Commentary (Horowitz): Sentinel Node Evaluation in Gynecologic Cancer

I would like to compliment the authors on an excellent review of sentinel node evaluation in gynecologic cancer-in particular, vulvar and cervical cancer. The authors have been at the forefront of minimally invasive surgery for gynecologic malignancies. They have published extensively about their experience with laparoscopy and radical trachelectomy. Now this group brings forth another technique that may revolutionize the way we treat women with vulvar and cervical carcinoma.

The authors provide a comprehensive review of the data pertaining to sentinel node evaluation. This is a technique that has been used extensively for breast cancer. Through the use of isosulfan blue dye (Lymphazurin 1%) and/or technetium (Tc)-99 lymphoscintigraphy, oncologic surgeons have been able to reduce the morbidity of axillary lymph node dissection by identifying the sentinel lymph node.

Findings in Vulvar Cancer

Several studies have assessed the utility of sentinel node evaluation in vulvar cancer. Indeed, the Gynecologic Oncology Group performed a study evaluating the role and sensitivity of this technique in vulvar cancer, but the results are not yet available.

I concur with the authors that the majority of patients with clinical stage I/II vulvar cancer do not benefit from the node dissection. As they state, only 10% to 15% have lymph nodes that are histologically positive for carcinoma. Even with recent modifications that preserve the saphenous vein during the inguinofemoral node dissection, patients continue to experience the delayed complication of lymphedema. This technique will further decrease lymphedema by identifying the sentinel lymph node.

Sentinel node sampling in vulvar cancer requires considerable expertise. According to most learning curve estimates, it is recommended that at least 10 studies be performed to develop this expertise.

Comprehensive Review of Data

The authors review 12 series including more than 353 cases of vulvar cancer. In all of these studies, the institutions used a combination of blue dye and lymphoscintigraphy. An overall false-negative rate < 1% was reported by the authors. It should be stressed that sentinel node mapping is not the standard of care in treating vulvar cancer and should be performed in a study setting. Furthermore, the role of microscopically positive nodes identified after several sections must be clarified. I agree with the authors that treatment algorithms must be established before sentinal node evaluation becomes a standard of care.

Pioneers in minimally invasive techniques for the treatment of cervical cancer as well, the authors also review the data on sentinel node evaluation in cervical cancer patients. They have reviewed 12 studies incorporating 323 patients. As they note, in patients with stage IA2-IB2 disease, approximately 15% will have positive lymph nodes. The morbidity of this procedure- which is compounded when postoperative radiation is administered-is significant for such a small yield. Irrespective of the technique used for a pelvic node dissection (laparoscopy or laparotomy), complications such as vascular injury, paresthesia, pain, lymphocysts, lymphedema, and nerve injury can occur.

Simple Technique

The technique described is quite simple, with Tc-99 injected into the periphery of the cervical lesion. A lymphoscintigram is obtained, and films are made available for the surgeon in the operating room. This will assist in mapping the location of lymph nodes.

During surgery, 2 to 4 mL of isosulfan blue dye is injected into the four quadrants of the cervix. Lymph nodes can be selectively resected laparoscopically by identifying the blue-stained lymph nodes and/or identifying hot lymph nodes with a laparoscopic gamma probe. Each blue lymph node is also evaluated by the gamma probe. This procedure is done bilaterally. All lymph nodes selected are sent for frozen section. If all are histologically negative, a complete lymph node dissection is performed.

Malur et al[1] reported a detection rate of 55% with isosulfan blue, 76% with Tc-99, and 90% when both modalities are used. Levenback et al[2] confirmed the importance of the combined method, achieving a 60% detection rate with isosulfan blue and 100% with combined modalities. In the current review, the authors report their own detection rates of 79% to 93% with combined modalities.

As in vulvar cancer, sentinel node evaluation in cervical cancer also has a learning curve. This technique permits laparoscopically resected sentinel nodes with a learning curve of 20 cases. A lower detection rate was reported with cervical vs vulvar sentinel node evaluation, which is thought to be secondary to the complexity and steeper learning curve.

Evolving Science

As our knowledge of molecular biology continues to improve, the definition of histologically positive nodes is evolving. Through the use of in situ hybridization and reverse transcriptase- polymerase chain reaction (RTPCR) assays, pathologists are able to identify micrometastasis. The prognostic significance of these findings is unknown. In addition, their role in changing therapeutic intervention strategies is unclear at the present time. Additional prospective studies must be performed to evaluate the role of micrometastases in the treatment of these malignancies.

Although the complications of this technique are minimal, they do exist and can be devastating. A decrease in pulse oximetry readings secondary to the blue dye interfering with the optimal sensor reading has been reported. This is similar to that reported with the injection of indigo carmine dye. Allergic reactions can also occur from the blue dye and may result in anaphylaxis.

Conclusions

The concept of sentinel node evaluation is exciting. The technique is, however, associated with a learning curve of approximately 10 to 20 patients. This necessitates performing lymph node dissection on these patients to ensure the adequacy of sampling if the initial frozen section is histologically negative. Both cervical and vulvar sentinel node evaluation are experimental and should be done after permission has been obtained through a facility's institutional review board.

Once again, I would like to commend the authors on providing us with a thorough review of sentinel node evaluation in vulvar and cervical cancer.

Financial Disclosure:The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

References:

1. Malur S, Krause N, Kohler C, et al: Sentinel lymph node detection in patients with cervical cancer. Gynecol Oncol 80:254-257, 2001.
2. Levenback C, Coleman RL, Burke TW, et al: Lymphatic mapping and sentinel node identification in patients with cervix cancer undergoing radical hysterectomy and pelvic lymphadenectomy. J Clin Oncol 20:688-693, 2002.