The notion of effective detection of metastasis (and therefore selection of patients who would benefit from lymph node dissection) by identifying and sampling the first lymphatic landing site has long been explored. Advances in breast cancer and melanoma, along with the predictable sequence of penile lymphatic drainage have led this thrust. Cabañas28
is credited with the original description of sentinel lymph node dissection, exploiting a predictable nodal landing site superomedial to the sapheno-femoral junction.
This technique was expanded at the MD Anderson Cancer Center to include dissection of all superficial nodes medial to the saphenous vein and superior to the superficial external pudendal vein.29
Even with this modification, the false-negative rate was 25%. Horenblas and colleagues30
at the Netherlands Cancer Institute adapted dynamic sentinel node biopsy (DSNB) techniques for use in carcinoma of the penis and first published their results in 2000. They performed lymphoscintigraphy with technetium 99m nanocolloid injected into the dermis around the primary tumour in 55 patients with stage T2 or greater disease with clinically negative groins on the day before surgery and injected patent blue dye on the day of surgery. The combination of the dye for lymphatic tracking and node colouring with a gamma detection probe for detection of the sentinel node allowed for determination of the first landing site of the lymphatic drainage of the tumour. This node, when identified, was resected, and pathological analysis performed. Full node dissection was undertaken 2 weeks later in the event of a positive sentinel node. Two of 24 patients with negative sentinel node biopsies subsequently presented with metastatic disease to the inguinal nodes. Several other centres have since published sentinel node series, with false-negative rates of 11%–29%.31–33
Two recent studies involved sentinel node biopsy concomitant with groin dissection, an approach that allowed for pathological assessment of false-negative rates. Thirty-one such patients were recently reviewed at the MD Anderson Cancer Center.32
Two of 7 groins that harboured metastatic disease had negative sentinel node biopsies. Perdona and colleagues33
compared groups of clinically node-negative patients with stage T2–T3 penile cancer who underwent either radical lymph node dissection alone or DSNB followed by groin dissection. They achieved a false-negative rate of 11% and confirmed the utility of combining lymphoscintigraphy with intraoperative lymphatic mapping with blue dye, as 23% of “hot” nodes did not demonstrate dye uptake. Hadway and colleagues34
from London, UK, published the first British series of DSNB for penile cancer. They performed ultrasound and fine-needle aspiration on each patient on the day of surgery and noted a false-negative rate for fine-needle aspiration of over 50% in those groins that ultimately harboured sentinel node metastasis. Their false-negative rate for DSNB at a median follow-up of 11 months was 5%, as only 1 patient with a negative sentinel node biopsy had subsequently developed nodal metastases.
The major limitation of assessing inguinal node status via sentinel node biopsy has been the high rate of false-negative groins and this has led most centres to note that a more extensive dissection remains the standard of care. The group at the Netherlands Cancer Institute has since taken measures to try to decrease the false-negative rate of DSNB by altering its protocol.35
Rigorous serial sectioning of sentinel nodes with immunohisto chemical analysis is now routinely undertaken, as some small metastatic deposits were not found on prior sectioning protocols. They noted also that cancer was being found in groins where no sentinel node was found and have proposed full dissection for these groins based on the idea that a node infiltrated with cancer may no longer function as a drainage node and thus the lymph drainage is diverted either to an adjacent node or to the contralateral groin. Preoperative high-resolution ultrasound is now used in all patients there and has shown efficacy in detecting small-volume metastatic deposits, confirmed by fine-needle aspiration. These patients would then undergo radical lymphadenectomy. Results of these modifications in a cohort of 58 patients have recently been published, with a reduction of the false-negative rate to 4.8%.36
It has been noted, however, that there is likely a long learning curve to the procedure of about 20 cases (troublesome in a condition with such a low prevalence) and that the radiological and pathological expertise required are likely to be available only in large and experienced centres.37
This may have an impact on the adoption and use of DSNB in Canada, where the accrual of a high-volume case series would be expected to take a very long time for any single centre. This may expose patients to the risk of false-negative DSNB interrogation, with the resultant potential for decreased survival in late disease discovery.