Human Papilloma Virus HPV Infection

HPV infection occurs in 15-85 of cases of SCC penis. HPV-16 and 18 are the most frequently detected types. Specifically, HPV-16 is present in 25-95 of cases and HPV-18 in the remaining 5-75 of the cases. Rarely, other HPV types are detected in penile cancer.37 In contrast to the established role of HPV as a risk factor, little is known about its prognostic significance in penile SCC. In 1992 Wiener et al. documented no significant difference in survival between patients with HPV-positive and...

Performance of Ultrasound and MRI in Primary TUmor Staging

Corpus Cavernosum Ultrasound

The majority of penile lesions are primary squamous cell tumors, although melanoma,23 basal cell carcinoma,24 sarcoma,25 and lymphoma26 have also been reported, and metastases are common enough to account for several case series,27,28 with bladder the commonest site of origin - either by hematogenous or urethral spread of transitional cell carcinoma.29,30 On MRI primary tumors are of intermediate signal lower than the contents of the corpora (particularly when tumescent) but higher than the low...

Chemotherapy

While overall cancer-specific survival rates of 80-90 in early stage penile cancer have been reported with surgery alone. Higher stage disease (i.e., bilateral inguinal metastases, extranodal extension, pelvic nodal metastases) requires additional treatment in order to achieve a cure. The neoadjuvant paradigm aims to treat systemic disease prior to surgery as in other conditions, such as bladder cancer.17 Three contemporary series have shown that selected patients can benefit from induction...

References

Shergill IS, Rao A, Arya M, Patel H, Gill IS. Nanotechnology and potential applications in urology. BJUInt. 2006 97 219-220. 4. BECON Nanoscience and Nanotechnology Symposium Report. 2006. National Institutes of Health Bioengineering Consortium. 1-6-2000. 5. National Institutes of Health Bioengineering Consortium. BECON Nanoscience and Nanotechnology Symposium Report. 1-6-2000. Available at URL www.becon.nih.gov becon_symposia.htm. 6. Sahoo SK, Ma W, Labhasetwar V. Efficacy of...

Epidemiology of Penile Cancer

Penile cancer occurs predominantly in elderly men although the disease may also occasionally present in young men. The mean age at diagnosis of patients with penile cancer is 60 years and the age-related incidence is highest at 70 years. The incidence has remained stable over recent years with an age-standardized incidence of 0.3-1.0 per 100,000 in Western Europe and the United States, accounting for 0.4-0.6 of all malignancies in this part of the world.1,2 The incidence is significantly higher...

Introduction Molecular Concept of Penile Carcinogenesis

Penile cancer is a rare disease, particularly in developed countries.1 Large case series for molecular studies are relatively limited. Only a few, albeit important, studies evaluating the molecular etiopathogenesis of penile carcinoma have been published to date. Based on these studies, a model of penile carcinogenesis describing the molecular alterations that accumulate during the pathogenesis of penile carcinoma has been proposed.2 In this molecular concept, the etiology of penile carcinoma...

HPVMediated Penile Carcinogenesis

HPV is associated with anogenital tumor formation and is an important factor in the development of in-situ and invasive epithelial tumors. Our understanding of HPV DNA integration into the human genome has resulted from research investigating SCC of the cervix and from the development of an HPV-specific quadrivalent vaccine. HrHPV-associated penile cancers are thought to arise from the progression of precursor lesions caused by an hrHPV infection. HrHPV infections have a strong association with...

HPVIndependent Penile Carcinogenesis

Penile carcinomas that are not associated with hrHPV are thought to arise from the progression of precursor lesions at sites of chronic irritation or injury, such as lichen sclerosus. Although the causative agent of these lesions has not been completely elucidated, inflammation is recognized as a critical component of tumor development or progression in these cases.2 Studies evaluating the molecular biology of non-HPV associated penile cancer have suggested that, in general, gene alterations...

HPV Infection and Penile Cancer

Much of our understanding of how HPV infection may lead to premalignant lesions and invasive tumors is based on studies of carcinogenesis in cervical cancer. However, while almost 100 of cervical SCCs are related to sexually transmitted HPV infection, rates of HPV in penile cancer are reported between 30 to 100 .1-6 The reasons for this wide range include geographical variations and different cultural attitudes towards sex between the reporting centers, as well as technical differences in the...

Presentation and Evaluation of Patients with Advanced Penile Cancer

Patients with advanced disease present with a host of constitutional symptoms. They may be cachectic, lethargic, and anemic particularly if an ulcerating inguinal mass has been bleeding intermittently. The performance status of these patients will determine the extent to which they will tolerate a multimodality approach to the management of their disease. Another feature of advanced disease is the development of hypercalcemia in the absence of osseous metastases. This has been reported in...

Locally Advanced Penile Cancer

Traditionally patients with penile cancer have been surgically managed using one of three procedures, circumcision for preputial tumors, partial penectomy for distal tumors involving the glans penis or distal penile shaft, total penectomy combined with a perineal urethrostomy for more extensive tumors infiltrating into the proximal penile shaft. These techniques have been utilized in order to ensure clear tumor margins which traditionally have been defined as being 2 cm. However, studies have...

Risk Factors for the Development of Urethral Cancer

The risk factors associated with the development of urethral cancer include advancing age, chronic inflammation of the urethra, and urethral stricture disease. Previous urethral surgery and radiotherapy are also risk factors as are immunosuppression and smoking. Infection of the distal urethra with HPV-16 has also been implicated.2,14 A study by Cupp et al. reported that all six of their patients diagnosed with distal urethral carcinomas and one at the penoscrotal junction was HPV-16 positive...

Staging of Urethral Cancer

The most commonly used staging system utilizes the TNM classification as indicated in the 2010 AJCC cancer staging handbook (Table 8.3).13 The alternative staging system known as the Whitmore classification is shown in Table 8.4.15 Table 8.4 The Whitmore classification of urethral tumors Stage 0 Confined to mucosa only (in situ carcinoma) Stage A Into but not beyond lamina propria Stage B Into but not beyond the substance of the corpus spongiosum, or into but not beyond the prostate Stage C...

The Clinical Presentation of Male Urethral Cancer

The diagnosis of early urethral cancer is difficult and the presentation is often delayed by which time the tumor is obvious. Urethral bleeding, urethral discharge, and hematuria are common presenting symptoms as are urinary frequency and obstructive voiding symptoms (Table 8.5). Recurrent urethral strictures, penile pain, and even a palpable mass in the penile urethra may also be a presenting feature. In the later stages periurethral abscesses, urethrocutaneous fistulae, and incontinence may...

The Diagnosis and Investigation of Urethral Cancer

The management of urethral cancer depends on the anatomical location of the tumor and the staging of the primary lesion and the status of the inguinal lymph nodes. Examination of the penis may reveal a discrete nodular lump in the anterior urethra. More distal tumours progressively infiltrate the glans spongiosum and eventually extend out of the urethral meatus (Fig. 8.2). The physical examination should also include a bilateral inguinal examination in order to detect the presence of palpable...

The Role of Radiotherapy in the Management of Urethral Cancer

External beam radiotherapy (EBRT) and brachytherapy implants or a combination of both have been used in the management of urethral tumors. Historically EBRT has been used in the adjuvant setting following surgery for male urethral cancer but is often a primary treatment for urethral cancers in females. A number of studies have shown that the outcomes following radiotherapy alone are poor.3 3 However, these studies involve selected patients who may have presented with poor prognostic features or...

Penile Cancer Imaging

As regards neoplasms of the penis, it has been demonstrated that lymphotropic nano-particle-enhanced magnetic resonance imaging (LNMRI) with ferumoxtran-10 can accurately predict the pathological status of regional lymph nodes.33,34 Ferumoxtran-10 is made up of superparamagnetic iron oxide nanoparticles, which are phagocytosed by macrophages in normal lymph nodes and these show homogeneous uptake of ferumoxtran-10 and appear dark on T2-weighted MR images. However, lymph nodes containing...

Patients Experiences Prior to and at the Time of Diagnosis of Penile Cancer

Psychology undoubtedly plays a role in the delay in diagnosis that is commonly seen in this disease as evidenced by the frequency with which patients present with advanced cancer, and the significant delay that commonly occurs between the development of symptoms and the presentation to a physician. For instance, in one series of 700 men, over 50 had at least T2 disease at the time of diagnosis and treatment1 while in a second series of men with a localized tumor of the penis, treated by laser...

Molecular Biology of Penile Cancer

Much of the research into penile cancer has been based upon clinicopathologic factors as predictors of metastasis or survival. Focus is now shifting toward genetic and epigenetic events in penile cancer. Recently, an excellent review on this topic was published by Muneer et al.26 They discuss the complexity of interaction of HPV within the cell, much of which is derived from cervical cancer research in women. In a systematic review of 31 papers published between 1986 and 2008, constituting data...

Total Glans Resurfacing TGR

Although the topical therapies described may be successful, they all have limitations and side effects. They require high levels of patient compliance and can be awkward to apply, often causing discomfort to the patients. Furthermore, the diffuse nature of EQ poses the risk of insufficient treatment and recurrence. Patients therefore need careful long-term surveillance and frequent re-treatment. The technique of TGR offers a surgical alternative. This procedure, first described by Bracka for...

Management of the Groin in Clinically Node Positive cN Patients

Surgery remains the cornerstone of treatment in patients with metastatic disease in the groins. Cure can be attained in approximately 80 of patients who have one or two involved inguinal nodes without extranodal extension.1-7 Preoperatively, inguinal nodal involvement can be found with FNAC or excision biopsy. We prefer FNAC as it is easily performed in an out-patient setting, it is relatively noninvasive, and it does not interfere with the subsequent lymphadenectomy. Although the reported...

Chemotherapy for Metastatic Disease

The data on the use of single-agent chemotherapy are limited due to the studies involving small numbers and mixed populations whereby chemotherapy has been administered in different settings and stages of the disease. Small studies have demonstrated modest efficacy of bleomycin, methotrexate, cisplatin, and 5-FU, either as single agents or as combination therapy, as illustrated in Table 12.1. The use of bleomycin was first reported in 1969 whereby twice weekly intravenous intramuscular...

Surgical Excision

Weeks After Mohs Surgery

Patients developing an extensive field change or recurrent disease are best managed by surgical excision. Repeated topical therapy can result in unsightly scarring and a denuded glans that can make clinical monitoring difficult. Intractable in situ disease or non-invasive verrucous disease can be effectively treated by excising the diseased area with an adequate margin combined with split thickness skin grafting, or by underlying corpus spongiosum in quadrants Fig. 5.12 Glans resurfacing...

Penile Carcinomas with Glandular Features

Penile Cancer

Adenosquamous carcinoma is a rare SCC variant characterized by the presence of solid squamous tumor nests intermingled with areas of glandular differentiation. About a dozen cases have been reported.9 16,60-64 The tumor originates in the glans Fig. 3.17 Carcinomas with glandular features. (a) In adenosquamous carcinoma areas of glandular differentiation are intermingled with squamous features. Tumor is highly infiltrative and squamous areas are of high grade. (b) The pseudogland, a structure...

Adjuvant Chemotherapy

The role of adjuvant chemotherapy is uncertain. Studies published in the 1980s suggested a potential benefit of adjuvant chemotherapy in patients with documented inguinal metastases who were treated with inguinal lymphadenectomy combined with adjuvant chemotherapy using VBM (vincristine, bleomycin, methotrexate).9,18 However, these small uncontrolled studies do not justify the implementation of adjuvant chemotherapy as standard care. Patients with pelvic nodal involvement and extranodal...

Neoadjuvant Chemotherapy

Interestingly, durable complete remissions can be obtained in patients with primary resectable and nonresectable locally advanced nodal and soft tissue disease by neoadjuvant chemotherapy followed by surgical removal of residual disease.9 10 In a review on advanced penile carcinoma, Culkin and Beer combined the results of all available studies on cisplatin-based induction chemotherapy. 1 1 Clinical responses were found in 24 of 35 patients (69 ) and 15 of the responding patients (43 ) underwent...

Nomograms

Nomograms are mathematical predictive models integrating prognostic information arising from the main clinical and or pathological variables, thus improving their prognostic accuracy. The first nomograms concerning penile cancer were published by Ficarra and Kattan in 2006. Three nomograms were published with the aim of predicting inguinal lymph node involvement44 and 5-year cancer-specific survival of penile cancer patients.45 More recently, Baghat et al. proposed a similar nomogram again with...

Penile Cancer Prognostic Index

In 2009 Chaux et al. proposed a new integrated pathological tool to predict lymph node involvement and survival in patients with penile SCC. This system included Tumor thickness Growth pattern Grade Lymphatic and or Vascular embolization Corpora cavernosa infiltration absent Corpus spongiosum infiltration Urethra infiltration Clinical lymph node stage 50 100 150 200 250 300 350 400 450 500 0.9 0.85 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.05 0.01 Fig. 10.6 Kattan Nomogram predicting 5-year...

Effects of Treatment for Penile Cancer on Quality of Life

Penile Cancer

Data regarding quality of life following surgery for penile cancer has been reviewed.17 The authors in this review identified 128 men from 6 separate studies in whom quality-of-life data had been collected, of which 5 were retrospective studies. Control groups were rarely assessed. They found that any conclusions from the data were limited by the many and varied instruments used to assess quality of life, by the methodology used to collect the data, and the small numbers of patients studied and...

Surgical Procedures to Gain Additional Penile Length

A number of techniques can be utilized in order to gain additional penile length. 1. The penis can be completely degloved and this allows division of the suspensory ligament. Reattachment to the inferior pubic bone with 2 0 ethibond sutures ensures that the penis does not retract back (Fig. 7.6). 2. Where there is a prominent peno-scrotal web, a scrotoplasty can be performed which again allows the patient to hold on to the penile shaft and direct voiding while standing.10 3. In patients with a...

Malignant Melanoma and Nonepithelial Tumors 351 Malignant Melanoma

Penile Cancer Images

Primary malignant melanoma of the penis is a rare disease accounting for less than 1 of all penile cancers.23,96 Preferential location is in the glans (60-80 of all cases), followed by the penile shaft and foreskin.97 Melanomas of the distal penile urethra are even rarer but have been reported and tend to affect the fossa navicularis and infrequently the pendulous urethra or meatus urethralis.23,98,99 Grossly, they present as small, brown or black, often ulcerating, lesions and the clinical...

Nanotechnology and Cancer Treatment

Nanotechnology allows the opportunity to deliver powerful cytotoxic agents to specific cancer cells without deleterious effects to other organ systems. However, lack of progress in avoiding degradation in vivo before achievement of therapeutic benefit has impeded major advances to date. Nonetheless, some examples exemplify the exception to this. Liposomal delivery systems have now overcome take-up by the reticuloendothelial system, which has historically compromised effectiveness.23...

Artificial Erection Technique

We routinely use intracavernosal prostaglandin E1 (alprostadil) at a dose of 10 mg when scanning tumors with both ultrasound and MRI. This stretches the tunica albuginea, making defects or invasion easier to see, and it increases contrast between intermediate signal tumor and high signal corpus spongiosum or caverno-sum. For patients with erectile dysfunction, the dose may be increased to 20 mg (especially if it has been used before), and in young patients with normal erections it can be...

Characteristics of HPVRelated Precursor Lesions

Intraepithelial Lesion Penis

Characteristics of HPV-related precursor lesions are presented in Fig. 1.1. Genital Bowen's disease, erythroplasia of Queyrat (EQ), and Bowenoid papulosis (BP) are clinical presentations of high-grade PIN. Bowen's disease and EQ are usually found in elderly men, being present on the follicle bearing skin and the mucosa of the penis (i.e., glans or prepuce), respectively. Bowen's disease presents as a single, scaly plaque, located on keratinized genital skin. EQ usually presents as one or more...

Penile Cancer and Its Precursor Lesions 141 Penile Cancer and Adjacent Lesions

Penile cancers are thought to arise from the progression of precursor lesions and can be subdivided into HPV-positive and HPV-negative cases. The HPV prevalence differs significantly by histological subtype. Similar to vulvar and head and neck carcinomas, squamous cell carcinoma of the basaloid and warty type display the strongest association with hrHPV (ranging from 66 to 100 ) and their etiological relationship with hrHPV infection is most plausible.4 19,32,33 The remaining penile squamous...

Vascular Invasion

Penile Lymphedema

Several reports have established the value of vascular (either lymphatic or venous) invasion as a prognostic factor for penile cancer metastasis.133 135138 155 Lymphatic invasion is observed more frequently (Fig. 3.20b) although venous invasion can Table 3.3 2009 TNM classification of penile cancer T - primary tumor TX T0 Tis Ta NX Regional lymph nodes cannot be accessed N0 No palpable or visibly enlarged inguinal lymph node N1 Palpable mobile unilateral inguinal lymph node N2 Palpable mobile...

Malignant Epithelial Tumors with Clear Cell Features 3461 Clear Cell Carcinoma

Penile Cancer

Clear cell carcinomas of the penis are rare tumors of probably sweat gland origin characterized by the presence of neoplastic cells with intracytoplasmic prominent PAS-positive material.19 Tumors preferentially affect the foreskin inner mucosa and are consistently HPV positive, mainly genotype 16. Clear cell carcinomas are composed of solid proliferations of clear cells, sometimes with geographical areas of necrosis. Histology is of a high-grade tumor with evident nuclear atypias. Extensive...

Minimally Invasive Staging Techniques

To circumvent the above-mentioned dilemmas regarding lymphadenectomy, minimally invasive staging techniques have been developed. The basis of these techniques is to limit the morbidity in patients with pathological node-negative (pN0) groins, and to identify occult metastases at the earliest opportunity. Only patients with proven lymphatic spread undergo a completion therapeutic radical lymphadenectomy. In the last two decades, two approaches have been introduced worldwide modified inguinal...

Chemoradiotherapy

In locoregionally advanced disease (large inoperable primary tumor, N2 N3 or extra nodal extension), survival rates are poor despite extensive surgical treatment so new treatment strategies are required. As described in the previous sections surgery, radiotherapy and chemotherapy are all effective modalities in the treatment of penile cancers. Therefore, a multimodality approach with combinations of these modalities seems a logical step. Radiotherapy (RT) in combination with concurrent...

Psychological Effects in Men Who Have Undergone Treatment for Penile Cancer

The psychological effects of penile cancer surgery have been poorly researched, although it is relatively easy to speculate on the relevant issues. Mental illness has been observed in 20 of men who have undergone treatment for penile cancer, most commonly related to anxiety disorders. 1 3 The central theme relates to the patient's perception that masculinity has somehow been lost or diminished.4 There will be a notable change in the appearance of the penis, and a probable loss of length for...

Ultrasound and MR Appearance of Lymph Nodes

Liquefaction Lymph Node Ultrasound

Normal lymph nodes are usually ovoid in shape, with a fatty hilum and an organized vascular pattern radiating from the hilum57 (Fig. 4.14). Some features, such as focal areas of necrosis, are highly specific for malignancy, and in general malignant nodes tend toward roundness and may lose their fatty hilum58 (Fig. 4.15). One recent study of the use of ultrasound in 44 patients, the majority of whom had penile cancer, showed that in 42 44 patients with metastasis at least one of the following...

Sexual Experiences Following Treatment for Penile Cancer

Once surgery has taken place, the fears that initially dominated, namely the fears for recurrence and survival are gradually replaced by concerns regarding rehabilitation, particularly regarding urinary and sexual function. A number of studies have investigated sexual function following surgery for penile cancer, but the literature regarding voiding function is extremely limited. Studies investigating patients who have undergone a partial or total penectomy for penile cancer have been limited...

Genital Lichen Sclerosus Et Atrophicus LS

Condyloma Acuminata Papule

Balanitis Xerotica Obliterans (BXO) is now better defined as the male genital variant of lichen sclerosus et atrophicus (LS). It was initially described as a chronic, progressive, scleroatrophic inflammatory process of unknown etiology affecting the glans penis, prepuce, and in advanced cases, the anterior urethra and meatus, either individually or in any combination. It occurs almost exclusively in uncircumcised men. Lesions classically appear as pale, atrophic plaques, which may coalesce and...

The Use of Chemotherapy and Chemoradiation

Penis Needle

Combination therapy in the form of chemotherapy and radiotherapy is utilized in an attempt to improve the long-term outcomes for patients diagnosed with urethral Fig. 8.7 Interstitial brachytherapy of the penile urethra using hypodermic needle and plastic template. The penis is kept away from the testicles using a sponge (From Gerbaulet et al.34. Reprinted with permission) Fig. 8.7 Interstitial brachytherapy of the penile urethra using hypodermic needle and plastic template. The penis is kept...

The Radial Artery Forearm Flap Phalloplasty

Penile Cancer

This is often considered the gold standard phalloplasty as it allows the formation of a cylindrical and sensate phallus with a urethra that reaches the tip and which is less prone to complications. The disadvantage is that it leaves a considerable donor site defect on the arm which some patients find unacceptable. The nondominant forearm is used in all patients having checked the vascular competency of the superficial and deep palmar arteries with an Allen test followed by a duplex ultrasound...

Abdominal Pubic Phalloplasty

Pubic Phalloplasty

This technique is commonly used for phallus reconstruction in transsexuals but can be modified for use in penile cancer patients although no published data are available for this group.29 The advantages of this technique are that there is no donor site defect on the arm and that the operating time is shorter. The phallus however is relatively insensate, hairy, and prone to urethral complications.29 The phallus is fashioned from a flap of anterior abdominal wall skin, 12 cm wide and 12-14 cm...

Growth Factor Receptors and Tyrosine Kinases

Growth factor receptors mitigate their intracellular signal transduction pathway via intracellular tyrosine kinases that modulate cellular functions such as protein synthesis, cell turnover, cell adhesion and migration, among other processes. Several growth factor receptor inhibitors and tyrosine kinase inhibitors (TKIs) have been developed in the last decade. They have entered clinical use, notably in renal cell cancer where agents such as sunitinib, sorafenib, and bevacizumab are showing...

Penile Cancer Staging Modifications to the 6th Edition TNM Staging System

The TNM staging system is a widely accepted staging tool. However, deficiencies in the 6th edition of the American Joint Committee on Cancer (AJCC) were highlighted in a report of 513 cases treated over a 50-year period at a single center.1 They described no difference in survival between stages T2 and T3 and nodal stages N1 and N2. Importantly based upon their own data they recommended changes in the staging system (i.e., the existing sixth edition TNM) with more meaningful prognostic...

Giant Condyloma Accuminatum Bushke Lowenstein Tumor

Condyloma acuminata are warty, exophytic growths which can affect any part of the anogenital region and are generally considered benign. On the penis, lesions typically occur around the coronal sulcus and frenulum, but can also be found as flat lesions on the penile shaft. They can occasionally extend into the anterior urethra, but extension into the posterior urethra and bladder is usually only seen in immuno-compromised patients.22 They are due to infection with low-risk HPV types 6 and...

Determination of Malignancy in Hyperplasias and Extremely Low Grade Neoplasms

Pseudohyperplastic Carcinomas Penis

Squamous hyperplasias are very common penile lesions that often accompany diverse benign and malignant conditions, sometimes simulating neoplastic processes.35,36 Their morphological aspect is variegated and the surgical pathologist should be aware of their proteiform presentation and learn to separate them from significant neoplastic conditions. Squamous hyperplasias commonly are flat on the surface and on the interface between lesion and stroma, but other variants such as verrucous,...

Antero Lateral Thigh Flap Phalloplasty

The anterolateral thigh flap is another good option for phallic reconstruction.33 This is a musculocutaneous (perforator) rather than a fasciocutaneous based-flap and is based on the perforator vessels through vastus lateralis and rectus femoris from the descending branch of the lateral circumflex femoral artery (Chap. 7). The ALT flap is very reliable from a vascular point of view and is commonly used in reconstructive surgery. Rubino et al. described the ALT flap in order to create a...