Penile (Penis) Cancer
Cancer can affect any part of the penis, but is most common on the foreskin and on the glans (the sensitive bulbous end of the penis). It is most commonly diagnosed in med aged over 50. The vast majority (about 95%) are squamous cell carcinoma (cancer developing in the flat skin cells). Less common types of penile cancer include verrucous carcinoma (Buschke-Lowenstein tumor), melanoma, basal cell carcinoma, adenocarcinoma (sweat glands) and penile sarcoma.
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National Cancer Institute
PDQ summaries are written and frequently updated by editorial boards of experts Further info.
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Penile cancer (cancer of the penis)
Macmillan Cancer SupportContent is developed by a team of information development nurses and content editors, and reviewed by health professionals. Further info.
American Cancer Society
Orchid
Information about penile cancer, diagnosis, post-treatment and research. There is also includes a PDF leaflet.
Oncolink
Article by Charles Wood, MD covering risk factors, diagnosis, staging, treatment and prognosis.
Information for Health Professionals / Researchers (6 links)
- PubMed search for publications about Penile Cancer - Limit search to: [Reviews]
PubMed Central search for free-access publications about Penile Cancer
MeSH term: Penile Neoplasms
US National Library of MedicinePubMed has over 22 million citations for biomedical literature from MEDLINE, life science journals, and online books. Constantly updated.
National Cancer InstitutePDQ summaries are written and frequently updated by editorial boards of experts Further info.
Patient UKPatientUK content is peer reviewed. Content is reviewed by a team led by a Clinical Editor to reflect new or updated guidance and publications. Further info.
Epidemiology of uncommon male genital cancers
Rob Verhoeven (thesis)
Detailed thesis by Rob Verhoeven covering testicular, penile and scrotal cancers based on population based data from the Netherlands.
Medscape
Detailed referenced article by Stanley Brosman, MD. covering a detailed overview, workup and treatment.
Oncolex - Oslo University Hospital (Norway) and MD Andersen (USA)
Detailed reference article covering etiology, histology, staging, metastatic patterns, symptoms, differential diagnoses, prognosis, treatment and follow-up.
Latest Research Publications
This list of publications is regularly updated (Source: PubMed).
Hu J, Li H, Cui Y, et al.
Comparison of clinical feasibility and oncological outcomes between video endoscopic and open inguinal lymphadenectomy for penile cancer: A systematic review and meta-analysis.
Medicine (Baltimore). 2019; 98(22):e15862 [PubMed] Related Publications
Comparison of clinical feasibility and oncological outcomes between video endoscopic and open inguinal lymphadenectomy for penile cancer: A systematic review and meta-analysis.
Medicine (Baltimore). 2019; 98(22):e15862 [PubMed] Related Publications
BACKGROUND: To compare the clinical feasibility and oncological outcomes of video endoscopic inguinal lymph node dissection (VE-ILND) and open inguinal lymph node dissection (O-ILND) in the management of penile cancer.
METHODS: We searched published articles in the PubMed, Embase, Cochrane Library, Web of science, China National Knowledge Infrastructure, and Wanfang databases. Data were extracted by 2 independent authors, and meta-analysis was performed by using Review Manager software version 5.3.
RESULTS: Ten studies were included. Compared with the O-ILND group, the VE-ILND group exhibited less intraoperative blood loss (standardized mean difference [SMD] = 3.12; 95% confidence intervals [95% CIs] [1.27, 4.98]; P = .001), shorter hospital stay (SMD = 1.77; 95% CIs [0.94, 2.60]; P < .001), shorter drainage time (SMD = 2.69; 95% CI [1.47, 3.91]; P < .001), reduced wound infection rate (odds ratio [OR] = 10.62; 95% CI [4.01, 28.10]; P < .001); reduced skin necrosis rate (OR = 7.48; 95% CI [2.79, 20.05]; P < .001), lower lymphedema rate (OR = 3.23; 95% CI [1.51, 6.88]; P = .002), equivalent lymphocele rate (OR = 0.83; 95% CI [0.31, 2.23]; P = .720), and parallel recurrence rate (OR = 1.54; 95% CI [0.41, 5.84]; P = 0.530). However, the number of dissected lymph nodes (OR = 0.25; 95% CI [0.03, 0.47]; P = .030) was slightly increased in the O-ILND group. GRADE recommendations of primary outcomes were shown in a summary of findings table.
CONCLUSIONS: For perioperative outcomes, VE-ILND is superior to O-ILND. For short-term oncological outcomes, VE-ILND is comparable to O-ILND. However, long-term oncological control still requires further verification.
METHODS: We searched published articles in the PubMed, Embase, Cochrane Library, Web of science, China National Knowledge Infrastructure, and Wanfang databases. Data were extracted by 2 independent authors, and meta-analysis was performed by using Review Manager software version 5.3.
RESULTS: Ten studies were included. Compared with the O-ILND group, the VE-ILND group exhibited less intraoperative blood loss (standardized mean difference [SMD] = 3.12; 95% confidence intervals [95% CIs] [1.27, 4.98]; P = .001), shorter hospital stay (SMD = 1.77; 95% CIs [0.94, 2.60]; P < .001), shorter drainage time (SMD = 2.69; 95% CI [1.47, 3.91]; P < .001), reduced wound infection rate (odds ratio [OR] = 10.62; 95% CI [4.01, 28.10]; P < .001); reduced skin necrosis rate (OR = 7.48; 95% CI [2.79, 20.05]; P < .001), lower lymphedema rate (OR = 3.23; 95% CI [1.51, 6.88]; P = .002), equivalent lymphocele rate (OR = 0.83; 95% CI [0.31, 2.23]; P = .720), and parallel recurrence rate (OR = 1.54; 95% CI [0.41, 5.84]; P = 0.530). However, the number of dissected lymph nodes (OR = 0.25; 95% CI [0.03, 0.47]; P = .030) was slightly increased in the O-ILND group. GRADE recommendations of primary outcomes were shown in a summary of findings table.
CONCLUSIONS: For perioperative outcomes, VE-ILND is superior to O-ILND. For short-term oncological outcomes, VE-ILND is comparable to O-ILND. However, long-term oncological control still requires further verification.
Kwon WA, Yoon MY, Kim SH, et al.
Single-Center Analysis of Human Papillomavirus Infection and P16INK4A Expression among Korean Patients with Penile Cancer.
Biomed Res Int. 2019; 2019:6940582 [PubMed] Free Access to Full Article Related Publications
Single-Center Analysis of Human Papillomavirus Infection and P16INK4A Expression among Korean Patients with Penile Cancer.
Biomed Res Int. 2019; 2019:6940582 [PubMed] Free Access to Full Article Related Publications
Purpose: This study aimed to evaluate the statuses of P16INK4A expression and human papillomavirus (HPV) infection among patients with penile cancer at a single Korean institution.
Patients and Methods: Fourteen patients with penile cancer at our center were retrospectively identified and their clinicopathological data were analyzed. The patients' HPV and P16INK4A expression status (a known tumor suppressor protein) were tested using genotyping with a DNA chip assay and immunohistochemical staining, respectively. The results regarding HPV status were compared to those from another Asian study.
Results: The mean age at diagnosis was 60 years (range: 34-86 years). The median tumor size was 3.0 cm (range: 0.6-4.7 cm). Ten tumors were located on the penile glans. Five patients tested positive for HPV DNA (5/14, 36%) and all cases involved HPV type 16 (5/5, 100%). Positive expression of P16INK4A was observed in 6 cases (6/14, 43%). Among the HPV positive cases, 80% of cases (4/5) were also positive for P16INK4A. The prevalence of HPV infection in our study (36%) was higher than in a previous Asian study (23%).
Conclusions: This is the first study to evaluate the prevalence of HPV infection and P16INK4A expression among patients with penile cancer at a single Korean institution. The prevalence of HPV (36%) was slightly higher than the results from a previous Asian study. Additional multi-center studies are needed to better understand penile cancer in Korea and to identify biomarkers that can determine high-risk cases and predict their prognosis.
Patients and Methods: Fourteen patients with penile cancer at our center were retrospectively identified and their clinicopathological data were analyzed. The patients' HPV and P16INK4A expression status (a known tumor suppressor protein) were tested using genotyping with a DNA chip assay and immunohistochemical staining, respectively. The results regarding HPV status were compared to those from another Asian study.
Results: The mean age at diagnosis was 60 years (range: 34-86 years). The median tumor size was 3.0 cm (range: 0.6-4.7 cm). Ten tumors were located on the penile glans. Five patients tested positive for HPV DNA (5/14, 36%) and all cases involved HPV type 16 (5/5, 100%). Positive expression of P16INK4A was observed in 6 cases (6/14, 43%). Among the HPV positive cases, 80% of cases (4/5) were also positive for P16INK4A. The prevalence of HPV infection in our study (36%) was higher than in a previous Asian study (23%).
Conclusions: This is the first study to evaluate the prevalence of HPV infection and P16INK4A expression among patients with penile cancer at a single Korean institution. The prevalence of HPV (36%) was slightly higher than the results from a previous Asian study. Additional multi-center studies are needed to better understand penile cancer in Korea and to identify biomarkers that can determine high-risk cases and predict their prognosis.
Hölters S, Khalmurzaev O, Pryalukhin A, et al.
Challenging the prognostic impact of the new WHO and TNM classifications with special emphasis on HPV status in penile carcinoma.
Virchows Arch. 2019; 475(2):211-221 [PubMed] Related Publications
Challenging the prognostic impact of the new WHO and TNM classifications with special emphasis on HPV status in penile carcinoma.
Virchows Arch. 2019; 475(2):211-221 [PubMed] Related Publications
The evidence concerning prognostic parameters for clinical decision-making in penile cancer is either weak or missing. We therefore analysed the prognostic value of the revised TNM and WHO classification systems on relapse and survival with special emphasis on HPV status. We collected clinical data and tissue samples of 121 patients from centres in Germany and Russia. HPV genotyping and p16
Seniaray N, Verma R, Khanna S, et al.
Uncommon Penio-Scrotal Metastases of Prostate Cancer Detected on 68Ga PSMA PET/CT.
Clin Nucl Med. 2019; 44(5):424-425 [PubMed] Related Publications
Uncommon Penio-Scrotal Metastases of Prostate Cancer Detected on 68Ga PSMA PET/CT.
Clin Nucl Med. 2019; 44(5):424-425 [PubMed] Related Publications
A 68-year-old man, a known case of carcinoma prostate (Gleason score 4 + 4), status post transurethral resection of prostate cancer and radiotherapy, on hormonal treatment with rising prostate-specific antigen 9.0 ng/mL and penile swelling underwent Ga-PSMA PET/CT scan for metastatic workup and restaging. The study revealed abnormal tracer uptake in the prostatic bed region, the pelvic and inguinal lymph nodes, and metastases to the glans of penis and scrotum. The penile and scrotal lesion was proved to be metastatic adenocarcinoma from prostate on fine-needle aspiration cytology.
Related: 
Prostate Cancer
Prostate Cancer
Bada M, Berardinelli F, Nyiràdy P, et al.
Adherence to the EAU guidelines on Penile Cancer Treatment: European, multicentre, retrospective study.
J Cancer Res Clin Oncol. 2019; 145(4):921-926 [PubMed] Related Publications
Adherence to the EAU guidelines on Penile Cancer Treatment: European, multicentre, retrospective study.
J Cancer Res Clin Oncol. 2019; 145(4):921-926 [PubMed] Related Publications
PURPOSE: The European Association of Urology (EAU) guidelines for penile cancer (PC) are exclusively based on retrospective studies and have low grades of recommendation. The aim of this study was to assess the adherence to guidelines by investigating the management strategies for primary tumours and inguinal lymph nodes.
METHODS: We retrospectively reviewed the clinical charts of 176 PC patients who underwent surgery in eight European centres from 2010 to 2016. The stage and grade were assessed according to the 2009 AJCC-UICC TNM classification system. To assess adherence rates, we compared theoretical and practical adherence to the EAU guidelines.
RESULTS: Overall, 176 patients were enrolled. Partial amputation was the most frequent surgical approach (39%). 53.7% of tumours were stage Tis-T1b and the remaining 46.3% were stage T2-T4. Palpable lymph nodes were detected in 30.1% of patients and 45.1% underwent lymphadenectomy (LY). A sizeable group of tumours (43.2%) were N0. For primary treatment, adherence to the EAU guidelines was good (66%). In non-adherent cases, reasons for discrepancy were patient's choice (17%), surgeon's preference (36%), and other causes (47%). For LY, the guideline adherence was 70%, with either patient's or surgeon's choice or other causes accounting for discrepancy in 28, 20, and 52% of non-adherent cases, respectively.
CONCLUSION: Adherence to the EAU guidelines for PC was quite high across the eight European centres involved in the study. This notwithstanding, strategies for further improvement should be developed and evenly adopted.
METHODS: We retrospectively reviewed the clinical charts of 176 PC patients who underwent surgery in eight European centres from 2010 to 2016. The stage and grade were assessed according to the 2009 AJCC-UICC TNM classification system. To assess adherence rates, we compared theoretical and practical adherence to the EAU guidelines.
RESULTS: Overall, 176 patients were enrolled. Partial amputation was the most frequent surgical approach (39%). 53.7% of tumours were stage Tis-T1b and the remaining 46.3% were stage T2-T4. Palpable lymph nodes were detected in 30.1% of patients and 45.1% underwent lymphadenectomy (LY). A sizeable group of tumours (43.2%) were N0. For primary treatment, adherence to the EAU guidelines was good (66%). In non-adherent cases, reasons for discrepancy were patient's choice (17%), surgeon's preference (36%), and other causes (47%). For LY, the guideline adherence was 70%, with either patient's or surgeon's choice or other causes accounting for discrepancy in 28, 20, and 52% of non-adherent cases, respectively.
CONCLUSION: Adherence to the EAU guidelines for PC was quite high across the eight European centres involved in the study. This notwithstanding, strategies for further improvement should be developed and evenly adopted.
Song L, Wang Y, Weng G
Metastasis in penile corpus cavernosum from esophageal squamous carcinoma after curative resection: a case report.
BMC Cancer. 2019; 19(1):162 [PubMed] Free Access to Full Article Related Publications
Metastasis in penile corpus cavernosum from esophageal squamous carcinoma after curative resection: a case report.
BMC Cancer. 2019; 19(1):162 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Metastasis in penile corpus cavernosum from esophageal squamous carcinoma is a rare but fatal disease, which was reported in cases without series studies.
CASE PRESENTATION: An 84-year-old male smoker, who had a history of curative resection of esophageal squamous carcinoma 12 months before, presented with aggressive dysuria and penis pain for 1 month. Ultrasonic guided biopsy diagnosed metastatic squamous carcinoma from the primary in the esophagus. The accurately modulated conformal radiotherapy and non-steroidal antiinflammatory drugs achieved to alleviate the penis pain temporarily. But the disease progressed and disseminated in a short period. He died of multiple metastases and cancer cachexia in 4 months.
CONCLUSIONS: Primary esophageal cancer metastasis to penile corpus cavernosum refers to short onset time of metastasis, extensive dissemination, bad response to treatment and poor prognosis. Palliative therapy to patients with the disease could achieve temporary local symptom relief, but not prolong survival time. More research is necessary to understand the underlying mechanism of esophagheal metastasis.
CASE PRESENTATION: An 84-year-old male smoker, who had a history of curative resection of esophageal squamous carcinoma 12 months before, presented with aggressive dysuria and penis pain for 1 month. Ultrasonic guided biopsy diagnosed metastatic squamous carcinoma from the primary in the esophagus. The accurately modulated conformal radiotherapy and non-steroidal antiinflammatory drugs achieved to alleviate the penis pain temporarily. But the disease progressed and disseminated in a short period. He died of multiple metastases and cancer cachexia in 4 months.
CONCLUSIONS: Primary esophageal cancer metastasis to penile corpus cavernosum refers to short onset time of metastasis, extensive dissemination, bad response to treatment and poor prognosis. Palliative therapy to patients with the disease could achieve temporary local symptom relief, but not prolong survival time. More research is necessary to understand the underlying mechanism of esophagheal metastasis.
Related: Cancer of the Esophagus Esophageal Cancer
Cancer of the Esophagus Esophageal Cancer
Guevara JFA, Fernández SL, Claros OR, et al.
Kaposi sarcoma of th e penis in anHIV-negative patient.
Einstein (Sao Paulo). 2019; 17(1):eRC4504 [PubMed] Free Access to Full Article Related Publications
Kaposi sarcoma of th e penis in anHIV-negative patient.
Einstein (Sao Paulo). 2019; 17(1):eRC4504 [PubMed] Free Access to Full Article Related Publications
Kaposi sarcoma is an angioproliferative disorder that ranges from a single indolent skin lesion to respiratory and gastrointestinal/visceral involvement. Kaposi sarcoma is rare in non-immunosuppressed patients. Nineteen cases of penile Kaposi sarcoma in HIV-negative patients were reported in 2012. We present the case report of a 48-year-old male patient with no previous medical history, who came to our urology clinic presenting a purple-color papule on the penis glans. Lab tests revealed negative serology for HIV, but tissue PCR was positive for human herpesvirus 8. Histopathology examination after lesion excision was compatible with Kaposi sarcoma. No other cutaneous or mucosal lesions were present. Primary Kaposi sarcoma of the penis is rare, but may occur in non-immunosuppressed patients.
Related: Kaposi Sarcoma
Kaposi Sarcoma
Daklan S, Daryakar A
Lymphangioma circumscriptum of glans penis: a report of two cases.
Dermatol Online J. 2018; 24(8) [PubMed] Related Publications
Lymphangioma circumscriptum of glans penis: a report of two cases.
Dermatol Online J. 2018; 24(8) [PubMed] Related Publications
Lymphangioma circumscriptum is a developmental anomaly of lymphatic vessels, which appear as aggregates of clear or hemorrhagic vesicles on the skin or mouth. Glans penis involvement is very uncommon. Because of the sensitivity of the area, possible functional, cosmetic, or psychologic disturbances can result. Lymphangioma circumscriptum is rarely found on this location; hence, vigilance and awareness of this entity is necessary for a swift and proper diagnosis. Two cases are presented on the account of their rarity and unique representation.
Meneses AD, Mattos PAL, Eulálio WMN, et al.
Initial experience of video endoscopic inguinal Lymphadenectomy in a center located at northeast brazilian region.
Int Braz J Urol. 2019 Mar-Apr; 45(2):325-331 [PubMed] Free Access to Full Article Related Publications
Initial experience of video endoscopic inguinal Lymphadenectomy in a center located at northeast brazilian region.
Int Braz J Urol. 2019 Mar-Apr; 45(2):325-331 [PubMed] Free Access to Full Article Related Publications
INTRODUCTION: Video endoscopic inguinal lymphadenectomy - VEIL - has emerged as an alternative to reduce post-surgical complications (PSC) in patients with penile cancer submitted to inguinal lymphadenectomy (IL). In some series, these PSC are observed in more than 50% of patients. The objectives of the present study are to describe the initial experience of VEIL in a Hospital in Teresina, PI, Brazil, and to analyze PSC incidence.
MATERIAL AND METHODS: Retrospective descriptive study of patients submitted to VEIL from March 2014 to November 2015. Data were collected regarding surgical time, bleeding, complications, lymph node number, conversion, global complications, drainage time, cellulitis, lymphocele, cutaneous necrosis, miocutaneous necrosis and hospitalization time.
RESULTS: 20 lower limbs of 11 patients were operated. Mean age was 51.4 (24-72) years. Mean surgical time was 85 (60-120) minutes. No patient showed intrasurgical complications, bleeding > 50 mL or conversion. Three surgeries evolved with lower limb edema, 2 with lymphoceles and one patient had cutaneous necrosis and another bulging of surgical wound. Mean time of hospitalization was 4 (2-11) days. A mean of 5.8 (1-12) lymph nodes were dissected in each surgery.
CONCLUSION: VEIL is a safe and easy technique with lower incidence of PSC that can be reproduced in small centers.
MATERIAL AND METHODS: Retrospective descriptive study of patients submitted to VEIL from March 2014 to November 2015. Data were collected regarding surgical time, bleeding, complications, lymph node number, conversion, global complications, drainage time, cellulitis, lymphocele, cutaneous necrosis, miocutaneous necrosis and hospitalization time.
RESULTS: 20 lower limbs of 11 patients were operated. Mean age was 51.4 (24-72) years. Mean surgical time was 85 (60-120) minutes. No patient showed intrasurgical complications, bleeding > 50 mL or conversion. Three surgeries evolved with lower limb edema, 2 with lymphoceles and one patient had cutaneous necrosis and another bulging of surgical wound. Mean time of hospitalization was 4 (2-11) days. A mean of 5.8 (1-12) lymph nodes were dissected in each surgery.
CONCLUSION: VEIL is a safe and easy technique with lower incidence of PSC that can be reproduced in small centers.
Ong KJ, Checchi M, Burns L, et al.
Systematic review and evidence synthesis of non-cervical human papillomavirus-related disease health system costs and quality of life estimates.
Sex Transm Infect. 2019; 95(1):28-35 [PubMed] Related Publications
Systematic review and evidence synthesis of non-cervical human papillomavirus-related disease health system costs and quality of life estimates.
Sex Transm Infect. 2019; 95(1):28-35 [PubMed] Related Publications
BACKGROUND: Many economic evaluations of human papillomavirus vaccination should ideally consider multiple disease outcomes, including anogenital warts, respiratory papillomatosis and non-cervical cancers (eg, anal, oropharyngeal, penile, vulvar and vaginal cancers). However, published economic evaluations largely relied on estimates from single studies or informal rapid literature reviews.
METHODS: We conducted a systematic review of articles up to June 2016 to identify costs and utility estimates admissible for an economic evaluation from a single-payer healthcare provider's perspective. Meta-analyses were performed for studies that used same utility elicitation tools for similar diseases. Costs were adjusted to 2016/2017 US$.
RESULTS: Sixty-one papers (35 costs; 24 utilities; 2 costs and utilities) were selected from 10 742 initial records. Cost per case ranges were US$124-US$883 (anogenital warts), US$6912-US$52 579 (head and neck cancers), US$12 936-US$51 571 (anal cancer), US$17 524-34 258 (vaginal cancer), US$14 686-US$28 502 (vulvar cancer) and US$9975-US$27 629 (penile cancer). The total cost for 14 adult patients with recurrent respiratory papillomatosis was US$137 601 (one paper).Utility per warts episode ranged from 0.651 to 1 (12 papers, various utility elicitation methods), with pooled mean EQ-5D and EQ-VAS of 0.86 (95% CI 0.85 to 0.87) and 0.74 (95% CI 0.74 to 0.75), respectively. Fifteen papers reported utilities in head and neck cancers with range 0.29 (95% CI 0.0 to 0.76) to 0.94 (95% CI 0.3 to 1.0). Mean utility reported ranged from 0.5 (95% CI 0.4 to 0.61) to 0.65 (95% CI 0.45 to 0.75) (anal cancer), 0.59 (95% CI 0.54 to 0.64) (vaginal cancer), 0.65 (95% CI 0.60 to 0.70) (vulvar cancer) and 0.79 (95% CI 0.74 to 0.84) (penile cancer).
CONCLUSIONS: Differences in values reported from each paper reflect variations in cancer site, disease stages, study population, treatment modality/setting and utility elicitation methods used. As patient management changes over time, corresponding effects on both costs and utility need to be considered to ensure health economic assumptions are up-to-date and closely reflect the case mix of patients.
METHODS: We conducted a systematic review of articles up to June 2016 to identify costs and utility estimates admissible for an economic evaluation from a single-payer healthcare provider's perspective. Meta-analyses were performed for studies that used same utility elicitation tools for similar diseases. Costs were adjusted to 2016/2017 US$.
RESULTS: Sixty-one papers (35 costs; 24 utilities; 2 costs and utilities) were selected from 10 742 initial records. Cost per case ranges were US$124-US$883 (anogenital warts), US$6912-US$52 579 (head and neck cancers), US$12 936-US$51 571 (anal cancer), US$17 524-34 258 (vaginal cancer), US$14 686-US$28 502 (vulvar cancer) and US$9975-US$27 629 (penile cancer). The total cost for 14 adult patients with recurrent respiratory papillomatosis was US$137 601 (one paper).Utility per warts episode ranged from 0.651 to 1 (12 papers, various utility elicitation methods), with pooled mean EQ-5D and EQ-VAS of 0.86 (95% CI 0.85 to 0.87) and 0.74 (95% CI 0.74 to 0.75), respectively. Fifteen papers reported utilities in head and neck cancers with range 0.29 (95% CI 0.0 to 0.76) to 0.94 (95% CI 0.3 to 1.0). Mean utility reported ranged from 0.5 (95% CI 0.4 to 0.61) to 0.65 (95% CI 0.45 to 0.75) (anal cancer), 0.59 (95% CI 0.54 to 0.64) (vaginal cancer), 0.65 (95% CI 0.60 to 0.70) (vulvar cancer) and 0.79 (95% CI 0.74 to 0.84) (penile cancer).
CONCLUSIONS: Differences in values reported from each paper reflect variations in cancer site, disease stages, study population, treatment modality/setting and utility elicitation methods used. As patient management changes over time, corresponding effects on both costs and utility need to be considered to ensure health economic assumptions are up-to-date and closely reflect the case mix of patients.
Stoehr R, Wendler O, Giedl J, et al.
No Evidence of Microsatellite Instability and Loss of Mismatch-Repair-Protein Expression in Squamous Cell Carcinoma of the Penis.
Pathobiology. 2019; 86(2-3):145-151 [PubMed] Related Publications
No Evidence of Microsatellite Instability and Loss of Mismatch-Repair-Protein Expression in Squamous Cell Carcinoma of the Penis.
Pathobiology. 2019; 86(2-3):145-151 [PubMed] Related Publications
OBJECTIVE: Microsatellite instability (MSI) and a defective mismatch repair (MMR) system were described as beneficial tumor features for response to immune checkpoint therapy (PD-1 blockade). Meanwhile, the FDA approved PD-1/PD-L1 inhibition treatment for any solid tumor showing MSI and/or defects in the MMR system. For squamous cell carcinoma (SCC) of the penis, no data on the frequency of MSI and altered MMR protein expression are available to date. Therefore, we investigated the MSI status and the expression of MMR proteins in a large cohort of penile SCCs.
METHODS: The MSI status of 105 archival formalin-fixed, paraffin-embedded penile SCCs was analyzed using the 5 markers of the NCI consensus panel for MIS testing (BAT25, 26, D2S123, D17S250, and D5S346), or, in cases without representative nontumorous tissue using a validated panel of 5 quasimonomorphic mononucleotide repeat markers (BAT 25, 26 and NR21, 24, 27). The expression of the MMR proteins MLH1, MSH2, MSH6, and PMS2 was analyzed using immunohistochemistry and a tissue microarray of a subset of penile SCCs from our cohort (n = 75).
RESULTS: Overall, in 96/105 cases, at least 4 microsatellite markers gave interpretable results. None of the cases showed MSI. Immunohistochemistry for MMR proteins was analyzable in 70/75 cases. All cases showed a regular expression of the MMR proteins.
CONCLUSION: MSI and defects in MMR protein expression are not regular features of penile SCC and might not act as biomarkers for PD-1/PD-L1 blockade therapy in penile carcinoma.
METHODS: The MSI status of 105 archival formalin-fixed, paraffin-embedded penile SCCs was analyzed using the 5 markers of the NCI consensus panel for MIS testing (BAT25, 26, D2S123, D17S250, and D5S346), or, in cases without representative nontumorous tissue using a validated panel of 5 quasimonomorphic mononucleotide repeat markers (BAT 25, 26 and NR21, 24, 27). The expression of the MMR proteins MLH1, MSH2, MSH6, and PMS2 was analyzed using immunohistochemistry and a tissue microarray of a subset of penile SCCs from our cohort (n = 75).
RESULTS: Overall, in 96/105 cases, at least 4 microsatellite markers gave interpretable results. None of the cases showed MSI. Immunohistochemistry for MMR proteins was analyzable in 70/75 cases. All cases showed a regular expression of the MMR proteins.
CONCLUSION: MSI and defects in MMR protein expression are not regular features of penile SCC and might not act as biomarkers for PD-1/PD-L1 blockade therapy in penile carcinoma.
Zhu Y, Gu WJ, Xiao WJ, et al.
Important Therapeutic Considerations in T1b Penile Cancer: Prognostic Significance and Adherence to Treatment Guidelines.
Ann Surg Oncol. 2019; 26(2):685-691 [PubMed] Related Publications
Important Therapeutic Considerations in T1b Penile Cancer: Prognostic Significance and Adherence to Treatment Guidelines.
Ann Surg Oncol. 2019; 26(2):685-691 [PubMed] Related Publications
BACKGROUND: The clinical implications and contemporary management of T1b penile cancer are unknown. National treatment guidelines advocate surgical lymph node examination (SLNE) for T1b disease.
OBJECTIVE: The aim of this study was to evaluate the prognosis of T1b disease and adherence to corresponding treatment guidelines.
METHODS: We analyzed 296 patients from two academic centers, and 1263 patients from the Surveillance, Epidemiology, and End Results (SEER) registry (median follow-up 48.3 and 21 months, respectively). Multivariate Cox and Fine-Gray regressions were applied for penile cancer-specific survival (PCSS) analyses.
RESULTS: In the academic center cohort, 28.3% of T1 patients had T1b disease, all of whom underwent SLNE. Nodal metastases were detected in 86.7% of T1b patients and 13.2% of T1a patients (p < 0.001). Using T1a as a reference, PCSS was significantly poorer in the T1b patients, with an adjusted hazard ratio (aHR) of 4.10 (p = 0.03). In the SEER cohort, 16.8% of T1 patients were classified as T1b. SLNE was performed in 21.7% of the T1b patients versus 38.2% of the T2 patients (p = 0.002). The probability of nodal metastases was 2.23-fold higher in T1b patients than in T1a patients (p < 0.001). In clinical N0M0 patients without SLNE, compared with T1a disease, T1b was associated with an aHR of 4.40 and a subdistribution HR of 4.53 for PCSS (both p = 0.003).
CONCLUSIONS: T1b penile cancer is strongly associated with nodal metastases and adverse PCSS, and is poorly managed according to guidelines recommended in the nationwide registry.
OBJECTIVE: The aim of this study was to evaluate the prognosis of T1b disease and adherence to corresponding treatment guidelines.
METHODS: We analyzed 296 patients from two academic centers, and 1263 patients from the Surveillance, Epidemiology, and End Results (SEER) registry (median follow-up 48.3 and 21 months, respectively). Multivariate Cox and Fine-Gray regressions were applied for penile cancer-specific survival (PCSS) analyses.
RESULTS: In the academic center cohort, 28.3% of T1 patients had T1b disease, all of whom underwent SLNE. Nodal metastases were detected in 86.7% of T1b patients and 13.2% of T1a patients (p < 0.001). Using T1a as a reference, PCSS was significantly poorer in the T1b patients, with an adjusted hazard ratio (aHR) of 4.10 (p = 0.03). In the SEER cohort, 16.8% of T1 patients were classified as T1b. SLNE was performed in 21.7% of the T1b patients versus 38.2% of the T2 patients (p = 0.002). The probability of nodal metastases was 2.23-fold higher in T1b patients than in T1a patients (p < 0.001). In clinical N0M0 patients without SLNE, compared with T1a disease, T1b was associated with an aHR of 4.40 and a subdistribution HR of 4.53 for PCSS (both p = 0.003).
CONCLUSIONS: T1b penile cancer is strongly associated with nodal metastases and adverse PCSS, and is poorly managed according to guidelines recommended in the nationwide registry.
Hu X, Chen M, Li Y, et al.
Overexpression of ID1 promotes tumor progression in penile squamous cell carcinoma.
Oncol Rep. 2019; 41(2):1091-1100 [PubMed] Related Publications
Overexpression of ID1 promotes tumor progression in penile squamous cell carcinoma.
Oncol Rep. 2019; 41(2):1091-1100 [PubMed] Related Publications
Penile squamous cell carcinoma (PSCC) occurs more frequently in developing countries, and is commonly diagnosed at an advanced stage with an unfavorable prognosis. At present, few biomarkers for PSCC have been identified and used in clinical practice. Aberrant expression of inhibitor of DNA binding 1 (ID1) has been suggested as a potential regulator of tumor progression in various types cancer. Herein, we evaluated ID1 expression in PSCC and analyzed its association with the clinicopathological parameters of PSCC. Our findings indicated that ID1 overexpression is associated with histological subtype and lymph node metastasis. Kaplan‑Meier survival analysis showed that the overexpression of ID1 is associated with unfavorable cancer‑specific survival. In Cox proportional hazard models, ID1 overexpression was found to be an independent predictor of cancer‑specific survival. Furthermore, we investigated the function of ID1 in PSCC using a PSCC cell line Penl1. Silencing of ID1 expression retarded cell growth, inhibited clonogenesis, and attenuated cell migration and invasion in Penl1 cells. ID1 may regulate key oncogenic and metastasis‑related molecules, as depletion of ID1 expression affected the levels of p‑AKT, p16, PTEN and cleaved caspase‑3, and reduced MMP2/9 secretion in Penl1 cells. Nevertheless, the mRNA expression of p16 and PTEN increased following ID1 knockdown, suggesting that ID1 may repress p16 and PTEN expression in Penl1 cells. Therefore, overexpression of ID1 could serve as a potential prognostic biomarker for the clinical management of PSCC. Strategies targeting ID1‑regulated signaling pathways may have therapeutic benefit in PSCC.
Antwerpen I, Gstrein L, Moskovszky L, et al.
Primary urethral squamous cell carcinoma: a unique manifestation of a penile tumor.
J Int Med Res. 2019; 47(2):999-1004 [PubMed] Free Access to Full Article Related Publications
Primary urethral squamous cell carcinoma: a unique manifestation of a penile tumor.
J Int Med Res. 2019; 47(2):999-1004 [PubMed] Free Access to Full Article Related Publications
This case report describes a unique manifestation of a primary urethral squamous cell carcinoma (SCC) as the underlying pathology in an 80-year-old male patient who underwent partial penectomy due to an enlarging penile mass. Persistent pain in the right knee was discovered to be a pathologic fracture using magnetic resonance imaging. Computed tomography-guided biopsy confirmed metastatic SCC. Whole-body positron emission tomography revealed systemic dissemination to multiple sites. Orthopedic knee replacement was performed in combination with local radiotherapy. Palliative chemotherapy was rejected due to poor performance status. Primary urethral SCC is rare and an uncommon cause of advanced penile cancer. These findings could be of great interest to clinicians for two reasons. First, a tumor's appearance can be misleading. Consequently, histological work-up in accordance with clinical guidelines is necessary for accurate diagnosis. Second, a more comprehensive investigation is required when clinical symptoms persist despite the use of conventional treatment. Our case is an instance in which persistent pain masked the presence of downstream metastasis. We believe that these aforementioned points are of significant clinical importance and present a salient learning opportunity.
Related: Urethral Cancer
Urethral Cancer
Li ZS, Ornellas AA, Schwentner C, et al.
A modified clinicopathological tumor staging system for survival prediction of patients with penile cancer.
Cancer Commun (Lond). 2018; 38(1):68 [PubMed] Free Access to Full Article Related Publications
A modified clinicopathological tumor staging system for survival prediction of patients with penile cancer.
Cancer Commun (Lond). 2018; 38(1):68 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The 8th American Joint Committee on Cancer tumor-node-metastasis (AJCC-TNM) staging system is based on a few retrospective single-center studies. We aimed to test the prognostic validity of the staging system and to determine whether a modified clinicopathological tumor staging system that includes lymphovascular embolization could increase the accuracy of prognostic prediction for patients with stage T2-3 penile cancer.
METHODS: A training cohort of 411 patients who were treated at 2 centers in China and Brazil between 2000 and 2015 were staged according to the 8th AJCC-TNM staging system. The internal validation was analyzed by bootstrap-corrected C-indexes (resampled 1000 times). Data from 436 patients who were treated at 15 centers over four continents were used for external validation.
RESULTS: A survivorship overlap was observed between T2 and T3 patients (P = 0.587) classified according to the 8th AJCC-TNM staging system. Lymphovascular embolization was a significant prognostic factor for metastasis and survival (all P < 0.001). Based on the multivariate analysis, only lymphovascular embolization showed a significant influence on cancer-specific survival (CSS) (hazard ratio = 1.587, 95% confidence interval = 1.253-2.011; P = 0.001). T2 and T3 patients with lymphovascular embolization showed significantly shorter CSS than did those without lymphovascular embolization (P < 0.001). Therefore, a modified clinicopathological staging system was proposed, with the T2 and T3 categories of the 8th AJCC-TNM staging system being subdivided into two new categories as follows: t2 tumors invade the corpus spongiosum and/or corpora cavernosa and/or urethra without lymphovascular invasion, and t3 tumors invade the corpus spongiosum and/or corpora cavernosa and/or urethra with lymphovascular invasion. The modified staging system involving lymphovascular embolization showed improved prognostic stratification with significant differences in CSS among all categories (all P < 0.005) and exhibited higher accuracy in predicting patient prognoses than did the 8th AJCC-TNM staging system (C-index, 0.739 vs. 0.696). These results were confirmed in the external validation cohort.
CONCLUSIONS: T2-3 penile cancers are heterogeneous, and a modified clinicopathological staging system that incorporates lymphovascular embolization may better predict the prognosis of patients with penile cancer than does the 8th AJCC-TNM staging system. Trial registration This study was retrospectively registered on Chinese Clinical Trail Registry: ChiCTR16008041 (2016-03-02). http://www.chictr.org.cn.
METHODS: A training cohort of 411 patients who were treated at 2 centers in China and Brazil between 2000 and 2015 were staged according to the 8th AJCC-TNM staging system. The internal validation was analyzed by bootstrap-corrected C-indexes (resampled 1000 times). Data from 436 patients who were treated at 15 centers over four continents were used for external validation.
RESULTS: A survivorship overlap was observed between T2 and T3 patients (P = 0.587) classified according to the 8th AJCC-TNM staging system. Lymphovascular embolization was a significant prognostic factor for metastasis and survival (all P < 0.001). Based on the multivariate analysis, only lymphovascular embolization showed a significant influence on cancer-specific survival (CSS) (hazard ratio = 1.587, 95% confidence interval = 1.253-2.011; P = 0.001). T2 and T3 patients with lymphovascular embolization showed significantly shorter CSS than did those without lymphovascular embolization (P < 0.001). Therefore, a modified clinicopathological staging system was proposed, with the T2 and T3 categories of the 8th AJCC-TNM staging system being subdivided into two new categories as follows: t2 tumors invade the corpus spongiosum and/or corpora cavernosa and/or urethra without lymphovascular invasion, and t3 tumors invade the corpus spongiosum and/or corpora cavernosa and/or urethra with lymphovascular invasion. The modified staging system involving lymphovascular embolization showed improved prognostic stratification with significant differences in CSS among all categories (all P < 0.005) and exhibited higher accuracy in predicting patient prognoses than did the 8th AJCC-TNM staging system (C-index, 0.739 vs. 0.696). These results were confirmed in the external validation cohort.
CONCLUSIONS: T2-3 penile cancers are heterogeneous, and a modified clinicopathological staging system that incorporates lymphovascular embolization may better predict the prognosis of patients with penile cancer than does the 8th AJCC-TNM staging system. Trial registration This study was retrospectively registered on Chinese Clinical Trail Registry: ChiCTR16008041 (2016-03-02). http://www.chictr.org.cn.
Kearns JT, Winters BD, Holt SK, et al.
Pathologic Nodal Involvement in Patients With Penile Cancer With Cavernosal Versus Spongiosal Involvement.
Clin Genitourin Cancer. 2019; 17(1):e156-e161 [PubMed] Related Publications
Pathologic Nodal Involvement in Patients With Penile Cancer With Cavernosal Versus Spongiosal Involvement.
Clin Genitourin Cancer. 2019; 17(1):e156-e161 [PubMed] Related Publications
BACKGROUND: The American Joint Committee on Cancer recently proposed new TNM staging for penile cancer, with proposed T2 as spongiosal invasion and T3 as cavernosal invasion. We sought to validate the proposed staging system for predicting pathologic nodal involvement using the National Cancer Data Base.
PATIENTS AND METHODS: Invasive penile cancer cases from 2010 to 2012 were identified. Differences in demographic and pathologic factors between T2 and T3 tumors were compared using χ
RESULTS: There were 378 T2 and 524 T3 patients with penile cancer. Compared with T2 tumors, T3 tumors were larger (mean size, 5.8 cm vs. 4.3 cm), had higher positive surgical margin rates (12% vs. 9%), and were more likely to have lymphovascular invasion (42% vs. 31%) (all P < .05). In multivariable analysis, both T2 (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.2-3.3) and T3 (OR, 2.3; 95% CI, 1.4-3.6) remained significantly associated with risk of positive lymph nodes compared with T1 disease, but there was no increase in risk between T2 and T3 disease (OR, 1.1; 95% CI, 0.7-1.8; P = .56).
CONCLUSION: The proposed new American Joint Committee on Cancer staging system for the penile cancer distinguishes spongiosal (T2) from cavernosal (T3) involvement. There does not appear to be a difference in positive lymph node status between the 2 grades when other clinical and pathologic variables are considered.
PATIENTS AND METHODS: Invasive penile cancer cases from 2010 to 2012 were identified. Differences in demographic and pathologic factors between T2 and T3 tumors were compared using χ
RESULTS: There were 378 T2 and 524 T3 patients with penile cancer. Compared with T2 tumors, T3 tumors were larger (mean size, 5.8 cm vs. 4.3 cm), had higher positive surgical margin rates (12% vs. 9%), and were more likely to have lymphovascular invasion (42% vs. 31%) (all P < .05). In multivariable analysis, both T2 (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.2-3.3) and T3 (OR, 2.3; 95% CI, 1.4-3.6) remained significantly associated with risk of positive lymph nodes compared with T1 disease, but there was no increase in risk between T2 and T3 disease (OR, 1.1; 95% CI, 0.7-1.8; P = .56).
CONCLUSION: The proposed new American Joint Committee on Cancer staging system for the penile cancer distinguishes spongiosal (T2) from cavernosal (T3) involvement. There does not appear to be a difference in positive lymph node status between the 2 grades when other clinical and pathologic variables are considered.
Huang KB, Liu RY, Peng QH, et al.
EGFR mono-antibody salvage therapy for locally advanced and distant metastatic penile cancer: Clinical outcomes and genetic analysis.
Urol Oncol. 2019; 37(1):71-77 [PubMed] Related Publications
EGFR mono-antibody salvage therapy for locally advanced and distant metastatic penile cancer: Clinical outcomes and genetic analysis.
Urol Oncol. 2019; 37(1):71-77 [PubMed] Related Publications
PURPOSE: There are limited therapeutic options for patients with advanced penile squamous cell carcinoma (PSCC) after chemotherapy failure. Thus, we evaluated the feasibility of salvage treatment using the epidermal growth factor receptor (EGFR) mono-antibody nimotuzumab in chemotherapy-failed PSCC patients and explored potential response or resistance biomarkers.
MATERIALS AND METHODS: Six chemotherapy-failed PSCC patients with locally advanced disease or distant metastasis were enrolled consecutively to nimotuzumab treatment. Clinical responses and side effects were evaluated, and genetic characteristics of cancer specimens were analyzed through the next-generation sequencing of hotspot regions in cancer-related genes.
RESULTS: Two of 6 patients showed partial responses, one was identified as having stable disease, while the other 3 had disease progression after nimotuzumab therapy. Side effects were all welltolerated. Genetic analysis revealed that TP53, CDKN2A, RB1, SMAD4, FLT3, and PIK3CA were the most frequently mutated genes in PSCC specimens, while altered KRAS, HRAS, EGFR, ERBB2, and FLT3 may be correlated with nimotuzumab resistance. Furthermore, 3 patients that were human papillomavirus-positive each showed clinical response or stable disease.
CONCLUSIONS: EGFR mono-antibody may be a potential modality for locally advanced PSCC patients after chemotherapy failure. Further large-scale clinical studies are needed to elucidate the role of human papillomavirus status and critical gene mutations in the clinical response to EGFR-targeted therapy.
MATERIALS AND METHODS: Six chemotherapy-failed PSCC patients with locally advanced disease or distant metastasis were enrolled consecutively to nimotuzumab treatment. Clinical responses and side effects were evaluated, and genetic characteristics of cancer specimens were analyzed through the next-generation sequencing of hotspot regions in cancer-related genes.
RESULTS: Two of 6 patients showed partial responses, one was identified as having stable disease, while the other 3 had disease progression after nimotuzumab therapy. Side effects were all welltolerated. Genetic analysis revealed that TP53, CDKN2A, RB1, SMAD4, FLT3, and PIK3CA were the most frequently mutated genes in PSCC specimens, while altered KRAS, HRAS, EGFR, ERBB2, and FLT3 may be correlated with nimotuzumab resistance. Furthermore, 3 patients that were human papillomavirus-positive each showed clinical response or stable disease.
CONCLUSIONS: EGFR mono-antibody may be a potential modality for locally advanced PSCC patients after chemotherapy failure. Further large-scale clinical studies are needed to elucidate the role of human papillomavirus status and critical gene mutations in the clinical response to EGFR-targeted therapy.
Related: EGFR
EGFR
Kristiansen S, Svensson Å, Drevin L, et al.
Risk Factors for Penile Intraepithelial Neoplasia: A Population-based Register Study in Sweden, 2000-2012.
Acta Derm Venereol. 2019; 99(3):315-320 [PubMed] Related Publications
Risk Factors for Penile Intraepithelial Neoplasia: A Population-based Register Study in Sweden, 2000-2012.
Acta Derm Venereol. 2019; 99(3):315-320 [PubMed] Related Publications
Studies on risk factors for penile intraepithelial neo-plasia have been small in size, have not distinguished penile intraepithelial neoplasia from invasive cancer, and have relied on self-reported information. This study investigated risk factors for penile intraepithelial neoplasia in a cohort of 580 penile intraepithelial neoplasia cases and 3,436 controls using information from 7 Swedish registers. Cases with penile intraepithelial neoplasia had increased odds ratios (ORs) for inflammatory skin diseases (14.7, 95% CI 6.5-33.4) including lichen planus (12.0, 95% CI 3.0-48.0), indicating lichen planus to be an important risk factor. Increased ORs were also observed for diseases of the prepuce (4.0, 95% CI 2.2-7.4), immunosuppressive drugs (5.0, 95% CI 2.5-9.8), penile surgical procedures (4.8, 95% CI 2.2-10.8), balanitis (9.2, 95% CI 5.0-16.8), genital warts (9.9, 95% CI 4.3-22.7) and organ transplantation (7.0, 95% CI 2.4-20.8). This study demonstrates important risk factors for penile intraepithelial neoplasia, providing knowledge that can help prevent the development of penile cancer.
Sakamoto J, Shigehara K, Nakashima K, et al.
Etiological role of human papillomavirus infection in the development of penile cancer.
Int J Infect Dis. 2019; 78:148-154 [PubMed] Related Publications
Etiological role of human papillomavirus infection in the development of penile cancer.
Int J Infect Dis. 2019; 78:148-154 [PubMed] Related Publications
OBJECTIVE: To examine the association between human papillomavirus (HPV) infection and penile cancer among Japanese patients.
METHODS: Thirty-four patients with penile cancer were enrolled in this study. DNA was extracted from paraffin-embedded tumor tissue samples, and HPV-DNA tests and genotyping were performed. For all of the samples, in situ hybridization (ISH) was performed to locate HPV-DNA in tumor tissue. Furthermore, expression levels of p16-INK4a, mini-chromosome maintenance protein 7(mcm-7), HPV-L1, and Ki-67 were analyzed using immunohistochemical methods.
RESULTS: HPV and high-risk (HR)-HPV were detected in 14 (41.1%; 95% confidence interval (CI) 24.6-57.7%) and 12 (35.2%; 95% CI 19.2-51.4%) cases, respectively. HPV16 was the most frequently detected HPV type. Among the HR-HPV-positive cases, a punctate HR-HPV-DNA signal pattern was detected by ISH in tumor cell nuclei. P16-INK4a was expressed in 66.7% (95% CI 42.8-90.1%) of HR-HPV-positive cases and was significantly more frequent and stronger in HR-HPV-positive cases than in HPV-negative cases. There was no significant difference in the occurrence or distribution of mcm-7 or Ki-67 expression between HPV-positive and HPV-negative cases. HPV-L1 expression was not observed in any of the cases examined.
CONCLUSIONS: HPV infection may have had an etiological role in 41% of the examined cases of penile cancer in Japan.
METHODS: Thirty-four patients with penile cancer were enrolled in this study. DNA was extracted from paraffin-embedded tumor tissue samples, and HPV-DNA tests and genotyping were performed. For all of the samples, in situ hybridization (ISH) was performed to locate HPV-DNA in tumor tissue. Furthermore, expression levels of p16-INK4a, mini-chromosome maintenance protein 7(mcm-7), HPV-L1, and Ki-67 were analyzed using immunohistochemical methods.
RESULTS: HPV and high-risk (HR)-HPV were detected in 14 (41.1%; 95% confidence interval (CI) 24.6-57.7%) and 12 (35.2%; 95% CI 19.2-51.4%) cases, respectively. HPV16 was the most frequently detected HPV type. Among the HR-HPV-positive cases, a punctate HR-HPV-DNA signal pattern was detected by ISH in tumor cell nuclei. P16-INK4a was expressed in 66.7% (95% CI 42.8-90.1%) of HR-HPV-positive cases and was significantly more frequent and stronger in HR-HPV-positive cases than in HPV-negative cases. There was no significant difference in the occurrence or distribution of mcm-7 or Ki-67 expression between HPV-positive and HPV-negative cases. HPV-L1 expression was not observed in any of the cases examined.
CONCLUSIONS: HPV infection may have had an etiological role in 41% of the examined cases of penile cancer in Japan.
Related: MKI67
MKI67
Velazquez N, Press B, Renson A, et al.
Development of a Novel Prognostic Risk Score for Predicting Complications of Penectomy in the Surgical Management of Penile Cancer.
Clin Genitourin Cancer. 2019; 17(1):e123-e129 [PubMed] Related Publications
Development of a Novel Prognostic Risk Score for Predicting Complications of Penectomy in the Surgical Management of Penile Cancer.
Clin Genitourin Cancer. 2019; 17(1):e123-e129 [PubMed] Related Publications
INTRODUCTION: Penectomy for PC is useful in staging, disease prognosis, and treatment. Limited studies have evaluated its surgical complications. We sought to assess these complications and determine predictive models to create a novel risk score for penectomy complications.
PATIENTS AND METHODS: A retrospective review of patients undergoing PC surgical management from the 2005-2016 American College of Surgeons National Surgical Quality Improvement Program was performed. Data were queried for partial and total penectomy among those with PC. To develop predictive models of complications, we fit LASSO logistic, random forest, and stepwise logistic models to training data using cross-validation, demographic, comorbidity, laboratory, and wound characteristics as candidate predictors. Each model was evaluated on the test data using receiver operating characteristic curves. A novel risk score was created by rounding coefficients from the LASSO logistic model.
RESULTS: A total of 304 cases met the inclusion criteria. Overall incidence of penectomy complications was 19.7%, where urinary tract infection (3.0%), superficial surgical site infection (3.0%), and bleeding requiring transfusion (3.9%) were most common. LASSO logistic, random forest, and stepwise logistic models for predicting complications had area under the curve (AUC) [95% confidence interval] values of 0.66 [0.52-0.81], 0.73 [0.63-0.83], and 0.59 [0.45-0.74], respectively. Eleven variables were included in the risk score. The LASSO model-derived risk score had moderately good performance (area under the curve [95% confidence interval] 0.74 [0.66-0.82]). Using a cutoff point of 6, the score attains sensitivity 0.58, specificity 0.74, and kappa 0.26.
CONCLUSION: PC management through penectomy is associated with appreciable complications rates. Predictive models of penectomy complications performed moderately well. Our novel prognostic risk score may allow for improved preoperative counseling and risk stratification of men undergoing surgical management of PC.
PATIENTS AND METHODS: A retrospective review of patients undergoing PC surgical management from the 2005-2016 American College of Surgeons National Surgical Quality Improvement Program was performed. Data were queried for partial and total penectomy among those with PC. To develop predictive models of complications, we fit LASSO logistic, random forest, and stepwise logistic models to training data using cross-validation, demographic, comorbidity, laboratory, and wound characteristics as candidate predictors. Each model was evaluated on the test data using receiver operating characteristic curves. A novel risk score was created by rounding coefficients from the LASSO logistic model.
RESULTS: A total of 304 cases met the inclusion criteria. Overall incidence of penectomy complications was 19.7%, where urinary tract infection (3.0%), superficial surgical site infection (3.0%), and bleeding requiring transfusion (3.9%) were most common. LASSO logistic, random forest, and stepwise logistic models for predicting complications had area under the curve (AUC) [95% confidence interval] values of 0.66 [0.52-0.81], 0.73 [0.63-0.83], and 0.59 [0.45-0.74], respectively. Eleven variables were included in the risk score. The LASSO model-derived risk score had moderately good performance (area under the curve [95% confidence interval] 0.74 [0.66-0.82]). Using a cutoff point of 6, the score attains sensitivity 0.58, specificity 0.74, and kappa 0.26.
CONCLUSION: PC management through penectomy is associated with appreciable complications rates. Predictive models of penectomy complications performed moderately well. Our novel prognostic risk score may allow for improved preoperative counseling and risk stratification of men undergoing surgical management of PC.
Teh J, Op't Hoog S, Nzenza T, et al.
Penile cancer information on the internet: a needle in a haystack.
BJU Int. 2018; 122 Suppl 5:22-26 [PubMed] Related Publications
Penile cancer information on the internet: a needle in a haystack.
BJU Int. 2018; 122 Suppl 5:22-26 [PubMed] Related Publications
INTRODUCTION: Penile cancer is a disease with high morbidity and mortality and is rare in developed countries. In the developing world, the incidence is significantly higher, and accounts for 1-2% of malignant disease in men. Penile cancer is associated with delayed diagnosis, often due to psychological factors. Web based resources are especially important when obtaining information from health professionals is challenging, such as when symptoms are embarrassing or stigmatised.
OBJECTIVE: To assess the quality of information about penile cancer on the internet and to compare the quality of information from developed countries with developing countries.
METHOD: Health on the Net (HON) principles were applied to websites using the Google search engine imbedded with HON toolbar. This was used to assess 750 websites in English, French, German, Spanish and Portuguese by two independent examiners using the key word 'penile cancer' in all languages. The first 150 websites in each language were analysed. Further analysis was completed comparing results between languages and site sponsors.
RESULTS: Of the 750 websites analysed, 10.4% were HON accredited. There were significantly more HON accredited websites in English and French compared with Portuguese (P = 0.009 and P = 0.0007). A total of 45% of websites were sponsored by Commercial enterprise and 27% were sponsored by Government organisations.
CONCLUSION: A lack of validation of penile cancer internet resources should be appreciated by clinicians. Additionally, there is a discrepancy in the quality of websites between languages, with significantly more resources available in the developed world. Limited available web resources in Spanish and Portuguese contribute to disparities in information access and disease outcomes.
OBJECTIVE: To assess the quality of information about penile cancer on the internet and to compare the quality of information from developed countries with developing countries.
METHOD: Health on the Net (HON) principles were applied to websites using the Google search engine imbedded with HON toolbar. This was used to assess 750 websites in English, French, German, Spanish and Portuguese by two independent examiners using the key word 'penile cancer' in all languages. The first 150 websites in each language were analysed. Further analysis was completed comparing results between languages and site sponsors.
RESULTS: Of the 750 websites analysed, 10.4% were HON accredited. There were significantly more HON accredited websites in English and French compared with Portuguese (P = 0.009 and P = 0.0007). A total of 45% of websites were sponsored by Commercial enterprise and 27% were sponsored by Government organisations.
CONCLUSION: A lack of validation of penile cancer internet resources should be appreciated by clinicians. Additionally, there is a discrepancy in the quality of websites between languages, with significantly more resources available in the developed world. Limited available web resources in Spanish and Portuguese contribute to disparities in information access and disease outcomes.
Azizi M, Tang DH, Verduzco D, et al.
Impact of PI3K-AKT-mTOR Signaling Pathway Up-regulation on Prognosis of Penile Squamous-Cell Carcinoma: Results From a Tissue Microarray Study and Review of the Literature.
Clin Genitourin Cancer. 2019; 17(1):e80-e91 [PubMed] Related Publications
Impact of PI3K-AKT-mTOR Signaling Pathway Up-regulation on Prognosis of Penile Squamous-Cell Carcinoma: Results From a Tissue Microarray Study and Review of the Literature.
Clin Genitourin Cancer. 2019; 17(1):e80-e91 [PubMed] Related Publications
PURPOSE: To assess the prognostic value of PI3K-AKT-mTOR signaling pathway up-regulation in a contemporary cohort of penile squamous-cell carcinoma (PSCC) patients.
PATIENTS AND METHODS: Tissue microarrays were constructed for 57 patients with invasive PSCC treated at our institution between 2000 and 2013. Immunohistochemical staining was performed for PTEN, AKT, and S6. Human papillomavirus (HPV) in-situ hybridization for high-risk subtypes was also performed. Biomarker expression was evaluated by a semiquantitative H score. Overall survival, disease-specific survival and recurrence-free survival stratified by biomarker expression (low vs. high) were estimated by the Kaplan-Meier method. Multivariable Cox regression models were used to determine predictors of mortality and recurrence.
RESULTS: HPV in-situ hybridization was positive in 23 patients (40%). PTEN was down-regulated in 43 patients (75%), while phosphorylated-AKT (p-AKT) and phosphorylated-S6 (p-S6) were up-regulated in 27 (47%) and 12 patients (21%), respectively. In multivariable Cox regression models, patients with low expression of p-AKT had an increased risk of recurrence (hazard ratio [HR] = 3.95; 95% confidence interval [CI], 1.47-10.59; P = .02), while those with low expression of p-S6 had an increased risk of overall mortality (HR = 6.15; 95% CI, 1.55-24.36; P = .01). HPV status was an independent predictor of overall survival (HR = 6.99; 95% CI, 2.42-20.16; P < .001) and disease-specific survival (HR = 6.74; 95% CI, 2.02-22.48; P = .002).
CONCLUSION: PI3K-AKT-mTOR signaling pathway up-regulation and HPV coinfection in PSCC are associated with favorable disease. mTOR pathway biomarkers along with HPV status may represent novel prognosticators for risk stratification of PSCC patients and may help guide treatment decisions and follow-up strategies. These findings require further investigation.
PATIENTS AND METHODS: Tissue microarrays were constructed for 57 patients with invasive PSCC treated at our institution between 2000 and 2013. Immunohistochemical staining was performed for PTEN, AKT, and S6. Human papillomavirus (HPV) in-situ hybridization for high-risk subtypes was also performed. Biomarker expression was evaluated by a semiquantitative H score. Overall survival, disease-specific survival and recurrence-free survival stratified by biomarker expression (low vs. high) were estimated by the Kaplan-Meier method. Multivariable Cox regression models were used to determine predictors of mortality and recurrence.
RESULTS: HPV in-situ hybridization was positive in 23 patients (40%). PTEN was down-regulated in 43 patients (75%), while phosphorylated-AKT (p-AKT) and phosphorylated-S6 (p-S6) were up-regulated in 27 (47%) and 12 patients (21%), respectively. In multivariable Cox regression models, patients with low expression of p-AKT had an increased risk of recurrence (hazard ratio [HR] = 3.95; 95% confidence interval [CI], 1.47-10.59; P = .02), while those with low expression of p-S6 had an increased risk of overall mortality (HR = 6.15; 95% CI, 1.55-24.36; P = .01). HPV status was an independent predictor of overall survival (HR = 6.99; 95% CI, 2.42-20.16; P < .001) and disease-specific survival (HR = 6.74; 95% CI, 2.02-22.48; P = .002).
CONCLUSION: PI3K-AKT-mTOR signaling pathway up-regulation and HPV coinfection in PSCC are associated with favorable disease. mTOR pathway biomarkers along with HPV status may represent novel prognosticators for risk stratification of PSCC patients and may help guide treatment decisions and follow-up strategies. These findings require further investigation.
Omorphos S, Saad Z, Kirkham A, et al.
Zonal mapping of sentinel lymph nodes in penile cancer patients using fused SPECT/CT imaging and lymphoscintigraphy.
Urol Oncol. 2018; 36(12):530.e1-530.e6 [PubMed] Related Publications
Zonal mapping of sentinel lymph nodes in penile cancer patients using fused SPECT/CT imaging and lymphoscintigraphy.
Urol Oncol. 2018; 36(12):530.e1-530.e6 [PubMed] Related Publications
PURPOSE: To define the anatomical location of sentinel lymph nodes (SLN) in penile cancer patients based on Daseler's original zonal description using a combination of single photon emission computed tomography-computed tomography (SPECT-CT), cross sectional imaging and lymphoscintigraphy and characterise the limits of Zone V.
MATERIALS AND METHODS: Patients with primary penile cancer ≥T1G2 were included in the study. A total of 113 groins with impalpable inguinal lymph nodes (cN0) underwent planar lymphoscintigraphy and SPECT-CT. The sentinel lymph nodes were mapped on cross sectional imaging according to Daseler's anatomical description. Using measurements from fixed anatomical landmarks, a custom-made software program mapped the SLNs. SLNs were mapped to the previously undefined Zone V using 3 approaches to avoid observational bias: (a) as perceived by the uroradiologist, (b) limiting Zone V to a 5 mm radius from the sapheno-femoral junction or (c) using a 10 mm radius from the sapheno-femoral junction.
RESULTS: Using SPECT-CT, drainage to the groins was seen in 109 of the 113 cN0 groins (96.5%). The majority of the SLNs were located in the central and superior quadrants with 38.2% lying within Zone I, 45% in Zone II and 13% in Zone V. More importantly, sentinel lymph nodes were still localised to the inferior zones with 3% located in Zone III and 0.8% in Zone IV.
CONCLUSIONS: Using a hybrid of SPECT-CT, cross sectional imaging and lymphoscintigraphy we have demonstrated that SLNs may be located in the inferior zones. We also define the limits of Zone V as an area of 5 mm radius from the sapheno-femoral junction.
MATERIALS AND METHODS: Patients with primary penile cancer ≥T1G2 were included in the study. A total of 113 groins with impalpable inguinal lymph nodes (cN0) underwent planar lymphoscintigraphy and SPECT-CT. The sentinel lymph nodes were mapped on cross sectional imaging according to Daseler's anatomical description. Using measurements from fixed anatomical landmarks, a custom-made software program mapped the SLNs. SLNs were mapped to the previously undefined Zone V using 3 approaches to avoid observational bias: (a) as perceived by the uroradiologist, (b) limiting Zone V to a 5 mm radius from the sapheno-femoral junction or (c) using a 10 mm radius from the sapheno-femoral junction.
RESULTS: Using SPECT-CT, drainage to the groins was seen in 109 of the 113 cN0 groins (96.5%). The majority of the SLNs were located in the central and superior quadrants with 38.2% lying within Zone I, 45% in Zone II and 13% in Zone V. More importantly, sentinel lymph nodes were still localised to the inferior zones with 3% located in Zone III and 0.8% in Zone IV.
CONCLUSIONS: Using a hybrid of SPECT-CT, cross sectional imaging and lymphoscintigraphy we have demonstrated that SLNs may be located in the inferior zones. We also define the limits of Zone V as an area of 5 mm radius from the sapheno-femoral junction.
Martins VA, Pinho JD, Teixeira Júnior AAL, et al.
P16INK4a expression in patients with penile cancer.
PLoS One. 2018; 13(10):e0205350 [PubMed] Free Access to Full Article Related Publications
P16INK4a expression in patients with penile cancer.
PLoS One. 2018; 13(10):e0205350 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Infection with human papillomavirus (HPV) is reported to be present in 30-50% of penile cancer cases. The immunohistochemical test for p16INK4a is used as an indicator of the presence of HPV and as a prognostic marker for squamous cell carcinomas in various sites. However, the role of this marker in penile carcinoma has not yet been completely elucidated. The aim of this study was to analyze whether the expression of p16INK4a is associated with the presence of HPV, histological parameters, and survival in penile cancer.
METHODS: A study was conducted from 2014 to 2016 that included 55 patients with penile carcinoma. HPV DNA was detected through PCR using fresh tumor tissue, and immunohistochemistry was performed for analysis of p16INK4a protein using paraffin-embedded tissue. Evaluation of histological parameters was performed following complete embedding of the tumor tissue in paraffin.
RESULTS: HPV DNA (low-risk and high-risk genotypes) was found in 49 (89.1%) cases, and 46/49 (93.9%) showed high-oncogenic risk HPV (HR-HPV). Of the 22 cases positive for p16INK4a, HR-HPV DNA was present in 21 (95.5%) (p = 0.032). Regarding histological parameters, p16INK4a and HR-HPV were significantly associated only with tumor subtype (p = 0.036 and p = 0.032, respectively); all carcinomas with basaloid characteristics were positive for p16INK4a. Although HPV+ patients had a higher disease-free survival (p <0.001), p16INK4a expression was not associated with patient survival.
CONCLUSIONS: Our study, using fresh tissue samples, showed the highest incidence of HPV compared to that observed in the literature. Expression of the p16INK4a protein was significantly associated with the presence of HR-HPV and this expression may serve as a marker for the presence of the virus. The p16INK4a protein was not associated with the histological prognostic parameters, with the exception of tumor subtype, nor with patient survival. In the results, we showed that the objective of the present study was reached.
METHODS: A study was conducted from 2014 to 2016 that included 55 patients with penile carcinoma. HPV DNA was detected through PCR using fresh tumor tissue, and immunohistochemistry was performed for analysis of p16INK4a protein using paraffin-embedded tissue. Evaluation of histological parameters was performed following complete embedding of the tumor tissue in paraffin.
RESULTS: HPV DNA (low-risk and high-risk genotypes) was found in 49 (89.1%) cases, and 46/49 (93.9%) showed high-oncogenic risk HPV (HR-HPV). Of the 22 cases positive for p16INK4a, HR-HPV DNA was present in 21 (95.5%) (p = 0.032). Regarding histological parameters, p16INK4a and HR-HPV were significantly associated only with tumor subtype (p = 0.036 and p = 0.032, respectively); all carcinomas with basaloid characteristics were positive for p16INK4a. Although HPV+ patients had a higher disease-free survival (p <0.001), p16INK4a expression was not associated with patient survival.
CONCLUSIONS: Our study, using fresh tissue samples, showed the highest incidence of HPV compared to that observed in the literature. Expression of the p16INK4a protein was significantly associated with the presence of HR-HPV and this expression may serve as a marker for the presence of the virus. The p16INK4a protein was not associated with the histological prognostic parameters, with the exception of tumor subtype, nor with patient survival. In the results, we showed that the objective of the present study was reached.
Jacob JM, Ferry EK, Gay LM, et al.
Comparative Genomic Profiling of Refractory and Metastatic Penile and Nonpenile Cutaneous Squamous Cell Carcinoma: Implications for Selection of Systemic Therapy.
J Urol. 2019; 201(3):541-548 [PubMed] Related Publications
Comparative Genomic Profiling of Refractory and Metastatic Penile and Nonpenile Cutaneous Squamous Cell Carcinoma: Implications for Selection of Systemic Therapy.
J Urol. 2019; 201(3):541-548 [PubMed] Related Publications
PURPOSE: Metastatic penile squamous cell carcinoma is an aggressive malignancy with limited treatment options. We compared the potential therapy impacting genomic alterations between metastatic penile squamous cell carcinoma and nonpenile metastatic cutaneous squamous cell carcinoma.
MATERIALS AND METHODS: DNA was extracted from 40 μ of formalin fixed, paraffin embedded samples from 78 cases of metastatic penile squamous cell carcinoma and 338 of metastatic cutaneous squamous cell carcinoma. Comprehensive genomic profiling was performed using a hybrid capture, adaptor ligation based, next generation sequencing assay to a mean coverage depth of greater than 500×. The tumor mutational burden was determined on 1.1 Mbp of sequenced DNA and microsatellite instability was determined on 114 loci.
RESULTS: Potential targeted therapy opportunities in metastatic penile squamous cell carcinoma cases included alterations in the MTOR pathway ( NF1 genomic alterations in 7% and PTEN genomic alterations in 4%) and in the DNA repair pathway ( BRCA2 and ATM genomic alterations in 7% each) and tyrosine kinase ( EGFR genomic alterations in 6%, and FGFR3 and ERBB2 genomic alterations in 4% each). The tumor mutational burden was significantly higher in predominantly ultraviolet light exposed metastatic squamous cell carcinoma than in metastatic penile squamous cell carcinoma, making metastatic squamous cell carcinoma potentially more responsive to immunotherapies than metastatic penile squamous cell carcinoma. Microsatellite high status was extremely rare for metastatic penile and metastatic cutaneous squamous cell carcinoma. CD274 ( PD-L1) amplification was also rare in both tumor types.
CONCLUSIONS: Metastatic penile squamous cell carcinoma is a unique subtype of squamous cell carcinoma with distinctive genomic features which contrast with those identified in metastatic cutaneous squamous cell carcinoma of nonpenile ultraviolet light exposed skin. Although not rich in predictors of the response to immunotherapy (the tumor mutational burden and microsatellite instability are low), more than a quarter of metastatic penile squamous cell carcinoma cases may potentially benefit from existing and available therapies targeting MTOR, DNA repair and tyrosine kinase pathways.
MATERIALS AND METHODS: DNA was extracted from 40 μ of formalin fixed, paraffin embedded samples from 78 cases of metastatic penile squamous cell carcinoma and 338 of metastatic cutaneous squamous cell carcinoma. Comprehensive genomic profiling was performed using a hybrid capture, adaptor ligation based, next generation sequencing assay to a mean coverage depth of greater than 500×. The tumor mutational burden was determined on 1.1 Mbp of sequenced DNA and microsatellite instability was determined on 114 loci.
RESULTS: Potential targeted therapy opportunities in metastatic penile squamous cell carcinoma cases included alterations in the MTOR pathway ( NF1 genomic alterations in 7% and PTEN genomic alterations in 4%) and in the DNA repair pathway ( BRCA2 and ATM genomic alterations in 7% each) and tyrosine kinase ( EGFR genomic alterations in 6%, and FGFR3 and ERBB2 genomic alterations in 4% each). The tumor mutational burden was significantly higher in predominantly ultraviolet light exposed metastatic squamous cell carcinoma than in metastatic penile squamous cell carcinoma, making metastatic squamous cell carcinoma potentially more responsive to immunotherapies than metastatic penile squamous cell carcinoma. Microsatellite high status was extremely rare for metastatic penile and metastatic cutaneous squamous cell carcinoma. CD274 ( PD-L1) amplification was also rare in both tumor types.
CONCLUSIONS: Metastatic penile squamous cell carcinoma is a unique subtype of squamous cell carcinoma with distinctive genomic features which contrast with those identified in metastatic cutaneous squamous cell carcinoma of nonpenile ultraviolet light exposed skin. Although not rich in predictors of the response to immunotherapy (the tumor mutational burden and microsatellite instability are low), more than a quarter of metastatic penile squamous cell carcinoma cases may potentially benefit from existing and available therapies targeting MTOR, DNA repair and tyrosine kinase pathways.
Zhang L, Hu J, Ali Zirakzadeh A, et al.
Detection of micro-metastases by flow cytometry in lymph nodes from patients with penile cancer.
BMC Urol. 2018; 18(1):86 [PubMed] Free Access to Full Article Related Publications
Detection of micro-metastases by flow cytometry in lymph nodes from patients with penile cancer.
BMC Urol. 2018; 18(1):86 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The tumor draining lymph node concept was first described in penile cancer for staging. Immunohistochemistry and histopathology evaluations are routinely used in clinical practice to examine lymph nodes for metastasis. However, these methods are time-consuming with low diagnostic accuracy and micro-metastases might be missed. In this study, we aim to evaluate detection of metastatic cells in draining lymph nodes by flow cytometry.
METHODS: To assess the sensitivity of micro-metastasis detection by FACS (Fluorescence-activated cell sorting), HeLa cells were titrated into Peripheral blood mononuclear cells (PBMCs) and expression of pan-cytokeratin AE1/AE3 was analyzed. Single cell suspensions were separately prepared from 10 regional lymph nodes obtained from 5 patients with invasive penile cancer undergoing radical surgery and lymph node dissection. Lymph node dereived cells were examined for cell surface expression of EpCAM, E-cadherin and intracellular expression of pan-cytokeratin AE1/AE3 by FACS.
RESULTS: Ten lymph nodes from 5 penile cancer patients were investigated in a head-to-head comparison between FACS and pathology examination of sections. All metastatic lymph nodes verified by pathology examination were also identified by FACS. Two additional lymph nodes with micro-metastases were diagnosed by FACS only.
CONCLUSIONS: FACS analyses of pan-cytokeratin AE1/AE3 stained single cells from tumor draining lymph nodes can be used to detect micro-metastases in patients with penile cancer patients.
METHODS: To assess the sensitivity of micro-metastasis detection by FACS (Fluorescence-activated cell sorting), HeLa cells were titrated into Peripheral blood mononuclear cells (PBMCs) and expression of pan-cytokeratin AE1/AE3 was analyzed. Single cell suspensions were separately prepared from 10 regional lymph nodes obtained from 5 patients with invasive penile cancer undergoing radical surgery and lymph node dissection. Lymph node dereived cells were examined for cell surface expression of EpCAM, E-cadherin and intracellular expression of pan-cytokeratin AE1/AE3 by FACS.
RESULTS: Ten lymph nodes from 5 penile cancer patients were investigated in a head-to-head comparison between FACS and pathology examination of sections. All metastatic lymph nodes verified by pathology examination were also identified by FACS. Two additional lymph nodes with micro-metastases were diagnosed by FACS only.
CONCLUSIONS: FACS analyses of pan-cytokeratin AE1/AE3 stained single cells from tumor draining lymph nodes can be used to detect micro-metastases in patients with penile cancer patients.
Zhou X, Qi F, Zhou R, et al.
The role of perineural invasion in penile cancer: a meta-analysis and systematic review.
Biosci Rep. 2018; 38(5) [PubMed] Free Access to Full Article Related Publications
The role of perineural invasion in penile cancer: a meta-analysis and systematic review.
Biosci Rep. 2018; 38(5) [PubMed] Free Access to Full Article Related Publications
The significance of perineural invasion (PNI) present in penile cancer (PC) is controversial. In order to clarify the predictive role of PNI in the inguinal lymph node (ILN) metastases (ILNM) and oncologic outcome of patients, we performed this meta-analysis and systematic review. The search of PubMed, Embase, and Web of Science was conducted for appropriate studies, up to 20 January 2018. The pooled odds ratio (OR) and hazard ratio (HR) with their 95% confidence interval (CI) were applied to evaluate the difference in ILNM and oncologic outcome between patients present with PNI and those who were absent. A total of 298 in 1001 patients present with PNI were identified in current meta-analysis and systematic review. Significant difference was observed in ILNM between PNI present and absent from patients with PC (OR = 2.98, 95% CI = 2.00-4.45). Patients present with PNI had a worse cancer-specific survival (CSS) (HR = 3.58, 95% CI = 1.70-7.55) and a higher cancer-specific mortality (CSM) (HR = 2.20, 95% CI = 1.06-3.82) than those cases without PNI. This meta-analysis and systematic review demonstrated the predictive role of PNI in ILNM, CSS, and CSM for PC patients.
Suárez-Bonnet A, Willis C, Pittaway R, et al.
Molecular carcinogenesis in equine penile cancer: A potential animal model for human penile cancer.
Urol Oncol. 2018; 36(12):532.e9-532.e18 [PubMed] Related Publications
Molecular carcinogenesis in equine penile cancer: A potential animal model for human penile cancer.
Urol Oncol. 2018; 36(12):532.e9-532.e18 [PubMed] Related Publications
OBJECTIVES: To evaluate the expression of COX-2, E-cadherin, vimentin, 14-3-3σ, and Phosphatase and tensin homolog (PTEN) tumor-related proteins in equine penile papillomas (ePP) and squamous cell carcinomas (ePSCC), the occurrence of epithelial-mesenchymal transition (EMT) at the invasion front (IF) and compare our findings with current knowledge on human penile squamous cell carcinoma (hPSCC).
MATERIAL AND METHODS: We analyzed, by immunohistochemistry in 45 equine penile proliferative epithelial lesions, the expression of COX-2, E-cadherin, vimentin, 14-3-3σ, and PTEN using monoclonal antibodies. Tumors were histopathologically classified as well-differentiated or poorly differentiated using the IF grading scheme. Semiquantitative analysis was performed to determine down or up-regulation of the proteins and association with histopathological characteristics were statistically investigated using Mann-Whitney U test and/or Spearman's tests.
RESULTS: COX-2 was neo-expressed in 86.6% of the cases and expression progressively increased from ePP to ePSCC (P = 0.0003) and from well to poorly differentiated (P = 0.033). High COX-2 expression was associated with a high mitotic index (MI) (P = 0.026). In contrast to normal epidermis, ePSCC had very low E-cadherin expression in 64% of the cases (P = 0.0005). Vimentin was neo-expressed in 65% of poorly differentiated ePSCC at the IF indicating EMT. Cytoplasmic 14-3-3σ protein expression was reduced in 42% of the ePSCC and additionally, nuclear expression of 14-3-3σ in neoplastic keratinocytes and in the cytoplasm of stromal fibroblasts at the IF was features only found in ePSCC. PTEN protein showed a tendency to be decreased or lost in ePSCC.
CONCLUSIONS: Our study provides evidence of molecular abnormalities in ePSCC similar to those reported for human PSCC. The occurrence of EMT at the IF is a common event in ePSCC. Naturally occurring ePSCC could serve as a valuable preclinical animal model to explore upcoming therapeutic options for hPSCC.
MATERIAL AND METHODS: We analyzed, by immunohistochemistry in 45 equine penile proliferative epithelial lesions, the expression of COX-2, E-cadherin, vimentin, 14-3-3σ, and PTEN using monoclonal antibodies. Tumors were histopathologically classified as well-differentiated or poorly differentiated using the IF grading scheme. Semiquantitative analysis was performed to determine down or up-regulation of the proteins and association with histopathological characteristics were statistically investigated using Mann-Whitney U test and/or Spearman's tests.
RESULTS: COX-2 was neo-expressed in 86.6% of the cases and expression progressively increased from ePP to ePSCC (P = 0.0003) and from well to poorly differentiated (P = 0.033). High COX-2 expression was associated with a high mitotic index (MI) (P = 0.026). In contrast to normal epidermis, ePSCC had very low E-cadherin expression in 64% of the cases (P = 0.0005). Vimentin was neo-expressed in 65% of poorly differentiated ePSCC at the IF indicating EMT. Cytoplasmic 14-3-3σ protein expression was reduced in 42% of the ePSCC and additionally, nuclear expression of 14-3-3σ in neoplastic keratinocytes and in the cytoplasm of stromal fibroblasts at the IF was features only found in ePSCC. PTEN protein showed a tendency to be decreased or lost in ePSCC.
CONCLUSIONS: Our study provides evidence of molecular abnormalities in ePSCC similar to those reported for human PSCC. The occurrence of EMT at the IF is a common event in ePSCC. Naturally occurring ePSCC could serve as a valuable preclinical animal model to explore upcoming therapeutic options for hPSCC.
Related: PTEN
PTEN
Schlenker B, Schneede P
The Role of Human Papilloma Virus in Penile Cancer Prevention and New Therapeutic Agents.
Eur Urol Focus. 2019; 5(1):42-45 [PubMed] Related Publications
The Role of Human Papilloma Virus in Penile Cancer Prevention and New Therapeutic Agents.
Eur Urol Focus. 2019; 5(1):42-45 [PubMed] Related Publications
Penile cancer remains an aggressive disease with poor prognosis in advanced stages. Another specific problem of any rare disease is that the population is not aware of prevention strategies and higher chances for curation by early diagnosis. In penile carcinogenesis, two major pathways are known. Besides a non-human papilloma virus (HPV)-related pathway (mainly caused by phimosis and chronic inflammation), up to 50% of penile carcinomas are HPV-related (HPV high-risk types). Prophylactic HPV vaccination has proven its efficacy against cervical cancer; its B-cell-mediated immunity against HPV capsid proteins provides probably lifelong protection against specific HPV subtypes covered by the vaccine. Therefore, a consequent HPV vaccination program for children of both sexes might dramatically reduce the incidence of not only cervical cancer but also partially prevent penile cancer. However, for the treatment of already existing intracellular HPV infections, an antigen-specific T-cell immunity is necessary. Appropriate therapeutic HPV vaccines are under investigation. This article gives an overview about different levels of prevention of the HPV-related penile cancer.
Wei Z, Yu Z, Li H, et al.
The appropriate number of negative lymph nodes dissection for nonmetastatic penile cancer.
Andrologia. 2019; 51(1):e13154 [PubMed] Related Publications
The appropriate number of negative lymph nodes dissection for nonmetastatic penile cancer.
Andrologia. 2019; 51(1):e13154 [PubMed] Related Publications
Negative lymph nodes status has been attached more attention as a prognostic indicator for nonmetastatic penile cancer. We aimed to identify the appropriate number of negative lymph nodes dissection for nonmetastatic penile cancer using the Surveillance, Epidemiology and End Results database. A total of 1,470 nonmetastatic patients with penile squamous cell carcinoma were identified during 2004 and 2013. All patients were categorised according to different risk levels and lymphadenectomy. Univariate and multivariate Cox regression analyses were performed to evaluate the relationship between prognostic risk factors and cancer-specific survival. The optimal cut-off value of negative lymph nodes dissection was determined using the X-Tile program. A total of 1,470 patients were categorised into low- (pT1G1), intermediate- (pT1G2) or high-risk (pT1G3 and all higher stages) groups. In multivariate Cox analysis, lymphadenectomy improved the cancer-specific survival for patients in high-risk group (p = 0.014). Further, the optimal cut-off value of negative lymph nodes dissection for high-risk patients was 5 and patients with >5 negative lymph nodes had a higher cancer-specific survival (χ
