few studies have reported the T cell receptor (TCR) repertoire in patients with penile cancer. In the present study, we evaluated the TCR repertoires in tumor and adjacent normal tissues from 22 patients with penile squamous cell carcinoma (PSCC). Analysis of the T cell receptor beta-variable (TRBV) and joining (TRBJ) genes usage and analysis of complementarity determining region 3 (CDR3) length distribution did not show significant differences between tumor and matched normal tissues. Moreover, analysis of the median Jaccard index indicated a limited overlap of TCR repertoire between these groups. Compared with normal tissues, a significantly lower diversity and higher clonality of TCR repertoire was observed in tumor samples, which was associated with clinical characteristics. Further analysis of transcriptional profiles demonstrated that tumor samples with high clonality showed increased expression of genes associated with CD8 + T cells. In addition, we analyzed the TCR repertoire of CD4 + T cells and CD8 + T cells isolated from tumor tissues. We identified that expanded clonotypes were predominantly in the CD8 + T cell compartment, which presented with an exhausted phenotype. Overall, we comprehensively compared TCR repertoire between penile tumor and normal tissues and demonstrated the presence of distinct T cell immune microenvironments in patients with PSCC.

Radiotherapy Versus Partial Penectomy for T1 Squamous Cell Carcinoma of the Penis.

BACKGROUND: Radiotherapy (RT) represents an alternative treatment option for patients with T1 squamous cell carcinoma of the penis (SCCP), with proven feasibility and tolerability. However, it has never been directly compared with partial penectomy (PP) using cancer-specific mortality (CSM) as an end point. METHODS: In the Surveillance, Epidemiology, and End Results database (2000-2020), T1N0M0 SCCP patients treated with RT or PP were identified. This study relied on 1:4 propensity score-matching (PSM) for age at diagnosis, tumor stage, and tumor grade. Subsequently, cumulative incidence plots as well as multivariable competing risks regression (CRR) models addressed CSM. Additionally, the study accounted for the confounding effect of other-cause mortality (OCM). RESULTS: Of 895 patients with T1N0M0 SCCP, 55 (6.1%) underwent RT and 840 (93.9%) underwent PP. The RT and PP patients had a similar age distribution (median age, 70 vs 70 years) and more frequently harbored grade I or II tumors (67.3% vs 75.8%) as well as T1a-stage disease (67.3% vs 74.3%). After 1:4 PSM, 55 (100%) of the 55 RT patients versus 220 (26.2%) of the 840 PP patients were included in the study. The 10-year CSM derived from the cumulative incidence plots was 25.4% for RT and 14.4% for PP. In the multivariable CRR models, RT independently predicted a higher CSM than PP (hazard ratio, 1.99; 95% confidence interval, 1.05-3.80; p = 0.04). CONCLUSION: For the T1N0M0 SCCP patients treated in the community, RT was associated with nearly a twofold higher CSM than PP. Ideally, a validation study based on tertiary care institution data should be conducted to test whether this CSM disadvantage is operational only in the community or not.

[68Ga]Ga-FAPI-46 PET/CT for penile cancer - a feasibility study.

PURPOSE: Penile cancer is a rare entity and has a good prognosis in localized stage. Delayed surgical treatment of lymphatic disease is associated with poor overall survival but conventional imaging cannot detect occult lymph node metastasis sufficiently. Imaging cancer related fibroblasts has shown promising results as non-invasive staging tool in various tumor entities but has not yet been evaluated in penile cancer. METHODS: In this single-center pilot study, patients planned for surgical treatment for penile cancer underwent preoperatively [68Ga]Ga-FAPI-46 PET/CT. Post-operative histopathology was compared to [68Ga]Ga-FAPI-46 PET/CT results. RESULTS: From January 2022 to June 2022, a total number 11 patients with histopathologically proven penile cancer underwent surgery and received [68Ga]Ga-FAPI-46 PET/CT prior therapy. 8 primary tumor sites and 4 lymph node regions were analyzed. FAPI uptake was increased on primary tumor site (SUVmax 16.2 (9.1 - 25.8)). Histopathological proven lymph node regions showed highly increased FAPI uptakes (SUVmax 17.9 (16.4 - 23.5) on [68Ga]Ga-FAPI-46 PET/CT. CONCLUSION: In this first pilot cohort, there were no false-positive FAPI uptake which might allow the detection of occult lymph node metastasis by [68Ga]Ga-FAPI-46 PET/CT and might consequently lead to omitting lymph node regions during surgery that had no increased FAPI uptake pre-operatively.

Incidence, risk factors, and temporal trends of penile cancer: a global population-based study.

OBJECTIVES: To examine the global disease burden and country-specific trends of penile cancer incidence by age group and investigate its associations with several factors. MATERIALS AND METHODS: The Global Cancer Observatory database was interrogated for penile cancer incidence. The 10-year cancer incidence rates were collected from the Cancer Incidence in Five Continents Plus. The country-specific data were extracted from the World Health Organization Global Health Observatory and Global Burden of Disease databases for conducting risk factors analysis. The penile cancer incidence was presented using age-standardised rates. Its associations with various factors were examined by linear regression, while the incidence trend was estimated using joinpoint regression and presented as average annual percentage change with 95% confidence intervals in different age groups. RESULTS: There were an estimated 36 068 new cases of penile cancer in 2020. There was a considerable geographical disparity in the disease burden of penile cancer, with South America reporting the highest incidence. Overall, alcohol drinking, human immunodeficiency virus (HIV) infection, and unsafe sex were positively associated with a higher penile cancer incidence, while circumcision was found to be a protective factor. There has been a mixed trend in penile cancer incidence overall, but an increasing trend was found among younger males. CONCLUSIONS: There was a global variation in the penile cancer burden associated with prevalence of alcohol drinking, HIV infection, unsafe sex, and circumcision. The increasing penile cancer incidence in the younger population is worrying and calls for early detection and preventive interventions.

Efficacy of indocyanine green fluorescence-guided inguinal lymph node dissection for penile cancer: a randomised trial.

OBJECTIVES: To investigate the safety and efficacy of indocyanine green (ICG) fluorescence-guided inguinal lymph node dissection (ILND) in patients with penile cancer. PATIENTS AND METHODS: A prospective, single-blind, randomised controlled clinical trial (ChiCTR2100044584) was performed among patients with penile caner who underwent bilateral modified ILND at four centres in China between 1 April 2021 and 30 June 2022. Patients aged 18-80 years and diagnosed with squamous cell carcinomas were included. Each enrolled patient was randomly assigned to either ICG fluorescence-guided ILND by a laparoscopic or robot-assisted approach in one groin, with non-ICG fluorescence-guided ILND in the other groin acting as a control. The primary outcome was the number of retrieved ILNs. Secondary outcomes included complications according to the Clavien-Dindo classification and the ILN non-compliance (inadequate removal of ILNs) rate. RESULTS: A total of 45 patients were included in the intention-to-treat (ITT) analysis, and the 42 who completed the entire study were included in the per protocol (PP) analysis. There were no ICG-related complications in any of the patients. The results of the ITT and PP analyses indicated that the total number of unilateral ILNs retrieved was higher on the ICG side than on the non-ICG side (mean 13 vs 9 ILNs, difference 4 ILNs [95% CI 2.7-4.4], P = 0.007), and the number of unilateral deep and superficial ILNs was higher on the ICG side. Furthermore, the LN non-compliance rate was lower on the ICG side than on the non-ICG side. Additionally, there was no significant difference in local complications in the groins between the two sides (P > 0.05). CONCLUSION: An ICG fluorescence-guided ILND was safe for patients with penile cancer. This procedure can improve the number of ILNs retrieved and reduce the LN non-compliance rate without increased complications. ICG fluorescence-guided ILND is beneficial and recommended for selected patients with penile cancer.

Near-infrared fluorescence-assisted superficial inguinal lymph-node excision for low-risk penile cancer.

OBJECTIVE: Identification of superficial inguinal lymph nodes during low-risk penile cancer surgery using near-infrared (NIR) fluorescence to improve the accuracy of lymph-node dissection and reduce the incidence of missed micrometastases and complications. METHODS: Thirty-two cases were selected, which were under the criteria of < T1, and no lymph-node metastasis was found with magnetic resonance imaging (MRI) detection. Two groups were randomly divided based on the fluorescence technique, the indocyanine green (ICG) group and the non-ICG group. In the ICG group, the ICG preparation was subcutaneously injected into the edge of the penile tumor 10 min before surgery, and the near-infrared fluorescence imager was used for observation. After the lymph nodes were visualized, the superficial inguinal lymph nodes were removed first, and then, the penis surgery was performed. The non-ICG group underwent superficial inguinal lymph-node dissection and penile surgery. RESULTS: Among the 16 patients in the ICG group, we obtained 11 lymph-node specimens using grayscale values of images (4.13 ± 0.72 vs. 3.00 ± 0.82 P = 0.003) along with shorter postoperative healing time (7.31 ± 1.08 vs. 8.88 ± 2.43 P = 0.025), and less lymphatic leakage (0 vs. 5 P = 0.04) than the 16 patients in the non-ICG group. Out of 11, 3 lymph nodes that are excised were further grouped into fluorescent and non-fluorescent regions (G1/G2) and found to be metastasized. CONCLUSION: Near-infrared fluorescence-assisted superficial inguinal lymph-node dissection in penile carcinoma is accurate and effective, and could reduce surgical complications.

The Role of JAK-STAT-SOCS1 Axis in Tumorigenesis, Malignant Progression and Lymphatic Metastasis of Penile Cancer.

Background: To uncover the potential significance of JAK-STAT-SOCS1 axis in penile cancer, our study was the pioneer in exploring the altered expression processes of JAK-STAT-SOCS1 axis in tumorigenesis, malignant progression and lymphatic metastasis of penile cancer. Methods: In current study, the comprehensive analysis of JAK-STAT-SOCS1 axis in penile cancer was analyzed via multiple analysis approaches based on GSE196978 data, single-cell data (6 cancer samples) and bulk RNA data (7 cancer samples and 7 metastasis lymph nodes). Results: Our study observed an altered molecular expression of JAK-STAT-SOCS1 axis during three different stages of penile cancer, from tumorigenesis to malignant progression to lymphatic metastasis. STAT4 was an important dominant molecule in penile cancer, which mediated the immunosuppressive tumor microenvironment by driving the apoptosis of cytotoxic T cell and was also a valuable biomarker of immune checkpoint inhibitor treatment response. Conclusions: Our findings revealed that the complexity of JAK-STAT-SOCS1 axis and the predominant role of STAT4 in penile cancer, which can mediate tumorigenesis, malignant progression, and lymphatic metastasis. This insight provided valuable information for developing precise treatment strategies for patients with penile cancer.

"Bone in the penis" or fasciitis ossificans of the penis - a first time description of a pseudo-tumor at an extraordinary site.

BACKGROUND: Fasciitis ossificans is a rare subtype of nodular fasciitis, a benign soft tissue tumor with reactive characteristics. Due to its rapid growth, it is often misdiagnosed as a malignant tumor. While fasciitis ossificans commonly originates from the subcutaneous tissue and can appear throughout the body, it may also arise from extraordinary sites. CASE PRESENTATION: We report the first-ever documented case of fasciitis ossificans arising from the penis in a male patient who presented with a tumor on the glans penis. The tumor was surgically resected due to suspicion of penile cancer. Initial histopathological analysis led to a misdiagnosis of squamous cell carcinoma. However, pathological consultation ultimately confirmed the diagnosis of fasciitis ossificans of the penis originating from the glans penis by demonstrating ossification. CONCLUSION: This case underscores the importance of considering fasciitis ossificans in the differential diagnosis of soft tissue tumors, even in unusual locations such as penile soft tissue.

Case report of penile squamous cell carcinoma continuous treatment with BRCA2 mutation.

BACKGROUND: Penile squamous cell carcinoma (PSCC) is a highly aggressive malignancy with a poor prognosis. BRCA1/2 mutations are associated with impaired DNA double-strand break repair and are among the common mutations in penile cancer, potentially paving the way for poly ADP-ribose polymerase inhibitor therapy. CASE PRESENTATION: We report a 65-year-old male with PSCC who progressed to thigh metastasis at 10 months after partial penectomy. Next-generation sequencing showed that the penis primary lesion and metastatic thigh lesion harboured a BRCA2 mutation. Chemotherapy plus immunotherapy was used for treatment, and the thigh metastasis was found to involve no tumour. Progression-free survival (PFS) lasted for 8 months until the appearance of lung metastasis. Afterwards, the patient benefited from second-line therapy of olaparib with pembrolizumab and anlotinib, and his disease was stable for 9 months. The same BRCA2 was identified in the lung biopsy. Given the tumour mutation burden (TMB, 13.97 mutation/Mb), the patient received third-line therapy with nivolumab plus ipilimumab, but PFS only lasted for 3 months, with the appearance of right frontal brain metastasis. Then, the patient was treated with radiation sequential fluzoparib therapy as fourth-line treatment, and the treatment efficacy was evaluated as PR. Currently, this patient is still alive. CONCLUSIONS: This is the first report of penile cancer with BRCA2 mutation, receiving a combination treatment with olaparib and experiencing a benefit for 9 months. This case underscores the pivotal role of BRCA2 in influencing treatment response in PSCC, providing valuable insights into the application of targeted therapies in managing recurrent PSCC with BRCA2 alterations. This elucidation establishes a crucial foundation for further research and clinical considerations in similar cases.

Differences in overall survival of penile cancer patients versus population-based controls.

PURPOSE: To assess whether 5-year overall survival (OS) of squamous cell carcinoma of the penis (SCCP) patients differs from age-matched male population-based controls. METHODS: We relied on the Surveillance Epidemiology and End Results database (2004-2018) to identify newly diagnosed (2004-2013) SCCP patients. For each case, we simulated an age-matched control (Monte Carlo simulation), relying on the Social Security Administration (SSA) Life Tables with 5 years of follow-up. We compared OS between SCCP patients and population-based controls in a stage-specific fashion. Smoothed cumulative incidence plots displayed cancer-specific mortality (CSM) versus other-cause mortality (OCM). RESULTS: Of 2282 SCCP patients, the stage distribution was as follows: stage I 976 (43%) versus stage II 826 (36%) versus stage III 302 (13%) versus stage IV 178 (8%). At 5 years, OS of SCCP patients versus age-matched population-based controls was as follows: stage I 63% versus 80% (Δ = 17%), stage II 50% versus 80% (Δ = 30%), stage III 39% versus 84% (Δ = 45%), stage IV 26% versus 87% (Δ = 61%). At 5 years, CSM versus OCM in SCCP patients according to stage was as follows: stage I 12% versus 24%, stage II 22% versus 28%, stage III 47% versus 14%, and stage IV 60% versus 14%. CONCLUSION: SCCP patients exhibit worse OS across all stages. The difference in OS at 5 years between SCCP and age-matched male population-based controls ranged from 17% to 61%. At 5 years, CSM accounted for 12% to 60% of all deaths, across all stages.

Real world data of recurrent and survival rates of penile cancer patients in Songklanagarind hospital: Tumor stage as a predictor for disease-free survival.

OBJECTIVE: This study investigated disease-free survival and oncological outcomes in penile cancer patients treated surgically at a high-volume center and identified the prognostic factors for disease-free survival. METHODS: A retrospective analysis was conducted on primary penile cancer patients diagnosed and treated at Songklanagarind Hospital, Thailand, between January 2001 and December 2021. Disease-free survival (DFS) was assessed using Kaplan-Meier survival curves, and Cox proportional hazard models were used for multivariate analysis. RESULTS: The study included 188 patients with primary penile cancer. The majority (98.4%) were uncircumcised. Tumor staging revealed 40.6% with T1 tumors, 72.9% with well-differentiated tumors, and 23.5% diagnosed at stage IIIA. The recurrence rate was 19.1%, with a mean time to recurrence of 25.9 months. Disease-free survival rates at 1, 3, and 5 years were 81.1%, 70.9%, and 70.9%, respectively. Median overall survival was 16.43 months, with survival rates at 1, 3, and 5 years at 67.7%, 42.7%, and 35.4%, respectively. Cox proportional hazard models showed significant associations between disease-free survival and a higher T stage, a high level of CRP (>15 mg/L), delayed onset of symptoms, primary lesion location, groin node metastasis, lymphovascular invasion, and pelvic lymph node metastases. However, multivariate analysis revealed that a higher primary tumor stage (T) was the only independent prognostic factor for disease-free survival. CONCLUSION: This study presents one of the largest cohorts investigating disease-free survival outcomes in penile cancer treatment at a single institution over a prolonged period. A higher pathologic T stage is a significant prognostic factor for disease-free survival. Further large-scale prospective studies are needed for validation.

Penile carcinoma: A retrospective analysis of 93 patients at a tertiary care center in Jakarta, Indonesia.

OBJECTIVES: Penile carcinoma (PC) is a rare disease with considerable physical and psychological impact. To date, there is no data regarding PC prevalence and characteristics in Indonesia. This study aimed to analyze the characteristics of patients with PC in Indonesia and determine cumulative survival rates and time to disease progression. METHODS: This was a retrospective study of all patients diagnosed with PC at Cipto Mangunkusumo General Hospital from 1995 to 2014, with a minimum of 1 year follow-up. The outcomes of the study were cumulative survival rates and time-to-disease progression. RESULTS: Ninety-three subjects were recruited, with a mean age of 49.44 ± 13.62. Inguinal lymph node dissection (ILND) was performed in 49 (53%) patients. The mean survival in the ILND group was better compared to the non-ILND group (80.7 months vs. 67.1 months; p = 0.032). Time-to-progression in the ILND group was significantly longer than in the non-ILND group (71.7 months vs. 54.3 months; p = 0.022). No significant difference in survival between the total and partial penectomy (PP) groups was observed (p = 0.701). Time-to-progression in total penectomy (TP) was significantly longer than in PP (68 months vs. 56.0 months; p = 0.023). In Cox-regression analysis, after adjustment of other variables, history of ILND, higher stage of cancer, and older age were found to affect the survival of patients. CONCLUSION: ILND in PC led to better survival and reduced disease progression. The type of penectomy is only associated with progression but not survival. TP had a longer time to disease progression compared to PP.

Phallus preservation and reconstruction: 5-year outcomes of national penile cancer centralisation in the Republic of Ireland.

INTRODUCTION: Penile cancer is a rare urological malignancy with an age-standardised incidence of 0.8 per 100,000 person-years [1]. Given this low incidence it has been suggested that centralised care may improve patient outcomes in relation to phallus sparing surgery and nodal assessment [2]. We aim to assess the outcomes after 5-years of national centralisation of penile cancer care. METHODS: A retrospective analysis of prospectively collected data was performed. All patients undergoing penile cancer surgery from January 2018 to December 2022 following centralisation of care were included. The primary outcome was proportion of phallus sparing procedures performed. Secondary outcomes were patient characteristics, histologic outcomes and procedures performed. RESULTS: 124 patients underwent surgery in the study period. Mean age was 64.49 (±13.87). Overall, 82.3% of patients underwent phallus sparing surgery. This remained stable over the 5-year period from 2018 to 2022 â€‹at 92%, 85%, 76%, 79% and 78% respectively (p â€‹= â€‹0.534). 62.7% had reconstruction performed, including split-thickness skin graft neoglans formation, (57.8% [n â€‹= â€‹37]), preputial flap (32.8% [n â€‹= â€‹21]), glans resurfacing (4.7% [n â€‹= â€‹3]), shaft advancement flap (1.6% [n â€‹= â€‹1]), penile shaft skin graft (1.6% [n â€‹= â€‹1]), and partial penectomy with urethral centralisation (1.6% [n â€‹= â€‹1]). Phallus preservation was not affected by positive nodal status (OR 0.75 [95% CI 0.249-2.266], p â€‹= â€‹0.564) or T-stage ≥1b (OR 0.51 [95% CI 0.153-1.711], p â€‹= â€‹0.276). There has been a significant reduction in Nx nodal status from 64% in 2017 to 15% in 2021 (p â€‹= â€‹0.009). CONCLUSION: Centralisation of treatment for rare malignancies such as penile cancer may improve oncologic outcomes and rates of phallus preservation. This study has shown centralisation to has a high rate of phallus preservation. Further long-term analysis of outcomes in Ireland is required.

Fine scalpel surgery: preserving the dartos muscle in a patient with scrotal and perigenital giant Buschke-Löwenstein tumors.

Giant condyloma acuminatum (GCA), alternatively referred to as a Buschke-Löwenstein tumor (BLT), is an uncommon, benign, but locally aggressive form of verrucous carcinoma. The condition usually affects the male population under the age of 50 years; however, there have been rare reports of pediatric cases. Various risk factors such as smoking, diabetes, promiscuous behavior, poor hygiene, immunosuppression, and others are linked to the development of this condition. We present the case of a 26-year-old male patient who came to the dermatology department with primary complaints of 10-year-old verrucous tumor formations located in the perigenital and perianal areas. Serological tests for AIDS, hepatitis B, hepatitis C, Chlamydia trachomatis, and syphilis were negative. The routine blood tests were slightly abnormal. Histological verification of condylomata acuminata of Buschke-Löwenstein was made. Given the sensitive areas, surgery was advised. With several fine undermining scalpel excisions, the lesions in the scrotal and perigenital areas were removed and the dartos muscle was preserved. Electrodissection and shave curettage were not performed. The postoperative period passed without complications and no recurrences in the perigenital area were reported. We believe that our case report represents the first documented surgical approach for scrotal Buschke-Löwenstein tumor using exclusively fine undermining scalpel surgery. A brief literature review of the condition is presented, focusing on the currently available treatment options and highlighting the potential effectiveness of the surgical approach.

Preoperative Albumin-to-Alkaline Phosphatase Ratio as an Independent Predictor of Lymph Node Involvement in Penile Cancer.

Background and Objectives: To investigate the role of preoperative albumin-to-alkaline phosphatase ratio (AAPR) in predicting pathologic node-positive (pN+) disease in penile cancer (PC) patients undergoing inguinal lymph node dissection (ILND). Materials and Methods: Clinical data of patients with squamous cell carcinoma (SCC) PC + ILND at a single high-volume institution between 2016 and 2021 were collected and retrospectively analyzed. An AAPR was obtained from preoperative blood analyses performed within 30 days from their scheduled surgery. A ROC curve analysis was used to assess AAPR cutoff, in addition to the Youden Index. Logistic regression analysis was utilized for an odds ratio (OR), 95% confidence interval (CI) calculations, and an estimate of pN+ disease. A p value < 0.05 was considered to be as statistically significant. Results: Overall, 42 PC patients were included in the study, with a mean age of 63.6 ± 12.9 years. The AAPR cut-off point value was determined to be 0.53. The ROC curve analysis reported an AUC of 0.698. On multivariable logistic regression analysis lymphovascular invasion (OR = 5.38; 95% CI: 1.47-9.93, p = 0.022), clinical node-positive disease (OR = 13.68; 95% CI: 4.37-43.90, p < 0.009), and albumin-to-alkaline phosphatase ratio ≤ 0.53 (OR = 3.61; 95% CI: 1.23-12.71, p = 0.032) were predictors of pN+ involvement. Conclusions: Preoperative AAPR may be a potentially valuable prognostic marker of pN+ disease in patients who underwent surgery for PC.

Comprehensive genomic profiling of penile squamous cell carcinoma and the impact of human papillomavirus status on immune-checkpoint inhibitor-related biomarkers.

BACKGROUND: Advanced penile squamous cell carcinoma (pSCC) is a rare and aggressive malignancy with limited success of immune-checkpoint inhibitors (ICIs). Approximately half of pSCC cases are associated with human papillomavirus (HPV) infection. METHODS: Evaluation was done retrospectively of the landscape of somatic alterations and ICI-related biomarkers in pSCC by using the Caris Life Sciences data set with the aim to establish signatures for HPV-dependent oncogenesis. The pSCC tumors were analyzed by using next-generation sequencing (NGS) of DNA and RNA. Programmed death ligand 1 (PD-L1) expression was evaluated by immunohistochemistry (IHC). Microsatellite instability (MSI) was tested by fragment analysis, IHC (SP142; ≥1%), and NGS. Tumor mutational burden (TMB)-high was defined as ≥10 mutations/Mb. HPV16/18 status was determined by using whole-exome sequencing (WES) when available. Significance was adjusted for multiple comparisons (q value < .05). RESULTS: NGS of the overall cohort (N = 108) revealed TP53 (46%), CDKN2A (26%), and PIK3CA (25%) to be the most common mutations. Overall, 51% of tumors were PD-L1+, 10.7% had high TMB, and 1.1% had mismatch repair-deficient (dMMR)/MSI-high status. Twenty-nine patients had their HPV status made available by WES (HPV16/18+, n = 13; HPV16/18-, n = 16). KMT2C mutations (33% vs. 0%) and FGF3 amplifications (30.8% vs. 0%) were specific to HPV16/18+ tumors, whereas CDKN2A mutations (0% vs. 37.5%) were exclusive to HPV16/18- tumors. TMB-high was exclusively found in the HPV16/18+ group (30.8%). The two groups had comparable PD-L1 and dMMR/MSI-H status. CONCLUSIONS: In a large and comprehensive NGS-based evaluation of somatic alterations in pSCC, HPV16/18+ versus HPV16/18- pSCCs were molecularly distinct tumors. Our finding that TMB-high is exclusive to HPV16/18+ tumors requires confirmation in larger data sets. PLAIN LANGUAGE SUMMARY: Penile squamous cell carcinoma (pSCC) is a rare and aggressive malignancy in the advanced setting, with poor prognosis and little success with immune-checkpoint inhibitors (ICIs) in an unselected patient approach. Human papillomavirus (HPV) infection is a known risk factor for pSCC; its impact on genomic tumor profiling is less defined. Using next-generation sequencing, we explored the genetic landscape and ICI-related biomarkers of pSCC and HPV-driven oncogenic molecular signatures. Our results indicate that HPV-positive and HPV-negative pSCCs are molecularly distinct tumors. Increased tumor mutational burden is associated with HPV-positive tumors, and could serve as a biomarker for predicting therapeutic response to ICI-based therapies. Our results support the growing literature indicating that HPV status in pSCC can be used to guide patient stratification in ICI-based clinical trials.

Comparison of two hybrid sentinel node tracers: indocyanine green (ICG)-99mTc-nanocolloid vs. ICG-99mTc-nanoscan from a nuclear medicine and surgical perspective.

BACKGROUND: Lymph node (LN) metastasis is a relevant predictor for survival in patients with a.o. penile cancer (PeCa), malignant melanoma. The sentinel node (SN) procedure comprises targeted resection of the first tumour-draining SNs. Here, the hybrid tracer indocyanine green (ICG)-99mTc-nanocolloid has been used for several years to combine optical and nuclear detection. Recently, the resource of the nanocolloid precursor stopped production and the precursor was replaced by a different but chemically comparable colloid, nanoscan. Our aim was to study the performance of ICG-99mTc-nanoscan compared to ICG-99mTc-nanocolloid from a nuclear and surgical perspective. METHODS: Twenty-four patients with either PeCa or head-and-neck (H&N) melanoma and scheduled for a SN procedure were included. The initial group (n = 11) received ICG-99mTc-nanocolloid until no longer available; the second group (n = 13) received ICG-99mTc-nanoscan. Tracer uptake was assessed on lymphoscintigraphy and single-photon emission (SPECT). Intraoperatively, SNs were identified using gamma tracing and fluorescence imaging. Ex vivo (back-table) measurements were conducted to quantify the fluorescence emissions. Chemical analysis was performed to compare the ICG assembly on both precursors. RESULTS: The mean tracer uptake in the SNs was similar for ICG-99mTc-nanocolloid (2.2 ± 4.3%ID) and ICG-99mTc-nanoscan (1.8 ± 2.6%ID; p = 0.68). 3 SNs (interquartile range (IQR) 3-4) were detected on lymphoscintigraphy in PeCa patients receiving ICG-99mTc-nanoscan compared to 2 SNs (IQR 2-3) in PeCa patients receiving ICG-99mTc-nanocolloid (p = 0.045), no differences were observed in H&N patients. Back-table measurements of resected SNs revealed a lower total fluorescence intensity in the ICG-99mTc-nanoscan group (24*109 arbitrary units (A.U) IQR 1.6*109-14*109 in the ICG-99mTc-nanocolloid group versus 4.6*109 A.U. IQR 2.4*109-42*109 in the ICG-99mTc-nanoscan group, p = 0.0054). This was consistent with a larger degree of "stacked" ICG observed in the nanoscan formulation. No tracer-related adverse events were reported. CONCLUSIONS: Based on this retrospective analysis, we can conclude that ICG-99mTc-nanoscan has similar capacity for SN identification as ICG-99mTc-nanocolloid and can safely be implemented in SN procedures.

Outcomes of penile sarcomatoid squamous cell carcinoma from a single tertiary referral centre: a matched cohort study.

OBJECTIVE: To report the oncological survival outcomes of men with penile sarcomatoid squamous cell carcinoma (sSCC). PATIENTS AND METHODS: A retrospective analysis of men with penile sSCC diagnosed between January 2010 and January 2020 in a single centre was conducted. Disease-specific (DSS), recurrence-free (RFS) and metastasis-free (MFS) survival were evaluated. Outcomes were compared with a non-sarcomatoid penile SCC cohort matched to age, type of surgery and tumour stage. Kaplan-Meier plots were used to estimate survival outcomes. RESULTS: In all, 1286 men were diagnosed with penile SCC during the study period and of these 38 (3%) men had sSCC. The median (interquartile range) age and follow-up was 70 (57-81) years and 16 (7-44) months, respectively. Operations performed included: circumcision, one (2.6%); wide local excision, four (10.5%); glansectomy, 11 (29%); partial penectomy, 10 (26%); subtotal/total penectomy, 12 (32%). The Kaplan-Meier estimated 12-, 24- and 36-month DSS was 62% (vs non-sarcomatoid, 67%), 43% (vs non-sarcomatoid, 67%) and 36% (vs non-sarcomatoid, 67%), respectively (P = 0.03). The Kaplan-Meier estimated 12- and 24-month RFS was 47% (vs non-sarcomatoid, 60%) and 28% (vs non-sarcomatoid, 55%), respectively (P = 0.01). The MFS was 52% (vs non-sarcomatoid, 62%) at 12 months and 37% (vs non-sarcomatoid, 57%) at 24 months (P = 0.04). CONCLUSIONS: Sarcomatoid differentiation was associated with a lower DSS, RFS and MFS. Due to the rarity of its incidence and aggressiveness, expert histological review and multidisciplinary management is required in a specialist penile cancer centre.

First-line programmed death receptor-1 (PD-1) inhibitor and epidermal growth factor receptor (EGFR) blockade, combined with platinum-based chemotherapy, for stage IV penile cancer.

OBJECTIVES: To evaluate the anti-tumour activity and safety of anti-programmed death receptor-1 (PD-1) antibody plus epidermal growth factor receptor blockade combined with platinum-based chemotherapy (PEP) as first-line therapy for stage IV penile squamous cell carcinoma (PSCC). PATIENTS AND METHODS: We conducted a retrospective review of 17 patients with stage IV PSCC undergoing first-line PEP at Sun Yat-sen University Cancer Center between January 2018 and September 2021. Clinical responses were assessed using the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Adverse events (AEs) were graded according to Common Terminology Criteria for Adverse Events version 5.0. RESULTS: Of 17 patients who received first-line PEP, 13 were observed to have partial responses. Twelve patients subsequently received consolidated surgery. Nine of these achieved pN0 status, of whom six with locally advanced PSCC achieved pathological complete response. The median (range) follow-up time was 24.87 (3.63-29.40) months. Median PFS and median OS were not reached, with 2-year PFS and OS rates being 68.4% (95% confidence interval [CI] 48.7-96.1) and 62.9% (95% CI 41.6-95), respectively. Eight patients experienced Grade 3 or 4 treatment-related AEs. No Grade 5 AEs or death associated with treatment was observed. CONCLUSIONS: Anti-PD-1 antibody plus epidermal growth factor receptor blockade and platinum-based chemotherapy showed promising anti-tumour activity, acceptable toxicity, and satisfying long-term survival for stage IV PSCC. Larger clinical trials are needed to validate our findings.

Performance of indocyanine green in sentinel lymph node mapping and lymph node metastasis in penile cancer: systematic review, meta-analysis, and single-center experience.

PURPOSE: The aim of this study was to investigate the overall sensitivity and specificity of indocyanine green (ICG)-near-infrared (NIR) fluorescence imaging in the detection of sentinel lymph node metastasis (SLNM) in penile cancer. METHODS: We searched PubMed, Embase, Web of Science, Scopus, and the Cochrane Library databases to identify manuscripts where ICG was intravenously administered prior to or during penile cancer surgery, with no restriction on language or publication status. The results extracted are presented as forest plots. RESULTS: Seven studies were included in the analysis. The median sensitivity and specificity of ICG-NIR imaging for SLNM detection were 100 and 4%, respectively; the pooled sensitivity was 100.0% (95% confidence interval [CI] 97.0-100.0) and specificity was 2.0% (95% CI 1.0-3.0). There was no significant difference in the diagnostic results between different injection sites and doses in each experimental group. CONCLUSION: To our knowledge, this meta-analysis is the first to summarize the diagnostic performance of ICG-NIR imaging for SLNM detection in penile cancer. ICG is sensitive in the imaging of SLN tissue, which can consequently improve the accuracy of lymph node detection. However, the specificity is very low.