AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• References

Penile carcinoma

Penile malignancies are uncommon, but, when they are diagnosed, they are psychologically devastating to the patient and often present a challenge to the urologist. Benign, premalignant, and malignant conditions must be distinguished from each other. Malignancies are usually squamous cell carcinomas and behave similarly to those occurring elsewhere on the skin.

Patients with carcinoma of the penis tend to delay seeking medical attention. Of these patients, 15-50% delay seeking medical attention for more than 1 year. This delay is attributed to embarrassment, guilt, fear, ignorance, and personal neglect. Patients often try to treat themselves with various skin creams and lotions. These may appear to be effective for a time, which further delays the diagnosis.

Delays may also occur because of the physician. Patients report that they receive various salves and antibiotics from their primary care physicians before they see a urologist. Whether or not delays in diagnosis and therapy affect survival is uncertain, but the ability to eliminate the cancer and retain a functioning and cosmetically satisfactory result is affected.

History of the Procedure

The typical therapy for penile cancer has been surgical. Superficial carcinomas have been managed with local resection, while invasive disease has been managed with partial or total penectomy and some degree of lymphadenectomy.

If men are diagnosed with invasive disease but no evidence of nodal metastases, some can be treated with local resection and penile reconstruction. Radiation therapy is applicable for some of these men.

The presence of a sentinal node has been identified in many of these men. Various imaging techniques have shown increasing sensitivity for finding these nodes and sparing some patients the need for bilateral inguinal lymphadenectomy.

Problem

Penile tumors can originate anywhere on the penis but are most commonly found on the glans (48%) and prepuce (21%). Tumors involve the glans and prepuce in 9%, the coronal sulcus in 6%, and the shaft in less than 2%. The common sites of origin may be related to constant exposure to smegma and other irritants within the prepuce.

Patients who are diagnosed with penile cancer have a variety of treatment options if the tumor is smaller than 2 cm and particularly if it is confined to the prepuce. The cancers tend to remain confined to the skin for long periods, but, when they invade into the deeper tissues, they have a greater propensity to invade lymphatics and blood vessels.

Frequency

Penile cancer is rare in Western countries; approximately 1000 men each year are diagnosed with this disease. This cancer accounts for 0.4-0.6% of all malignancies in the United States and Europe. In the rest of the world, the situation is different and represents an important health problem. Penile carcinoma represents 20-30% of all cancers diagnosed in men living in Asia, Africa, or South America.

In urban India, the age-adjusted incidence varies from 0.7-2.3 cases per 100,000 men. In rural India, the rate is 3 cases per 100,000 men. This accounts for more than 6% of all malignancies in men.

In Brazil the age-adjusted incidence is 8.3 cases per 100,000 people. In Uganda, this is the most commonly diagnosed cancer, with 1% of men being diagnosed by age 75 years.

The disease rarely occurs in circumcised men, particularly if they were circumcised as a neonate.

Penile cancer tends to be a disease of older men, with an abrupt increase in incidence in men aged approximately 60 years; incidence peaks in men aged 80 years. However, the tumor is not unusual in younger men. One study reported that 22% of the patients were younger than 40 years and 7% were younger than 30 years.

Etiology

The frequency of penile carcinoma varies according to hygienic practices and cultural and religious beliefs. Phimosis is present in at least 25-75% of men with this disease. Information about the presence of phimosis is often not recorded in underdeveloped countries.

Circumcision has been well established as an effective prophylactic measure for this type of cancer. Data from most large series have demonstrated that the disease is almost never observed in individuals who are circumcised in the neonatal period. The disease is found more frequently when circumcision is delayed until puberty. Adult circumcision offers little or no protection.

No firm evidence indicates that smegma acts as a carcinogen, although this belief is widely held. The role of viral infection continues to be studied. Both penile cancer in men and cervical cancer in women have been associated with the presence of herpes virus infection and human papilloma virus infection. In women whose sexual partners had penile cancer, the prevalence of cervical cancer is increased 3- to 8-fold. Human papilloma viruses 16 and 18 have been found in one third of men with penile cancer. Whether these viruses are involved with causation of the cancer or are found as saprophytes has not been determined.

Abnormalities considered to be premalignant include cutaneous horns, pseudoepitheliomatous keratotic and micaceous balanitis, balanitis xerotica obliterans, giant condyloma, and bowenoid papulosis (bowenoid papulosis is a benign condition). Penile intraepithelial neoplasia is also considered a precursor, but only 5-15% of these lesions develop into invasive squamous cell carcinoma. When carcinoma in situ (CIS) occurs on the glans, it is termed erythroplasia of Queyrat; however, when it occurs on the follicle-bearing skin of the shaft, it is termed Bowen disease.

The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program was used to gather data on 1605 men diagnosed with squamous cell carcinoma of the penis. CIS was diagnosed in 37% of this population, localized disease was diagnosed in 39%, regional disease was present in 13%, distant disease was present in 2.3%, and unstaged disease remained in 7.9%.

The proportion of men presenting annually with CIS tended to increase, although the number of men with localized disease decreased. Older age at the time of diagnosis was associated with a higher stage of disease.

The mean time until death from cancer was 66.6 months for those with CIS, 50.1 months for those with localized disease, 32.4 months for those with regional disease, and 7.4 months for those with distant metastases. Overall, 22.4% of the patients in this database died of this cancer.

Pathophysiology

Penile cancers begin as small lesions on the glans or prepuce. They gradually grow laterally along the surface, covering the entire glans and prepuce and invading the corpora and shaft of the penis. The cancers may be papillary and exophytic or flat and ulcerative. Untreated, penile autoamputation can occur.

The growth rates of the papillary and ulcerative lesions are similar, but the flat ulcerative lesions have a tendency to metastasize to the lymph nodes earlier and, therefore, are associated with a lower 5-year survival rate. Cancers larger than 5 cm and those involving more than 75% of the shaft are associated with a high prevalence of nodal metastases and a lower survival rate, but a consistent relationship among the size of the cancer, the presence of inguinal node metastases, and survival has not been identified.

The Buck fascia, which surrounds the corpora, acts as a temporary barrier. Eventually, the cancer penetrates the Buck fascia and the tunica albuginea, where the cancer has access to the vasculature and from which systemic spread is possible.

Metastasis to the femoral and inguinal lymph nodes is the earliest path for tumor dissemination. The lymphatics of the prepuce join with those from the shaft. These drain into the superficial inguinal nodes.

The lymphatics of the glans follow a different path and join those draining the corpora. A circular band of lymphatics that drains to the superficial nodes is located at the base of the penis.

The superficial inguinal nodes drain to the deep inguinal nodes, which are beneath the fascia lata. From here, drainage is to the pelvic nodes. Multiple cross connections exist at all levels, permitting bilateral penile lymphatic drainage.

Untreated, metastatic enlargement of the regional nodes leads to skin necrosis, chronic infection, and, eventually, death from sepsis or hemorrhage secondary to erosion into the femoral vessels. Clinically apparent distant metastases to the lung, liver, bone, or brain are unusual until late in the course of the disease, often after the primary disease has been treated. Distant metastases are usually associated with regional node involvement.

Penile carcinoma follows a relentless and progressive course that is fatal for most untreated patients within 2 years. Spontaneous remission has not been reported.

Clinical

Patients present with a lesion that has failed to heal, a subtle induration in the skin, a small excrescence, a papule, a pustule, a warty growth, or a large exophytic growth. A cancer may be a shallow erosion or a deep ulceration with rolled edges. Because most of these patients are uncircumcised, they may have a phimosis that obscures the tumor and allows it to grow undetected. Many men do not seek medical attention until the cancer has eroded through the prepuce and become malodorous because of infection and necrosis. Occasionally, this cancer is found incidentally on histopathology during a circumcision.

Rarely, a mass, an ulceration, a suppuration, or hemorrhage may manifest in the inguinal area because of nodal metastases.

Few symptoms are associated with the development of these cancers. Even when significant local destruction of tissue occurs, pain is infrequent. Patients with advanced metastatic cancer may report weakness, weight loss, and fatigue; the penile lesion may bleed.

The presence of a nonhealing penile lesion usually prompts the patient to visit a physician. While a carcinoma may manifest as a hyperemic patch on the glans characteristic of erythroplasia of Queyrat or as an ulcerated growth on the inner surface of the prepuce, the differential diagnosis includes benign and premalignant lesions.

Penile lesions can be categorized as benign, premalignant, and malignant neoplasms.

Benign lesions include pearly penile papules, hirsute papillomas, and coronal papillae. These lesions do not require treatment and are usually found on the glans in uncircumcised males. Rashes, ulcerations from irritation, and allergic reactions or infections must be considered.

Some histologically benign lesions are potentially malignant (premalignant) or have been associated with the presence of squamous cell carcinoma. The most common is balanitis xerotica obliterans. This is a variation of lichen sclerosis et atrophicus and manifests as a white patch on the prepuce or glans, where it usually involves the urethral meatus.

Leukoplakia manifests as solitary plaque or multiple whitish plaques, which often involve the meatus. Leukoplakia has been associated with squamous cell carcinoma.

Viral lesions include condyloma acuminata, which are soft papillomatous growths. They are known as venereal warts and have a predilection for the genital and perineal regions. These lesions are usually sexually transmitted by the human papilloma virus (see Human Papillomavirus for more information). Viral types 6, 11, 42, and 44 are associated with low-grade dysplasia. Types 16, 18, 31, 33, 35, and 39 are associated with neoplastic changes.

Kaposi sarcoma manifests as a cutaneous neovascular lesion that is raised, usually painful, and often ulcerated with a bluish discoloration. Patients with AIDS are predisposed to develop this condition.

Giant condyloma acuminata or a Buschke-Löwenstein tumor differs from the standard condyloma in that it displaces, invades, and destroys adjacent structures by compression, whereas the standard condyloma remains superficial and never invades. Despite their large size and invasive potential, Buschke-Löwenstein tumors show no signs of malignant change upon histologic examination.

Malignant carcinomas include variants of squamous cell carcinoma such as CIS, erythroplasia of Queyrat, or Bowen disease. The diagnosis depends on their appearance and the site of origin. Erythroplasia involves the glans, prepuce, or penile shaft, while similar lesions on the remainder of the genitalia and perineum are termed Bowen disease. Regardless of the terminology and clinical presentation, these are carcinomas with the same malignant potential; biopsies should be performed, and the carcinoma should be staged and treated.

INDICATIONS

Section 3 of 11  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• References

The indications for therapy and the options for therapy depend on the histologic diagnosis of cancer established by biopsy findings, the location and size of the tumor, and the presence or absence of palpable inguinal lymphadenopathy. All of these patients require therapy because spontaneous regression does not occur and because the cancer ultimately causes death.

Rippentrop et al studied the surgical therapy status for the 1605 men identified in the Surveillance, Epidemiology, and End Results database. Surgical therapy was recorded in 1422 patients, of whom 721 (50.7%) received some form of surgery. Excisional biopsy was performed in 19.7%, and topical therapy with laser or cryoablation was used in 0.3%. Of those undergoing surgery, 13.1% had partial penectomy without lymphadenectomy, 2.1% had a combined procedure, and only 0.5% had radical surgery.

RELEVANT ANATOMY

Section 4 of 11  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• References

The anatomy of the penis has important implications for the diagnosis and treatment of penile cancer. Embryologically, the 3 erectile bodies of the penis arise from the paired genital tubercles, which give rise to the corpora cavernosa, the caudal portion of the urogenital sinus that creates the corpora spongiosum, and the paired urethral folds, which join in the midline.

For purposes of description, the penis may be divided into the root, which is located within the superficial perineal pouch and is the primary fixation point; the body, which contains the 3 corpora and the overlying tissues; and the glans, which sits as a cap on the corpora cavernosa but is a part of the corpora spongiosa.

The superficial fascia is continuous with dartos fascia posteriorly and with the Scarpa and Camper fascia anteriorly. The superficial fascia consists of a single layer with loose connections to the overlying skin.

The corpora are covered by a layer of dense fibrous tissue called the tunica albuginea. The corpora cavernosa are incompletely separated by the septum penis, a thin layer of fibrous tissue continuous with the tunica albuginea. The fascia overlying the corpora cavernosa blends with the fascia of the urogenital diaphragm. The erectile tissue within the corpora is composed of a spongelike network of endothelium-lined sinusoidal spaces.

CONTRAINDICATIONS

Section 5 of 11  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• References

No contraindications to either curative or palliative therapy are known.

WORKUP

Section 6 of 11  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• References

Lab Studies

• No specific laboratory studies or tumor markers are diagnostic for penile cancer.
• A general evaluation, which includes a CBC count; a chemistry panel with liver function tests; and an assessment of cardiac, pulmonary, and renal status, is helpful as a baseline and to detect any unsuspected problems.
• Patients with advanced disease may be anemic, with leukocytosis and hypoalbuminemia.
• Hypercalcemia has been found in some patients in the absence of metastases.

Imaging Studies

• MRI and ultrasonography are useful for local cancer staging and to assess the inguinal lymph nodes. These studies may be helpful for detecting tumor invasion into the corpora. MRI produces sharp images of the penile structures, is accurate for demonstrating invasion of the corpora, and can help the physician determine the extent of the cancer along the surface of the penis in patients with tumors larger than 2 cm.
• Both MRI and CT scanning can demonstrate enlarged pelvic and retroperitoneal lymph nodes.
• Rarely, chest radiography can help detect metastases, unless the patient has advanced disease.

Diagnostic Procedures

• The most important diagnostic test is a biopsy.
• • This may be an excisional biopsy if the cancer is small or the lesion is confined to the prepuce and a circumcision is acceptable.
  • The biopsy should contain tissue beneath the tumor, if this is feasible, in order to help stage the disease.
• CT-guided fine-needle aspiration of enlarged lymph nodes may aid the urologist in planning therapy.
• Sentinel node biopsies may be of assistance in determining the need for extensive inguinal lymphadenectomy

Histologic Findings

Most penile cancers are squamous cell carcinomas that demonstrate keratinization, epithelial pearl formation, and various degrees of mitotic activity. The normal rete pegs are disrupted, and invasive lesions penetrate the basement membrane and surrounding structures.

Erythroplasia of Queyrat, a red, velvety, well-marginated lesion usually occurring on the glans, is characterized by atypical hyperplastic cells that appear disoriented and vacuolated and have hyperchromatic nuclei and multiple mitotic figures. The submucosa shows capillary proliferation and ectasia with a surrounding inflammatory infiltrate rich in plasma cells.

Staging

No universal staging system has been established for penile cancer. A detailed and accurate assessment of the primary tumor, including identification of regional and distant metastatic disease, is important for selecting appropriate therapy and for assessing and communicating results.

The Jackson and TNM systems are used, although the TNM system is preferable. In the Jackson system, characteristics of the primary lesion, such as size and confinement to the epidermis (superficial or invasive), are not used. The presence and extent of nodal metastases is not addressed. Histologic criteria are not used, even though the grade and extent of invasion is important.

Most penile cancers are low grade, but correlation between grade and survival is lacking. High-grade disease is associated with regional lymph node metastases. The strongest predictor for survival is the presence or absence of nodal metastases.

The optimum surgical margin has been reduced from the classical 2 cm to 1 cm or, in some instances, to 0.5 cm, without any adverse consequences related to cancer recurrence or survival. The advantage of a smaller margin is important because nearly 80% of penile squamous cell carcinomas are distal, presenting on the prepuce, glans, or in the coronal sulcus. These lesions can be managed with local excision and reconstruction.

• The Jackson classification is as follows:
• • Stage I (A): The tumor is confined to the glans, prepuce, or both.
  • Stage II (B): The tumor extends onto the shaft of the penis.
  • Stage III (C): The tumor has inguinal metastasis that is operable.
  • Stage IV (D): The tumor involves adjacent structures and is associated with inoperable inguinal metastasis or distant metastasis.
• The TNM classification of the primary tumor (T) is below. Note that the following description is devoid of N (node) and M (metastasis) descriptions. These stages simply relate the presence or absence of nodal and distant metastases.
• • TX: Primary tumor cannot be assessed.
  • T0: Primary tumor is not evident.
  • Tis: CIS is present.
  • Ta: Noninvasive verrucous carcinoma is present.
  • T1: Tumor invades subepithelial connective tissue.
  • T2: Tumor invades corpora spongiosum or cavernosum.
  • T3: Tumor invades the urethra or prostate.
  • T4: Tumor invades other adjacent structures.

TREATMENT

Section 7 of 11  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• References

Medical therapy

Intraepithelial neoplasms such as Bowen disease or erythroplasia of Queyrat may be treated with topical 5-fluorouracil. This causes denudation of the malignant areas while preserving the skin. The use of this therapy depends on whether adequate biopsy specimens were obtained to ascertain that no invasion has occurred beyond the basement membrane.

Radiation therapy

Radiation therapy can be used as an alternative to surgery in selected patients. The psychological trauma associated with partial or complete penectomy has encouraged radiation therapists to explore various techniques of treatment for this disease. The number of patients who are candidates for radiation therapy is quite small. One of the advantages of radiation therapy is the potential to maintain potency.

Radiation therapy has disadvantages. Squamous cell carcinomas tend to be resistant, and the high tumor dose (ie, 0.6 Gy) necessary to treat the tumor may cause urethral fistulae, strictures, penile necrosis, pain, and edema. If the cancer is infected, the therapeutic effect of the radiation is diminished, while the risk of complications is increased.

Candidates for radiation therapy include young men with small (ie, <3 cm), superficial, exophytic lesions or noninvasive cancers on the glans or coronal sulcus. Other candidates are patients who refuse surgery or who have metastatic disease and need some form of palliative therapy.

Circumcision is recommended prior to initiating radiation therapy for cancers involving the prepuce. This allows better evaluation of the tumor stage and minimizes the morbidity associated with therapy. Morbidity includes swelling, irritation, moist desquamation, phimosis, and infection.

• External beam radiation therapy
• • A variety of dose-fractionated schedules have been reported, but the most widely accepted schedule for cancers smaller than 4 cm is 4,000 cGy in 20 fractions over 4 weeks to the entire shaft of the penis. Megavoltage beams with low-energy photons are delivered by opposed ports. The primary lesion and margins are boosted with an additional 0.02 Gy.
  • In carefully selected patients, the local control rate varies from 60-90%. Salvage surgery can be performed if local recurrence or significant adverse effects occur.
• Brachytherapy
• • Two techniques have been described. In one, a radioactive mold is placed over the penis and is worn by the patient for 12 h/d for 7 days. This delivers a 0.6-Gy dose to the tumor and a 0.5-Gy dose to the urethra. The other technique uses iridium Ir 192, which is placed into the penis and is removed when the predetermined dose has been delivered.
  • Circumcision is recommended prior to therapy, and the tumor should be smaller than 4 cm with less than 1 cm of corporal invasion. When these criteria are met, local control rates with penile preservation range from 58-89%.

Chemotherapy

A wide variety of agents and schedules have been used to treat patients with metastases beyond the pelvic and inguinal lymph nodes. The most commonly used drugs are cisplatin, bleomycin, methotrexate, and fluorouracil. Response rates for cisplatin monotherapy range from 15-23%, and these have been largely partial responses of short duration. Bleomycin alone or combined with radiation or vincristine and methotrexate has yielded a partial and/or complete response rate of 45%.

Surgical therapy

The standard of therapy for the primary cancer is local excision and either partial or total penectomy. The low prevalence of distant metastases, the morbidity associated with untreated local disease, the success of long-term palliation, and the survival rates, even in patients with advanced local disease, support the use of aggressive local therapy.

In patients with small tumors confined to the prepuce, a circumcision may be adequate. Attempts to treat cancers larger than 1.5 cm have lead to a recurrence rate of 50%. Margins of 2 cm are necessary to reduce local recurrences. Frozen sections at the time of surgery are often helpful, and a careful review of the specimen and permanent sections with the pathologist helps determine if the resection has been adequate.

A partial amputation is appropriate when the cancer involves the glans and distal shaft. A 2-cm margin is necessary, and attempts to limit the resection can result in a return to surgery to remove the recurrent tumor.

Local wedge resection is feasible in some situations, but this is associated with a recurrence rate of 50%. If surgical resection by either wedge or partial penectomy does not provide an adequate margin, a total penectomy should be considered. If the amount of residual penis and urethra is inadequate to allow the patient to urinate while standing, a perineal urethrostomy can be performed.

Another surgical technique is the Mohs micrographic surgery (MMS), which is applicable for some patients with noninvasive disease. This involves removing the skin cancer by excising thin layers of tissue and examining them microscopically. With a surgeon experienced in MMS, the ability to remove the cancerous tissue while preserving normal structures makes this an attractive technique because the results are similar to those obtained from more radical surgery.

In 2001, Brandes et al reported their experience using MMS in 20 patients who had 28 cancers and 28 procedures. Eighteen of these cancers were on the penile shaft and 10 were on the glans. The average size of the MMS defect was 44.9 X 30.9 mm². Five MMS procedures were terminated because of positive margins. Four patients had tumor invading the urethra, and one had a defect too extensive to continue the procedure.

CIS was present in 13 patients, squamous cell carcinoma occurred in 10, and verrucous carcinoma was found in 4. The tumors were staged as Tis in 5, T1 in 2, T2 in 8, and T3 in 2. No patients had clinical evidence of nodal or other metastatic disease. All patients with T2-3 disease or high-grade histologic findings were advised to have lymphadenectomy, but all refused.

Skin defects were treated by primary repair or granulation in 8 patients, skin grafts were used in 8 patients, and reconstructive surgery and urethroplasty were used in 5 patients.

The average follow-up time was 40 months (range, 3-109 mo). Nineteen of 20 patients were still alive, and 1 died from an unrelated cause without evidence of cancer. Local tumor recurrence developed in 6 (30%) of 20 patients. Three of these patients had Tis, one had stage T1, one had T2, and 1 had T2 verrucous disease. Tumor progression occurred in 1 of 6 patients with stages T1-T2 squamous cell carcinoma. No patient developed nodal or other metastatic disease. Two patients had more than one recurrence, and these were treated with MMS. The authors concluded that although the recurrence rate was high (30%), the survival rate was high and the rate of progression was low.

Laser surgery has been used for patients with superficial benign and malignant lesions. This therapy has been applied in cases of local and limited invasive disease. Four types of lasers have been used. They include carbon dioxide, Nd:YAG, argon, and potassium-titanyl-phosphate (KTP) lasers.

The carbon dioxide laser vaporizes tissue but only penetrates to a depth of 0.01 mm and can coagulate blood vessels smaller than 0.5 mm. The Nd:YAG laser can penetrate 3-6 mm depending on the power and can coagulate vessels as large as 5 mm. The argon and KTP lasers have less tissue penetration than the carbon dioxide laser and are rarely used.

Following the treatment of the primary tumor, consider management of the inguinal lymph nodes. These nodes may be enlarged because of cancer or infection. They are better assessed after a course of antibiotic therapy.

Bilateral inguinal lymphadenectomy should be performed if palpable lymph nodes are present after the primary tumor has been treated and the patient has been taking antibiotics. This surgery is usually performed several weeks after the primary tumor has been removed and the penile wound has healed.

The decision to resect the inguinal nodes in patients with no evidence of adenopathy, either clinically or after imaging studies, is controversial. Because of the morbidity associated with this surgery, some urologists have contended that observing these patients is safe. The cure rate for patients with cancer-positive inguinal nodes approaches 80%. The decision often depends on the grade of the cancer and its local extent. Cancers that have invaded through the basement membrane are much more likely to have nodal metastases than superficial tumors.

The indications for pelvic lymphadenectomy have not been clearly delineated. When 2 or more inguinal nodes contain cancer, the probability of pelvic node involvement is increased. Patients with cancer-negative lymph nodes rarely have pelvic node involvement.

Sentinel node biopsy or limited inguinal node dissection superficial to the fascia lata has been advocated. Resection of the sentinel inguinal lymph node is more controversial because many investigators have reported that the predictive information obtained from this procedure is too limited and is often inaccurate in predicting the extent of the cancer. Superficial dissection has been used for patients with no palpable nodes, but the procedure is extended to the deep fascia and femoral canal if any nodes are positive for cancer.

The value of sentinel node biopsy was evaluated by Horenblas et al in 2001 in 69 patients with clinical stage T2-3 squamous cell carcinoma. These patients had a combination of lymphoscintigraphy and intradermal patent blue dye injected around the tumor. The sentinel nodes were identified and resected.

Images of 158 sentinel nodes were obtained in 118 inguinal areas. Lymphatic drainage was bilateral in 55 patients (80%), unilateral in 12 (17%), and absent in 2 (3%). The sentinel nodes were identified on images in 117 of the 118 inguinal regions. Discrepancies between the images and the surgical findings were encountered in 26 patients (38%). The sentinel nodes were blue and radioactive in 73% of patients and radioactive alone in 27%.

Two of 5 patients with unilateral pN1 disease had a contralateral cancer-positive sentinel node. Metastases were found in other lymph nodes in 3 patients who had a cancer-positive sentinel node. Unilateral lymph node metastases were identified in 2 patients who originally had cancer-negative sentinel nodes. In one of these patients, the pathologist found a micrometastasis upon review of the original specimen.

Also in 2001, Izawa et al conducted a similar study in 30 patients. They used isosulfan blue dye and lymphoscintigraphy to evaluate the sentinel nodes in patients with T1-3 squamous cell carcinoma. Preoperative and intraoperative lymphoscintigraphy were performed in 14 patients. They found that at least one lymph node was either blue or had detectable gamma activity in 28 patients. Eleven inguinal fields in 9 patients had metastases, 5 of which were not palpable.

Preoperative details

After a short course of antibiotic therapy, surgery for the primary tumor can be completed. This allows for better staging and a chance for any lymph nodes enlarged secondary to infection to heal. No other specific study or preparation is necessary.

Intraoperative details

If the procedure is a biopsy, adequate depth is important to allow the pathologist to stage the depth of the tumor and determine if any invasion has occurred. Patients having local excisions or partial or total penectomy should have a 2-cm tumor-free margin. Serial frozen sections are used to achieve this goal. The local recurrence rate is significant, and attempts to salvage a portion of the penis often lead to a second surgery.

When only a short segment of penis is retained, a urethral reconstruction can be attempted to allow the patient to stand and direct his stream during urination. If the penis is too short, the patient may be better served with a perineal urethrostomy.

Several weeks following removal of the primary tumor, the inguinal lymph nodes can be resected if the surgeon determines that this procedure is appropriate. Several techniques have been described for this procedure. An inguinal incision provides good exposure for the superficial lymph nodes, but exposure of the femoral canal is difficult. An incision extending across the inguinal crease allows good exposure for both areas, but the large flap is more prone to complications. Some surgeons stage these bilateral procedures, but most complete the surgery at a single sitting. Adequate wound drainage is important because a large amount of serous fluid usually collects.

Postoperative details

Infection, undrained serous collections, ischemia and necrosis of the inguinal skin flaps, and peripheral edema are the postoperative problems that should be prevented as much as possible. Preservation of the dermis, Scarpa fascia, and saphenous vein help reduce the chances of these problems occurring. Phlebitis and pulmonary embolism are additional concerns. Compression devices on the lower extremities and low-dose heparin therapy have been advocated.

Mortality from this procedure has led to attempts to perform penile surgery and lymphadenectomy at the same sitting. Sepsis has been the cause of death. The current mortality rate is less than 1% by separating these procedures. The healing process is slow, and patients can expect to have limited activities for 6-8 weeks. Peripheral edema may be a permanent condition.

Follow-up

Patient follow-up is necessary to evaluate healing following the use of medicines applied to the tumor and following surgery, laser therapy, or radiation therapy. The frequency of follow-up visits depends on the therapy, but long-term observation is necessary to detect any areas of tumor recurrence.

Tumors can recur locally or distally. Physical examination can detect local recurrences or recurrence in the inguinal lymph nodes. Chest radiography and CT scanning of the abdomen and pelvis can help detect recurrences in the lungs or lymph nodes.

For excellent patient education resources, visit eMedicine's Men's Health Center and Cancer and Tumors Center. Also, see eMedicine's patient education article Cancer: What You Need to Know.

COMPLICATIONS

Section 8 of 11  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• References

Few surgical complications are involved in excision of the primary tumor or partial or complete penectomy. They include infection, edema, or urethral stricture if a new urethral meatus must be constructed.

Complications associated with inguinal node dissections are more common and are generally associated with more extensive dissections. Early complications include wound infection, seroma, skin flap necrosis, phlebitis, and pulmonary embolus. Late complications include lymphedema of the scrotum and lower extremities. Mortality after node dissection has been reported only in those situations in which the surgery was performed when the nodes were infected and sepsis ensued.

Complications associated with radiation therapy are primarily observed when tumors larger than 4 cm are treated. Complications include urethral strictures, which are reported in up to 50% of the patients; urethral fistula; penile necrosis; edema; and penile pain. Surgery following radiation therapy has been necessary in 20-60% of the patients.

OUTCOME AND PROGNOSIS

Section 9 of 11  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• References

Prognosis is primarily related to the presence or absence of inguinal node metastasis. Untreated patients with inguinal metastases rarely survive 2 years. Of those with clinically palpable adenopathy and histologically proven metastases, 20-50% are alive at 5 years following inguinal lymphadenectomy. The results are even better when the extent of the nodal involvement is considered. An 82-88% 5-year survival rate has been reported when only 1-3 lymph nodes are involved.

Radiation therapy in a select group of patients with small superficial lesions has been successful in a large number of patients. Control rates of 90-100% have been reported. In a group of 10 patients treated at Memorial Sloan-Kettering Cancer Center by electron beam therapy, all were effectively treated as determined by negative findings on posttreatment biopsy specimens. The most common complication was urethral stricture, which occurred in 4 patients. Nine of the patients retained sexual function.

In 2001, Novak and Dvoaeek used interstitial brachytherapy with iridium wires to treat 28 patients with squamous cell carcinoma. Six patients had Tis, 11 had T1N0, and 4 had T2N0. The prescribed dose of 0.6-0.65 Gy was delivered in 2-7 days. Local tumor control was evident in all patients at a mean follow-up of 65 months. Cancer has not recurred.

Current techniques, such as intensity-modulated radiation therapy, will probably become more effective and produce fewer adverse effects.

FUTURE AND CONTROVERSIES

Section 10 of 11  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• References

The major controversy regarding penile cancer is the indication for inguinal lymphadenectomy. Patients with clinically palpable or radiologically demonstrable lymph nodes after an adequate course of antibiotic therapy should have surgery. Depending on the size and extent of the apparent nodal involvement, a decision must be made regarding a superficial node dissection, which is associated with less morbidity, or a full inguinal node dissection, which includes the nodes in the femoral triangle.

In patients with clinically negative nodes, an argument can be made for observation. Because up to 80% of patients with inguinal node metastases can be cured with lymphadenectomy, monitoring patients and withholding surgery until metastases become evident may be a possibility. The patient must be compliant. However, experience indicates that superficial dissections in patients with microscopic metastases have few complications and limited morbidity.

In 2001, Slaton et al examined a group of 78 patients with squamous cell carcinoma in an effort to identify prognostic factors that would help predict extranodal metastases and select candidates for adjuvant therapy.

They identified 78 patients who had undergone inguinal lymphadenectomy, 42 of whom had nodal metastases. They found that the presence of bilateral nodal metastases, which occurred in 16 (38%) of 42 patients, and extranodal extension, which was found in 25 (60%) of 42 patients, were independent predictors for progression. They suggested that such patients be considered candidates for adjuvant therapy.

In the future, patients with superficial penile cancers can expect effective treatment with either surgery or radiation therapy and can expect to retain a functioning penis. Those requiring more extensive resections or penectomy can undergo penile reconstruction, which has produced acceptable results.

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• References

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Article Last Updated: Mar 30, 2006