Epidemiology

The American Cancer Society estimated that in the United States about 1300 new cases of penile cancer would be diagnosed and an estimated 300 men would die of this cancer in 2009. The frequency of this rare cancer is about 1 in 100,00 men in the United States. The incidence in Europe is equally low, also accounting for less than 1% of male cancers. The prevalence of this malignancy is much greater in Asia, Africa, and South America, however, where it may account for up to 10% of cancers in men. Almost all penile cancers arise from the normal skin cells of the penis. Approximately 95% of these tumors are squamous cell carcinomas (SCCa). These cancers may develop anywhere on the penis but have a predilection for the foreskin in uncircumcised males or the glans penis. In general, these cancers actually grow slowly and when found in the early stages are quite amenable to surgical cure using several modalities to be discussed later in this article. Unfortunately, little has changed since the turn of the 20th century when Young described the clinical presentation at that time. The patients continue to be asymptomatic and therefore the lesions frequently ignored. Rarely do they interfere with normal voiding, and pain or discharge frequently is a late manifestation of secondary infection or invasion.

Verrucous carcinoma of the penis is an uncommon form of SCCa and usually felt to be of low malignant potential. Specifically, although they may grow quite large and they may invade the deep structures of the penis, they rarely metastasize. It is also referred to as a Buschke-Lowenstein tumor and may be mistaken for a large benign genital wart. Other cancers that may develop on the penis are also rare and represent less that 2% of penile malignancies. These include

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  Melanomas, which usually are discovered late associated with systemic metastatic disease

  
  
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  Basal cell carcinoma, a slow-growing lesion unlikely to spread beyond the local disease

  
  
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  Adenocarcinoma, which arises from the sweat glands in the skin of the penis and is also called Paget disease of the penis

  
  
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  Rare sarcomas, which develop from blood vessels, muscle cells, and other connective tissues present in the penis.

Carcinoma in situ (TIS) is the earliest stage of SCCa of the penis. It remains an intraepithelial process, and therefore preinvasive. When this lesion involves the glans penis, it is referred to as erythroplasia of Queyrat, first described in 1911. Lesions on the shaft of the penis are called Bowen disease. In this stage of penile cancer, the abnormal cells are confined to the upper layers of the skin and are amenable to local excision, yet have a potential to recur if the local therapy is inadequate. TIS when inadequately treated may indeed progress to invasive carcinoma, in approximately 10% of cases, although metastases rarely occur. Clearly, understanding the pathologic nature of the patient’s cancer is essential to defining the appropriate initial management and establishment of his follow-up course of treatment or observation. Cancer eradication with attempts at organ preservation is the primary goal of this therapy.

The primary goal of the surgical management of penile cancer remains the complete eradication of the malignancy with minimal impact of function and cosmetic aspect of patient self-image, whenever possible. This aim should be readily achievable using modern methods of surgical intervention with stages TIS and T ₁ , noninvasive carcinoma, and limited early invasive disease. Stage T ₁ is defined in the TNM classification of penile cancer as a lesion 2 cm or less in maximal dimension but strictly superficial in its invasiveness or primarily exophytic in character. T ₂ disease is defined as larger tumors, between 2 and 5 cm, demonstrating minimal invasion. Invasive, stage T ₃ SCCa represents larger tumors, which involve deep structures of the penis, including corpora and urethra. T ₄ malignancies directly involve adjacent anatomic structures. Functional organ preservation recently has been shown feasible in selected cases of the more invasive lesions as well (T ₁ and small anatomically suitable T ₂ cancers). Standard therapy with necessary amputation of the penis in part or in total, however, still may be required, especially when there is delay in diagnosis and therefore extensive local disease or when local recurrence is documented following conservative primary treatments. A formal pathologic assessment via biopsy for histologic documentation and depth of invasion is the first necessary surgical step in diagnosis and staging required in order before consideration of the appropriate subsequent therapy. This may take the form of a punch biopsy, excisional biopsy of a relatively small tumor of the glans or foreskin, or an incisional biopsy of a larger lesion that cannot be excised completely. The biopsy always should include a portion of adjacent normal tissue with the specimen to allow optimal evaluation of the depth of invasion of the cancer. A dorsal slit may be required to gain adequate exposure of the preputial cavity. If a lesion involves the urethral meatus, urethroscopy is indicated to evaluate the urethra, and directed biopsies are performed if any suspicious areas are noted. As with most cancers, prognosis depends upon both grade and stage, with higher-grade tumors and those tumors involving the corporal bodies or with lymph node involvement less likely to be cured regardless of treatment. Human papillomavirus (HPV) infection is an established causal agent for at least 40% of penile SCCa.

Anatomy

Intimate understanding of normal anatomy ( Fig. 1 ) is a fundamental requirement for any surgical procedure, yet especially cogent when considering modifications of long-standing surgical approaches to maximize both oncologic outcome and quality of life. Functional and cosmetic results are paramount in modern penile cancer surgery. Fortunately, where surgical procedures and approaches have changed over the last several decades, penile anatomy has remained refreshingly unchanged, although vascular variations are noted. The penis is comprised of three erectile bodies, the paired corporus cavernosum, and the corpus spongiosum. The corporus cavernosum is covered with a dense fibrous tunica albuginea and is incompletely separated by the septum penis. The erectile tissue is composed of endothelial-lined sinusoidal spaces, which are fed via multiple small helicine arteries, which with increase in blood flow flood these spaces and by virtue of compression of equally small emissary veins are responsible the maintenance of an erection. The corpus spongiosum surrounds the urethra and in its distal extent becomes the glans penis. There is a deep fascia (Bucks) and a superficial fascia (dartos). At the root of the penis, there is continuity between the deep penile fascia and the fascia of the external oblique muscles, which extends over the pubic symphysis. The crura are attached to the pubic arch, and two ligaments support the penis, the more superficial fundiform ligament and a deeper triangular suspensory ligament that apically attaches directly to the pubic symphysis. The main arterial blood supply of the penis is from the hypogastric artery, which continues as the internal pudendal artery and then as the penile artery. There are three terminal branches of the penile artery, the bulbomembranous artery, the cavernosal artery, and the dorsal penile artery. There is a superficial venous system of veins that drains to the saphenous system (primarily to the left saphenous vein when a single superficial dorsal vein is present), an intermediate drainage system comprised of the deep dorsal veins and circumflex veins, and the deep venous system of crural veins and the emissary veins from the proximal corporus cavernosum. There is both somatic and autonomic nerve innervation of the penis. The somatic innervation is supplied via the pudendal nerve (S2-S4), with a shared innervation of the external sphincter (S2-S3). The parasympathetic nerves arise from S2-S4 and the sympathetic of the pelvic plexus arises from T11-L2. Lymphatic drainage of the penis is also important, although not as it relates to surgical management of penile cancer, but rather as a source of predictable regional cancer spread. The skin of the penis and prepuce drain primarily to the superficial inguinal lymph nodes. The lymphatic drainage of the glans penis and corporal bodies are somewhat more unpredictable, with possible paths to superficial or deep inguinal nodes or even the external iliac lymph chain.

Anatomy of the penis.

Anatomy

Intimate understanding of normal anatomy ( Fig. 1 ) is a fundamental requirement for any surgical procedure, yet especially cogent when considering modifications of long-standing surgical approaches to maximize both oncologic outcome and quality of life. Functional and cosmetic results are paramount in modern penile cancer surgery. Fortunately, where surgical procedures and approaches have changed over the last several decades, penile anatomy has remained refreshingly unchanged, although vascular variations are noted. The penis is comprised of three erectile bodies, the paired corporus cavernosum, and the corpus spongiosum. The corporus cavernosum is covered with a dense fibrous tunica albuginea and is incompletely separated by the septum penis. The erectile tissue is composed of endothelial-lined sinusoidal spaces, which are fed via multiple small helicine arteries, which with increase in blood flow flood these spaces and by virtue of compression of equally small emissary veins are responsible the maintenance of an erection. The corpus spongiosum surrounds the urethra and in its distal extent becomes the glans penis. There is a deep fascia (Bucks) and a superficial fascia (dartos). At the root of the penis, there is continuity between the deep penile fascia and the fascia of the external oblique muscles, which extends over the pubic symphysis. The crura are attached to the pubic arch, and two ligaments support the penis, the more superficial fundiform ligament and a deeper triangular suspensory ligament that apically attaches directly to the pubic symphysis. The main arterial blood supply of the penis is from the hypogastric artery, which continues as the internal pudendal artery and then as the penile artery. There are three terminal branches of the penile artery, the bulbomembranous artery, the cavernosal artery, and the dorsal penile artery. There is a superficial venous system of veins that drains to the saphenous system (primarily to the left saphenous vein when a single superficial dorsal vein is present), an intermediate drainage system comprised of the deep dorsal veins and circumflex veins, and the deep venous system of crural veins and the emissary veins from the proximal corporus cavernosum. There is both somatic and autonomic nerve innervation of the penis. The somatic innervation is supplied via the pudendal nerve (S2-S4), with a shared innervation of the external sphincter (S2-S3). The parasympathetic nerves arise from S2-S4 and the sympathetic of the pelvic plexus arises from T11-L2. Lymphatic drainage of the penis is also important, although not as it relates to surgical management of penile cancer, but rather as a source of predictable regional cancer spread. The skin of the penis and prepuce drain primarily to the superficial inguinal lymph nodes. The lymphatic drainage of the glans penis and corporal bodies are somewhat more unpredictable, with possible paths to superficial or deep inguinal nodes or even the external iliac lymph chain.

Anatomy of the penis.

Laser excision or ablation therapy

Penile laser surgery has been used clinically for treating selective penile cancers for 30 years. The lasers most commonly reported for this purpose are the carbon dioxide (CO ₂ ), neodymium:yttrium-aluminum-garnet (Nd:YAG), and less commonly, the potassium titanyl phosphate (KTP) lasers. The limitation of the CO ₂ laser is its depth of penetration, which is only 0.1 mm and therefore thought only suitable for carcinoma in situ lesions. Recent data published by Bandieramonte, however, demonstrate effective cancer control and 10-year recurrence-free survival of greater than 80% in patients with either in situ or T ₁ cancers. The 10-year salvage amputation rate was 5.5%, and there was no significant difference between TIS and T ₁ outcomes. Local recurrence was predictable using histologic parameters of margin status, depth of invasion, and tumor extension. This represents a significant improvement in long-term outcomes over earlier data reported by van Bezooijen in 2001, when local recurrence rates of up to 50% where documented. Colecchia recently reported using CO ₂ laser surgery on 56 patients with T ₁ SCCa. He noted that although 13 patients developed local recurrences, including 4 patients with multiple recurrences, that only 1 of the 13 patients required partial penectomy to control the local disease. With a median follow-up of 66 months, none of the patients died of penile SCCa, and the two patients found to have low-volume regional lymph node involvement were salvaged with lymphadenectomy.

Localized surgical management with the Nd:YAG laser produces protein denaturation at a depth of 6 mm. This has led to a preferential use of the Nd:YAG laser in cases where there is concern regarding possibility of SCCa beyond CIS. In Sweden, Windahl reported on a prospective study where the primary treatment of localized SCCa was with the CO ₂ laser, and the recurrences were then treated successfully with follow-up Nd:YAG laser therapy. The authors felt that the success of this combination local therapy was associated with highly satisfactory cosmetic results and function. Organ-preserving Nd:YAG laser surgery for TIS, T1, and selected cases of T2 invasive cancers is a reasonable first approached to oncologic cure (control) of penile SCCa. Long-term follow-up studies clearly demonstrate a relatively high recurrence rate, yet oncologic outcome and ultimate disease-free survival do not appear to be compromised by local recurrence, when long-term (>4 years) follow-up is assured. Indeed, this may be the best initial treatment option for those patients with grade 2 stage T ₁ tumors. Meijer and colleagues have suggested widening the field of initial laser excision as a means to successfully decrease the incidence of local recurrence, when laser therapy is used.

It is quite obvious that the cosmetic outcome of laser excision is superior to penile amputation. Laser treatment of localized penile carcinoma preserves satisfactory sexual function and self-image related to cosmesis allowing for improved quality-of-life assessment. Compared with other surgical options, men who undergo laser surgery are more likely to resume their normal sexual activities.