Partial and Total Penectomy in the Management of Invasive Squamous Cell Carcinoma of the Penis
FERNANDO P. SECIN
AGUSTÍN R. ROVEGNO
ANA MARÍA AUTRÁN GÓMEZ
RAFAEL SÁNCHEZ-SALAS
Penile cancer is an uncommon malignancy with specific geography-related incidence. Although high incidence rates account for up to 10% to 20% of all malignancies in developing continents, such as Asia, Africa, and South America, its incidence in Europe is low (one case per 100,000 people) (1). In the United States, it is estimated that 1,570 men will be diagnosed and 310 will die from this disease in 2013 (2).
There is an increasing body of literature supporting the association between sexually transmitted viral disease and penile cancer. Human papilloma viruses (HPV), especially types 16, 18, 31, and 33, are the most frequently detected types in penile cancer (3). In a large case series by Dillner et al. (4), HPV DNA was identified in penile neoplastic tissue. The authors found that in penile intraepithelial neoplasia, between 70% and 100% of the lesions were positive for HPV DNA, whereas invasive penile cancer was positive for HPV in only 40% to 50% of the cases (4).
However, the most important risk factor for invasive penile cancer is the presence of an intact foreskin. Penile cancer is rarely seen in Jews or in Igbos, an ethnic group of southeastern Nigeria, who ritually circumcise males on the eighth day of birth. The lowest incidence of penile cancer has been reported in Israeli Jews (0.1/100.000), making an argument in favor of the protective effect of circumcision (5). Schoen et al. (6) observed that the relative risk of invasive penile cancer for uncircumcised to circumcised men was 22:1. In a case-control study, neonatal circumcision was associated with a threefold decreased risk of cancer development, albeit 20% of penile cancer patients had been circumcised neonatally. When compared to men circumcised at birth, the risk for penile cancer was 3.2 times greater among those uncircumcised and 3.0 times greater on those circumcised after the neonatal period (7).
It appears that, enclosed preputial environment, associated with poor genital hygiene of the foreskin, chronic irritation, and exposure to certain etiologic agents, such as viruses, smegma, and hydrocarbons, may also play a causative role in the development of this tumor (8). A retrospective review of approximately 15,000 surgical specimens collected from the Igbos of Nigeria, over a period of 13 years, revealed four cases of penile carcinoma. One tumor arose at the glans penis. This localization pattern suggests that, in circumcised males, smegma-induced squamous carcinoma of the glans can be virtually abolished but not the ordinary squamous carcinoma that can develop by chance on the rest of the penis (9).
Other risk factors identified by case-control studies included chronic inflammatory conditions, such as balanoposthitis and lichen sclerosus, and PUVA treatment. PUVA is psoralen and ultraviolet A (UVA) photochemotherapy, traditionally used to treat psoriasis, vitiligo, atopic dermatitis, or alopecia areata. A consistent association was found between penile cancer and smoking, a dose-dependent association not explained by investigated confounding factors such as sexual history. Cervical cancer in the wife was not consistently associated with cancer of the penis in the husband (4).
Preventive measures that could be considered to reduce the risk of penile cancer include prevention of phimosis, local hygiene, treatment of chronic inflammatory conditions, limiting PUVA treatment, smoking cessation, and prevention of HPV infection (4).
Around 95% of penile cancers are squamous cell carcinoma (SCC) originating in the epithelium covering the glans, coronal sulcus, and/or foreskin. Several histologic subtypes have been described, each with distinctive clinicopathologic and outcome characteristics. The most common subtype is the SCC, representing 48% to 65% of penile carcinomas. Penile verruciform tumors encompass verrucous, warty (condylomatous), and papillary, not otherwise specified carcinomas. As a group, verruciform tumors are low-grade, with low metastatic and mortality rates. In contrast, basaloid and sarcomatoid carcinomas are among the most aggressive penile tumors. Other SCC variants, such as carcinoma cuniculatum and pseudohyperplastic, adenosquamous, and acantholytic carcinomas, are rare (10).
Penile cancer has a predictable natural history. In brief, it initially involves the glans in almost half of patients, followed by prepuce and/or penile shaft locations. Buck fascia and tunica albuginea penetration allows for infiltration of the corpus cavernosum, permeating the lymphatic system. Lymphatic spread is the rule. Tumor initially spreads to the superficial inguinal lymph nodes to continue into the deep inguinal and pelvic nodes. “Skip” lymphatic drainage is rare. If untreated, the inguinal metastases will enlarge, ulcerate through the skin (causing infection), or grow into the femoral vessels, producing potentially dangerous hemorrhage. Untreated patients with penile SCC usually die within 2 years of diagnosis due to uncontrollable locoregional growth or distant metastases. Hematologic metastases, spread to distant sites (e.g., lungs, liver, bone, and brain), are less common (1% to 10% in most large series) and usually occur late in the disease course. Distant metastases in the absence of regional node metastases are unusual (8).
Effective surgical intervention plays an essential role, in both the diagnosis and management of the primary disease, and is crucial for accurate staging and treatment of regional
inguinal and pelvic lymph nodes. Goals of surgical treatment for the primary tumor are excision with adequate margins and preservation of as much functional penis as possible for upright voiding and erectile function (11).
inguinal and pelvic lymph nodes. Goals of surgical treatment for the primary tumor are excision with adequate margins and preservation of as much functional penis as possible for upright voiding and erectile function (11).
Recent advances in the primary management of penile cancer have highlighted that penile-preserving approaches can be employed in select patients, whereby offering the potential of improved quality of life and erectile function preservation. Several clinical variables must be evaluated before considering penile-preserving approaches, including the primary tumor stage, grade, location of the lesion, and ability to maintain a “functional” penis. Complete tumor excision with negative surgical margins at the primary tumor site must never be compromised in order to eliminate the nidus for cancer dissemination as well as a potential site of local symptomatic recurrence. As we incorporate new surgical techniques to our armamentarium, we must ensure that cancer-specific outcomes of these approaches meet the established survival offered by the standard surgical treatment (12).
Delayed or incomplete surgical resections can have significant negative impact on patient survival, a situation made worse by the absence of effective systemic chemotherapy once metastatic disease occurs. Regional inguinal and pelvic lymph node dissection (PLND) remains an integral component of the treatment of invasive penile cancer with evidence mounting that a survival advantage exists for patients undergoing early prophylactic as opposed to therapeutic groin dissection (13). The management of lymph node involvement is described in Chapter 63.
DIAGNOSIS
The primary tumor may present as a nonhealing ulcer (Fig. 65.1), papule, indurated mass, or exophytic growth (Fig. 65.2). It may be associated with penile bleeding or purulent discharge. Physical examination of the primary penile lesion should evaluate and document the number of lesions, tumor dimensions (size), sites involved (foreskin, glans, shaft), color, morphology (flat, papillary, nodular, ulcerating, fungating), relationship with other structures (corpus spongiosum, corpora cavernosa, urethra), and boundaries (edges) (11) (Fig. 65.3).
 FIGURE 65.1 A nonhealing ulcer following circumcision. |
 FIGURE 65.2 Erythematous elevated and indurated lesion in glans. |
 FIGURE 65.3 Ulcerated penile tumor compromising the urethra. |
Clinical staging of the primary tumor can be incorrect in 26% of patients (Table 65.1). Understaging results from histologic infiltration not clinically evident and overstaging of absent infiltration may result from edema and infection (14).
All penile lesions that appear suspicious for malignancy should undergo histologic evaluation, using one of the following methods: incisional biopsy, tissue core biopsy, fine needle aspiration cytology, brush biopsy, or excisional biopsy (14).
For small discrete lesions, the biopsy procedure can be, at the same time, diagnostic and therapeutic. The biopsy specimen, regardless of location, must contain adequate underlying tissue to allow the pathologist to determine the depth of tumor invasion, an important predictor of local tumor recurrence and regional nodal metastases (15,16).
Some lesions are considered premalignant in SCC of the penis. Lesions sporadically associated with SCC of the penis are cutaneous horns and bowenoid papulosis. Lesions at intermediate risk of developing SCC include lichen sclerosus/balanitis xerotica obliterans (Fig. 65.4). Up to one-third of penile erythroplasia of Queyrat or Bowen disease will transform to invasive SCC and are thus considered high risk of developing SCC of the penis (17).
TABLE 65.1 2009 TUMOR-NODES-METASTASES CLINICAL CLASSIFICATION OF PENILE CANCER | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
For tumors involving only the prepuce, circumcision can be both diagnostic and therapeutic. Tumors involving the glans, glans and prepuce, coronal sulcus, or shaft are best approached with an initial excisional biopsy that includes ample underlying soft tissue to accurately determine the depth of invasion (11).
When deciding for a diagnostic biopsy only, an incision biopsy is the preferable option, taking a wedge of tissue that includes the tumor and adjacent normal tissue to improve histologic diagnosis. However, the histologic type and grade can be misinterpreted in 30%, the depth of invasion has been undetermined in 91%, and vascular invasion can be missed in 88% of cases (18).
Physical examination of the inguinal and pelvic areas to assess the lymph nodes is mandatory. Between 30% and 60% of patients presenting with SCC of the penis have enlarged lymph nodes in the groin (11). Ultrasound-guided fine needle aspiration cytology is indicated for both palpable and nonpalpable inguinal nodes because complete inguinal lymp node dissection (LND) is indicated in patients with regional node positivity (Fig. 65.5). Antibiotic treatment for 3 to 6 weeks before inguinal LND in patients with palpable inguinal nodes is recommended. Pelvic computerized tomography (CT) and magnetic resonance imaging (MRI) are not useful in patients with nonpalpable nodes. However, they are indicated in those with large, palpable inguinal nodes or in patients with confirmed inguinal lymph node metastasis (LNM) to detect iliac LNMs (Fig. 65.6). Abdominal CT and chest radiography or CT are advisable if the pelvic CT findings are positive to rule out distant metastasis (14,19) (Fig. 65.7). Positron emission tomography/CT is a promising method for detection of distant metastatic lesions and therapeutic strategy planning in penile cancer. However, few studies support its use possible due to its low incidence (20).
 FIGURE 65.4 Balanitis xerotica obliterans, a premalignant condition. |
 FIGURE 65.5 Ulcerated right inguinal nodes with a relatively small penile lesion. |
A full discussion with the patient concerning the degree of penile resection required, the anticipated functional deficit, and
the necessary reconstruction required is needed. Occasionally, plastic surgical consultation is requested if a wide local excision with complex rotational flap coverage is contemplated. If total penectomy is planned, a psychiatric consultation is recommended to be certain the patient has the emotional capacity to tolerate such a procedure (11).
the necessary reconstruction required is needed. Occasionally, plastic surgical consultation is requested if a wide local excision with complex rotational flap coverage is contemplated. If total penectomy is planned, a psychiatric consultation is recommended to be certain the patient has the emotional capacity to tolerate such a procedure (11).
 FIGURE 65.6 Pelvic CT to evaluate lymph node extension. |
 FIGURE 65.7 Chest CT scan show images consistent with lung metastasis. |
The extent of the negative margin required is controversial in penile cancer. Although a 2-cm surgical margin has been traditionally proposed, more recent data suggest that for low-risk tumors a 1-cm clearance is adequate for grade 1 and 2 lesions, and 1.5 cm for grade 2 tumors (21). Nonetheless, experts recommend sending a frozen section of the proximal margin at the time of tumor resection to assure a microscopically negative margin (11).
Molecular markers are not of clinical use in SCC of the penis. SCC antigen is not sensitive in small tumor burden and has little prognostic significance for survival after surgery (22). Lymph node metastases are also correlated with the expression of p53, Ki-67, and E-cadherin, but these markers are not useful in clinical practice (23).
Stage Ta-Tis
Treatment options for patients with Stage Ta-Tis penile cancer include 5% 5-fluorouracil (5-FU), 5% imiquimod cream; wide local excision including circumcision, cryotherapy, glansectomy, or laser treatment. The advantages of topical chemotherapy include simple application, low rates of toxicity, and adverse events. The disadvantages include risk of prolonged therapy (average duration of treatment of 4 to 6 weeks with estimated healing time of 4 to 8 weeks), local recurrence, and poor therapeutic efficacy in immunocompromised patients (26).
Laser therapy, either carbon dioxide (CO2) or neodymiumyttrium-aluminum-garnet (Nd:YAG), has been successfully used as a first-line therapy for premalignant lesions and early stages of penile cancer since the 1980s. The CO2 laser has a tissue penetration of 0.1 mm, whereas Nd:YAG laser penetrates to a depth of 4.2 mm. That is why laser is contraindicated in tumors with >6 mm depth invasion, T2 tumors and in patients not compliant to close follow-up due to its high recurrence rate (27).
The advantages of laser therapy include good functional and cosmetic outcomes and avoidance of surgery, assuming that oncologic outcome and survival are not affected by local recurrence. The disadvantages of laser therapy include its high recurrence rates, reported to be between 3.1% and 48%. The Nd:YAG laser can cause significant tissue coagulation and prevent accurate histologic diagnosis, resulting in understaging of the disease. Although the CO2 laser does not cause significant tissue coagulation, it is limited by its lower tissue penetration compared with the Nd:YAG laser (28,29).
Cryotherapy is more commonly used in the treatment of genital warts and premalignant lesions than in penile cancer. A study comparing cryotherapy and topical 5-FU in the treatment of Bowen disease showed that the risk of recurrence after cryotherapy (13.4%) was greater than after 5-FU treatment (9%) (26,30).
Although cryotherapy and laser therapy can effectively treat selected patients with small superficial lesions, their effectiveness for overtly invasive penile cancers is uncertain and their use should not be considered an alternative to standard resection.
Stage T1G1-3 of the Foreskin
For patients with an invasive tumor confined to the prepuce, a penile-preserving strategy using circumcision is strongly recommended. Careful assessment of the glans is required to exclude dysplasia or carcinoma in situ. Alone, circumcision is curative for low-grade, low-stage preputial disease. The disadvantage of circumcision is the reported recurrence rate of 50% at 2 years, indicating the need for regular close surveillance (31).
Stage T1G1-3 of Glans
For patients with stage T1G1-3 of the glans, who can guarantee regular follow-up examinations, a penile-preserving strategy is strongly recommended. Choice of the treatment
will be influenced by the size and location of the tumor and the possible side effects. Meticulous follow-up and/or selfexamination are advisable in order to detect and rapidly treat local recurrence.
will be influenced by the size and location of the tumor and the possible side effects. Meticulous follow-up and/or selfexamination are advisable in order to detect and rapidly treat local recurrence.
Treatment options include the following:
Wide local excision (WLE) with wide negative margins, with or without split or full-thickness skin graft, can be performed for precancerous lesions, discrete lesions, extensive preputial disease (where circumcision alone is not curative), and T1 low-grade tumors of the shaft. A 1- to 1.5-cm negative margin may adequate for low-risk tumors (21). Contraindications to WLE include tumor in close proximity to the urethra, urethral involvement, or lesions extending more than half of the glans penis. The disadvantages may include potential tumor recurrence and significant deformity or deviation of the penis during erections (32).
Mohs micrographic surgery could be used with concurrent microscopic evaluation to ensure that a tumor-free plane is obtained. The indications for performing penile Mohs surgery are carcinoma in situ or verrucous carcinoma (which are of low to intermediate grade and have an exophytic growth pattern); lesions of the distal penis or glans penis, otherwise amenable to partial penectomy; and the desire for penile-preserving surgery in compliant patients. Higher than 85% 5-year survival rates have been reported with this procedure. The success rate is shown to be stage-dependent. The advantages of the Mohs technique include proper tumor mapping and excision of the tumor with no positive margins, and preservation of uninvolved penile tissue, with improved cosmetic or functional outcome. The disadvantage of the Mohs technique is its poorer local control as evidenced by the high rates (30%) of local recurrence after one procedure (33,34). However, most recurrences were suitable for further Mohs surgery. Contraindications to Mohs surgery include advanced tumor stage amenable to partial penectomy and, in instances where the involvement of the urethra, or the size of the defect, outweighs potential cosmetic or functional results. Complications, such as meatal stenosis or glans disfigurement, have been reported (26).
Glansectomy can be partial or complete. Recent studies have shown that a margin of 0.5 cm may be oncologically safe (35). Depending on the size of the defect, reconstruction can follow three techniques: (a) primary closure, (b) preputial or scrotal skin flap, or (c) skin grafting. Potential disadvantage of glansectomy is cancer recurrence in the remaining glans. Complications associated to reconstruction of the glans include loss, or graft contraction, graft overgrowth over the external urethral meatus, penile tethering by flaps, loss of penile length, and decreased penile sensitivity (36,37).Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
