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Nodal Staging in Penile Carcinoma by Dynamic Sentinel Node Biopsy After Previous Therapeutic Primary Tumour Resection
Niels M. Graafland a, Renato A. Valdés Olmos b, Willem Meinhardt a, Axel Bex a, Henk G. van der Poel a, Hester H. van Boven c, Omgo E. Nieweg d, Simon Horenblas a 
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Accepted 22 June 2010, Published online 1 July 2010
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Abstract
Background
Dynamic sentinel node biopsy (DSNB) is used to evaluate the nodal status of patients with penile carcinoma and clinically node-negative groins. This minimally invasive procedure is usually done at the same time as the treatment of the primary tumour.
Objective
Our aim was to evaluate results of so-called postresection DSNB, that is, DSNB after previous resection of the penile tumour.
Design, setting, and participants
All 40 patients who had undergone DSNB after previous penile carcinoma resection with histopathologically tumour-negative margins between February 2003 and July 2009 were analysed. Twenty patients (50%) had known unilateral nodal involvement, and DSNB was used to stage the clinically normal contralateral groin. Hence the study concerned 60 groins without palpable nodes. The median time between primary tumour resection and DSNB was 2.8 mo. The technique of postresection DSNB was similar to the standard procedure.
Measurements
The sentinel node visualisation rate, identification rate, histopathologic results, and outcome during follow-up were investigated.
Results and limitations
A sentinel node was visualised on the lymphoscintigrams of 56 of the 60 eligible groins (93%). A sentinel node was identified intraoperatively in all these 56 groins. A median of two sentinel nodes were removed. Histopathologic analysis revealed involvement of seven groins (12%) in seven patients (18%). The median size of these metastases was 6 mm. Additional dissemination was found in one completed ipsilateral inguinal node dissection specimen. No recurrences developed in the groins from which one or more tumour-free sentinel nodes had been taken during a median follow-up of 28 mo after the primary tumour resection. A potential limitation of this study is the short follow-up and relatively small cohort number.
Conclusions
Postresection DSNB is a suitable procedure to stage clinically node-negative penile carcinoma after previous therapeutic primary tumour resection. The results seem similar to the favourable experience with DSNB in patients with their tumour still present.
Keywords: Dynamic sentinel node biopsy, Occult metastasis, Penile carcinoma, Penile neoplasms, Prognosis, Staging.
Article Outline
1. Introduction
Optimal management of penile carcinoma patients with clinically normal lymph nodes is controversial [1]. Since 1994, we have used dynamic sentinel node biopsy (DSNB) to evaluate the nodal status of such patients [2]. This minimally invasive procedure entails the removal of only the lymph nodes on the direct lymphatic drainage pathway from the tumour [2], [3], and [4]. A complete inguinal lymphadenectomy is done if the sentinel node is involved. In 2001, the DSNB procedure was modified to increase its sensitivity [4]. This procedure has not changed since then and is usually carried out together with treatment of the primary tumour. However, sometimes the penile tumour has already been removed at the referring hospital for logistical or other reasons. As is done with other tumours (eg, melanoma) [5], [6], and [7], we perform a so-called postresection DSNB in such cases (ie, DSNB after previous therapeutic penile tumour resection). The objective of the current study was to evaluate our experience with this approach in terms of sentinel node visualisation rate, identification rate, histopathologic results, and outcome during follow-up.
2. Patients and methods
The study population consisted of all 40 patients who underwent DSNB at our tertiary referral hospital following therapeutic penile squamous cell carcinoma resection with histopathologically tumour-negative margins. This group constitutes 15% of the 259 penile cancer patients staged with DSNB between February 2003 and July 2009. The first 22 patients had also been included in a previously published study reporting on the results of the complete series between 2001 and November 2007 [8].
Until 2004, DSNB was used to stage patients with penile tumours T2 or higher with at least one clinically node-negative groin. Patients with Tis and T1 tumours were managed with close surveillance and subsequent lymphadenectomy when metastasis became clinically apparent. Since 2004, DSNB has also been performed in patients with T1G2–G3 tumours because an interim analysis showed a substantial risk of occult metastasis in these subgroups [9]. Preoperative ultrasound of the inguinal lymphatic region with fine-needle aspiration cytology (FNAC) of suspicious lymph nodes is routinely performed. Ipsilateral inguinal lymphadenectomy is done if FNAC reveals dissemination.
Seventeen of the 40 patients developed unilateral inguinal metastasis during surveillance after previous primary tumour resection, and DSNB was used to stage the contralateral clinically noninvolved groin. Preoperative ultrasound-guided FNAC showed unilateral inguinal nodal involvement in 3 of the remaining 23 patients with bilateral nonpalpable lymph nodes. Hence 40 patients and 60 clinically node-negative groins proceeded to postresection DSNB, including 20 patients who underwent bilateral DSNB. None of the patients had a primary tumour recurrence at the time. The median time between penile tumour resection and postresection DSNB was 2.8 mo. Table 1 shows the patient and tumour characteristics.
Table 1
Patient and tumour characteristics
| No. of patients | 40 |
| Median age, yr (range) | 66 (33–90) |
| Median interval between penile operation and DSNB, mo (range) | 2.8 (0.5–31) |
| Previous therapeutic penile operation, No. (%) | |
| Local excision | 15 (38) |
| Glansectomy | 1 (3) |
| Partial amputation | 24 (60) |
| pT stage according to 2002 TNM classification, No. (%) | |
| pTis | 1 (3) |
| pT1 | 13 (33) |
| pT2 | 25 (63) |
| pT3 | 1 (3) |
| Histologic grade penile tumour, No. (%) | |
| pTis | 1 (3) |
| Well differentiated | 5 (13) |
| Intermediately differentiated | 25 (63) |
| Poorly differentiated | 7 (18) |
| Unknown* | 2 (5) |
| EAU risk group per patient, No. (%) | |
| Low risk (pTis, pT1G1)† | 2 (5) |
| Intermediate risk (pT1G2) | 10 (25) |
| High risk (pT2 or higher or G3) | 28 (70) |
| Clinical nodal status per patient, No. (%) | |
| Bilateral node negative | 23 (58) |
| Unilateral node positive | 17 (43) |
| Preoperative ultrasound-guided FNAC result per patient, No. (%) | |
| Bilateral tumour negative | 20 (50) |
| Unilateral tumour positive | 3 (8) |
| Tumour positive in clinical unilateral node positive groin | 17 (43) |
DSNB = dynamic sentinel node biopsy; EAU = European Association of Urology; FNAC = fine-needle aspiration cytology.
*
†
The technique of postresection DSNB was essentially similar to sentinel node biopsy with a penile tumour still present and was published in detail previously [4], and [8]. The only difference was that the technetium Tc 99m nanocolloid was injected around the resection wound or scar instead of around the tumour. The sentinel node was defined as a lymph node on a direct lymphatic drainage pathway from the area of the primarily resected tumour [10]. Completion ipsilateral inguinal node dissection was carried out in the case of a tumour-positive sentinel node. Groins with tumour-negative sentinel nodes were subsequently observed. All patients were routinely followed according to a previously published standard protocol, with particular attention to the groins and using ultrasound or computed tomography if necessary [8]. Detailed information on patient characteristics, preoperative examinations, surgical procedures, histopathologic findings, and follow-up was recorded prospectively.
3. Results
Preoperative lymphoscintigraphy depicted sentinel nodes in 56 of the 60 eligible clinically node-negative groins (93%). A sentinel node was harvested in all these 56 groins. A median of two (mean: 2.1; range: 1–5) sentinel nodes were removed per groin. One of the four groins without visualisation was not surgically explored because the risk of occult metastasis was considered low. This concerned a patient with a pTis tumour removed 27 mo earlier and a unilateral node-positive groin. The remaining three groins without preoperative visualisation of a hot spot were explored in search of nodes that were either blue or radioactive or were suspicious on palpation. In two of these groins some palpably enlarged lymph nodes (n = 2 and n = 3, respectively) were removed, but these were free of disease. Elective lymphadenectomy was not performed.
Histopathologic analysis revealed involved sentinel nodes in seven groins (12%) of seven patients (18%). Table 2 provides a detailed overview. The median diameter of the metastasis in these nodes was 6 mm (mean: 5.8 mm; range: 2–10 mm). Completion ipsilateral inguinal lymphadenectomy was performed in these seven patients. Additional dissemination was found in one dissection specimen.
Table 2
Histopathologic results of the seven groins with involved sentinel nodes
| No. of groins with | |
| One ipsilateral involved sentinel node | 4 |
| Two ipsilateral involved sentinel nodes | 3 |
| Maximal diameter of metastasis in involved sentinel nodes, mm | |
| One ipsilateral involved sentinel node | 3/5/7/7 |
| Two ipsilateral involved sentinel nodes | 2, 6*/3, 8†/6, 10 |
| No. of additional metastasis in completion ipsilateral inguinal dissected specimens | 1 |
| Maximal diameter of additional metastasis, mm | 10 |
| No. of groins with extranodal extension | 1 |
*
†
The median hospital stay of the 20 patients who had undergone bilateral DSNB was 1 d (range: 0–7 d). The hospital stay of the other 20 patients was guided by the contralateral inguinal node dissection.
No recurrences developed in the groins from which one or more tumour-free sentinel nodes had been taken during a median follow-up of 28 mo (range: 6–75 mo) after the primary tumour resection. All 20 patients who had undergone bilateral DSNB were alive without evidence of disease at their last follow-up visit.
4. Discussion
This study demonstrates that postresection DNSB is feasible as a staging method in detecting occult lymph node involvement. Postresection DSNB revealed occult metastasis in 12% of clinically node-negative groins (7 of 60 eligible groins) of seven patients (18%) leading to early therapeutic lymphadenectomy. This finding supports the favourable experience with DSNB in patients with their tumour still present [8]. The visualisation rate of 93% in this study also concurs with previously published series (90–97%) [3], [11], and [12]. These two findings suggest unimpaired lymphatic flow.
In 2008, Ornellas et al recommended elective lymphadenectomy in all clinically node-negative patients, as opposed to close surveillance [13]. The rationale is a suggested survival advantage as a result of the early removal of lymph node metastases [14], and [15]. Approximately 20% of clinically node-negative patients have occult metastasis. We believe these patients can now be identified and unnecessary lymphadenectomy can be avoided in the remaining 80% of patients. This is particularly advantageous because at least 35% of groin dissections are associated with postoperative or long-term morbidity [16]. DSNB has evolved into a minimally invasive procedure with a sensitivity of 93–95% and with an associated morbidity of 5–7% per groin [4], [8], and [17].
This is the first study specifically describing nodal staging with DSNB in penile cancer after previous penile tumour resection. Good results have been obtained in melanoma patients who had undergone a prior wide local excision of their lesion [5], [6], and [7]. One may speculate that postponed sentinel node biopsy may provide tumour cells in the lymphatics with extra time to reach the node. Another advantage may be removal of the often infected primary tumour before embarking on the lymph node biopsy, possibly reducing the risk of postoperative infection.
The limited duration of follow-up and relatively small number of patients prevent firm conclusions about the safety and sensitivity of postresection DSNB. Definitive conclusions on the sensitivity of this approach require longer follow-up and a larger cohort number.
5. Conclusions
Postresection DSNB is a suitable procedure to stage clinically node-negative penile carcinoma after previous therapeutic primary tumour resection. The sentinel node visualisation rate of 93%, identification rate of 100%, and detection of occult metastasis in 12% of clinically node-negative groins indicate this minimally invasive procedure is feasible and seems reliable. The results are so far similar to the favourable experience with DSNB in patients with their tumour still present.
Author contributions: Simon Horenblas had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Graafland, Valdés Olmos, Meinhardt, Nieweg, Horenblas.
Acquisition of data: Graafland.
Analysis and interpretation of data: Graafland, Valdés Olmos, Nieweg, Horenblas.
Drafting of the manuscript: Graafland, Horenblas.
Critical revision of the manuscript for important intellectual content: Valdés Olmos, Meinhardt, Bex, van der Poel, van Boven, Nieweg, Horenblas.
Statistical analysis: None.
Obtaining funding: None.
Administrative, technical, or material support: None.
Supervision: Horenblas.
Other (specify): None.
Financial disclosures: I certify that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/ affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None.
Funding/Support and role of the sponsor: None.
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Footnotes
a Department of Urology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
b Department of Nuclear Medicine, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
c Department of Pathology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
d Department of Surgical Oncology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
Corresponding author. Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital Urology, Plesmanlaan 121, Amsterdam 1066 CX, The Netherlands. Tel. +31 205122611; Fax: +31 205122554.
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