Penile Squamous Cell Carcinoma Research Articles

A Clinical Nomogram for Predicting Overall Survival in Patients With T1/T2 Penile Squamous Cell Carcinoma

BackgroundTo evaluate the overall survival (OS) and construct a nomogram to predict the OS of patients with penile squamous cell carcinoma (PSCC). MethodsThis retrospective study analyzed data of patients with PSCC from the First Affiliated Hospital of Soochow University between 2012 and 2022. R software was used to explore factors influencing OS in PSCC. Kaplan–Meier method and log-rank test were employed for OS estimation. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify these factors. A nomogram was created to identify the independent prognostic factors. The model was evaluated by concordance index, receiver operating characteristic (ROC) curves, and calibration plots. ResultsA total of 159 patients with T1/T2 PSCC were included in the analysis. Patients with T2/N2 stage, older age, larger tumor size, high preoperative systemic immune-inflammation index (SII), and poor preoperative nutrition had a higher incidence of poor OS. Age, T/N stage, tumor size and SII were identified as independent prognostic indicators. A prognostic nomogram was formulated, and its predictive accuracy for estimating OS in PSCC patients was validated through ROC curves and calibration plots. ConclusionThe nomograms, based on age, T/N stage, tumor size, and high preoperative SII, provide a valuable tool for predicting 1-, 2-, and 3-year OS in patients with T1/T2 PSCC without distant metastases.

Enhanced Prognostic Factors for Disease-Free Survival in Penile Squamous Cell Carcinoma: Insights from Songklanagarind Hospital

ObjectiveThis study aimed to investigate disease-free survival (DFS) outcomes and associated prognostic factors among surgically treated penile cancer patients at Songklanagarind Hospital, Thailand, over a 20-year period. MethodsA retrospective analysis was conducted on 208 primary penile cancer patients treated between January 2001 and December 2022. Disease-free survival was assessed using Kaplan-Meier survival curves, and Cox proportional hazard models were employed for multivariate analysis. ResultsAll of patients (100%) were squamous cell carcinoma of penis, with 38.9% having T1 tumors, 70.7% well-differentiated tumors, and 32.6% diagnosed at stage III. The recurrence rate was 16.8%, with a mean time to recurrence of 25.9 months. Disease-free survival rates at 1, 3, and 5 years were 82.1%, 72%, and 70.2%, respectively. Median overall survival was 18.2 months, with rates at 1, 3, and 5 years at 68.7%, 44.7%, and 36.4%, respectively. Significant associations were found between disease-free survival and higher T stage, clinical chronic inflammation, delayed onset of symptoms, primary lesion location, groin node metastasis, lymphovascular invasion, and pelvic lymph node metastases. However, multivariate analysis revealed that higher primary tumor stage (T) was the only independent prognostic factor for disease-free survival. ConclusionThis study provides valuable insights into disease-free survival outcomes in penile cancer treatment at a single institution over an extended period. Higher pathologic T stage emerged as the sole independent prognostic factor for disease-free survival. Further validation through large-scale prospective studies is warranted.

Response to comment on: Long-term outcomes of penile squamous cell carcinoma in men age ≤50 years old compared with men >50 years old.

Response to comment on: Long-term outcomes of penile squamous cell carcinoma in men age ≤50 years old compared with men >50 years old.

Development and validation of HPV-associated and HPV-independent penile squamous cell carcinoma prognostic nomogram.

The aim of this study was to introduce HPV-associated and HPV-independent histologic classifications to analyze prognostic factors and develop a prognostic nomogram for patients with penile squamous cell carcinoma (PSCC). Data of 1502 PSCC patients between 2010 and 2020 were accessed from the SEER database, and the patients were randomly divided into a training set and a validation set. Independent risk factors for PSCC patients prognosis were analyzed by using univariate and multivariate COX proportional hazards regression, and was used for the construction of the nomogram, and the predictive performance of the model was evaluated by C-index, calibration curve and ROC curve. Kaplan-Meier analysis was applied to explore the impact of HPV-related factors on patient survival, while propensity score matching (PSM) and inverse probability treatment weighting (IPTW) techniques were used to balance other confounding factors like individual clinical and pathological factors, and to evaluate the differences in overall survival (OS) and cause-specific survival (CSS) between subgroups. The results indicated that histologic type, Grade classification, T/M stage, surgical methods and chemotherapy were independent risk factors affecting OS and CSS in PSCC patients. In addition, age and marital status were significantly associated with OS, while lymph node metastasis was an independent prognostic factor for CSS, the validation results of the model showed that the nomogram had a superior predictive performance compared with the American Joint Committee on Cancer staging system. In addition, subgroup analyses prior to and after IPTW and PSM adjustments showed that HPV-associated group had better OS and CSS than HPV-independent group. Our study developed and validated a nomogram using a novel histologic classification and achieved satisfactory results, which can better help clinicians to predict the prognosis of penile squamous cell carcinoma patients.

Fluorescence-guided surgery using cetuximab-800CW in patients with penile carcinoma.

To investigate the feasibility of fluorescence molecular imaging (FMI), using cetuximab-800CW, as an intraoperative tool to determine surgical margins in penile squamous cell carcinoma (PSCC). A total of 11 patients with PSCC received 75 mg cetuximab followed by 15 mg cetuximab-800CW 2 days before surgery. FMI of the whole excision specimen and tissue slices was performed. Fluorescence visualisation was correlated to histopathology. Based on tumour and healthy tissue regions of interest, mean fluorescence intensity was calculated for each individual patient. Significant differences between tumour and healthy mean fluorescence intensity were found with tumour-to-background ratios of a median (IQR) of 1.51 (0.99) and a mean (SD) of 1.51 (0.32) in the excision specimen and tissue slices, respectively. One patient showed a high relative fluorescence intensity with a signal-to-background ratio of 1.79, corresponding to a tumour-positive margin on fresh frozen sectioning. In this Phase I study we showed that cetuximab-800CW seems suitable to discriminate PSCC from background tissue. The tracer was well tolerated, and no false positive spots were seen.

Robotic or open superficial inguinal lymph node dissection as staging procedures for clinically node negative high risk penile cancer

ObjectiveTo evaluate perioperative and oncologic outcomes of a cohort of clinically node negative high-risk penile cancer patients undergoing robotic assisted inguinal lymph node dissection (RAIL) compared to patients undergoing open superficial inguinal lymph node dissection (OSILND). Patients and methodsWe retrospectively reviewed the clinical characteristics and outcomes of clinically node negative high-risk penile cancer patients undergoing RAIL at MDACC from 2013-2019. We sought to compare this to a contemporary open cohort of clinically node negative patients treated from 1999 to 2019 at MDACC and Moffit Cancer Center (MCC) with an OSILND. Descriptive statistics were used to characterize the study cohorts. Comparison analysis between operative variables was performed using Fisher's exact test and Wilcoxon's rank-sum test. The Kaplan-Meier method was used to estimate survival endpoints. ResultsThere were 24 patients in the RAIL cohort, and 35 in the OSILND cohort. Among the surgical variables, operative time (348.5 minutes vs. 239.0 minutes, P < 0.01) and the duration of operative drain (37 vs. 22 days P = 0.017) were both significantly longer in the RAIL cohort. Complication incidences were similar for both cohorts (34.3% for OSILND vs. 33.3% for RAIL), with wound complications making up 33% of all complications for RAIL and 31% of complications for OSILND. No inguinal recurrences were noted in either cohort. The median follow-up was 40 months for RAIL and 33 months for OSILND. ConclusionsWe observed similar complication rates and surgical variable outcomes in our analysis apart from operative time and operative drain duration. Oncological outcomes were similar between the two cohorts. RAIL was a reliable staging and potentially therapeutic procedure among clinically node negative patients with penile squamous cell carcinoma with comparable outcomes to an OSILND cohort.

Rapid Progressivity in a 62-Year-Old Circumcised Man with Penile Cancer: A Case Report

Penile cancer is a rare malignancy globally, including in Indonesia, with notable morbidity and mortality rates. This case report discusses a 62-year-old male with a penile mass, emphasizing the diagnostic challenges and the importance of early intervention in penile cancer cases. The patient presented with a progressively growing penile mass, dysuria, and penile pain. Clinical examination revealed a palpable, reddish mass on the penile shaft with unclear borders, a urethral fistula, and enlarged inguinal lymph nodes. Laboratory results showed white blood cell count, haemoglobin, platelet count, glucose, blood urea nitrogen, and creatinine abnormalities. An open biopsy suggested verrucous carcinoma, later revised to penile squamous cell carcinoma with inguinal lymph node metastases. Penile cancer, particularly squamous cell carcinoma, primarily affects older, uncircumcised men. Verrucous carcinoma, though rare, is associated with poor hygiene and lack of circumcision. Notably, misdiagnoses may occur due to the limited scope of open biopsies. Penile cancer is preventable, and its significant risk factors are modifiable. Penile carcinoma, although uncommon, poses severe consequences for affected individuals. Early diagnosis and intervention are crucial for improved outcomes. This case highlights the challenges in diagnosis, emphasizing the need for comprehensive assessments and awareness of the modifiable risk factors associated with penile cancer.

Abstract 4403: The crosstalk between the tumor microbiome and epigenomic changes in penile squamous cell carcinoma

Abstract Penile squamous cell carcinoma (PSCC) is approximately three times more prevalent in Puerto Rico when compared to other ethnic groups in the United States. Moreover, the mortality rate for PSCC among Puerto Rican men is significantly higher when compared to the US population. Infection with human papillomavirus (HPV) has been identified as a risk factor for an average of 48% of PSCC cases in Puerto Rico. The molecular etiology of HPV+ and HPV- PSCC remains poorly understood. To date, the role of the microbiota in the pathogenesis of PSCC is unknown, as there are no studies that characterize the microbiome in association with penile cancer. Furthermore, the role of DNA methylation, which is an epigenetic alteration that can be found in cancer cells that can lead to changes in gene expression and cellular function, is also unknown. Therefore, there is an urgent need to address this knowledge gap. This study aims to analyze the DNA methylation patterns and bacterial communities in HPV-positive and HPV-negative PSCC tissues from Puerto Rican men. DNA was extracted from twenty-one fresh PSCC tissue samples from Puerto Rican patients. HPV status and genotyping were determined using the DNA ELISA kit HPV SPF10 protocol. DNA methylation assay was performed using the Infinium Methylation EPIC v2.0 BeadChip Kit to identify and compare average DNA methylation levels (%) in 7 HPV-positive and 14 HPV-negative penile cancer samples. Microbiota analyses were performed using 16S rRNA genes with the Illumina MiSeq platform. Demultiplexed data was deposited in QIITA for quality control and bioinformatic analyses and downstream analyses were done in R and Qiime2. Our results demonstrated that 45 loci methylation patterns were significantly different between HPV-positive and HPV-negative samples, with an adjusted p-value &amp;lt;0.1 (Benjamini-Hochberg method). Three loci methylation patterns were significantly affected by species diversity and richness. The abundance of Firmicutes, Proteobacteria, Bacteroidetes, Fusobacteria, and Actinobacteria was individually associated with number of affected loci (27, 19, 12, 6, and 3, respectively). We found that HPV status is associated with methylation patterns and microbiome in PSCC in Puerto Rican men. Both changes may be involved in triggering inflammatory responses and oncogenesis. Although many challenges must be overcome to dissect the specific interactions of coinfecting bacteria and methylation patterns during the penile cancer infectious process, our findings demonstrate that microbes may be involved in these cellular processes. Citation Format: Jorge Viera-Vera, Yarelis M. Roque-Reyes, Daniel Santiago-Negron, María Sánchez-Vázquez, Yakshi Ortiz Maldonado, Gabriel Borges-Vélez, Jasmine Figueroa-Díaz, Carlos A. Rivera-López, Niki M. Zacharias Millward, María J. Marcos-Martínez, Filipa Godoy-Vitorino, Antonio Puras-Baez, Julie Dutil, Josué Pérez-Santiago, Magaly Martínez-Ferrer. The crosstalk between the tumor microbiome and epigenomic changes in penile squamous cell carcinoma [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 4403.

Clinicopathology, Penile, SCC CLINICOPATHOLOGICAL CHARACTERISTICS OF PENIS SQUAMOS CELL CARCINOMA AT PROF. Dr. I G.N.G. HOSPITAL DENPASAR BALI 2016-2020

Penile cancer has an incidence range of 1% of all cancers in men. The most common type of penile cancer is squamous cell carcinoma (SCC).Objective: To determine the clinicopathological characteristics of penile squamous cell carcinoma at Prof I G.N.G.Ngoerah Hospital, Denpasar in 2016-2020 based on age, histologic subtype, histological grading, tumor size, pT stage, lymph node metastasis, and lymphovascular invasion. Methods: This study is a descriptive observational study of 78 cases of penile SCC at Prof I G.N.G.Ngoerah Hospital Denpasar for the period 2016 to 2020. The sample that were obtained from secondary data is cross-sectional (cross sectional) with total sampling technique, which uses patient medical record data at the Anatomical Pathology Installation. Prof I G.N.G.Ngoerah Hospital, Denpasar. Results: The most cases of penile SCC in this study were found in the 51-60 year age group (34.6%) with the usual type of SCC histological subtype (73,1%), grade II (61.5%), tumor size between 5 to 10 cm (35.9 %), pT2 stage (25.6%), negative lymph node metastasis (34.6%) and negative lymphovascular invasion (35.9%).

Re: Assessment of PD-L1, TROP2, and NECTIN-4 Expression in Penile Squamous Cell Carcinoma

Re: Assessment of PD-L1, TROP2, and NECTIN-4 Expression in Penile Squamous Cell Carcinoma

Transcriptomic, Proteomic, and Genomic Mutational Fraction Differences Based on HPV Status Observed in Patient-Derived Xenograft Models of Penile Squamous Cell Carcinoma.

Metastatic penile squamous cell carcinoma (PSCC) has only a 50% response rate to first-line combination chemotherapies and there are currently no targeted-therapy approaches. Therefore, we have an urgent need in advanced-PSCC treatment to find novel therapies. Approximately half of all PSCC cases are positive for high-risk human papillomavirus (HR-HPV). Our objective was to generate HPV-positive (HPV+) and HPV-negative (HPV-) patient-derived xenograft (PDX) models and to determine the biological differences between HPV+ and HPV- disease. We generated four HPV+ and three HPV- PSCC PDX animal models by directly implanting resected patient tumor tissue into immunocompromised mice. PDX tumor tissue was found to be similar to patient tumor tissue (donor tissue) by histology and short tandem repeat fingerprinting. DNA mutations were mostly preserved in PDX tissues and similar APOBEC (apolipoprotein B mRNA editing catalytic polypeptide) mutational fractions in donor tissue and PDX tissues were noted. A higher APOBEC mutational fraction was found in HPV+ versus HPV- PDX tissues (p = 0.044), and significant transcriptomic and proteomic expression differences based on HPV status included p16 (CDKN2A), RRM2, and CDC25C. These models will allow for the direct testing of targeted therapies in PSCC and determine their response in correlation to HPV status.

Clinical Outcomes and Prognostic Factors in Patients With Penile Carcinoma: A Sub-Analysis From Meet-URO 23 (I-RARE) Registry Study

IntroductionPenile squamous cell carcinoma (PSCC) is a rare tumor with an aggressive behavior. The Meet-URO 23/I-RARE registry includes rare genitourinary malignancies. We extracted patients with PSCC to conduct a retrospective study aimed at assessing clinical outcomes and prognostic factors. Patients and MethodsPrimary endpoints were overall survival and progression-free survival. Prognostic factors for OS and PFS were analyzed using univariate and multivariate analysis.From the Meet-URO 23/I-RARE database, we extracted 128 patients with diagnosis of PSCC. About 48% of patients underwent first-line of therapy. ResultsIn the overall population, median OS from diagnosis was 34.6 months. Significant differences in median OS were observed according to ECOG PS at diagnosis (57.3 months vs. 8.3 months; P < .001), and median age (≤77y 88.8 months vs. >77y 26 months; P = .013). At multivariate analysis, ECOG PS 2-4 at diagnosis (HR 3.04) and lymph node metastases (HR 2.49) were independently associated with a higher risk of death.Among patients undergoing first-line therapy (n = 61), median OS was 12.3 months, and a statistically significant difference was found according to type of response to first-line (DCR 24.4 months vs. PD 7.1 months; P < .001). Multivariate analysis showed that only age >77 years was associated with a worse OS (HR 2.16). A statistically significant difference in PFS was found according to platinum plus 5-fluorouracil versus platinum plus taxane (4.9 vs. 3.4 months; P = .036) and regimens with 2 versus 3 drugs (3.4 vs. 8.6 months; P = .019). At the multivariate analysis only regimens with platinum plus taxane were associated with worse PFS (HR 2.83). ConclusionIn our registry study, PSCC is confirmed to be an aggressive disease. Poor ECOG PS, presence of lymph node metastases, and higher age at diagnosis appear to be associated with worse survival outcomes.

Impact of pathologic features on local recurrence in penile squamous cell carcinoma after penectomy

BackgroundPenile squamous cell carcinoma (PSCC) is a rare malignancy that may be cured in cases of local disease by resection of the primary tumor. Risk factors and patterns of local recurrence (LR) have not been well described in cases requiring partial or radical penectomy. In this study, we evaluated risk factors for LR and the impact of frozen and final margin assessment. Materials and methodsWe evaluated 119 patients with PSCC who had undergone partial or radical penectomy from 2007 to 2023. Data regarding clinical and pathologic features were collected by retrospective chart review. The primary outcome of interest was LR. Determinants of LR were analyzed by Student's t, Fisher's exact, chi-square and logistic regression analysis. Predictive statistics of frozen margin status on final margin were assessed and LR rates for subsets of frozen and final margin interaction were defined. Finally, all cases of positive margins and LR were described to highlight patterns of LR and the importance of margin status in these cases. ResultsThere were 8 (6.7%) cases of local recurrence. There were no significant predictors of LR, although a trend toward increased LR risk was observed among those with a positive final margin. Positive final margins were found in 15 (13%) cases. Frozen margin analysis was utilized in 79 cases, of which 10 (13%) were positive. The sensitivity, specificity, positive predictive value, and negative predictive value of frozen margin status for final margins were 44%, 92%, 40%, and 93%, respectively. There were no LR among cases in which frozen margin was not sent. Analysis of all cases with positive margin and/or LR identified three subsets of patients: CIS or focally positive margin resulting in either no LR or LR managed with minimal local intervention, bulky disease in which survival is determined by response to subsequent therapy rather than local recurrence, and clinically significant local recurrence requiring continued surveillance and intervention despite negative margins. ConclusionsLR is rare, even in cases of larger, proximal tumors requiring partial or radical penectomy. In this study, no statistically significant risk factors for local recurrence were identified; however, analysis of frozen and final margins provided insight into the importance of margin status and patterns of local recurrence. When feasible, visibly intra-operative negative margins are an excellent predictor of low risk for LR, and, in cases of CIS or focally positive margins, further resection to achieve negative margins is unlikely to reduce the risk of clinically significant LR. Additionally, in cases of bulky disease, the goals of resection should be focused toward palliation and next line therapy.

Long-term outcomes of penile squamous cell carcinoma in men age ≤50 years old compared with men >50 years old from a single tertiary referral centre: a propensity score matched analysis.

Penile cancer (PeCa) is rare, and the oncological outcomes in younger men are unclear. We aimed to analyse and compare oncological outcomes of men age ≤50 years (y) and >50 years with PeCa. A retrospective analysis of men ≤50 y with penile squamous cell carcinoma managed at a tertiary centre was performed. A propensity score matched cohort of men >50 y was identified for comparison. Matching was according to tumour, nodal stage and the types of primary surgery. Overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS), and metastasis-free survivals (MFS) were estimated using Kaplan-Meier plots and compared using log-rank tests. Between 2005-2020, 100 men ≤50 y (median (IQR) age, 46 y (40-49)) were identified and matched with 100 men >50 y (median (IQR) age, 65 y (59-73)). 10, 24, 32, 34 men age ≤50 y were diagnosed in 2005-2007, 2008-2012, 2013-2016 and 2017-2020 respectively. Median (IQR) follow-up was 53.5 (18-96) months. OS at 2 years: ≤50 y, 86%>50 y, 80.6%; 5 years: ≤50 y, 78.1%, >50 y, 63.1%; 10 years: ≤50 y, 72.3%, >50 y, 45.6% (p = 0.01). DSS at 2 years: ≤50 y, 87.2%>50 y, 87.8%; 5 years: ≤50 y, 80.9%>50 y, 78.2%; 10 years: ≤50 y, 78%, >50 y, 70.9% (p = 0.74). RFS was 93.1% in the ≤50 y group (vs. >50 y, 96.5%) at 2 year, and 90% (vs. >50 y, 88.5%) at 5 years, p = 0.81. Within the ≤50 y group, 2 years and 5 years MFS was 93% (vs. >50 y, 96.5%), and 89.5% (vs. >50 y, 92.7%) respectively, (p = 0.40). There were no statistical significance in DFS, RFS and MFS in men age ≤50 y and >50 y. PeCa in younger patients is fatal, public awareness and patient education are crucial for early detection and management.

Spontaneous Penile Amputation in a HIV Patient: Case Presentation

Penile tumor is the rarest urogenital tumor in males (1%). Around 95% of penile tumors are squamous cell carcinomas. We report a case of penile squamous cell carcinoma in a 69-year-old male who presented spontaneous penile amputation with a necrotic stump. The patient was tested positive for HIV1. He benefitted from a total penectomy with a supra-pubic cystostomy (SPC) and antiretroviral therapy. The suprapubic catheter is changed monthly while awaiting perineal urethrostomy.

Penile cancer care in the Netherlands: increased incidence, centralisation, and improved survival.

To evaluate penile squamous cell carcinoma (PSCC) incidence and centralisation trends in the Netherlands over the past three decades, as well as the effect of centralisation of PSCC care on survival. In the Netherlands PSCC care is largely centralised in one national centre of expertise (Netherlands Cancer Institute [NCI], Amsterdam). For this study, the Netherlands Cancer Registry, an independent nationwide cancer registry, provided per-patient data on age, clinical and pathological tumour staging, follow-up, and vital status. Patients with treatment at the NCI were identified and compared to patients who were treated at all other centres. The age-standardised incidence rate was calculated with the European Standard Population. The probability of death due to PSCC was estimated using the relative survival. Multivariable Cox regression analysis was performed to evaluate predictors of survival. A total of 3160 patients were diagnosed with PSCC between 1990 and 2020, showing a rising incidence (P < 0.001). Annual caseload increased at the NCI (1% in 1990, 65% in 2020) and decreased at other (regional) centres (99% to 35%). Despite a relatively high percentage of patients with T2-4 (64%) and N+ (33%) at the NCI, the 5-year relative survival was higher (86%, 95% confidence interval [CI] 82-91%) compared to regional centres (76%, 95% CI 73-80%, P < 0.001). Patients with a pathological T2 tumour were treated with glans-sparing treatment more often at the reference centre than at the regional centres (16% vs 5.0%, P < 0.001). After adjusting for age, histological grading, T-stage, presence of lymph node involvement and year of diagnosis, treatment at regional centres remained a predictor for worse survival (hazard ratio 1.22, 95% CI 1.05-1.39; P = 0.006). The incidence of PSCC in the Netherlands has been gradually increasing over the past three decades, with a noticeable trend towards centralisation of PSCC care and improved relative survival rate.

Neoadjuvant Platinum-Based chemotherapy and lymphadenectomy for penile cancer: an international, Multi-Institutional, Real-World study.

This study investigated the efficacy and safety of neoadjuvant chemotherapy (NAC) for locally advance penile squamous cell carcinoma (PSCC), for which current evidence is lacking. Included patients had locally advanced PSCC with clinical lymph node metastasis treated with at least one dose of NAC prior to planned consolidative lymphadenectomy. Objective response rates (ORR) were assessed using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. The primary and secondary outcomes were overall survival and progression-free survival, estimated by the Kaplan-Meier method. Treatment-related adverse events (trAEs) were graded per the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. 209 patients received NAC for locally advanced and clinically node-positive PSCC.The study population consisted of 7% of patients with stage II disease, 48% with stage III, and 45% with stage IV. Grade 2 TrAEs occurred in 35 (17%) patients, and no treatment related mortality was observed. 201 (97%) completed planned consolidative lymphadenectomy. During follow up, 106 (52.7%) patients expired, with a median OS of 37.0 months (95% CI 23.8-50.1), and median PFS of 26.0 months (95% CI 11.7-40.2). ORR was 57.2%, with 87 (43.2%) having partial response and 28 (13.9%) having a complete response. Patients with objective response to NAC had a longer median OS (73.0 vs 17.0 months, p < .01) compared to those who did not. The lymph-node pathologic complete response rate (ypN0) was 24.8% in the cohort. NAC with lymphadenectomy for locally advanced PSCC is well tolerated and active to reduce the disease burden and improve long term survival outcomes.

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

BackgroundPenile 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 presentationWe 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.ConclusionsThis 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.

Trop-2: A promising new therapeutic target in penile squamous cell carcinoma.

12 Background: Penile squamous cell carcinoma (PSCC) is an infrequent yet progressively prevalent malignancy. Despite ongoing advancements in personalized and immunotherapeutic approaches, patients grappling with the diagnosis of locally advanced or metastasized PSCC still confront a limited therapeutic arsenal, leading to an unfavorable prognosis. Consequently, an imperative mandate arises to explore alternative therapeutic modalities, particularly antibody-drug-conjugates (ADCs), which have demonstrated significant clinical efficacy in the context of metastatic solid tumor pathologies. Our aim was to ascertain the potential utility of ADCs targeting Trop-2 in both localized PSCC (PRIM) and patient-matched distant metastases (MET). Methods: Immunohistochemical analysis of Trop-2 expression was conducted in PRIM ( N=40) and their corresponding METs ( N=9, including lymph node and lung metastases). We assessed overall survival (OS) by stratifying patients into subgroups based on Trop-2 expression: weak (H-score 15-99) versus moderate/strong (H-score 100-300). Additionally, we explored the relationship between Trop-2 and HPV-dependency. Furthermore, Trop-2 mRNA expression levels were quantified via qRT-PCR, and an enzyme-linked immunosorbent assay was employed to measure Trop-2 in serum samples derived from PRIM ( N=40) and a healthy control group ( N=10). Results: We found a statistically significant increase in Trop-2 mRNA expression levels in individuals afflicted with PSCC compared to healthy controls ( p&lt;0.0001). Moreover, a notable elevation in Trop-2 protein expression was observed in the serum specimens obtained from PSCC patients ( p&lt;0.01). The majority of patients exhibited moderate to strong Trop-2 expression, indicative of a robust median H-score of 280 (interquartile range: 210-300). Subgroup analysis revealed a correlation between Trop-2 expression and HPV status ( p&lt;0.01), demonstrating discernible associations with more favorable clinical outcomes, as evidenced by the log-rank (Mantel-Cox) test ( p&lt;0.05). Conclusions: Trop-2 protein expression in PSCC holds prognostic significance. Furthermore, the elevated Trop-2 levels in both PRIM and PSCC metastases suggest that the Trop-2-targeted ADC, Sacituzumab govitecan, may emerge as a promising novel therapeutic intervention for these patients.

A phase 2 study of the combination dostarlimab with niraparib in patients with penile carcinoma that has progressed following chemotherapy.

TPS13 Background: Penile squamous cell carcinoma (PSCC) is a rare and deadly cancer, with limited therapy options in patients with disease progressive on platinum chemotherapy. Patients are encouraged to enroll in clinical trials since the overall survival is less than 5 months with standard therapy. Development of efficacious treatment options for patients with chemotherapy refractory PSCC, remains an unmet need. Preclinical work suggests synergic activity between PARP inhibitors and immune checkpoint inhibitors in PSCC animal models. The niraparib plus dostarlimab combination may generate a robust antitumor immune response in cisplatin refractory patients with PSCC. Methods: This is an open-label, multi-center, Simon 2 stage design, phase 2 study to evaluate the efficacy and safety of the combination of niraparib and dostarlimab in patients with advanced relapsed/refractory PSCC. Patients must provide a sufficient tumor tissue sample for molecular and immune testing at screening. Blood samples will be collected at C1D1 for exploratory molecular testing, at C3D1 and at the time of investigator-assessed partial response (PR) or complete response (CR), and at the end of treatment visit. Niraparib at 200 mg daily will be administered orally once daily on days 1 to 21 and dostarlimab intravenously once every three weeks for cycles 1 to 4 and once every 6 weeks thereafter. Niraparib will be administered at 200 mg, oral, once daily, from days 1 through 21 until progression of disease or toxicity. Eligible patients must have histologically confirmed stage III (unresectable) or stage IV penile cancer according to the American Joint Committee on Cancer (AJCC) staging system, have had progression of disease or poor tolerance to one line of platinum therapy, have a life expectancy of more than 12 weeks, have an ECOG PS of 0 or 1 (ECOG PS 2 can be included after discussion with PI), measurable disease per Immune-Modified Response Evaluation Criteria in Solid Tumors iRECIST, adequate organ function, and must not have received any prior immuno-oncology regimens, cancer vaccines, adoptive cell therapies, or other cytokine therapies. The primary efficacy endpoint is Investigator-assessed confirmed overall response rate (ORR). Tumor response will be evaluated using iRECIST. Patients who receive at least 1 complete dose of either study drug will be considered evaluable for response. The secondary endpoints are to estimate the progression free survival (PFS) overall survival measured duration of Response (DOR) and to evaluate the safety and tolerability of the niraparib and dostarlimab combination in patients with PSCC. Six patients of the 25-patient target enrollment have been enrolled. Clinical trial information: NCT05526989 .