Sentinel lymph node technique in endometrial cancer, Part 2

As reviewed in Part 1, surgery is indicated for the staging and treatment of endometrial cancer. Lymph node status is one of the most important factors in determining prognosis and the need for adjuvant treatment. The extent of lymph node evaluation is controversial as full lymphadenectomy carries risks, including increased operative time, blood loss, nerve injury, and lymphedema.

Two trials have found no survival benefit from lymphadenectomy for endometrial cancer; however, other evidence suggests that women without known nodal status may be more likely to receive radiotherapy.^1,2,3

Given these issues, the sentinel lymph node technique strikes a balance between the risks and benefits of lymph node evaluation in endometrial cancer.

Sentinel lymph nodes (SLN) are the first nodes to drain a tumor site, and thus, are typically the first to demonstrate occult malignancy. The use of the SLN technique as an alternative to complete lymphadenectomy in endometrial cancer has been well described, although its accuracy and the validity of its use are still debated.

The viability of the SLN technique is predicated on the ability to achieve mapping of dye or tracer from the tumor to the first lymph node to drain the tumor. The lymphatic drainage of the endometrium is complex and unlike vulvar or breast cancer, endometrial cancer is less accessible for peritumoral injection. Several injection techniques have been described; cervical injection is the easiest to achieve and has been found to have similar or higher SLN detection than hysteroscopic or fundal injections.^4,5

There are a number of techniques for SLN detection, each with unique benefits and risks. Visual identification of blue dye, most frequently isosulfan blue, is the “colorimetric method” and has been used most commonly with cervical injection for endometrial cancer. Injection of isosulfan blue does not require specialized equipment, however visualization in obese patients is inferior.⁶

Technetium sulfur colloid (Tc) is a radioactive tracer that can be detected by gamma probes. A preoperative lymphoscintigraphy and a handheld gamma probe are used to map lymphatics. This technique has limitations, including the additional time and coordination of procedures, as well as some evidence of poor correlation between lymphoscintigraphy and surgical SLN mapping.⁷

Indocyanine green (ICG) is a fluorescent dye that has excellent signal penetration and allows for real-time visual identification using near-infrared fluorescence imaging. The bilateral detection rate with ICG appears comparable or better than blue dye.⁸ Combinations of dye, either ICG plus Tc or Tc plus blue dye, may be also used to increase SLN detection.

The accuracy of the SLN technique is the cornerstone to its success. In a prospective multicenter study – Senti-Endo – patients with early-stage disease underwent pelvic SLN assessment with cervical injection of a combination of dyes followed by systematic pelvic node dissection. The overall negative predictive value was 97% with three patients who had positive lymph nodes that were not detected, all of whom had a type 2 endometrial cancer.⁹

With the uptake of the SLN technique, many institutions have protocols surrounding the technique to ensure appropriate SLN detection and evaluation. Physicians using this technique should adhere to protocols supported by National Comprehensive Cancer Network guidelines, taking care to remove any suspicious lymph nodes and perform a full side-specific lymphadenectomy if bilateral mapping is not achieved.

The extent of lymphadenectomy and application of the SLN technique in high-risk endometrial cancer remains controversial. These patients are at higher risk for unsuccessful mapping and isolated para-aortic metastasis. Retrospective series have suggested equivalent oncologic outcomes for women with high-grade cancers who have been staged by SLN biopsy, compared with selective or complete lymphadenectomy.^10,11

We await the results of a large prospective trial in which patients undergo comprehensive lymphadenectomy in addition to SLN biopsy to assess the accuracy of the technique (NCT01673022).

Pathologic evaluation of SLNs is frequently done with ultrastaging, which describes additional sectioning and staining of the node. This technique frequently identifies isolated tumor cells and micrometastasis (collectively called low-volume disease) in addition to macrometastasis. The clinical and prognostic significance of low-volume disease is unknown and additional investigation is urgently needed to determine appropriate adjuvant therapy and follow-up for these patients.

The SLN technique is an acceptable approach to assess clinical stage I endometrial cancer. Physicians should consider adding the SLN biopsy to their routine staging techniques prior to exclusively adopting the new technique. They should take care to adhere to SLN algorithms and monitor outcomes.

References

1. J Natl Cancer Inst. 2008;100(23):1707-16.

2. Lancet. 2009 Jan;373(9658):125-36.

3. Am J Obstet Gynecol. 2011 Dec;205(6):562.e1–9.

4. Gynecol Oncol. 2013 Nov;131(2):299-303.

5. Int J Gynecol Cancer. 2013 Nov;23(9):1704-11.

6. Gynecol Oncol 2014 Aug;134(2):281-6.

7. Gynecol Oncol. 2009 Feb;112(2):348-352.

8. Gynecol Oncol. 2014 May;133(2):274-7.

9. Lancet Oncol. 2011 May;12(5):469-76.

10. Ann Surg Oncol. 2016 Jan;23(1):196-202.

11. Gynecol Oncol. 2016 Mar;140(3):394-9.

Dr. Rossi is an assistant professor in the division of gynecologic oncology at the University of North Carolina, Chapel Hill. Dr. Sullivan is a clinical fellow in the division of gynecologic oncology at UNC, Chapel Hill. Dr. Rossi and Dr. Sullivan reported having no relevant financial disclosures.

As reviewed in Part 1, surgery is indicated for the staging and treatment of endometrial cancer. Lymph node status is one of the most important factors in determining prognosis and the need for adjuvant treatment. The extent of lymph node evaluation is controversial as full lymphadenectomy carries risks, including increased operative time, blood loss, nerve injury, and lymphedema.

Two trials have found no survival benefit from lymphadenectomy for endometrial cancer; however, other evidence suggests that women without known nodal status may be more likely to receive radiotherapy.^1,2,3

Given these issues, the sentinel lymph node technique strikes a balance between the risks and benefits of lymph node evaluation in endometrial cancer.

Sentinel lymph nodes (SLN) are the first nodes to drain a tumor site, and thus, are typically the first to demonstrate occult malignancy. The use of the SLN technique as an alternative to complete lymphadenectomy in endometrial cancer has been well described, although its accuracy and the validity of its use are still debated.

The viability of the SLN technique is predicated on the ability to achieve mapping of dye or tracer from the tumor to the first lymph node to drain the tumor. The lymphatic drainage of the endometrium is complex and unlike vulvar or breast cancer, endometrial cancer is less accessible for peritumoral injection. Several injection techniques have been described; cervical injection is the easiest to achieve and has been found to have similar or higher SLN detection than hysteroscopic or fundal injections.^4,5

There are a number of techniques for SLN detection, each with unique benefits and risks. Visual identification of blue dye, most frequently isosulfan blue, is the “colorimetric method” and has been used most commonly with cervical injection for endometrial cancer. Injection of isosulfan blue does not require specialized equipment, however visualization in obese patients is inferior.⁶

Technetium sulfur colloid (Tc) is a radioactive tracer that can be detected by gamma probes. A preoperative lymphoscintigraphy and a handheld gamma probe are used to map lymphatics. This technique has limitations, including the additional time and coordination of procedures, as well as some evidence of poor correlation between lymphoscintigraphy and surgical SLN mapping.⁷

Indocyanine green (ICG) is a fluorescent dye that has excellent signal penetration and allows for real-time visual identification using near-infrared fluorescence imaging. The bilateral detection rate with ICG appears comparable or better than blue dye.⁸ Combinations of dye, either ICG plus Tc or Tc plus blue dye, may be also used to increase SLN detection.

The accuracy of the SLN technique is the cornerstone to its success. In a prospective multicenter study – Senti-Endo – patients with early-stage disease underwent pelvic SLN assessment with cervical injection of a combination of dyes followed by systematic pelvic node dissection. The overall negative predictive value was 97% with three patients who had positive lymph nodes that were not detected, all of whom had a type 2 endometrial cancer.⁹

With the uptake of the SLN technique, many institutions have protocols surrounding the technique to ensure appropriate SLN detection and evaluation. Physicians using this technique should adhere to protocols supported by National Comprehensive Cancer Network guidelines, taking care to remove any suspicious lymph nodes and perform a full side-specific lymphadenectomy if bilateral mapping is not achieved.

The extent of lymphadenectomy and application of the SLN technique in high-risk endometrial cancer remains controversial. These patients are at higher risk for unsuccessful mapping and isolated para-aortic metastasis. Retrospective series have suggested equivalent oncologic outcomes for women with high-grade cancers who have been staged by SLN biopsy, compared with selective or complete lymphadenectomy.^10,11

We await the results of a large prospective trial in which patients undergo comprehensive lymphadenectomy in addition to SLN biopsy to assess the accuracy of the technique (NCT01673022).

Pathologic evaluation of SLNs is frequently done with ultrastaging, which describes additional sectioning and staining of the node. This technique frequently identifies isolated tumor cells and micrometastasis (collectively called low-volume disease) in addition to macrometastasis. The clinical and prognostic significance of low-volume disease is unknown and additional investigation is urgently needed to determine appropriate adjuvant therapy and follow-up for these patients.

The SLN technique is an acceptable approach to assess clinical stage I endometrial cancer. Physicians should consider adding the SLN biopsy to their routine staging techniques prior to exclusively adopting the new technique. They should take care to adhere to SLN algorithms and monitor outcomes.

References

1. J Natl Cancer Inst. 2008;100(23):1707-16.

2. Lancet. 2009 Jan;373(9658):125-36.

3. Am J Obstet Gynecol. 2011 Dec;205(6):562.e1–9.

4. Gynecol Oncol. 2013 Nov;131(2):299-303.

5. Int J Gynecol Cancer. 2013 Nov;23(9):1704-11.

6. Gynecol Oncol 2014 Aug;134(2):281-6.

7. Gynecol Oncol. 2009 Feb;112(2):348-352.

8. Gynecol Oncol. 2014 May;133(2):274-7.

9. Lancet Oncol. 2011 May;12(5):469-76.

10. Ann Surg Oncol. 2016 Jan;23(1):196-202.

11. Gynecol Oncol. 2016 Mar;140(3):394-9.

Dr. Rossi is an assistant professor in the division of gynecologic oncology at the University of North Carolina, Chapel Hill. Dr. Sullivan is a clinical fellow in the division of gynecologic oncology at UNC, Chapel Hill. Dr. Rossi and Dr. Sullivan reported having no relevant financial disclosures.

As reviewed in Part 1, surgery is indicated for the staging and treatment of endometrial cancer. Lymph node status is one of the most important factors in determining prognosis and the need for adjuvant treatment. The extent of lymph node evaluation is controversial as full lymphadenectomy carries risks, including increased operative time, blood loss, nerve injury, and lymphedema.

Two trials have found no survival benefit from lymphadenectomy for endometrial cancer; however, other evidence suggests that women without known nodal status may be more likely to receive radiotherapy.^1,2,3

Given these issues, the sentinel lymph node technique strikes a balance between the risks and benefits of lymph node evaluation in endometrial cancer.

Sentinel lymph nodes (SLN) are the first nodes to drain a tumor site, and thus, are typically the first to demonstrate occult malignancy. The use of the SLN technique as an alternative to complete lymphadenectomy in endometrial cancer has been well described, although its accuracy and the validity of its use are still debated.

The viability of the SLN technique is predicated on the ability to achieve mapping of dye or tracer from the tumor to the first lymph node to drain the tumor. The lymphatic drainage of the endometrium is complex and unlike vulvar or breast cancer, endometrial cancer is less accessible for peritumoral injection. Several injection techniques have been described; cervical injection is the easiest to achieve and has been found to have similar or higher SLN detection than hysteroscopic or fundal injections.^4,5

There are a number of techniques for SLN detection, each with unique benefits and risks. Visual identification of blue dye, most frequently isosulfan blue, is the “colorimetric method” and has been used most commonly with cervical injection for endometrial cancer. Injection of isosulfan blue does not require specialized equipment, however visualization in obese patients is inferior.⁶

Technetium sulfur colloid (Tc) is a radioactive tracer that can be detected by gamma probes. A preoperative lymphoscintigraphy and a handheld gamma probe are used to map lymphatics. This technique has limitations, including the additional time and coordination of procedures, as well as some evidence of poor correlation between lymphoscintigraphy and surgical SLN mapping.⁷

Indocyanine green (ICG) is a fluorescent dye that has excellent signal penetration and allows for real-time visual identification using near-infrared fluorescence imaging. The bilateral detection rate with ICG appears comparable or better than blue dye.⁸ Combinations of dye, either ICG plus Tc or Tc plus blue dye, may be also used to increase SLN detection.

The accuracy of the SLN technique is the cornerstone to its success. In a prospective multicenter study – Senti-Endo – patients with early-stage disease underwent pelvic SLN assessment with cervical injection of a combination of dyes followed by systematic pelvic node dissection. The overall negative predictive value was 97% with three patients who had positive lymph nodes that were not detected, all of whom had a type 2 endometrial cancer.⁹

With the uptake of the SLN technique, many institutions have protocols surrounding the technique to ensure appropriate SLN detection and evaluation. Physicians using this technique should adhere to protocols supported by National Comprehensive Cancer Network guidelines, taking care to remove any suspicious lymph nodes and perform a full side-specific lymphadenectomy if bilateral mapping is not achieved.

The extent of lymphadenectomy and application of the SLN technique in high-risk endometrial cancer remains controversial. These patients are at higher risk for unsuccessful mapping and isolated para-aortic metastasis. Retrospective series have suggested equivalent oncologic outcomes for women with high-grade cancers who have been staged by SLN biopsy, compared with selective or complete lymphadenectomy.^10,11

We await the results of a large prospective trial in which patients undergo comprehensive lymphadenectomy in addition to SLN biopsy to assess the accuracy of the technique (NCT01673022).

Pathologic evaluation of SLNs is frequently done with ultrastaging, which describes additional sectioning and staining of the node. This technique frequently identifies isolated tumor cells and micrometastasis (collectively called low-volume disease) in addition to macrometastasis. The clinical and prognostic significance of low-volume disease is unknown and additional investigation is urgently needed to determine appropriate adjuvant therapy and follow-up for these patients.

The SLN technique is an acceptable approach to assess clinical stage I endometrial cancer. Physicians should consider adding the SLN biopsy to their routine staging techniques prior to exclusively adopting the new technique. They should take care to adhere to SLN algorithms and monitor outcomes.

References

1. J Natl Cancer Inst. 2008;100(23):1707-16.

2. Lancet. 2009 Jan;373(9658):125-36.

3. Am J Obstet Gynecol. 2011 Dec;205(6):562.e1–9.

4. Gynecol Oncol. 2013 Nov;131(2):299-303.

5. Int J Gynecol Cancer. 2013 Nov;23(9):1704-11.

6. Gynecol Oncol 2014 Aug;134(2):281-6.

7. Gynecol Oncol. 2009 Feb;112(2):348-352.

8. Gynecol Oncol. 2014 May;133(2):274-7.

9. Lancet Oncol. 2011 May;12(5):469-76.

10. Ann Surg Oncol. 2016 Jan;23(1):196-202.

11. Gynecol Oncol. 2016 Mar;140(3):394-9.

Dr. Rossi is an assistant professor in the division of gynecologic oncology at the University of North Carolina, Chapel Hill. Dr. Sullivan is a clinical fellow in the division of gynecologic oncology at UNC, Chapel Hill. Dr. Rossi and Dr. Sullivan reported having no relevant financial disclosures.