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 Table of Contents  
EDITORIAL
Year : 2019  |  Volume : 3  |  Issue : 2  |  Page : 25-27

Role of fertility-sparing surgery in gynecological malignancy


Department of Obstetrics and Gynaecology, Calcutta National Medical College and Hospital, Kolkata, West Bengal, India

Date of Web Publication18-Sep-2019

Correspondence Address:
Dr. Priyanka Priyadarshini
Department of Obstetrics and Gynaecology, Calcutta National Medical College and Hospital, Kolkata - 700 014, West Bengal
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/oji.oji_35_19

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How to cite this article:
Priyadarshini P. Role of fertility-sparing surgery in gynecological malignancy. Oncol J India 2019;3:25-7

How to cite this URL:
Priyadarshini P. Role of fertility-sparing surgery in gynecological malignancy. Oncol J India [serial online] 2019 [cited 2019 Dec 12];3:25-7. Available from: http://www.ojionline.org/text.asp?2019/3/2/25/266982



Gynecological malignancy in reproductive age group is not uncommon. Around 12.5% of women with female genital tract malignancy are aged <45 years at the time of diagnosis.[1] Earlier, cancer treatment emphasized mainly on the survival outcome. But now, with the advent of newer chemotherapeutic agents, better surgical techniques, and newer treatment regimens, mortality rates are decreasing, and more emphasis can be given to improve the morbidity profile following cancer treatment. And, talking about morbidity, fertility preservation is one of the major concerns of young patients seeking cancer treatment.

Cervical, ovarian, and endometrial carcinomas are the three most common gynecological cancers. Majority of these cancers are found in elderly patients. However, 40% of cervical cancer, 12% of ovarian cancer, and 5% of endometrial cancer patients are seen in reproductive age group.[2] Thus, we focus to address the role of fertility preservation in these malignancies, particularly in young patients. Nowadays, delaying age of first pregnancy has resulted in more patients seeking fertility preservation surgeries.

Thus as physicians, we are expected to provide adequate information and opulence of the options available in the field of fertility-sparing branch in cancer treatment. Explicit knowledge of the nature of the disease; proper patient selection; meticulous surgery by a surgeon specialized in gynecological oncology; proper informed consent from the patient and their relatives, especially in the view of oncologic and obstetric outcomes related to the surgery as well as the alternative approaches; and timely regular follow-up are the most important prerequisite for a successful outcome. Having said that, optimal cancer therapy should always supersede fertility preservation as a primary objective.

Radical pelvic surgery, chemotherapy, and/or pelvic radiation are the treatment options for gynecological malignancies, but these lead to loss in ovarian function and fertility. Although radical surgery is the established cornerstone in the management of gynecological malignancies, fertility-sparing techniques should be incorporated in the therapeutic strategies in early or not bulky forms of the disease.

Fertility-sparing surgery (FSS) is the technique to retain the patient's uterus and ovarian tissue enough to allow future conception. Organ-preserving surgeries in properly selected patients with gynecologic cancers have equally good cure rates as radical surgery. However, it is important to have a proper counseling with the patient and her caretakers, and physicians should explain what is the standard treatment for her cancer, what are the possible fertility preservation surgeries, the oncological risks she will be subjected to on resorting to fertility-preserving surgeries, and the subsequent likely need for reproductive technologies to ensure conception.[2] Assisted reproductive technologies, especiallyin vitro fertilization (IVF), require helping achieve a pregnancy. Ovarian tissue, oocyte, or embryo cryopreservation can be considered prior to definitive cancer therapies. The risk of premature delivery and the consequences of prematurity should be properly counseled to the patient.[3]


  Cervical Cancer Top


Because of the effective and widespread use of screening, many women with cervical carcinoma are diagnosed at a relatively young age and early stage. Conventionally, early-stage cervical cancers are treated by either radical hysterectomy or chemoradiation. Such treatment may result in permanent infertility. However, fertility preservation can be possible in the precursor of invasive cancer and selective early-stage cancer.[2] It is possible to preserve the fundus and adnexa in most small cancers confined to the cervix in order to maintain future childbearing. Conization, neoadjuvant chemotherapy followed by cone biopsy, radical trachelectomy, and ovarian transposition are the different FSS techniques in cervical cancer.

Stage 1A1 cervical cancer with no lymph-vascular space invasion (LVSI) can be effectively treated with conization not requiring lymphadenectomy due to rare chance of nodal and parametrium involvement and carries excellent fertility outcomes. However, conization may cause cervical stenosis and increase the risk of obstetric complications, particularly premature delivery rate.[2] Some investigators have recommended the use of neoadjuvant chemotherapy followed by a simple cone biopsy and pelvic lymphadenectomy to reduce morbidity and the radicality of surgery. This option may allow tumors above 2 cm to be treated but will have a damaging effect on ovarian function due to chemotherapy. Radical trachelectomy is the fertility preservation surgery for Stage IA1 cervical cancer with LVSI, Stage IA2 cancers, and Stage IB1 cancers <2 cm. In this procedure, the cervix with medial parametrium and upper 2-cm vaginal cuff will be removed retaining the uterus and adnexa to allow future pregnancy. Cervical cerclage is done at the level of isthmus to prevent cervical incompetence.[2] Irregular bleeding, dysmenorrhea, cervical stenosis, amenorrhea, and rarely deep dyspareunia are the possible complications of the procedure. Young patients with gynecological malignancies requiring pelvic radiotherapy may be tried with ovarian transposition to preserve ovarian function for future IVF techniques. Ovaries with their attached blood supply are surgically detached from the uterus and transposed to an area outside the planned radiation field, i.e., the paracolic gutters above the pelvis. The eligibility criteria for ovarian transposition are any gynecologic malignancy that requires pelvic radiation therapy with or without hysterectomy, age <40 years, cervical cancer <3 cm in diameter, cervical cancer confined to the cervix, no evidence of LVSI or lower uterine segment involvement, and pelvic magnetic resonance imaging (MRI) to assess the extent of tumor. There is chance of subsequent benign ovarian cysts, and ovarian failure, mostly related to ischemia. Furthermore, there is a possibility of occult metastasis to the ovary in few adenocarcinomas of cervix, usually resulting in subsequent relapse and death. Thus, the problems and sequelae associated with ovarian transposition have made it less appealing in recent years.[3]


  Endometrial Carcinoma Top


Majority of the endometrial cancers at younger age group present in early stage and at low grade with an excellent prognosis. Surgical staging which includes hysterectomy, bilateral salpingo-oophorectomy, and assessment of pelvic and para-aortic lymph nodes is the standard initial treatment. Younger patients may desire fertility-sparing options, i.e., conservative management but with multiple complexities which include inadequately staged and treated endometrial cancer, risk of synchronous or metachronous cancer, and lack of uniformity in the medical management and surveillance. As a fertility-preserving option, hormonal treatment is the most common medical treatment. Hormonal treatments commonly used are (a) high-dose oral progestins such as medroxyprogesterone acetate and megestrol acetate, (b) local high-dose progestins such as levonorgestrel-releasing intrauterine device, (c) gonadotropin-releasing hormone (GnRH) agonist, (d) hydroxyprogesterone, (e) oral contraceptives, (f) tamoxifen, and (g) letrozole. Furthermore, some reports of surgical management are available. Hence, a combination of hysteroscopic resection of abnormal endometrium and GnRH agonist can be performed, with good safety and fertility outcomes. However, retaining the uterus to preserve fertility may subject the patients to disease progression.[4] Hence, it is important to select proper candidates for fertility preservation, and MRI scan helps to select candidates for uterine preservation, i.e., the tumor is not infiltrating the myometrium with no enlarged lymph nodes and no synchronous ovarian tumor.[3] After initial response, close monitoring of the patient is important due to the risk of disease progression.


  Ovarian Carcinoma Top


Radical surgery with the primary objective of maximal tumor reduction is the cornerstone in the management of ovarian cancer. However, it leads to permanent sterility. Therefore, fertility-sparing techniques, i.e., uterine and contralateral adnexal preservation, should be increasingly incorporated in the therapeutic strategies for early or nonbulky disease with low-risk groups, i.e., Stage 1A and 1B with Grade 1 or 2. Furthermore, high-risk, early-stage ovarian cancers can be tried with FSS. Proper counseling with a strict follow-up should be done. Multi-institutional, prospective, well-designed studies are required in order to know oncologic outcomes and quality of life.[5]

The strategy for organ-preserving techniques in borderline ovarian tumors (BOTs) and early epithelial ovarian cancer (EOC) is preservation of the contralateral ovary and uterus or even in highly specialized cases, peritonectomy of the pelvis and uterus serosa to avoid the need of hysterectomy. After FSS, the subsequent systemic chemotherapy-induced gonadotoxicity can be decreased by applying concomitant ovarian hormonal protection. GnRH analogs help to induce fertility-sparing treatment and offer a hope for conception after completion of the anticancer treatment.[6],[7] Fertility preservation may be adopted in germ cell cancers, borderline tumors, sex cord-stromal tumors, and even early EOCs. However, an adequate operative staging to unmask occult advanced disease should be the therapeutic concern. It includes unilateral salpingo-oophorectomy with a thorough surgical staging including pelvic and para-aortic lymphadenectomy, multiple peritoneal biopsies, and omentectomy.[2] Several guidelines such as the American College of Obstetrics and Gynecology, and the European Society for Medical Oncology have been recommend fertility preservation for Stage IA cancer ovary, highly or moderately differentiated with nonclear cell histology. However, data regarding the role of FSS in invasive EOCs are retrospective nonrandomized series only, particularly low-grade Stage IA tumor with favorable histology. As data regarding unfavorable histology or higher stage disease are conflicting, there is lack in bulk of evidence to estimate the risk of leaving a microscopic tumor in the contralateral ovary.[6] Patients with hereditary syndromes are not suitable for fertility preservation. Proper follow-up should be done with clinical examination, ultrasonography, and tumor markers. Assisted reproductive techniques are safe in borderline and germ cell tumors but with limited role in epithelial cancers. Completion surgery after childbearing may be done in early epithelial cancers but usually not performed in germ cell and borderline tumors.[2] Data show that utero-ovarian preservation for young women with early-stage BOTs does not affect BOT-related survival outcome in comparison to ovarian preservation alone.[8]

In summary, FSS can be applied in selected patients of gynecological malignancies to preserve fertility. Patients should be carefully selected and extensively counseled regarding the deviation from the standard of care, the oncologic risks, and the subsequent possible need for reproductive technologies to ensure conception. Those patients wishing to preserve fertility should be directed to physicians or centers with the highest experience and expertise. Patients should understand the limited data availability, the undefined risks, and the requirement of intense follow-up. A multidisciplinary approach is crucial among gynecologic oncologists, reproductive endocrinologists, and perinatologists in order to know oncologic outcomes and quality of life.



 
  References Top

1.
Noone AM, Howlader N, Krapcho M, Miller D, Brest A, Yu M, et al., editors. Seer Cancer Statistics Review, 1975-2015. Bethesda, MD: National Cancer Institute; 2017. Available from: https://seer.cancer.gov/csr/1975_2015/. [Last accessed on 2018 Apr].  Back to cited text no. 1
    
2.
Rema P, Ahmed I. Fertility sparing surgery in gynecologic cancer. J Obstet Gynaecol India 2014;64:234-8.  Back to cited text no. 2
    
3.
Leitao MM Jr., Chi DS. Fertility-sparing options for patients with gynecologic malignancies. Oncologist 2005;10:613-22.  Back to cited text no. 3
    
4.
Tock S, Jadoul P, Squifflet JL, Marbaix E, Baurain JF, Luyckx M. Fertility sparing treatment in patients with early stage endometrial cancer, using a combination of surgery and GnRH agonist: A monocentric retrospective study and review of the literature. Front Med (Lausanne) 2018;5:240.  Back to cited text no. 4
    
5.
Ditto A, Bogani G, Martinelli F, Raspagliesi F. Fertility-sparing surgery in high-risk ovarian cancer. J Gynecol Oncol 2015;26:350-1.  Back to cited text no. 5
    
6.
Fotopoulou C, Braicu I, Sehouli J. Fertility-sparing surgery in early epithelial ovarian cancer: A viable option? Obstet Gynecol Int 2012;2012:238061.  Back to cited text no. 6
    
7.
Kim SS, Lee JR, Jee BC, Suh CS, Kim SH, Ting A, et al. Use of hormonal protection for chemotherapy-induced gonadotoxicity. Clin Obstet Gynecol 2010;53:740-52.  Back to cited text no. 7
    
8.
Mandelbaum RS, Blake EA, Machida H, Grubbs BH, Roman LD, Matsuo K. Utero-ovarian preservation and overall survival of young women with early-stage borderline ovarian tumors. Arch Gynecol Obstet 2019;299:1651-8.  Back to cited text no. 8
    




 

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