The role of lymphadenectomy in endometrial cancer, Part 1

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The role of lymphadenectomy in endometrial cancer, Part 1

Endometrial cancer is the most common gynecologic malignancy in the United States. Fortunately, most endometrial cancers present at an early stage with excellent overall survival – approximately 85% – in clinical stage I disease. Since 1988, the International Federation of Gynecology and Obstetrics (FIGO) staging of endometrial cancer has required surgical staging reflecting increasing data on the prognostic significance of lymph node metastasis and the treatment implications for node positive cancers.

Indeed, lymph nodes represent the most common location for extrauterine spread in endometrial cancer. The lymphatic drainage from the uterus is to both the pelvic and the para-aortic lymph nodes. Lymphatic channels from the uterus can drain directly from the fundus via the infundibulopelvic ligament to the aortic lymph node chain, thereby bypassing the pelvic lymph nodes. As a result, there is a 2%-3% risk of isolated aortic metastasis with negative pelvic lymph nodes.

Dr. Paola A. Gehrig
Dr. Paola A. Gehrig

The extent of lymph node evaluation required for staging is debatable. The National Comprehensive Cancer Network (NCCN) guidelines recommend complete hysterectomy with bilateral salpingo-oophorectomy and additional procedures based on preoperative and intraoperative findings. During surgery, the surgeon should evaluate all peritoneal surfaces and the retroperitoneal lymphatic chains for abnormalities. All suspicious lymph nodes should be removed, but the extent of lymphadenectomy should be based on the NCCN guidelines.1 The NCCN offers the option for use of sentinel lymph node evaluation with adherence to specific staging algorithms for this technology.

Proponents of lymphadenectomy cite the need for accurate staging to guide adjuvant therapies, to provide prognostic information, and to eradicate metastatic lymph nodes with possible therapeutic benefit. However, criticisms of lymphadenectomy include a lack of randomized studies demonstrating a therapeutic benefit and the morbidity of lymphedema with its corresponding quality of life and cost implications. As a result, practices regarding lymph node evaluation vary widely.

There is conflicting data on whether there is a therapeutic benefit to performing lymphadenectomy. Retrospective studies have shown a benefit, but this was not seen in two prospective trials. There appears to be clear benefit for debulking of clinically enlarged nodal metastasis,2,3 and likely benefit to resection of microscopic metastasis, particularly with combined pelvic and aortic lymphadenectomy in high-risk endometrial cancers.4,5,6,7,8

Dr. Leslie H. Clark
Dr. Leslie H. Clark

The ASTEC trial by Kitchener et al and an Italian collaborative trial by Benedetti et al, however, both evaluated the role of lymph node dissection in predominantly low-risk endometrial cancer and found no benefit.9,10 Both studies documented no difference in overall survival, but increased morbidity with lymphadenectomy. No prospective trials have evaluated the role of lymphadenectomy in high-risk endometrial cancers.

Universal use of complete lymphadenectomy in all patients with endometrial cancer would subject a large percent of low risk patients to undo surgical risk. The two most commonly utilized strategies are risk factor based lymphadenectomy and sentinel lymph node evaluation.

Tumors are considered low risk if they are less than 2cm in size, grade 1 or 2, and superficially invasive (less than 50% myometrial invasion).11 The risk of lymph node metastasis in these patients was exceedingly low with no lymph node metastasis detect in more than 400 women who prospectively underwent this evaluation, thus lymphadenectomy can be safely avoided. Utilizing risk factor based lymphadenectomy does require the availability of reliable frozen section pathology evaluation, which may be a limitation for some institutions.

A key argument against routine use of systematic lymphadenectomy is the concern for postoperative complications and lymphedema. The estimated incidence of lymphedema following lymphadenectomy is 20%-30%.12 However, there are challenges in studying lymphedema that likely limit our understanding of the true incidence. The ASTEC trial and Italian cooperative trial have demonstrated that there is an eight-fold increased risk of lymphedema in women who undergo lymphadenectomy, compared with those who do not.13 The development of lymphedema requires ongoing treatment with associated costs of care. Thus, the selective lymphadenectomy or sentinel nodes have the ability to reduce healthcare costs.14 Sentinel lymph nodes will be covered in Part Two of this article.

References

1. J Natl Compr Canc Netw. 2014 Feb;12(2):248-80.

2. Gynecol Oncol. 2005 Dec;99(3):689-95.

3. Int J Gynecol Cancer. 2003 Sep-Oct;13(5):664-72.

4. Gynecol Oncol. 1995 Jan;56(1):29-33.

5. J Clin Oncol. 2005 Jun 1;23(16):3668-75.

6. Lancet. 2010 Apr 3;375(9721):1165-72.

7. Gynecol Oncol. 1998 Dec;71(3):340-3.

8. Cancer. 2006 Oct 15;107(8):1823-30.

9. Lancet. 2009 Jan 10;373(9658):125-36.

10. J Natl Cancer Inst. 2008 Dec 3;100(23):1707-16.

11. Gynecol Oncol. 2008 Apr;109(1):11-8.

12. Obstet Gynecol. 2014 Aug;124(2 Pt 1):307-15.

13. Cochrane Database Syst Rev. 2015 Sep 21;(9):CD007585.

14. Gynecol Oncol. 2014 Dec;135(3):518-24.

Dr. Gehrig is professor and director of gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Clark is a fellow in the division of gynecologic oncology, department of obstetrics and gynecology at the university. They reported having no financial disclosures relevant to this column. Email them at obnews@frontlinemedcom.com.

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Endometrial cancer is the most common gynecologic malignancy in the United States. Fortunately, most endometrial cancers present at an early stage with excellent overall survival – approximately 85% – in clinical stage I disease. Since 1988, the International Federation of Gynecology and Obstetrics (FIGO) staging of endometrial cancer has required surgical staging reflecting increasing data on the prognostic significance of lymph node metastasis and the treatment implications for node positive cancers.

Indeed, lymph nodes represent the most common location for extrauterine spread in endometrial cancer. The lymphatic drainage from the uterus is to both the pelvic and the para-aortic lymph nodes. Lymphatic channels from the uterus can drain directly from the fundus via the infundibulopelvic ligament to the aortic lymph node chain, thereby bypassing the pelvic lymph nodes. As a result, there is a 2%-3% risk of isolated aortic metastasis with negative pelvic lymph nodes.

Dr. Paola A. Gehrig
Dr. Paola A. Gehrig

The extent of lymph node evaluation required for staging is debatable. The National Comprehensive Cancer Network (NCCN) guidelines recommend complete hysterectomy with bilateral salpingo-oophorectomy and additional procedures based on preoperative and intraoperative findings. During surgery, the surgeon should evaluate all peritoneal surfaces and the retroperitoneal lymphatic chains for abnormalities. All suspicious lymph nodes should be removed, but the extent of lymphadenectomy should be based on the NCCN guidelines.1 The NCCN offers the option for use of sentinel lymph node evaluation with adherence to specific staging algorithms for this technology.

Proponents of lymphadenectomy cite the need for accurate staging to guide adjuvant therapies, to provide prognostic information, and to eradicate metastatic lymph nodes with possible therapeutic benefit. However, criticisms of lymphadenectomy include a lack of randomized studies demonstrating a therapeutic benefit and the morbidity of lymphedema with its corresponding quality of life and cost implications. As a result, practices regarding lymph node evaluation vary widely.

There is conflicting data on whether there is a therapeutic benefit to performing lymphadenectomy. Retrospective studies have shown a benefit, but this was not seen in two prospective trials. There appears to be clear benefit for debulking of clinically enlarged nodal metastasis,2,3 and likely benefit to resection of microscopic metastasis, particularly with combined pelvic and aortic lymphadenectomy in high-risk endometrial cancers.4,5,6,7,8

Dr. Leslie H. Clark
Dr. Leslie H. Clark

The ASTEC trial by Kitchener et al and an Italian collaborative trial by Benedetti et al, however, both evaluated the role of lymph node dissection in predominantly low-risk endometrial cancer and found no benefit.9,10 Both studies documented no difference in overall survival, but increased morbidity with lymphadenectomy. No prospective trials have evaluated the role of lymphadenectomy in high-risk endometrial cancers.

Universal use of complete lymphadenectomy in all patients with endometrial cancer would subject a large percent of low risk patients to undo surgical risk. The two most commonly utilized strategies are risk factor based lymphadenectomy and sentinel lymph node evaluation.

Tumors are considered low risk if they are less than 2cm in size, grade 1 or 2, and superficially invasive (less than 50% myometrial invasion).11 The risk of lymph node metastasis in these patients was exceedingly low with no lymph node metastasis detect in more than 400 women who prospectively underwent this evaluation, thus lymphadenectomy can be safely avoided. Utilizing risk factor based lymphadenectomy does require the availability of reliable frozen section pathology evaluation, which may be a limitation for some institutions.

A key argument against routine use of systematic lymphadenectomy is the concern for postoperative complications and lymphedema. The estimated incidence of lymphedema following lymphadenectomy is 20%-30%.12 However, there are challenges in studying lymphedema that likely limit our understanding of the true incidence. The ASTEC trial and Italian cooperative trial have demonstrated that there is an eight-fold increased risk of lymphedema in women who undergo lymphadenectomy, compared with those who do not.13 The development of lymphedema requires ongoing treatment with associated costs of care. Thus, the selective lymphadenectomy or sentinel nodes have the ability to reduce healthcare costs.14 Sentinel lymph nodes will be covered in Part Two of this article.

References

1. J Natl Compr Canc Netw. 2014 Feb;12(2):248-80.

2. Gynecol Oncol. 2005 Dec;99(3):689-95.

3. Int J Gynecol Cancer. 2003 Sep-Oct;13(5):664-72.

4. Gynecol Oncol. 1995 Jan;56(1):29-33.

5. J Clin Oncol. 2005 Jun 1;23(16):3668-75.

6. Lancet. 2010 Apr 3;375(9721):1165-72.

7. Gynecol Oncol. 1998 Dec;71(3):340-3.

8. Cancer. 2006 Oct 15;107(8):1823-30.

9. Lancet. 2009 Jan 10;373(9658):125-36.

10. J Natl Cancer Inst. 2008 Dec 3;100(23):1707-16.

11. Gynecol Oncol. 2008 Apr;109(1):11-8.

12. Obstet Gynecol. 2014 Aug;124(2 Pt 1):307-15.

13. Cochrane Database Syst Rev. 2015 Sep 21;(9):CD007585.

14. Gynecol Oncol. 2014 Dec;135(3):518-24.

Dr. Gehrig is professor and director of gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Clark is a fellow in the division of gynecologic oncology, department of obstetrics and gynecology at the university. They reported having no financial disclosures relevant to this column. Email them at obnews@frontlinemedcom.com.

Endometrial cancer is the most common gynecologic malignancy in the United States. Fortunately, most endometrial cancers present at an early stage with excellent overall survival – approximately 85% – in clinical stage I disease. Since 1988, the International Federation of Gynecology and Obstetrics (FIGO) staging of endometrial cancer has required surgical staging reflecting increasing data on the prognostic significance of lymph node metastasis and the treatment implications for node positive cancers.

Indeed, lymph nodes represent the most common location for extrauterine spread in endometrial cancer. The lymphatic drainage from the uterus is to both the pelvic and the para-aortic lymph nodes. Lymphatic channels from the uterus can drain directly from the fundus via the infundibulopelvic ligament to the aortic lymph node chain, thereby bypassing the pelvic lymph nodes. As a result, there is a 2%-3% risk of isolated aortic metastasis with negative pelvic lymph nodes.

Dr. Paola A. Gehrig
Dr. Paola A. Gehrig

The extent of lymph node evaluation required for staging is debatable. The National Comprehensive Cancer Network (NCCN) guidelines recommend complete hysterectomy with bilateral salpingo-oophorectomy and additional procedures based on preoperative and intraoperative findings. During surgery, the surgeon should evaluate all peritoneal surfaces and the retroperitoneal lymphatic chains for abnormalities. All suspicious lymph nodes should be removed, but the extent of lymphadenectomy should be based on the NCCN guidelines.1 The NCCN offers the option for use of sentinel lymph node evaluation with adherence to specific staging algorithms for this technology.

Proponents of lymphadenectomy cite the need for accurate staging to guide adjuvant therapies, to provide prognostic information, and to eradicate metastatic lymph nodes with possible therapeutic benefit. However, criticisms of lymphadenectomy include a lack of randomized studies demonstrating a therapeutic benefit and the morbidity of lymphedema with its corresponding quality of life and cost implications. As a result, practices regarding lymph node evaluation vary widely.

There is conflicting data on whether there is a therapeutic benefit to performing lymphadenectomy. Retrospective studies have shown a benefit, but this was not seen in two prospective trials. There appears to be clear benefit for debulking of clinically enlarged nodal metastasis,2,3 and likely benefit to resection of microscopic metastasis, particularly with combined pelvic and aortic lymphadenectomy in high-risk endometrial cancers.4,5,6,7,8

Dr. Leslie H. Clark
Dr. Leslie H. Clark

The ASTEC trial by Kitchener et al and an Italian collaborative trial by Benedetti et al, however, both evaluated the role of lymph node dissection in predominantly low-risk endometrial cancer and found no benefit.9,10 Both studies documented no difference in overall survival, but increased morbidity with lymphadenectomy. No prospective trials have evaluated the role of lymphadenectomy in high-risk endometrial cancers.

Universal use of complete lymphadenectomy in all patients with endometrial cancer would subject a large percent of low risk patients to undo surgical risk. The two most commonly utilized strategies are risk factor based lymphadenectomy and sentinel lymph node evaluation.

Tumors are considered low risk if they are less than 2cm in size, grade 1 or 2, and superficially invasive (less than 50% myometrial invasion).11 The risk of lymph node metastasis in these patients was exceedingly low with no lymph node metastasis detect in more than 400 women who prospectively underwent this evaluation, thus lymphadenectomy can be safely avoided. Utilizing risk factor based lymphadenectomy does require the availability of reliable frozen section pathology evaluation, which may be a limitation for some institutions.

A key argument against routine use of systematic lymphadenectomy is the concern for postoperative complications and lymphedema. The estimated incidence of lymphedema following lymphadenectomy is 20%-30%.12 However, there are challenges in studying lymphedema that likely limit our understanding of the true incidence. The ASTEC trial and Italian cooperative trial have demonstrated that there is an eight-fold increased risk of lymphedema in women who undergo lymphadenectomy, compared with those who do not.13 The development of lymphedema requires ongoing treatment with associated costs of care. Thus, the selective lymphadenectomy or sentinel nodes have the ability to reduce healthcare costs.14 Sentinel lymph nodes will be covered in Part Two of this article.

References

1. J Natl Compr Canc Netw. 2014 Feb;12(2):248-80.

2. Gynecol Oncol. 2005 Dec;99(3):689-95.

3. Int J Gynecol Cancer. 2003 Sep-Oct;13(5):664-72.

4. Gynecol Oncol. 1995 Jan;56(1):29-33.

5. J Clin Oncol. 2005 Jun 1;23(16):3668-75.

6. Lancet. 2010 Apr 3;375(9721):1165-72.

7. Gynecol Oncol. 1998 Dec;71(3):340-3.

8. Cancer. 2006 Oct 15;107(8):1823-30.

9. Lancet. 2009 Jan 10;373(9658):125-36.

10. J Natl Cancer Inst. 2008 Dec 3;100(23):1707-16.

11. Gynecol Oncol. 2008 Apr;109(1):11-8.

12. Obstet Gynecol. 2014 Aug;124(2 Pt 1):307-15.

13. Cochrane Database Syst Rev. 2015 Sep 21;(9):CD007585.

14. Gynecol Oncol. 2014 Dec;135(3):518-24.

Dr. Gehrig is professor and director of gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Clark is a fellow in the division of gynecologic oncology, department of obstetrics and gynecology at the university. They reported having no financial disclosures relevant to this column. Email them at obnews@frontlinemedcom.com.

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Fertility preservation in early cervical cancer

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Fertility preservation in early cervical cancer

Historically, the standard of care for women diagnosed with early cervical cancer has been radical hysterectomy. Thus, young women are not only being confronted with a cancer diagnosis, but may also be forced to cope with the loss of their fertility.

As many young women with cervical cancer were not accepting of this treatment, Dr. Daniel Dargent pioneered the vaginal radical trachelectomy as a fertility-preserving treatment option for early cervical cancer in 1994. There have now been more than 900 vaginal radical trachelectomies performed and they have been shown to have oncologic outcomes similar to those of traditional radical hysterectomy, while sparing a woman’s fertility (Int J Gynecol Cancer. 2013 Jul;23[6]:982-9).

Dr. Leslie Clark
Dr. Leslie Clark

Obstetric outcomes following vaginal radical trachelectomy are acceptable with 17% miscarriage rate in the first trimester (compared to 10%-20% in the general population) and 8% in the second trimester (compared to 1%-5% in the general population) (Am Fam Physician. 2007 Nov 1;76[9]:1341-6). Following vaginal radical trachelectomy, 64% of pregnancies deliver at term.

The usual criteria required to undergo radical trachelectomy include:

1) Reproductive age with desire for fertility.

2) Stage IA1 with LVSI (lymphovascular space invasion), IA2, or IB1 with tumor less than 2 cm.

3) Limited endocervical involvement via preoperative MRI.

4) Negative pelvic lymph nodes.

Preoperative PET scan can be used to evaluate nodal status, but suspicious lymph nodes should be evaluated on frozen section at the time of surgery. The presence of LVSI alone is not a contraindication to trachelectomy.

Courtesy Wikimedia Commons/John Hayman/Creative Commons License

A key limitation of vaginal radical trachelectomy is the specialized training required to perform this technically challenging procedure. Few surgeons in the United States are trained to perform vaginal radical trachelectomy. In response to this limitation, surgeons began to attempt radical trachelectomy via laparotomy (Gynecol Oncol. 2006 Dec;103[3]:807-13). Oncologic outcomes following fertility-sparing abdominal radical trachelectomy have been reported to be equivalent to radical hysterectomy. Concerns regarding the abdominal approach to radical trachelectomy include higher rates of second trimester loss (19%) when compared to the vaginal approach (8%), higher rate of loss of fertility (30%), and risk of postoperative adhesions.

The advent of minimally invasive surgery, particularly robotic surgery, now offers surgeons the ability to perform a procedure technically similar to radical hysterectomy using a minimally invasive approach. Given the similarity of procedural steps of radical trachelectomy to radical hysterectomy using the robotic platform, this procedure is gaining acceptance in the United States with an associated improved surgeon learning curve (Gynecol Oncol. 2008 Nov;111[2]:255-60). In addition, the use of minimally invasive surgery should result in less adhesion formation facilitating natural fertility options postoperatively.

Dr. John F. Boggess
Dr. John F. Boggess

Obstetric and fertility outcomes are limited following minimally invasive radical trachelectomy via laparoscopy or robotic surgery given the novelty of this procedure. Emerging obstetric outcomes appear reassuring, but further data are needed to fully understand the effects of this procedure on pregnancy outcomes and the need for assisted reproductive techniques to achieve pregnancy.

The management of pregnancies following radical trachelectomy is also an area with limited data, which presents a clinical challenge to obstetricians. Many gynecologic oncologists perform a permanent cerclage at the time of trachelectomy and recommend delivery via scheduled cesarean at term for all subsequent pregnancies prior to labor (usually 37-38 weeks).

At our institution, we recommend the use of progesterone from 16 to 36 weeks despite no clear evidence on the role of progesterone in this setting. Maternal-fetal medicine consultation should be considered to either follow these patients during their pregnancies or to perform a single consultative visit to guide antepartum care.

Some have advocated for less radical surgery, such as simple trachelectomy or large cold knife conization, as the risk of parametrial extension in these patients is low (Gynecol Oncol. 2011 Dec;123[3]:557-60). More data are needed to determine if this is a safe approach. Further, the use of neoadjuvant chemotherapy followed by cold knife conization for fertility preservation in women with larger tumors has been proposed. This may be a feasible option in women with chemo-sensitive tumors, but progression on chemotherapy and increased recurrences have been reported with this approach (Gynecol Oncol. 2008 Dec;111[3]:438-43).

Women of reproductive age diagnosed with early cervical cancer now have multiple options for fertility preservation. Ongoing research regarding obstetric and fertility outcomes is needed; however, oncologic outcomes appear to be equivalent.

Dr. Clark is a fellow in the division of gynecologic oncology, department of obstetrics and gynecology, at the University of North Carolina, Chapel Hill. Dr. Boggess is an expert in robotic surgery in gynecologic oncology and is a professor in the division of gynecologic oncology at UNC–Chapel Hill. They reported having no financial disclosures relevant to this column. Email them at obnews@frontlinemedcom.com.

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Historically, the standard of care for women diagnosed with early cervical cancer has been radical hysterectomy. Thus, young women are not only being confronted with a cancer diagnosis, but may also be forced to cope with the loss of their fertility.

As many young women with cervical cancer were not accepting of this treatment, Dr. Daniel Dargent pioneered the vaginal radical trachelectomy as a fertility-preserving treatment option for early cervical cancer in 1994. There have now been more than 900 vaginal radical trachelectomies performed and they have been shown to have oncologic outcomes similar to those of traditional radical hysterectomy, while sparing a woman’s fertility (Int J Gynecol Cancer. 2013 Jul;23[6]:982-9).

Dr. Leslie Clark
Dr. Leslie Clark

Obstetric outcomes following vaginal radical trachelectomy are acceptable with 17% miscarriage rate in the first trimester (compared to 10%-20% in the general population) and 8% in the second trimester (compared to 1%-5% in the general population) (Am Fam Physician. 2007 Nov 1;76[9]:1341-6). Following vaginal radical trachelectomy, 64% of pregnancies deliver at term.

The usual criteria required to undergo radical trachelectomy include:

1) Reproductive age with desire for fertility.

2) Stage IA1 with LVSI (lymphovascular space invasion), IA2, or IB1 with tumor less than 2 cm.

3) Limited endocervical involvement via preoperative MRI.

4) Negative pelvic lymph nodes.

Preoperative PET scan can be used to evaluate nodal status, but suspicious lymph nodes should be evaluated on frozen section at the time of surgery. The presence of LVSI alone is not a contraindication to trachelectomy.

Courtesy Wikimedia Commons/John Hayman/Creative Commons License

A key limitation of vaginal radical trachelectomy is the specialized training required to perform this technically challenging procedure. Few surgeons in the United States are trained to perform vaginal radical trachelectomy. In response to this limitation, surgeons began to attempt radical trachelectomy via laparotomy (Gynecol Oncol. 2006 Dec;103[3]:807-13). Oncologic outcomes following fertility-sparing abdominal radical trachelectomy have been reported to be equivalent to radical hysterectomy. Concerns regarding the abdominal approach to radical trachelectomy include higher rates of second trimester loss (19%) when compared to the vaginal approach (8%), higher rate of loss of fertility (30%), and risk of postoperative adhesions.

The advent of minimally invasive surgery, particularly robotic surgery, now offers surgeons the ability to perform a procedure technically similar to radical hysterectomy using a minimally invasive approach. Given the similarity of procedural steps of radical trachelectomy to radical hysterectomy using the robotic platform, this procedure is gaining acceptance in the United States with an associated improved surgeon learning curve (Gynecol Oncol. 2008 Nov;111[2]:255-60). In addition, the use of minimally invasive surgery should result in less adhesion formation facilitating natural fertility options postoperatively.

Dr. John F. Boggess
Dr. John F. Boggess

Obstetric and fertility outcomes are limited following minimally invasive radical trachelectomy via laparoscopy or robotic surgery given the novelty of this procedure. Emerging obstetric outcomes appear reassuring, but further data are needed to fully understand the effects of this procedure on pregnancy outcomes and the need for assisted reproductive techniques to achieve pregnancy.

The management of pregnancies following radical trachelectomy is also an area with limited data, which presents a clinical challenge to obstetricians. Many gynecologic oncologists perform a permanent cerclage at the time of trachelectomy and recommend delivery via scheduled cesarean at term for all subsequent pregnancies prior to labor (usually 37-38 weeks).

At our institution, we recommend the use of progesterone from 16 to 36 weeks despite no clear evidence on the role of progesterone in this setting. Maternal-fetal medicine consultation should be considered to either follow these patients during their pregnancies or to perform a single consultative visit to guide antepartum care.

Some have advocated for less radical surgery, such as simple trachelectomy or large cold knife conization, as the risk of parametrial extension in these patients is low (Gynecol Oncol. 2011 Dec;123[3]:557-60). More data are needed to determine if this is a safe approach. Further, the use of neoadjuvant chemotherapy followed by cold knife conization for fertility preservation in women with larger tumors has been proposed. This may be a feasible option in women with chemo-sensitive tumors, but progression on chemotherapy and increased recurrences have been reported with this approach (Gynecol Oncol. 2008 Dec;111[3]:438-43).

Women of reproductive age diagnosed with early cervical cancer now have multiple options for fertility preservation. Ongoing research regarding obstetric and fertility outcomes is needed; however, oncologic outcomes appear to be equivalent.

Dr. Clark is a fellow in the division of gynecologic oncology, department of obstetrics and gynecology, at the University of North Carolina, Chapel Hill. Dr. Boggess is an expert in robotic surgery in gynecologic oncology and is a professor in the division of gynecologic oncology at UNC–Chapel Hill. They reported having no financial disclosures relevant to this column. Email them at obnews@frontlinemedcom.com.

Historically, the standard of care for women diagnosed with early cervical cancer has been radical hysterectomy. Thus, young women are not only being confronted with a cancer diagnosis, but may also be forced to cope with the loss of their fertility.

As many young women with cervical cancer were not accepting of this treatment, Dr. Daniel Dargent pioneered the vaginal radical trachelectomy as a fertility-preserving treatment option for early cervical cancer in 1994. There have now been more than 900 vaginal radical trachelectomies performed and they have been shown to have oncologic outcomes similar to those of traditional radical hysterectomy, while sparing a woman’s fertility (Int J Gynecol Cancer. 2013 Jul;23[6]:982-9).

Dr. Leslie Clark
Dr. Leslie Clark

Obstetric outcomes following vaginal radical trachelectomy are acceptable with 17% miscarriage rate in the first trimester (compared to 10%-20% in the general population) and 8% in the second trimester (compared to 1%-5% in the general population) (Am Fam Physician. 2007 Nov 1;76[9]:1341-6). Following vaginal radical trachelectomy, 64% of pregnancies deliver at term.

The usual criteria required to undergo radical trachelectomy include:

1) Reproductive age with desire for fertility.

2) Stage IA1 with LVSI (lymphovascular space invasion), IA2, or IB1 with tumor less than 2 cm.

3) Limited endocervical involvement via preoperative MRI.

4) Negative pelvic lymph nodes.

Preoperative PET scan can be used to evaluate nodal status, but suspicious lymph nodes should be evaluated on frozen section at the time of surgery. The presence of LVSI alone is not a contraindication to trachelectomy.

Courtesy Wikimedia Commons/John Hayman/Creative Commons License

A key limitation of vaginal radical trachelectomy is the specialized training required to perform this technically challenging procedure. Few surgeons in the United States are trained to perform vaginal radical trachelectomy. In response to this limitation, surgeons began to attempt radical trachelectomy via laparotomy (Gynecol Oncol. 2006 Dec;103[3]:807-13). Oncologic outcomes following fertility-sparing abdominal radical trachelectomy have been reported to be equivalent to radical hysterectomy. Concerns regarding the abdominal approach to radical trachelectomy include higher rates of second trimester loss (19%) when compared to the vaginal approach (8%), higher rate of loss of fertility (30%), and risk of postoperative adhesions.

The advent of minimally invasive surgery, particularly robotic surgery, now offers surgeons the ability to perform a procedure technically similar to radical hysterectomy using a minimally invasive approach. Given the similarity of procedural steps of radical trachelectomy to radical hysterectomy using the robotic platform, this procedure is gaining acceptance in the United States with an associated improved surgeon learning curve (Gynecol Oncol. 2008 Nov;111[2]:255-60). In addition, the use of minimally invasive surgery should result in less adhesion formation facilitating natural fertility options postoperatively.

Dr. John F. Boggess
Dr. John F. Boggess

Obstetric and fertility outcomes are limited following minimally invasive radical trachelectomy via laparoscopy or robotic surgery given the novelty of this procedure. Emerging obstetric outcomes appear reassuring, but further data are needed to fully understand the effects of this procedure on pregnancy outcomes and the need for assisted reproductive techniques to achieve pregnancy.

The management of pregnancies following radical trachelectomy is also an area with limited data, which presents a clinical challenge to obstetricians. Many gynecologic oncologists perform a permanent cerclage at the time of trachelectomy and recommend delivery via scheduled cesarean at term for all subsequent pregnancies prior to labor (usually 37-38 weeks).

At our institution, we recommend the use of progesterone from 16 to 36 weeks despite no clear evidence on the role of progesterone in this setting. Maternal-fetal medicine consultation should be considered to either follow these patients during their pregnancies or to perform a single consultative visit to guide antepartum care.

Some have advocated for less radical surgery, such as simple trachelectomy or large cold knife conization, as the risk of parametrial extension in these patients is low (Gynecol Oncol. 2011 Dec;123[3]:557-60). More data are needed to determine if this is a safe approach. Further, the use of neoadjuvant chemotherapy followed by cold knife conization for fertility preservation in women with larger tumors has been proposed. This may be a feasible option in women with chemo-sensitive tumors, but progression on chemotherapy and increased recurrences have been reported with this approach (Gynecol Oncol. 2008 Dec;111[3]:438-43).

Women of reproductive age diagnosed with early cervical cancer now have multiple options for fertility preservation. Ongoing research regarding obstetric and fertility outcomes is needed; however, oncologic outcomes appear to be equivalent.

Dr. Clark is a fellow in the division of gynecologic oncology, department of obstetrics and gynecology, at the University of North Carolina, Chapel Hill. Dr. Boggess is an expert in robotic surgery in gynecologic oncology and is a professor in the division of gynecologic oncology at UNC–Chapel Hill. They reported having no financial disclosures relevant to this column. Email them at obnews@frontlinemedcom.com.

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