Relationship between NLR and penile squamous cell carcinoma: a systematic review and meta-analysis.

OBJECTIVE: We conducted this study to summarize the results of studies reporting the role of NLR (neutrophil to lymphocyte ratio) in PSCC (penile squamous cell carcinoma). METHODS: This meta-analysis was conducted using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria. A systematic search was conducted on PubMed, Scopus, and web of science up to March 10, 2023. Fourteen studies were included in the review. The NOS (Newcastle-Ottawa Scale) was used to determine the quality of the included studies. This meta-analysis was conducted on the studies reporting the relationship between NLR and survival using HR (hazard ratio) and 95% CI (confidence interval). RESULTS: There was a significant association between NLR levels and the prognosis, nodal stage, and anatomical tumor stage of PSCC patients. In the meta-analysis of the association of NLR with survival, NLR level was significantly associated with lower cancer-specific survival (HR = 3.51, 95% CI = 2.07-5.98, p < 0.001) and lower disease-free survival (HR = 2.88, 95% CI = 1.60-5.20, p < 0.001). However, NLR was found to have no association with the stage, grade, location, and size of the tumor. CONCLUSION: NLR has a significant diagnostic and prognostic value in PSCC.

Outcomes of Intraoperative Frozen Section Examination of Surgical Resection Margins of the Penis in Penile Cancer.

INTRODUCTION: Frozen section examination (FSE) of the tumor resection margins is important during penile-preserving surgery (PPS) in penile cancer. The margin status will impact on how much penile or urethral tissue is excised. We aim to evaluate the outcomes of intraoperative FSE of resection margins in PPS. PATIENTS AND METHODS: A retrospective analysis of patients with penile squamous cell carcinoma (SCC) who underwent a FSE of resection margins between 2010 and 2022 was conducted. FSEs were compared with the final histopathological analysis and the Diagnostic Testing Accuracy (DTA): sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated. RESULTS: Overall, 137 FSE were performed. The median (IQR) age was 65 (53-75) years. 118 (86.1%) patients had negative FSE margins, 16 (11.7%) had positive FSE margins and 3 (2.2%) had equivocal (atypical cells) results. The sensitivity, specificity, PPV, NPV and diagnostic accuracy of penile FSE were 66.7%, 100%, 100%, 93.2% and 94% respectively. 18 patients underwent further resection in the same episode due to a positive or equivocal FSE and 12 (66.7%) achieved negative margins. Limitations include the retrospective nature of the study and lack of control arm to compare with. CONCLUSIONS: Intraoperative FSE performed at our center for the assessment of penile SCC margins is 66.7% sensitive and 100% specific. FSE should be considered in PPS, as it's an essential and a reliable diagnostic tool in minimizing over-treatment.

First report of a neurofibrosarcoma in the penis of a bull.

Reproductive problems in cattle are frequent and have an important impact on production. In addition, inflammatory, traumatic and other diseases may be followed by the development of tumours, which are a cause of culling of breeding males. The main types of tumours diagnosed in the bull penis are fibropapilloma and squamous cell carcinoma. The aim of this study was to characterize a case of a tumour in the glans penis of a bull from a dairy farm in Santa Fe, Argentina. The neoplastic tissue was stained with haematoxylin and eosin and then analysed by immunohistochemistry to reveal its characteristic phenotype. Results showed positivity to vimentin, neuron specific enolase, proliferating cell nuclear antigen, S100 and glial fibrillary acidic protein. This suggested that the tumour was a neoplasm of neural origin, classified as neurofibrosarcoma, a peripheral nerve sheath tumour, here reported in the penis of a bull for the first time.

Disparities in Penile Cancer Incidence, Mortality, and Place of Death Trends From 1999 to 2020.

INTRODUCTION: Penile cancer is rare in the United States (US); however, disparities have been found in the incidence, treatment, and outcomes of penile cancer. There is a need for evaluation of recent trends in penile cancer mortality, incidence, and place of death across all demographics. MATERIALS AND METHODS: Using the CDC WONDER database, penile cancer-specific mortality (PNCSM) trends in the US were evaluated from 1999 to 2020 by race/ethnicity, age group, census region, and place of death. Penile cancer incidence trends for the US from 1995 to 2019 were gathered from the NAACCR database. Average annual percent changes for mortality and incidence rates were determined using Joinpoint regression modeling. Univariable and multivariable logistic regression were used to evaluate independent predictors associated with place of death. RESULTS: From 1999 to 2020, 5833 people died from penile cancer in the US. Overall PNCSM increased by 1.8% per year from 1999-2020 (95% CI, 1.3%, 2.2%). Non-Hispanic White patients and Hispanic patients had increasing PNCSM rates from 1999-2020 (2.1 [95% CI, 1.5%, 2.7%]; 1.9 [95% CI, 1.0%, 2.8%], respectively). From the place of death analysis, Hispanic patients were at higher odds of dying at home or hospice when compared to non-Hispanic White patients (adjusted odds ratio [aOR] = 1.19, P = .045). Age-adjusted incidence rates for all stages of penile cancer increased significantly from 1995-2016 (AAPC, 0.7% [95% CI, 0.4%, 1.0%]), driven by regional and distant penile cancer incidence rates (AAPC 1995-2019, regional: 2.0% [95% CI, 1.7%, 2.4%]; AAPC 1995-2019, distant: 2.5% [95% CI, 1.8%, 3.1%]). CONCLUSION: The increasing penile cancer-specific mortality and incidence rates indicate the need for further improvements in screening, diagnosis, and treatment. Widespread efforts across all demographics are needed to ensure early detection of the disease.

The Development and Feasibility of a Novel Electronic Patient-Reported Outcome Measures (Eproms) Questionnaire in patients with penile cancer.

BACKGROUND: Penile cancer (PeCa) is a rare cancer with surgical options that affect patients' quality-of-life. Patient-reported outcome measures (PROMs) are uncommonly utilized in this cohort despite their several patient-centered benefits and there are recommendations to further digitalize PROMs. This prospective, population-based study aimed to report the development and feasibility of a novel electronic patient-reported outcome measures (ePROMs) questionnaire for patients with PeCa. MATERIALS AND METHODS: A novel ePROMs questionnaire was developed and sent to patients 3 days before outpatient clinic appointments. The questionnaire included up to 30 items on patient symptomology and quality-of-life, including a self-reported quality-of-life score (rated 0 being worst and 100 being best). Data were collected for patients followed up between August 2021 and May 2022. The primary feasibility outcomes, adherence and engagement, were measured by response and drop-out rates. Differences in responders and nonresponders were also ascertained. Secondary outcomes explored the clinical utility of the questionnaire. Responders were subcategorized into 3 groups: circumcision (Ci), partial penectomy (PP) or total penectomy (TP) and differences were analyzed. This study was approved by the local Trust Governance Panel, including for ethical considerations. RESULTS: 220 adult males were sent ePROMs questionnaires, and 141 (64%) responded initially. The mean dropout rate of subsequent questionnaires was 56%. The maximum number of questionnaires sent to and completed by a patient was 8 (n = 1). Nonresponders were older (P < .0001), with poorer performance status (P < .0001) and lower body mass index (P = .0288). TP patients reported the lowest median quality-of-life score 68.50 (8-99), followed by the Ci group (72.0, 37-94) and the PP group (76.0, 10-99). CONCLUSIONS: Patients initially engaged and adhered to the ePROMs questionnaire but struggled to maintain this over time. Clinical data gathered by the questionnaire may be utilized to inform patient care. The questionnaire requires additional validation, research, and education.

Epidemiology of penile cancer in Poland compared to other European countries.

OBJECTIVES: To examine the epidemiology of penile cancer in Poland compared to other European countries. MATERIALS AND METHODS: Incidence and mortality data were acquired from the national cancer registries in Europe and WHO Mortality Database, respectively. The data are presented as age-standardised morbidity and mortality rates, calculated according to the standard population of the world. We utilised Joinpoint analysis to assess the trends in morbidity and mortality and calculated the average rate of increase or decrease (Annual Percentage Change, Average Annual Percentage Change). Additionally, we estimate the proxy survival rates for each country. RESULTS: Our study is the first to cover the incidence of penile cancer in many European countries and estimates an approximate survival rate for large populations, which is rarely cited in the literature. The 40+ age group presented graphically in the article covered more than 90% of penile cancer cases and deaths. In the countries examined, there was an excess of deaths over incidence in the oldest age groups (75 years or older). Poland had intermediate incidence and mortality rates. CONCLUSIONS: Unlike many European countries, Poland is witnessing an increasing trend of penile cancer mortality. The higher death toll among those aged 75 years or older may suggest a lack of recognition of cancer symptoms and inadequate attention to elderly patients by the healthcare system. There is also evidence of underreporting penile cancer cases. Establishing centralised healthcare systems for rare cancers is a commendable development that should be emulated by other European countries, including Poland.

[Factors affecting the postoperative prognosis of penile cancer].

OBJECTIVE: To investigate the risk factors affecting the prognosis of penile cancer after surgery. METHODS: We retrospectively analyzed the clinical data on 112 cases of penile cancer treated in Weifang People's Hospital from January 2013 to December 2023. Using the Kaplan-Meier survival curve, χ2 test, Fisher's exact test, and univariate and multivariate Cox risk regression analyses, we compared the clinical characteristics among different groups, and determined the independent prognostic risk factors for cancer-specific survival (CSS) of the patients. RESULTS: The 1-, 3- and 5-year CSS rates of the penile cancer patients were 78.2%, 66.1% and 63.7%, respectively. Kaplan-Meier analysis indicated a significant correlation of a higher neutrophil-to-lymphocyte ratio (NLR) with a lower CSS rate (P < 0.001). Multivariate Cox regression analysis showed high NLR (HR = 2.6; 95% CI: 1.031－6.558; P = 0.043) to be an independent risk factor for CSS. CONCLUSION: Preoperative NLR is an independent risk factor for the prognosis of penile cancer. In addition, older age, farmer or worker occupation, lower education, preoperative lymphocyte-to-monocyte ratio (LMR)≤2.81, preoperative fibrinogen (FIB)≥3.41 g/L, advanced tumor stage and tumor differentiation are associated with the poor prognosis the malignancy.

A model of tertiary lymphatic structure-related prognosis for penile squamous cell carcinoma.

BACKGROUND: We investigated the feasibility of the tertiary lymphoid structure (TLS) as a prognostic marker for penile squamous cell carcinoma(SCC). METHODS: We retrospectively collected data from 83 patients with penile squamous cell carcinoma. H&E-stained slides were reviewed for TLS density. In addition, clinical parameters were analyzed, the prognostic value of these parameters on overall survival (OS) was evaluated using ‒ Kaplan-Meier survival curves, and the prognostic value of influencing factors was evaluated using Cox multifactor design nomogram analysis. RESULT: BMI, T, N, and M are significant in the survival curve with or without tertiary lymphoid structure. BMI, T, N, M and TLS were used to construct a prognostic model for penile squamous cell carcinoma, and the prediction accuracy reached a consensus of 0.884(0.835-0.932), and the decision consensus reached 0.581(0.508-0.655). CONCLUSION: TLS may be a positive prognostic factor for penile squamous cell carcinoma, and the combination of BMI, T, N and M can better evaluate the prognosis of patients.

Complications and adverse events in lymphadenectomy of the inguinal area: worldwide expert consensus.

BACKGROUND: Inguinal lymph node dissection plays an important role in the management of melanoma, penile and vulval cancer. Inguinal lymph node dissection is associated with various intraoperative and postoperative complications with significant heterogeneity in classification and reporting. This lack of standardization challenges efforts to study and report inguinal lymph node dissection outcomes. The aim of this study was to devise a system to standardize the classification and reporting of inguinal lymph node dissection perioperative complications by creating a worldwide collaborative, the complications and adverse events in lymphadenectomy of the inguinal area (CALI) group. METHODS: A modified 3-round Delphi consensus approach surveyed a worldwide group of experts in inguinal lymph node dissection for melanoma, penile and vulval cancer. The group of experts included general surgeons, urologists and oncologists (gynaecological and surgical). The survey assessed expert agreement on inguinal lymph node dissection perioperative complications. Panel interrater agreement and consistency were assessed as the overall percentage agreement and Cronbach's α. RESULTS: Forty-seven experienced consultants were enrolled: 26 (55.3%) urologists, 11 (23.4%) surgical oncologists, 6 (12.8%) general surgeons and 4 (8.5%) gynaecology oncologists. Based on their expertise, 31 (66%), 10 (21.3%) and 22 (46.8%) of the participants treat penile cancer, vulval cancer and melanoma using inguinal lymph node dissection respectively; 89.4% (42 of 47) agreed with the definitions and inclusion as part of the inguinal lymph node dissection intraoperative complication group, while 93.6% (44 of 47) agreed that postoperative complications should be subclassified into five macrocategories. Unanimous agreement (100%, 37 of 37) was achieved with the final standardized classification system for reporting inguinal lymph node dissection complications in melanoma, vulval cancer and penile cancer. CONCLUSION: The complications and adverse events in lymphadenectomy of the inguinal area classification system has been developed as a tool to standardize the assessment and reporting of complications during inguinal lymph node dissection for the treatment of melanoma, vulval and penile cancer.

Brachytherapy and external beam radiation in the management of primary penile cancer - Game changer for organ preservation?

OBJECTIVE: In squamous cell carcinoma of the penis (PeCa), treatment options for primary tumors vary by disease stage and may include surgery, radiation, topical chemotherapy, or laser excision. This review aims to highlight the current evidence on the value of radiotherapy as an organ-preserving strategy in primary PeCa. MATERIAL AND METHODS: Manuscripts on primary PeCa treatment with external beam radiotherapy (EBRT) and brachytherapy were evaluated via Scopus, PubMed/MEDLINE, and Web of ScienceTM (2013-2023) to assess their efficacy and safety. Animal studies, studies with <5 patients, and case reports were excluded. RESULTS: Radiotherapy offers the potential for organ preservation with tumor control rates comparable to radical surgery, while disease-specific survival rates up to 70 % were experienced with EBRT. Brachytherapy (BT) is the preferred method of irradiation for glans-limited tumors, whereas a higher relapse risk is expected for tumors >4 cm. BT shows 73 % amputation-free survival at 8-10 years and 81 % progression-free survival at 5-10 years. Compared with BT, total amputation significantly improves 5-year disease-free survival rate. BT offers a superior 5-year local control and penile preservation rates compared to EBRT. Common acute toxicities of brachytherapy include radiodermatitis, sterile urethritis, and urethral adhesions. The primary late adverse events of BT are soft tissue necrosis (0-31 %) and meatal stenosis (0-43 %). CONCLUSION: BT is a favorable radiation modality, offering an efficient and conservative approach. HDR BT is favored for its enhanced dose distribution and radiation protection. Collaboration between radiation oncologists and urologists is essential in order to provide an optimal patient selection and manage toxicities thus optimizing patient outcomes.

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

BACKGROUND: To evaluate the overall survival (OS) and construct a nomogram to predict the OS of patients with penile squamous cell carcinoma (PSCC). METHODS: This 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. RESULTS: A 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. CONCLUSION: The 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.

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.

Quality of Life Evaluation after Partial Penile Amputation for Penile Cancer.

BACKGROUND: Penile cancer is most prevalent in developing countries. Both the physiological and psychological consequences for the patient are critical. These consequences result from both the cancer diagnosis and the treatment's effects. OBJECTIVE: The objective of this study was to evaluate the quality of life (QoL) of patients who have undergone partial penile amputation in terms of general well-being, sexual function, and urinary function. MATERIALS AND METHODS: This retrospective observational study included 32 patients who underwent partial penile amputation. The european organisation for research and treatment of cancer core quality of life questionnaire (EORTC QLQ C-30) questionnaire was completed postoperatively. Erectile function and satisfaction were assessed retrospectively after partial penile amputation using the International Index of Erectile Function-15. RESULTS: The mean age of the patients was 54.03 ± 16.02 years. The mean scores for erectile function, orgasm, sexual desire, satisfaction, and overall satisfaction were 16.28 ± 10.83, 7.50 ± 3.30, 5.72 ± 3.35, 8.84 ± 4.77, and 9.12 ± 0.83 preoperatively, and 14.03 ± 8.61, 6.88 ± 2.97, 5.72 ± 3.35, 7.94 ± 4.09, and 7.81 ± 1.00 postoperatively. Mean erectile function, orgasm, satisfaction, and overall satisfaction were significantly decreased postoperatively compared with preoperatively. Erectile function and overall satisfaction improved more in younger years from the preoperative to the postoperative period, whereas they improved less in older years. CONCLUSION: Although partial penile amputation for penile cancer provides adequate local disease management, appropriate counseling is crucial, especially when the QoL concerns general well-being, sexual function, and urinary function.

Résumé Contexte:Le cancer du pénis est plus répandu dans les pays en développement. Les conséquences physiologiques et psychologiques pour le patient sont cruciales. Ces conséquences résultent à la fois du diagnostic de cancer et des effets du traitement.Objectif:L'objectif de cette étude était d'évaluer la qualité de vie (QdV) des patients ayant subi une amputation partielle du pénis en termes de bien­être général, de fonction sexuelle et de fonction urinaire.Matériels et méthodes:Cette étude observationnelle rétrospective a inclus 32 patients ayant subi une amputation partielle du pénis. Le questionnaire de base sur la qualité de vie de l'organisation européenne pour la recherche et le traitement du cancer (EORTC QLQ C­30) a été complété en postopératoire. La fonction érectile et la satisfaction ont été évaluées rétrospectivement après une amputation partielle du pénis à l'aide de l'indice international de la fonction érectile­15.Résultats:L'âge moyen des patients était de 54,03 ± 16,02 ans. Les scores moyens pour la fonction érectile, l'orgasme, le désir sexuel, la satisfaction et la satisfaction globale étaient de 16,28 ± 10,83, 7,50 ± 3,30, 5,72 ± 3,35, 8,84 ± 4,77 et 9,12 ± 0,83 en préopératoire, et de 14,03 ± 8,61, 6,88 ± 2,97, 5,72. ± 3,35, 7,94 ± 4,09 et 7,81 ± 1,00 en postopératoire. La fonction érectile moyenne, l'orgasme, la satisfaction et la satisfaction globale étaient significativement diminués en postopératoire par rapport au préopératoire. La fonction érectile et la satisfaction globale se sont améliorées davantage dans les années plus jeunes, de la période préopératoire à la période postopératoire, alors qu'elles se sont moins améliorées dans les années plus âgées.Conclusion:Bien que l'amputation partielle du pénis pour le cancer du pénis permette une prise en charge locale adéquate de la maladie, un conseil approprié est crucial, en particulier lorsque la qualité de vie concerne le bien­être général, la fonction sexuelle et la fonction urinaire.