eMedicine Specialties > Urology > Cancer, Bladder, Penis, and Urethra

Penile Cancer: Treatment

Author: Stanley A Brosman, MD, Clinical Professor, Department of Urology, University of California at Los Angeles Medical School
Contributor Information and Disclosures

Updated: Dec 3, 2008

Treatment

Medical Therapy

The primary goal in the management of penile cancer is to eliminate the malignancy while preserving a cosmetically acceptable and functional penis. Achievement of this goal depends on early diagnosis and treatment, meaning that immediate biopsies of suspicious penile lesions are necessary.

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 penile cancer, but, unfortunately, few patients with penile cancer are candidates for radiation therapy. 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
    • Various 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 hours per day 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 involves 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 include 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% in patients with minimal metastatic disease.

Although chemotherapy has been generally ineffective in treating patients with large tumor burdens, Bermejo et al reported on 10 patients with pelvic and inguinal metastases who were managed with combination chemotherapy (ifosfamide, paclitaxel, cisplatin) followed by surgery. Four patients had a complete response, one a partial response, and 5 had stable disease. The median survival in this group was 26 months, although those with 3 or fewer nodal metastases had a median survival of 48 months.12

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 penile tumors confined to the prepuce, circumcision may be adequate. Attempts to treat cancers larger than 1.5 cm have led to a recurrence rate of 50%. Margins of 2 cm have traditionally been considered necessary to reduce local recurrences, but recent evidence has shown that such wide margins may not be needed, depending on the stage and grade of the cancer. Squamous cell cancers tend to require larger margins than Bowen disease. 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 repeated 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 via 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, perineal urethrostomy can be performed.

Another surgical technique is Mohs micrographic surgery (MMS), which is applicable in 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 with more radical surgery; however, more procedures are often necessary.

Shindel et al reported on 33 patients who underwent a total of 41 Mohs procedures. An average of 2.6 ± 1.4 stages was necessary. Five procedures were terminated because of positive margins or the defect size. Follow-up data were available in 25 patients at a mean time of 58 ± 63 months. Eight patients (32%) had recurrences; 7 were treated with additional MMS and one with penectomy. Two patients had tumor progression, and one died of metastatic disease.13

In 2001, Brandes et al reported their experience using MMS in 20 patients who had 28 cancers and 28 procedures.14 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 undergo lymphadenectomy, but all refused.

Skin defects were treated with 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.

Gulino and associates have reported on a surgical technique that utilizes the distal urethra for glans reconstruction. They have demonstrated the ability to dissect and mobilize the entire penile urethra and use the redundant portion to cover the cavernous apexes. They have reported that their patients were able to maintain functional use of their penis.15

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 penetrates only 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.

Ozsahin and colleagues conducted a retrospective study on men who received various therapies.16 They reviewed the medical records of 60 men with nonmetastatic invasive squamous cell carcinoma. Partial or total penectomy was performed in 27 men, brachytherapy in 8, and primary external beam radiotherapy in 21. Four patients refused radiotherapy after excisional biopsy revealed margin-positive disease. Twenty-two of the 27 men who underwent penectomy patients and 7 of the 8 who underwent brachytherapy received external beam radiation to manage recurrent local disease.

Local failure was more common in those who underwent organ-sparing procedures (56% vs 13%; P =0.008). No survival difference was found between those who underwent penectomy and those who underwent radiation therapy. The authors did not have the data to assess functional status.

This information emphasizes the need for careful follow-up in patients with penile cancer.

Lymphadenectomy

Following the treatment of the primary penile tumor, management of the inguinal lymph nodes must be addressed. The decision to resect the inguinal nodes in patients with no evidence of adenopathy, either clinically or after imaging studies, is controversial. The incidence of occult metastases in patients who have no palpable adenopathy is 20%-25%.

Kroon et al have reported that early resection confers a survival benefit over delayed resection.17 Because of the morbidity associated with this surgery, some urologists have contended that observing these patients is safe. The cure rate among patients with cancer-positive inguinal nodes approaches 80%. The decision to perform an inguinal lymphadenectomy 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.

A modified approach, as suggested by Bouchot et al, diminished the rate of complications by nearly 8-fold, but most of the patients (95%) had negative nodes.18 A modified inguinal lymphadenectomy has been advocated by D’Anacona et al. In this procedure, a 5-cm incision is made over the femoral canal. They advocate sparing the saphenous vein and using the adductor longus muscle as the median border, the femoral and saphenous veins as the lateral border, and the inguinal arcade as the superior border. Their complication rate decreased from 87.5% for the radical node dissection to 38.9% using the modified technique.19

Bilateral lymphadenectomy is necessary when the nodes are palpable or appear abnormal on CT scanning or MRI. The lymphatic drainage extends to both inguinal areas, and the typical radical lymphadenectomy is associated with high morbidity. The nodes may be palpable because of the cancer or because of the infection associated with the primary cancer. Even when cancer has spread to 1-2 lymph nodes, cure is possible in nearly 75% with only lymphadenectomy. Almost 20% of patients with limited pelvic lymph node involvement can be cured. Negative lymph nodes do not always mean that metastases has not occurred, since 20% of patients have occult inguinal metastases and 30% of those with positive nodal disease have pelvic node involvement.

The grade and stage of the primary tumor is predictive of lymph node status. Patients with high-grade and high-stage cancers are likely to have nodal disease. Tabatabaei and McDougal found that 80%-100% of these patients had positive nodes, compared with 24% of patients with well-differentiated cancer. They also found that 61%-75% of patients with T2 cancers had nodal metastases, compared with 5%-10% of those with T1 disease. This study also emphasizes that nodal metastases occur in a significant number of men, even those with low-stage, low-grade cancer.7

The various techniques that have been described to identify the sentinel lymph node have improved dramatically. This diagnostic tool has been shown to be predictive of nodal metastases in the other inguinal nodes but experience with at least 25 patients is necessary to achieve accurate results and few centers see this many patients. Combining the surgical technique advocated by D’Anacona with sentinel node biopsy should further reduce the morbidity associated with this procedure.

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. Others have reported that this procedure offers a high degree of accuracy in identifying the sentinel node and, in those with negative nodes, the morbidity associated with an inguinal lymphadenectomy can be avoided. 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.20 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.21

By using preoperative lymphoscintigraphy and intraoperative use of the gamma ray probe (dynamic sentinel node biopsy) as developed by Horenblas et al22 and confirmed by Perdona et al,23 there is little reason not to evaluate the inguinal nodes. The results are similar to those provided by standard node dissection, but the morbidity is minimal. Still, Novara and associates caution that, because of the potentially high morbidity associated with inguinal lymphadenectomy, the routine use of this surgery cannot be supported in every patient.11

Lont et al reported that the extent of inguinal node involvement is predictive of the presence of pelvic node disease. Patients with 1-2 positive nodes who have no extracapsular growth and no poorly differentiated cancer do not require pelvic node dissection and have a 90% 5-year survival rate.24

Tobias-Machado et al used a minimally invasive endoscopic procedure called video endoscopic inguinal lymphadenectomy (VEIL) for removing inguinal nodes in 10 patients, all with nonpalpable nodes.25 VEIL, a video endoscopic technology, was used to treat the nodes on one side, and standard open lymphadenectomy was performed on the other. The complication rate conferred by VEIL was much lower. This is another example of new surgical techniques that will be effective and will result in less morbidity.

The indications for pelvic lymphadenectomy have not been clearly delineated in the absence of evidence for pelvic lymphadenopathy. When 2 or more inguinal nodes contain cancer, the probability of pelvic node involvement is increased and pelvic surgery is advocated even if the disease is micrometastatic. Patients with cancer-negative inguinal lymph nodes rarely have pelvic node involvement. In the absence of evidence for pelvic lymphadenopathy, surgery is unnecessary.

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 biopsy is performed, adequate depth is important to allow the pathologist to stage the depth of the tumor and to determine if any invasion has occurred. Patients who undergo local excision 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, 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 in 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 postoperative complications that should be prevented, if possible. Preservation of the dermis, Scarpa fascia, and saphenous vein help reduce the likelihood of these problems. Phlebitis and pulmonary embolism are additional concerns. Compression devices on the lower extremities and low-dose heparin therapy have been advocated.

Mortality associated with 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

Follow-up in patients with penile cancer 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 be used to 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

Few surgical complications are associated with 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 when the surgery was performed when the nodes were infected, resulting in sepsis.

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.

More on Penile Cancer

Overview: Penile Cancer
Workup: Penile Cancer
Treatment: Penile Cancer
Follow-up: Penile Cancer
References
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Further Reading

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Keywords

penile cancer, penile carcinoma, penis cancer, penile malignancies, cancer of the penis, carcinoma of the penis, squamous cell carcinomas, SCCs, penile tumor, penis tumor, warty growth, exophytic growth, smegma, human papilloma virus, human papillomavirus, penile autoamputation, pearly penile papules, hirsute papillomas, coronal papillae, balanitis xerotica obliterans, leukoplakia, condyloma acuminata, venereal warts, Kaposi sarcoma, Buschke-Lowenstein tumor, penile carcinoma in situ, penile CIS, erythroplasia of Queyrat, Bowen disease, complete penectomy, partial penectomy, radical penectomy

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Contributor Information and Disclosures

Author

Stanley A Brosman, MD, Clinical Professor, Department of Urology, University of California at Los Angeles Medical School
Stanley A Brosman, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Association for Cancer Research, American Association for the Advancement of Science, American College of Surgeons, American Medical Association, American Society of Clinical Oncology, American Urological Association, Association of Clinical Research Professionals, International Society of Urological Pathology, Société Internationale d'Urologie (International Society of Urology), Society for Basic Urologic Research, Society of Surgical Oncology, Society of Urologic Oncology, and Western Section American Urological Association
Disclosure: Nothing to disclose.

Medical Editor

Gamal Mostafa Ghoniem, MD, FACS, Fellowship Program Director, Clinical Professor of Surgery, Head, Section of Voiding Dysfunction, Female Urology and Reconstruction, Cleveland Clinic Florida
Gamal Mostafa Ghoniem, MD, FACS is a member of the following medical societies: American College of Surgeons, American Urological Association, Society for Urology and Engineering, and Society of University Urologists
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Dan Theodorescu, MD, PhD, Paul Mellon Professor of Urologic Oncology, Department of Urology, University of Virginia Health Sciences Center
Dan Theodorescu, MD, PhD is a member of the following medical societies: American Cancer Society, American College of Surgeons, American Urological Association, Medical Society of Virginia, Society for Basic Urologic Research, and Society of Urologic Oncology
Disclosure: Nothing to disclose.

CME Editor

J Stuart Wolf Jr, MD, FACS, David A Bloom Professor of Urology, Director of Division of Minimally Invasive Urology, Department of Urology, University of Michigan
J Stuart Wolf Jr, MD, FACS is a member of the following medical societies: American College of Surgeons, American Urological Association, Catholic Medical Association, Endourological Society, Society for Urology and Engineering, Society of Laparoendoscopic Surgeons, Society of University Urologists, and Society of Urologic Oncology
Disclosure: Terumo Corporation Consulting fee Consulting; Omeros Corporation Consulting fee Consulting

Chief Editor

Bradley Fields Schwartz, DO, FACS, Associate Professor of Urology, Director, Center for Laparoscopy and Endourology, Department of Surgery, Southern Illinois University School of Medicine
Bradley Fields Schwartz, DO, FACS is a member of the following medical societies: American College of Surgeons, American Urological Association, Association of Military Osteopathic Physicians and Surgeons, Endourological Society, Society of Laparoendoscopic Surgeons, and Society of University Urologists
Disclosure: Nothing to disclose.

 
 
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