Controversies in the Management of Penile Cancer

273 Controversies in the Management of Penile Cancer

Guilherme Godoy

INTRODUCTION

Penile cancer is a rare tumor, accounting for only 0.4% to 0.6% of all malignancies in men (1, 2). Additionally, it has a profound social-psychological impact, further aggravated by the lack of awareness and public information. Affected men are often embarrassed about their condition, which delays their decision to seek medical attention. The limited number of cases seen by health care providers also contributes to delayed and suboptimal care for these men, especially in areas where supraregional specialized centers do not exist.

Despite all these challenges, basic understanding of the clinical natural history and the management of both primary lesions and regional lymph node metastasis are well defined. The primary tumor starts at the glans, sulcus, or foreskin, and advances to invade deeply into the corpora and urethra, toward the base of the penis. The pattern of metastatic spread is well described and predictable, starting in regional inguinal lymph nodes and progressing, in a stepwise fashion, to pelvic lymph nodes before disseminating to distant sites (3). Some controversies still exist, especially in the management of inguinal and pelvic lymph node metastasis. The following cases illustrate some of these situations.

Case 1: A 53-year-old White Hispanic male was referred to the urologic clinic 1 year after circumcision, with a fungating mass replacing the glans and a 3-cm mobile palpable area of lymphadenopathy in the right inguinal region. He underwent a partial penectomy revealing a pT3 moderately differentiated squamous cell carcinoma (SCC).

274Question 1: What should be the laterality and the extent of the inguinal lymph node dissection in patients with unilateral palpable lymphadenopathy?

This case illustrates the rapid progression of the primary tumor. There were inguinal lymph nodes slightly greater than 1 cm in the left side identified by surgical dissection, which were not palpable and nonspecific on imaging staging tests. Intraoperative mapping studies have observed that the lymphatic drainage from penile lesions is bilateral, with considerable crossover between sides (4, 5). In this particular case, the left inguinal nodes were negative; however, micrometastases are present in 20% to 25% of nonpalpable nodes. Conversely, palpable inguinal nodes are positive in 50% to 80% of cases (3, 6). Therefore, bilateral inguinal lymph node dissection is mandatory for adequate staging and offers potential therapeutic benefit.

Because of concerns with morbidity and complications associated with radical standard inguinal lymph node dissection templates, the use of fine needle aspiration and more limited templates have been proposed. However, in the presence of positive lymph node identified during frozen-section analysis, the procedure should be converted to a standard dissection template. In the abovementioned case, not only was a large lymph node palpable, but the primary tumor had high-risk features (pT3) that would indicate the need for the bilateral inguinal lymph node dissection. In situations like this, in the presence of unilateral palpable disease, limited templates can be performed on the contralateral side with dissection performed only superficially to the fascia lata, as long as there is no histological evidence of positive involvement observed during frozen-section analysis (7).

Question 2: He underwent bilateral inguinal lymph node dissection, including the deep inguinal nodes with sartorius muscle transposition flap in the right side and superficial dissection in the left side. A large lymph node (4.5 cm) was positive in the right side, while all lymph nodes from the left side were negative. What is the role of pelvic lymph node dissection in the setting of a histologically confirmed positive groin? When is a bilateral pelvic lymphadenectomy indicated?

275The role of the pelvic lymph dissection and whether it should be performed bilaterally or ipsilateral to the positive inguinal side are still controversial topics. There is also debate if adjuvant chemotherapy with TIP (paclitaxel, ifosfamide, cisplatin) or chemoradiation following the inguinal or the pelvic lymph node dissection is beneficial. A simplistic approach would be to omit the pelvic lymph node dissection only if the bilateral inguinal lymph node dissection is negative, since skip metastasis has not been reported (8, 9). Otherwise, all patients should undergo bilateral pelvic lymph node dissection. Although the presence of positive inguinal lymph nodes suggests the presence of systemic disease, the indication for a pelvic lymph node dissection is based on the potential therapeutic benefit and the lack of effective systemic therapy for advanced disease. Alternatively, a more selective approach would indicate ipsilateral pelvic lymph node dissection only in cases where there is poorly differentiated tumor present in the lymph node, extranodal extension, nodal size greater than 3.5 cm, or more than two lymph nodes involved (10, 11). If any of those high-risk features are present in both inguinal regions, a bilateral pelvic lymph node dissection is indicated, each side mandated for ipsilateral pelvic dissection. Recently, a multicenter international study has proposed that, besides the presence of bilateral extranodal extension, the finding of four or more inguinal lymph nodes (both sides combined) would indicate the need for a bilateral pelvic lymph node dissection (12).

Case 2: A 73-year-old African American male had a partial penectomy with negative margins for a pT3 well differentiated SCC. After the resection of the primary tumor, the previously palpable right inguinal lymphadenopathy resolved and became nonpalpable.

Question 3: What is the role of the dynamic sentinel node biopsy (DSNB) in the management of nonpalpable inguinal regions?

In centers where there is appropriate experience and expertise, DSNB can be performed as an alternative to inguinal lymph node dissection in men with clinically nonpalpable nodes, even in the presence of high-risk primary tumors such as the present case (13–15). There has been controversy about 276the reproducibility and true utility of the DNSB technique. However, recent refinements of the technique, such as the incorporation of fine needle aspiration under ultrasound guidance, have led to a decrease in the false-negative rate from 19% to 5% (14, 16). In centers lacking expertise in the DSNB technique, close surveillance of low-risk primary tumors (Tis, Ta, and T1a), and bilateral inguinal lymph node dissection in the intermediate/high-risk primary tumors (T1b, T2+), are the recommended approaches in men with clinically negative groins.

Question 4: Patient declined the recommendation for a bilateral inguinal lymph node dissection. After 9 months of follow-up, he again developed palpable and mobile lymph nodes in the right inguinal region. Is there a difference between immediate and delayed lymphadenectomy in men with nonpalpable nodes? Is a bilateral lymph node dissection necessary for a late unilateral nodal recurrence?

Evidence suggests that men with clinically negative groins and high-risk primary tumors have better oncological outcomes with immediate bilateral inguinal lymph node dissection than with a delayed dissection after the nodes become palpable. However, when the nodes become palpable during an initial period of observation, an ipsilateral inguinal lymph node dissection may be performed, since absence of disease development in the groin usually suggests freedom from disease on that side. There is debate about the minimum period of observation and also whether this practice should be widely recommended (7,17,18). In the presence of aggressive and bulky unilateral disease (≥4 cm nodes), a contralateral dissection should also be considered (7).

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