SPP1 is associated with adverse prognosis and predicts immunotherapy efficacy in penile cancer.

BACKGROUND: The effect of SPP1 in squamous cell carcinoma of the penis (PSCC) remained unknown. We attempted to clarify the function of the SPP1 gene in PSCC. METHOD: Eight paired penile cancer specimens (including penile cancer tissue, paracancerous tissue, and positive lymph node tissue) subjected to whole transcriptome sequencing were analysed to identify differentially expressed genes. We used immunohistochemistry to detect the expression of SPP1 protein and immune cell related proteins in penile cancer tissue. Then, we performed weighted gene coexpression network analysis (WGCNA) to identify the genes related to SPP1 in penile cancer tissue and positive lymph node tissue. Based on the GSE57955 dataset, the CIBERSORT and ssGSEA algorithms were carried out to investigate the immune environment of PSCC. GSVA analysis was conducted to identify the signaling pathways related to SPP1 subgroups. Enzyme-linked immunosorbent assay (ELISA) method was adopted to detect SPP1 level in the serum of 60 patients with penile cancer. RESULTS: Differential analysis indicated that SPP1 was the most differentially upregulated gene in both penile cancer tissues and positive lymph node tissues. Survival analysis suggested that the prognosis of the low-SPP1 group was significantly poorer than that of the high-SPP1 group. Subsequently, immune-related bioinformatics showed that SPP1 was significantly associated with B cells, CD8 + T cells, CD4 + T cells, macrophages, helper T cells, neutrophils and dendritic cells. The immunohistochemical results showed that the high-SPP1 group was characterized by relatively high expression of CD16 and relatively low expression of CD4. GSVA analysis indicated that high-SPP1 group was significantly associated with immune-related pathways such as PD-L1 expression and the PD-1 checkpoint pathway in cancer and the TNF signaling pathway. ELISA demonstrated that the serum level of SPP1 in patients with positive lymph node metastasis of penile cancer was significantly higher than that in patients with negative lymph node metastasis of penile cancer. CONCLUSION: Our study shows that the SPP1 gene might be an effective biomarker for predicting the prognosis and the efficacy of immunotherapy in PSCC patients.

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

OBJECTIVE: 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. PATIENTS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

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.

2022 European guideline for the management of balanoposthitis.

BACKGROUND: This guideline is an update to the 2014 edition of the European guideline for the management of balanoposthitis. Balanoposthitis describes inflammation of the glans penis and prepuce and is caused by a range of disparate conditions including infection, dermatoses and premalignancy. OBJECTIVE: The main objectives of this guideline are to aid recognition of the symptoms and signs and complications of penile skin conditions and to offer recommendations on the diagnostic tests and treatment for a selected group of these conditions. METHODS: The previous guideline was updated following a literature review and priority was given to randomized controlled trial and systematic review evidence. RESULTS: The updated guideline includes amended management for infective balanitis to provide clear guidance for Group A streptococcal infections, management of on going Lichen sclerosus (to include circumcision and supportive management to reduce the recurrence of genital herpes and warts), additional regimens for Zoonoid change, use of calcineurin inhibitors in management and risk of premalignancy and change of nomenclaturefrom Premalignant conditions to Penile Intraepithelial neoplasia (PeIN). CONCLUSION: Balanoposthitis has a widerange of causes high quality evidence specific to the management of penile disease is not available for all the conditions described.

Centralizing Penile Cancer Care in Germany and Austria: Just a Dream or a Fast-Approaching Reality? Results of a Survey Study among Urological Department Chairs and Modeling of Real Treatment Numbers of Penile Cancer Patients.

INTRODUCTION: In countries characterized by a centralization of therapy management, patients with penile cancer (PeCa) have shown improvements in guideline adherence and ultimately, improved carcinoma-specific survival. Germany and Austria (G + A) have no state-regulated centralization of PeCa management, and the perspectives of urological university department chairs (UUDCs) in these countries, who act as drivers of professional and political developments, on this topic are currently unknown. METHODS: Surveys containing 36 response options, including specific questions regarding perspectives on PeCa centralization, were sent to the 48 UUDC in G + A in January 2023. In addition to analyzing the responses, closely following the CROSS checklist, a modeling of the real healthcare situation of in-house PeCa patients in G + A was conducted. RESULTS: The response rate was 75% (36/48). 94% and 89% of the UUDCs considered PeCa centralization meaningful and feasible in the medium term, respectively. Among the UUDCs, 72% estimated centralization within university hospitals as appropriate, while 28% favored a geographically oriented approach. Additionally, 97% of the UUDCs emphasized the importance of bridging the gap until implementation of centralization by establishing PeCa second-opinion portals. No country-specific differences were observed. The median number of in-house PeCa cases at the university hospitals in G + A was 13 (interquartile range: 9-26). A significant positive correlation was observed between the annual number of in-house PeCa cases at a given university hospital and the perspective of the UUDCs that centralization as meaningful by its UUDC (0.024). Under assumptions permissible for modeling, the average number of in-house PeCa cases in academic hospitals in G + A was approximately 30 times higher than in nonacademic hospitals. CONCLUSION: This study provides the first data on the perspectives of UUDCs in G + A concerning centralization of PeCa therapy management. Even without state-regulated centralization in G + A, there is currently a clear focusing of PeCa treatments in university hospitals. Further necessary steps toward a structured PeCa centralization are discussed in this manuscript.

[Clinical characteristics and prognostic factors of distant metastatic penile cancer].

OBJECTIVE: To investigate the clinical features of distant metastatic penile cancer (DMPC) and the factors influencing its prognosis. METHODS: We searched the Surveillance, Epidemiology and End Results Database for cases of DMPC diagnosed between 2004 and 2019, analyzed their clinical characteristics and the cancer-specific survival (CSS) rates relating to different factors using the Kaplan-Meier method and the differences among the variables by log-rank test. We determined the variables independently associated with CSS by Cox regression analysis. RESULTS: According to the inclusion criteria, 108 cases of DMPC were identified. The patients were mainly married White people, with a median CSS of 9 months, and 1-, 2- and 3-year CSS rates of 36.4%, 17.8% and 13.5%, respectively. Pairwise comparison showed no statistically significant differences in the median overall CSS among the patients in the surgery, chemotherapy and surgery + chemotherapy groups (8 mo vs 9 mo vs 13 mo, P > 0.05). Race was an independent factor affecting the prognosis of CSS. CONCLUSION: Distant metastatic penile cancer is a rare malignancy with poor prognosis, for which there have been no existing ideal treatment options.

Pathological characterization and clinical outcome of penile intraepithelial neoplasia variants: a North American series.

Penile intraepithelial neoplasia (PeIN) is classified as human papillomavirus (HPV)- and non-HPV-related. This classification is associated with distinct morphologic subtypes. The natural history and prognosis of PeIN subtypes are not well known. This study aims to evaluate clinicopathological features, HPV status, and outcome of PeIN subtypes. Eighty-two lesions from 64 patients with isolated PeIN were retrospectively reviewed. Mean age was 59 years. Lesions were multicentric in 34% of patients and affected glans (33%), shaft (26%), and foreskin (20%). Histologically, 22% of patients had coexisting lesions, classified as hybrid and mixed. HPV-related PeIN (97%) included basaloid (59%), warty (8%), warty-basaloid (8%), hybrid (19%) and mixed (3%) types. P16 and HPV positivity occurred in 99% and 82% of lesions, respectively. HPV 16 was more common in basaloid PeIN. Multiple genotypes were detected in 35%, more commonly in hybrid PeIN (P = 0.051). Positive margins occurred in 63% of excisions. PeIN recurred in 48% of excisions and 30% of overall repeated procedures, and progression to invasive carcinoma occurred in 2%. At follow-up, 86% of patients had no evidence of disease and 12% were alive with disease. Lichen sclerosus occurred in non-HPV and HPV-related PeIN (100% and 47%).In conclusion, HPV-related and, more specifically basaloid PeIN were the predominant types and preferentially associated with HPV 16. While PeIN had a high recurrence rate, there was a slow and infrequent progression to invasive or metastatic carcinoma with multimodal treatments. Additional studies are needed to understand biology and natural history of PeIN.

Incidence of penile intraepithelial neoplasia and treatment strategies in Sweden 2000-2019.

OBJECTIVES: To analyse the incidence, treatment strategies and complications associated with penile intraepithelial neoplasia (PeIN) in Sweden over a period of 20 years. MATERIALS AND METHODS: Data on PeIN from the Swedish National Penile Cancer Register were analysed regarding treatment in relation to age, size of the PeIN lesion, localization of the PeIN lesion and complications using chi-squared tests and logistic regression. The incidence of PeIN was calculated and age-standardized according to the European Standard population. RESULTS: Between 2000 and 2019 a total of 1113 PeIN cases were reported. The age-standardized incidence of PeIN was 1.40 per 100 000 men (95% confidence interval [CI] 1.32-1.49). An increase in incidence over time was seen, with a standardized incidence rate of 2.37 (95% CI 1.56-3.70) in 2019 compared to the baseline year, 2000. Surgical or topical treatments were given in 75.0% and 14.6% of cases, respectively. The complication rate was higher in laser surgery (12.1%, 7/58) compared to local surgery (4.6%, 16/348; P = 0.03) with an age-adjusted odds ratio (OR) of 2.82 (95% CI 1.10-7.19; P = 0.03). Local surgery was more common than laser surgery in the last 5 years compared to the first 5 years of the study period: OR 5.75 (95% CI 2.94-11.27). Treatments with imiquimod and topical 5-fluorouracil (5-FU) were more common than destructive methods such as photodynamic therapy, cryotherapy, curettage and electrocautery in the last 5 years compared to the first 5 years: OR 9.48 (95% CI 2.29-39.24). CONCLUSIONS: A twofold increase in the age-standardized incidence of PeIN was seen in Sweden over 20 years. Complications were three times more common in laser surgery compared to local surgery. Changes in treatment showed an increase of treatment strategies such as local surgery and treatment with imiquimod and topical 5-FU over time.

The Clinical Complexity of Penile Cancer: Current Clinical-Epidemiological Data from the Database of the Free State of Saxony/Germany.

OBJECTIVES: The aim of this study was to assess penile cancer incidence, clinical characteristics, treatment options, transparency of clinical quality, and relative survival based on data from the clinical cancer registry. SUBJECTS AND METHODS: A total of 898 patients with tumours of the penis were diagnosed and analysed in the period from 2000 to 2018; they were documented in the 4 regional clinical cancer registries and summarized in the Command Office of these 4 registries. RESULTS: The standardized incidence rate increased from 0.86 in 2000 to 2.67 in 2018. Most tumours were located at the glans (42.9%) followed by the prepuce (19.5%) and corpus penis (6.9%); they were classified into pT1a/pT1b (20.0%/7.0%), pT2 (23.5%), pT3 (12.4%), and pT4 (0.8%). In only 32.0% of all documented cases, a stage-related lymphadenectomy (LND) was carried out. Negative surgical margins were found in only 70% and the Rx status in 15.1%. Primary metastasis was detected in pN1 (5.1%), pN2 (3.9%), pN3 (3.1%), and M1 status in 3.0%, respectively. The predominant therapy was surgery in 78.3%. The proportion of penile partial resections was significantly (p = 0.0045) regredient over the control period. Adjuvant chemotherapy was performed in 4.7%, adjuvant external-beam radiotherapy in 3.0%. The 5-year relative overall survival rate was 74.7% and ranged from 108.0% (stage 0) to 17.1% (stage IV). A total of 29 hospitals performed tumour operations. CONCLUSIONS: The multitude of clinical and epidemiological variables available in clinical cancer registries allows a safe assessment of tumour dynamics themselves, as well as good quality of transparency and broadly acceptable guideline adherence. Deviations from the accepted level of evidence were found in the grading definition, in the high quota of positive surgical margins, in the defensive indication position to the glans resurfacing/reconstruction and diagnostical LND. Based on these relevant findings in the database combined with the low frequency of the tumour in area/clinics/year, we recommended establishing SCCP reference clinics. This work is the first time that European standardized rate-based cancer registry data on penile cancer from Germany has been communicated.

Summary of the Clinical Practice Guidelines for Penile Cancer 2021 by the Japanese Urological Association.

Penile cancer is a rare cancer for which no medical guidelines have been established before in Japan. These guidelines aim to standardize, as much as possible, the therapeutic modality for penile cancer, for which empirical evidence is limited on a global scale, thereby bolstering therapeutic outcomes for patients with penile cancer. The new guidelines conform to the Minds Guide for Developing Clinical Practice Guidelines (2017) as much as possible. However, virtually no randomized comparative studies and meta-analyses based on such randomized studies have been conducted. Therefore, only the findings available at present were listed after conducting an exhaustive literature review of items with extremely low evidence levels and for which bodies of evidence and grades of recommendation were not evaluated. Clinical questions were set for items with a relatively large number of studies, including retrospective studies. However, since it is virtually impracticable to summarize bodies of evidence by systematic reviews, recommendation grades and evidence levels were discussed and determined by the consensus panel of the Preparatory Committee. The following were outlined: epidemiological, pathological, diagnostic, therapeutic, follow-up, and quality of life-related findings. Additionally, seven clinical questions were established to determine recommendation grades and evidence levels. We hope that these guidelines will prove to be useful to medical professionals engaged in clinical practice related to penile cancer in Japan and anticipate that critical reviews of the guidelines will lead to further refinement of the next edition.

Penile cancer in Ireland - A national review.

OBJECTIVE: Penile cancer is a rare malignancy, with a reported incidence of 1.5/100,000 males in the Republic of Ireland in 2015. The aim of this study was to perform the first national review and to evaluate clinicopathological factors affecting survival. SUBJECTS AND METHODS: All cases of penile cancer in Ireland between 1995 and 2010 were identified through the National Cancer Registry Ireland (NCRI) and analysed to identify factors affecting survival. RESULTS: 360 cases of penile cancer were identified, with a mean age at diagnosis of 65.5 years and 88% (n = 315) of cases occurred in those over 50. 91% (n = 328) of cases were squamous cell carcinomas (SCC). The majority of patients were treated surgically (n = 289), with 57% (n = 206) and 24% (n = 87) undergoing partial penectomy and total penectomy respectively. Only 18% (n = 65) received radiotherapy, and 8% (n = 27) received chemotherapy. Mean overall survival (OS) was 113 months, and five year disease specific survival (DSS) was 70% (95%CI: 59.1-77.8%). Age at diagnosis, nodal status and presence of metastatic disease were independent prognostic markers on multivariate analysis. CONCLUSION: This study represents the first national review of penile cancer in Ireland. The annual incidence and survival rates are comparable to European figures, though superior DSS has previously been reported from our institution, highlighting the role for centralisation of care in Ireland. LEVEL OF EVIDENCE: 2b.

French AFU Cancer Committee Guidelines - Update 2022-2024: penile cancer.

OBJECTIVE: To update French oncology guidelines concerning penile cancer. METHODS: Comprehensive Medline search between 2020 and 2022 upon diagnosis, treatment and follow-up of testicular germ cell cancer to update previous guidelines. Level of evidence was evaluated according to AGREE-II. RESULTS: Epidermoid carcinoma is the most common penile cancer histology. Physical examination is mandatory to define local and inguinal nodal cancer stage. MRI with artificial erection can help to assess deep infiltration in cases of organsparing intention. Node negative patients (defined by palpation and imaging) will present micro nodal metastases in up to 25% of cases. Invasive lymph node assessment is thus advocated except for low risk patients. Sentinel node dynamic biopsy is the first line technique. Modified bilateral inguinal lymphadenectomy is an option with higher morbidity. 18-FDG-PET is recommended in patients with palpable nodes. Chest, abdominal and pelvis computerized tomography is an option. Fine needle aspiration (when positive) is an easy way to assess inguinal palpable node pathological involvement. Its results determine the type of lymphadenectomy to be performed (for diagnostic or curative purposes). Treatment is mostly surgical. Free margins status is essential, but it also has to be organ-sparing when possible. Brachytherapy and topic agents can cure in selected cases. Lymph node assessment should be synchronous to the removal of the tumour when possible. Limited inguinal lymph node involvement (pN1 stage) can be cured with the only lymphadenectomy. In case of larger lymph node stage, one should consider multidisciplinary treatment including chemotherapy and inclusion in a trial. CONCLUSIONS: Penile cancer needs demanding surgery to be cured, surrounded by chemotherapy in node positive patients. Lymph nodes involvement is a major prognostic factor. Thus, inguinal node assessment cannot be neglected.

Penile cancer: potential target for immunotherapy?

PURPOSE: Penile cancer (PeCa) is a rare malignancy with a poor prognosis in advanced disease. There is still a limited understanding of the biological mediators that are important in the prognosis and therapy of the disease. This review aims to provide a summary of the immune micro-environment, molecular oncogenesis and the role of HPV in the disease applying to the potential of the use of immunotherapy. METHODS: Narrative, non-systematic review based on publications retrieved by PubMed and EMBASE search. RESULTS: The molecular mechanisms underlying penile carcinogenesis are complex, and human papillomavirus (HPV) infection is a well-characterized driver of penile cancer. Up to 50% of the penile carcinomas are HPV related. There is potential to improve prevention, treatment and follow-up strategies pertaining to the role of HPV in penile cancer. Immune response modifiers such as toll-like receptor agonists are being used in a topical fashion for penile intraepithelial neoplasia while immune checkpoint inhibitors are currently under clinical investigation for its application in penile cancer. CONCLUSIONS: The knowledge of prognosis-relevant biological pathways in penile cancer is expanding. HPV plays an important role in the carcinogenesis. This can lead to the identification of therapeutic targets which could significantly influence the prognosis of advanced penile cancer. Clinical trials are being conducted to pave the way for immune-modifying treatment modalities.

Radiotherapy plus chemotherapy versus chemotherapy alone in penile cancer patients with extracapsular nodal extension after inguinal lymph node surgery: a multi-institutional study.

PURPOSE: Because there is a lack of evidence, it is not generally recommended to use adjuvant radiotherapy plus chemotherapy to treat lymph node disease in penile cancer. The aim of this study was to determine the benefit of using adjuvant radiotherapy after inguinal surgery for penile cancer. METHODS: Multi-institutional data were obtained from a total of nine centers from April 2003 to April 2015 and retrospectively analyzed. pN3 patients with an extracapsular nodal extension who received adjuvant therapy after inguinal surgery were included. Cancer-specific survival (CSS) was estimated using the Kaplan-Meier method. The multivariate analysis was performed using a Cox proportional hazards model. RESULTS: A total of 93 pN3 patients met the inclusion criteria. During the study period, 32 (34.4%) and 61 (65.6%) of these patients received adjuvant radiotherapy plus chemotherapy (AR + AC) or adjuvant chemotherapy alone (AC). The median CSS in all patients was 12.0 months (interquartile range [IQR] 7.5-16.5). The Kaplan-Meier estimated 3-year CSS rate was significantly longer in the AR + AC group (28.5%) than the AC group (16.2%) (p = 0.036). AC + AR was associated with an improvement in CSS by 7.7 months (17.7 [IQR 3.8-31.6] vs. 10.0 [IQR 6.6-13.4] months). In the Cox regression analysis, AR + AC was an independent predictor of CSS [model a: HR 0.486 (95% CI 0.258-0.916), model b: HR 0.527 (95% CI 0.286-0.972)]. CONCLUSION: In conclusions, AR + AC was associated with improved CCS in patients with penile cancer who displayed an extracapsular nodal extension after inguinal surgery. This hypothesis requires further confirmation.

Log ODDS (LODDS) of positive lymph nodes as a predictor of overall survival in squamous cell carcinoma of the penis.

OBJECTIVE: To evaluate the role of logarithmic ODDS (LODDS) in the number of positive lymph nodes and the number of negative lymph nodes as a prognostic metric in the squamous cell carcinoma (SCC) penis. METHODS: Data were retrospectively collected from 96 cases of SCC penis that underwent bilateral groin dissection between 2010 and 2015 at our institute. Lymph node density (LND) and LODDS were calculated for all the patients and classified according to American Joint Committee on Cancer (AJCC) pN staging. Thresholds for LND (24% and 46%) and LODDS (-0.75 and 0) were established. Multivariate analysis of various cofactors was done with overall survival (OS) as a dependent factor. Three classification systems were compared using receiver operative characteristic (ROC) curve analysis. RESULTS: Univariate analysis showed that AJCC pN, LND, and LODDS were all significantly correlated with OS. However, only LODDS (HR, 11.185; p = .023) remained an independent prognostic factor through multivariate analysis. LODDS (log-likelihood = 3832 vs. 3798; p < .001) had better prognostic performance than pN and better discriminatory ability than LND (AIC = 3902 vs. 3928). LODDS had better power of discrimination than LND and pN. LODDS could predict survival in lymph node yield (LNY) < 15 (p < .001). CONCLUSION: LODDS is an independent predictor of OS in the SCC penis and has superior prognostic significance than the AJCC pN and LND classification systems.

Advanced Penile Cancer Presenting With Renal Failure.

"MK," a man aged 67 years, presented with fatigue and nausea to his primary care physician. Routine blood tests showed a stage III acute kidney injury and the patient was admitted urgently into the hospital for investigation. On initial assessment by the nursing staff, with urine dip and bladder scan, he was found to have a large fungating mass on his penis. Upon further questioning, MK reported having had trouble with urination for a number of years and that he had been concealing the mass for at least 1 year due to embarrassment. He required a suprapubic catheter as the mass had completely obstructed his urethra. Clinical examination revealed that the external component on the penile shaft was entirely destroyed by the tumor, with extension deep into the entirety of the scrotum, and perineal soft-tissue invasion was also apparent. CT staging scans confirmed the primary tumor and a suspicious left 1.2-cm inguinal lymph node but no distant metastases. MRI of the pelvis revealed complete replacement of the penis with tumor as well as invasion into the scrotum and bilateral groin soft tissue; additionally, early pubic bone invasion was present, with left groin lymphadenopathy. Biopsy verified squamous cell carcinoma of the penis, and discussion with the multidisciplinary team uroradiologist confirmed bony invasion.

Optimal treatment for penile verrucous carcinoma: a systematic literature review.

BACKGROUND: Verrucous carcinoma, a rare low-grade well-differentiated squamous cell carcinoma, is known for its favorable biological behavior and lack of metastatic potential. However, aggressive resection is problematic in terms of compromised function and aesthetics. Hence, more conservative treatments are needed. METHODS: To identify the up-to-date general biological behavior, diagnosis, and treatment trends, we searched PubMed using the keyword "penile verrucous carcinoma" without restrictions on publication date. RESULTS: Current treatments for penile verrucous carcinoma include wide surgical excision, seldom preventive lymphadenectomy, and conservative chemotherapy without surgery or local excision with safe margins. Despite the advent of partial penectomy to minimally impact function and aesthetics, affected patients experience psychosexual problems. Local excision can be used to save the penile shaft and glans penis without preventive lymphadenectomy or adjuvant therapy and can achieve good clinical prognosis with rare recurrence. CONCLUSIONS: To preserve the functional and cosmetic aspects, we recommend local excision, especially for tumors measuring < 3 cm and classified as stage T1 according to the 2016 tumor node metastasis clinical and pathological classification for penile cancer.

Penile Cancer: Managing Sexual Dysfunction and Improving Quality of Life After Therapy.

PURPOSE OF REVIEW: To review the most current literature on how the treatment for penile cancer can affect quality of life and to discuss current treatment options to overcome sexual dysfunction and ultimately improve patient wellbeing. RECENT FINDINGS: Multiple medical and surgical therapies exist to address the high incidence of sexual dysfunction following penile cancer treatment. Advancements and refinements in the neophalloplasty, penile prosthesis, and penile lengthening procedures have opened the door to improved long-term outcomes. Additionally, studies continue to highlight the severe psychological toll that penile cancer treatment can have on patients. We explore the potential options for addressing the inherent psychologic effects of these treatments and highlight the need for further research in this domain. Although rare, it is important for all urologists to be familiar with the treatments and post-treatment sequelae of penile cancer. Penile cancer is associated with dramatic decline in quality of life and sexual function. Multiple medical and surgical therapies exist that addresses these concerns. Additionally, urologists must also be mindful of the psychologic component regarding surgical disfigurement and the decline in sexual function.

Immunotherapy for the treatment of penile intraepithelial neoplasia associated with human papilloma virus type 16 using topical imiquimod and human papilloma virus vaccination.

Penile intraepithelial neoplasia (PeIN) is frequently associated with human papilloma virus (HPV). Three cases of PeIN associated with HPV-type 16 were successfully treated with topical imiquimod and concurrent HPV vaccination. Human papilloma vaccine protects against oncogenic human papilloma viruses. In New Zealand, a decline in incidence of PeIN is anticipated with the recent funding of human papilloma vaccine for boys and young men aged 9-26 years. Therefore, HPV vaccination may have a role for treatment of PeIN and prophylaxis.

A risk calculator predicting recurrence in lymph node metastatic penile cancer.

OBJECTIVES: To develop and externally validate a risk calculator for prediction of any cancer recurrence in patients with penile squamous cell carcinoma (pSCC) and inguinal lymph node metastases (ILNM), as to date no validated prognostic tool is available for patients with pSCC and ILNM. PATIENTS AND METHODS: The development cohort included 234 patients from seven referral centres. The external validation cohort included 273 patients from two additional referral centres. Cox regression identified predictors of any recurrence, which were used to develop a risk calculator. The risk-calculator grouped the development and the validation cohorts according to the individual risk of any recurrence at 24 months (24m-R). Adjuvant treatment effects were tested on overall survival (OS) according to the derived tertiles, within the development and validation cohorts. RESULTS: Positive surgical margins, pN3 , and ILNM ratio were associated with higher recurrence rate. The 2-year OS rates were lower for patients with high (>37%) and intermediate (19-37%) compared to low (<19%) 24m-R risk of recurrence, for both the development (43% and 58% vs 83%, P < 0.001) and validation cohort (44% and 50% vs 85%, P < 0.001). Results were confirmed in the subgroup of patients who did not receive adjuvant treatment (P < 0.001), but not in patients who did receive adjuvant treatments in both the development and validation cohorts (P > 0.1). CONCLUSION: Adjuvant treatment planning is crucial in patients with pSCC with ILNM, where only weak evidence is available. The current tool proved to successfully stratify patients according to their individual risk, potentially allowing better tailoring of adjuvant treatments.