Year : 2006 | Volume
: 22 | Issue : 4 | Page : 338--340
Role of dynamic lymphoscintigraphy in identifying inguinal nodal metastases in penile cancer
Paul K Hegarty, Suks Minhas
Institute of Urology, University College London Hospital, United Kingdom
Paul K Hegarty
Institute of Urology, University College Hospital, 235 Euston Road, London
The concept of sentinel lymph node was originally described in penile cancer. With technical developments and refinements it may have a role in staging men with penile cancer whose inguinal nodes are impalpable. We examined the current evidence supporting dynamic sentinel lymph node biopsy (DSLB). In particular we compared the false-negative rate compared to conventional inguinal lymph node dissection. Further, we discuss the advantages of the minimally invasive approach. Pioneering work in the Netherlands appears to be reducing the false-negative rates to acceptable levels. However, longer follow-up is necessary before recommending DSLB for cases of penile cancer with impalpable lymph nodes. Dynamic sentinel lymph node biopsy has great potential for avoiding the morbidity associated with inguinal lymph node dissection. More mature data is necessary prior to advocating its introduction outside of randomized controlled studies.
|How to cite this article:|
Hegarty PK, Minhas S. Role of dynamic lymphoscintigraphy in identifying inguinal nodal metastases in penile cancer.Indian J Urol 2006;22:338-340
|How to cite this URL:|
Hegarty PK, Minhas S. Role of dynamic lymphoscintigraphy in identifying inguinal nodal metastases in penile cancer. Indian J Urol [serial online] 2006 [cited 2020 Feb 26 ];22:338-340
Available from: http://www.indianjurol.com/text.asp?2006/22/4/338/29121
The standard of treatment of penile cancer is to cure patients without functional or cosmetic compromise. The primary tumor can usually be managed by glans excision or partial penectomy with reconstruction, minimizing psychological and functional impact. The management, however, of regional lymph nodes remains controversial.
In patients with clinically impalpable lymph nodes prophylactic lymphadenectomy aims to prevent the development of regional and distant metastases. If lymphadenectomy is delayed there is an inherent risk of higher morbidity and failure to control the cancer. The morbidity of prophylactic dissection is considerably lower than palliative dissection. Furthermore as mortality is often due to loco-regional recurrence, control of the regional lymph nodes is crucial to reducing death rates. Men with penile cancer who undergo lymphadenectomy for palpable disease have 33% survival, whereas survival is 84% for those undergoing lymphadenectomy with impalpable positive nodes. Guidelines published by the European Association of Urology (EAU) were set to prevent progression of any case at risk of micrometastatic disease. Patients whose primary tumor is considered to be of greater risk of micrometastatic lymph node disease are recommended for inguinal lymph node dissection. Recent data from our institution indicate that the guidelines succeed in preventing regional recurrence at the expense of over-treating 72% of men with impalpable lymph nodes. It is clear that more accurate prognostic indicators are needed to improve case selection.
The concept of sentinel nodes was originally described in penile cancer by Cabanas in 1977. He used lymphangiography performed via the dorsal lymphatics of the penis, to identify the lymph node close to the superficial epigastric vein as the sentinel node. However, the anatomical approach to identifying the sentinel node fell into disfavor when a number of false-negatives became apparent. In particular Pettaway et al described the nine-year experience of the MD Anderson Cancer Center. Twenty cases of penile cancer with clinically impalpable nodes had extended dissections centered on the anatomical sentinel node. Five out of the twenty "node negative" patients developed recurrences within ten months.
With technical improvements, interest in the role of the sentinel node in staging cancers has been renewed. In the management of patients with melanoma, Morton et al used a patent blue dye to identify the sentinel node through individual visualization of lymphatic channels originating in the primary tumor. Secondly, detection of the sentinel node is improved by lymphoscintigraphy with 99msub Tc-nanocolloid. This tracer facilitates surface location preoperatively and intracorporeal identification of the sentinel node by use of a gamma probe intraoperatively.
Sentinel lymph node biopsy may have a role in reducing the rate of negative lymphadenectomy. The pioneering group in the Netherlands describes 10 years of experience performing dynamic sentinel lymph node biopsy (DSLB). The technique was applied to 140 patients, of whom 31 were found to have the disease and underwent inguinal lymphadenectomy. Interestingly, 78% of these with positive sentinel lymph nodes had no further cancer identified in their lymph nodes. Those with sentinel nodes negative for cancer were observed. Of these, six patients (16%) subsequently developed nodal disease at a median of seven months, ranging from three to 27 months. Four of these have died since then. A false-negative rate of 16% needs to be compared with the rate of micrometastatic disease of 18% in a large prospective series from a single institution. It would seem from such a result that DSLB is more likely to miss the sentinel node if it is involved in cancer than can be accounted for by chance alone. The theoretical reasons for false-negative nodes include:
Site of injection, as the primary tumor will have been removed prior to DSLB.Insufficient tracer injection.Obstruction of lymphatic channels or node by tumor, with tracer going to uninvolved node.False-negative histopathology, typically with small-volume tumors.
Most cases with a false-negative sentinel node occurred earlier in the series and modifications in the technique such as preoperative ultrasound of the inguinal region may reduce the false-negative rate.
In a study of 27 patients, ultrasound-guided fine needle aspiration cytology (FNAC) resulted in no false-negative for DSLB procedure. However, the definition of failure to identify a false negative was based on eventual groin recurrence. With a follow-up of two to 36 months, it remains to be seen whether US-guided FNAC can reduce false-negative rates to zero. How ultrasound can specifically detect the cases that would have constituted a false-negative node is open to conjecture. Perhaps the nodes liable to be missed by DSLB are very full with tumor and thereby have more marked changes in their internal architecture. Used prior to DSLB this innovation has the advantage of redirecting patients to inguinal node clearance and skipping the DSLB procedure. The US-guided FNAC technique has been incorporated into routine DSLB protocol by the Netherlands group. Of their last 60 sentinel lymph node procedures performed, no recurrence has been observed; however, longer follow-up is necessary to confirm this belief. On its own US-guided FNAC has a sensitivity of only 39%, so it is best used as an adjunct to DSLB.
The preferred method of studying DSLB is to perform the technique and to continue onto an inguinal lymph node dissection at the same sitting. One group has begun this work, but has relatively small numbers. In this way, no patient is exposed to the risk of false-negative biopsy and the true accuracy of the technique is immediately known.
The clear advantage of sentinel lymph node biopsy is the reduced morbidity, reported at 8% as compared to approaching 88% for standard inguinal lymphadenectomy. There are a number of potential disadvantages of DSLB. First and most importantly, a false-negative rate of 16% is too high for it to be considered an advantage over the historical strategy of watchful waiting. Secondly, it requires considerable expertise with coordination of the surgeon, department of nuclear medicine and being able to predict when the patient will be in the theatre. Thirdly, there is a long learning curve, as the Netherlands group has spent over 10 years to achieve false-negative rates of 16%. If in future DSLB is proved superior to standard management, it will require careful planning, teaching and mentoring for its safe introduction. Finally, the estimated cost per case is up to 11000 euro, approximately 630 000 Indian Rupees. This must be balanced against the reduced cost of avoiding unnecessary formal lymph node dissection with its high rates of morbidity. A randomized study of DSLB against standard management according to EAU guidelines may clarify the role of DSLB. The primary endpoint needs to remain control of cancer, whereas the secondary endpoint ought to be reduced morbidity. We look forward to further reports from the group in the Netherlands.
Dynamic lymphoscintigraphy shows great promise in reducing the rate of unnecessary prophylactic inguinal lymph node dissection, however, current data is lacking in recommending it outside strictly controlled clinical trials.
|1||Minhas S, Kayes O, Hegarty P, Kumar P, Freeman A, Ralph D. What surgical resection margins are required to achieve oncological control in men with primary penile cancer? BJU Int 2005;96:1040-3.|
|2||Bevan-Thomas R, Slaton JW, Pettaway CA. Contemporary morbidity from lymphadenectomy for penile squamous cell carcinoma: The MD Anderson Cancer Centre experience. J Urol 2002;167:1638-42.|
|3||McDougal WS. Carcinoma of penis: Improved survival by early lymphadenectomy based on histological grade and depth of invasion of primary lesion. J Urol 1995;154:1364-6.|
|4||Algaba F, Horenblas S, Pizzocaro-Luigi Piva G, Solsona E, Windahl T; European Association of Urology. EAU guidelines on penile cancer. Eur Urol 2002;42:199-203.|
|5||Hegarty PK, Kayes O, Freeman A, Christopher AN, Ralph DJ, Minhas S. A prospective study of 100 cases of penile cancer managed according to EAU guidelines. BJU Int 2006;98:526-31.|
|6||Cabanas RM. An approach for the treatment of penile carcinoma. Cancer 1977;39:456-66.|
|7||Pettaway CA, Pisters LL, Dinney CP, Jularbal F, Swanson DA, von Eschenbach AC, et al . Sentinel lymph node dissection for penile carcinoma: The M. D. Anderson Cancer Center experience. J Urol 1995;154:1999-2003.|
|8||Morton DL, Wen DR, Wong JH, Economou JS, Cagle LA, Storm FK, et al . Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg 1992;127:392-9.|
|9||Horenblas S. Lymphadenectomy for squamous cell carcinoma of the penis. Part 1: Diagnosis of lymph node metastasis. BJU Int 2001;88:467-72.|
|10||Kroon BK, Horenblas S, Meinhardt W, van der Poel HG, Bex A, van Tinteren H, et al . Dynamic sentinel node biopsy in penile cancer: Evaluation of 10 years experience. Eur Urol 2005;47:601-6.|
|11||Kroon BK, Horenblas S, Deurloo EE, Nieweg OE, Teertstra HJ. Ultrasonography-guided fine-needle aspiration cytology before sentinel node biopsy in patients with penile carcinoma. BJU Int 2005;95:517-21.|
|12||Perdona S, Gallo L, Claudio L, Marra L, Gentile M, Gallo A. Role of crural inguinal lymphadenectomy and dynamic sentinel lymph node biopsy in lymph node staging in squamous-cell carcinoma of the penis. Our experience. Tumori 2003;89:276-9.|
|13||d'Ancona CA, de Lucena RG, de Oliveira Querne FA, Martins MH, Denardi F, Netto NR Jr. Long-term follow-up of penile carcinoma treated with penectomy and bilateral modified inguinal lymphadenectomy. J Urol 2004;172:498-501.|