Minimally Invasive Staging Techniques

To circumvent the above-mentioned dilemmas regarding lymphadenectomy, minimally invasive staging techniques have been developed. The basis of these techniques is to limit the morbidity in patients with pathological node-negative (pN0) groins, and to identify occult metastases at the earliest opportunity. Only patients with proven lymphatic spread undergo a completion therapeutic radical lymphadenectomy. In the last two decades, two approaches have been introduced worldwide: modified inguinal lymphadenectomy (MIL) and dynamic sentinel node biopsy (DSNB). Modified Inguinal Lymphadenectomy (MIL)

The MIL was proposed by Catalona in 1988 after being performed in six patients with invasive carcinoma of the penis or distal urethra.53 The aim of this approach is to remove all the lymph nodes that are the most probable location of first-line lymphatic invasion, and exclude the regions lateral to the femoral artery and caudal to the fossa ovalis. The lymph node packet can be analyzed by frozen section and if it confirms metastatic disease then a radical inguinal lymphadenectomy can be performed. The anatomic location of these lymph nodes was based on earlier lymphatic drainage studies. The medial margin of MIL was the adductor longus muscle, the lateral margin was the lateral border of the femoral artery, the superior margin was the external oblique muscle above the spermatic cord, and the inferior margin was the fascia lata just distal to the fossa ovalis. The advantage of this MIL is a smaller skin incision and a smaller node dissection resulting in reduced morbidity compared with standard lymphadenectomy. However, limiting the dissection field led to a high number of false-negative findings as reported by several other authors. Several case studies have attested to this unreliability with nodal recurrences after negative MIL varying from

0% to 15%.54-57 For example, Lopes et al. have described a prospective study of 13 cN0-patients staged with MIL in whom none had tumor-bearing lymph nodes in the dissected fields while two false-negative procedures came to light during follow-up.55 However, one of the problems associated with the MIL technique are the various boundaries used for the dissection. Two recent studies have suggested that for an optimal modified lymphadenectomy procedure, the traditional boundaries should be extended.19,22 Unfortunately, both studies used different anatomical fields. Hence direct comparison for the optimal boundaries of MIL remains to be defined. Zhu and associates advise the following boundaries for an optimal MIL: The medial margin is the medial surface of the adductor longus muscle, the lateral margin is the lateral surface of the saphenous vein and femoral artery, and the superior margin is the spermatic cord. All "superficial" and "deep" inguinal lymph nodes in the limits should be removed. Their assumption needs confirmation in prospective clinical studies. Dynamic Sentinel Node Biopsy (DSNB)

Sentinel node biopsy for penile cancer was first reported by Cabanas in 1977.58 This was based on lymphangiograms of the penis and the lymph node medial to the superficial epigastric vein was identified as being the first echelon lymph node or so called "sentinel node". It was assumed that a negative sentinel node was indicative for absence of further lymphatic spread and therefore no lymphadenectomy was indicated. Sentinel node surgery consisted of identification and removal of this lymph node with completion lymphadenectomy only in those with a tumor-positive lymph node. However, this initial "static" procedure, based on anatomic landmarks only, did not take into account individual drainage patterns. Several false-negative results were reported, and the technique was largely abandoned. The sentinel node procedure was revived by Morton et al. in 1992, by using patent blue-V or isosulfan blue dye as a tracer enabling individual lymphatic mapping.59 This technique with the addition of a preoperative radioactive tracer (technetium-99m-labeled nanocol-loid 99mTc) forms the basis of the modern sentinel node biopsy era and is also used in, for example, breast cancer and melanoma.

Since 1994, dynamic sentinel node biopsy (DSNB) has been performed at the authors' institution to stage cN0-patients.52 Technique of DSNB

Conventional lymphoscintigraphy is performed following the injection of 99mTc nanocolloid intradermally just proximal to the tumor or coronal sulcus. Commonly between 30 and 70 MBq are injected into 3-4 sites (Fig. 9.4a). Once localized the sentinel nodes are marked. Intraoperatively the penis is injected with patent blue dye (Blue Patenté V, Laboratoire Guerbet, Aulnay-Sous-Bois, France) in the same position as the nanocolloid. A gamma-ray detection probe is then used to identify and remove the radioactive lymph nodes which directly drain the penis as identified

Dslnb Penile Cancer
Fig. 9.4 (a) Patent blue injection at time of surgery. (b) Hand held gamma detector during surgery to identify spot with highest radiation. (c) Blue and radioactive sentinel node with blue efferent lymphatic channel

by the lymphoscintigraphy (Fig. 9.4b, c).15,52,60 Patients who are found to have tumor within the sentinel lymph nodes undergo a completion lymphadenectomy. Compared with the above-mentioned "static" procedure first described by Cabañas,58 the "dynamic" approach investigates the individual drainage patterns for each individual patient.

The DSNB procedure was first described by Horenblas et al. in 2001 in a report of 55 patients with T2 or greater tumors.61 With this dynamic approach a sensitivity of 80% was reported. However, the false-negative rates have raised concerns about its diagnostic accuracy. Furthermore, patients with negative sentinel nodes remained on rigid follow-up. During the years, the DSNB protocol has been modified after detailed analysis of the false-negative cases.62 The initial procedure was extended by pathological examination of the sentinel node by serial sectioning and immunohistochemi-cal staining instead of routine paraffin sections, and addition of preoperative ultrasonography with fine-needle aspiration cytology to detect pathologically enlarged nodes, that fail to pick up radioactivity. Furthermore, exploration of groins with nonvisualization on preoperative lymphoscintigram (occurring in approximately 4-6% of cN0-groins)1519,33 and intraoperative palpation of the wound have been introduced. The current modified procedure has evolved into a reliable minimally invasive staging technique with an associated sensitivity of 93-95% together with a low morbidity,52,63 and is comparable with the results in breast cancer and melanoma. Recently, in a large prospective series of 323 patients from two tertiary referral hospitals who use essentially the same protocol, DSNB was shown to be a reliable method with a low complication rate.60 The combined sensitivity of this procedure was 93% with a specificity of 100%. Complications occurred in less than 5% of explored groins and almost all were transient and could be managed conservatively. Some critics of the technique have pointed out that there is an associated learning curve as the false-negative rate diminished during the years from 20-22% initially to a recent 5-7%. However, in the above-mentioned recently published series from two hospitals, no learning curve could be demonstrated in the initial 30 procedures done at one of the two hospitals.60 DSNB is a versatile tool that can also be used in the following clinical settings: Unilateral cN0-patients, while the other node-positive side is managed by a formal lymphadenectomy; a second DSNB after initial tumor-negative DSNB in patients who developed a recurrence of a primary tumor. Recently Graafland et al. describe 12 patients, in whom a second DSNB was performed due to penile cancer recurrence. A new sentinel node was identified in 80%. Also in patients in whom the primary tumor has already been removed DSNB is still possible. In a series with 40 patients with clinically node-negative penile carcinoma after previous therapeutic primary tumor resection the results were similar to the favorable experience with the DSNB in patients with their tumor still present. Staging Recommendations

Currently, DSNB is recommended in cN0-groins of patients with penile tumors >T1G2 (Fig. 9.5). Only patients with a tumor-positive sentinel lymph node should undergo a therapeutic ipsilateral inguinal lymphadenectomy. Compliant patients with lower-risk tumors (pTis, pTa, and pT1G1) can be managed with close surveillance followed by lymphadenectomy if metastases become clinically apparent. All patients should undergo inguinal ultrasound with fine needle aspiration cytology (FNAC) of the lymph nodes if they are morphologically suspicious.

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