Introduction
Gynecologic oncology was defined as a subspecialty of obstetrics and gynecology in 1969. Gynecologic oncologists undergo fellowship training after residency to gain additional surgical expertise, including gastrointestinal, urologic, and complex abdominal and pelvic surgery. Gynecologic oncology requires a multidisciplinary approach to treatment, including surgery, chemotherapy, and radiation therapy. This chapter focuses on the surgical aspects of gynecologic oncology. Topics will include endometrial, cervical, ovarian, and vulvar carcinoma. Vaginal cancer is primarily treated with radiation therapy or with radical upper vaginal surgery, which is similar to the treatment of cervix cancer.
Anatomy
In performing gynecologic surgery, understanding the three-dimensional pelvic anatomy is critical. The true pelvis is a bowl-shaped structure formed from the sacrum, pubis, ilium, ischium, the ligaments that interconnect these bones and the muscles that line their inner surface ( Fig. 18.1 ). The true pelvis is considered to start at the level of the plane passing through the promontory of the sacrum, the arcuate line on the ilium, the iliopectineal line, and the posterior surface of the pubic crest. This plane or “inlet” lies at an angle of between 35 and 50 degrees up from the horizontal and above this the bony structures are sometimes referred to as the false pelvis.
Muscles arising within the pelvis form two groups. Piriformis and obturator internus, although forming part of the walls of the pelvis, are considered as primarily muscles of the lower limb. Levator ani and coccygeus form the pelvic diaphragm and delineate the lower limit of the true pelvis. The fasciae investing the muscles are continuous with visceral pelvic fascia above, perineal fascia below, and obturator fascia laterally ( Fig. 18.2 ).
The true pelvis contains the internal iliac arteries and veins and the lymphatics, which drain the majority of the pelvic viscera. The common and external iliac vessels and the lymphatics, which drain the lower limb, lie along the pelvic brim and in the lower retroperitoneum and are described together with the vessels of the true pelvis.
At the pelvic brim the common iliac vessels will bifurcate into the internal and external iliac vessels ( Fig. 18.3 ). The ureter will then cross over the iliac vessels from the lateral side to the medial. In surgery due to gynecologic cancer, this level is important as a defining location for pelvic and para-aortic lymph node dissections. The ovaries derive their blood supply directly from a branch of the aorta located within the infundibulopelvic ligament. The external iliac artery, after bifurcation at the level of sacral promontory, will travel along the iliopsoas muscle to provide blood to the lower limbs. From the anterior aspect of the external iliac artery, the inferior epigastric artery will branch off and travel along the anterior abdominal wall.
The internal iliac artery is the major blood supply to the pelvic organs. The anterior division of the internal iliac artery will supply blood to the bladder via the superior vesical artery and to the uterus via the uterine artery. The uterine artery will be the only vessel to cross the ureter horizontally (this is commonly referred to as “water under the bridge” where the ureter travels below the uterine artery as the artery crosses medially). The location of the ureter in relationship to the pelvic vessels is critical to understand surgically and a common area of concern to avoid iatrogenic injury.
The inferior hypogastric nerve plexus will innervate both the uterus and the urinary bladder, which is a combination of the inferior hypogastric nerve and the pelvic splanchnic nerve.
Endometrial Carcinoma
Introduction and Epidemiology
The endometrium is the inner lining of the uterus. During a woman’s menstrual cycle, this part of the uterus will undergo changes due to hormones, estrogen and progesterone. When high levels of estrogen are produced, the endometrium thickens in order to provide implantation for embryo during pregnancy. When a woman’s egg is not fertilized, estrogen levels drop, while progesterone levels increase, causing the endometrial lining to shed turning the lining into menstrual flow. The endometrium is also the initial mutation point for most uterine cancers. Cancers begin to form in the body when the DNA of a cell is mutated. Normal cells in the body have the ability to replicate as needed in the body, die when old and damaged, listen to signals to stop when come to close to other cells, and stay restricted to the specified area in the body. When a cell’s genes become mutated and form into cancer cells, the cells will begin to replicate out of control forming a tumor over time, ignore signaling from other cells and invade nearby tissue, and cells will deviate from their specified area and spread throughout the body forming new tumors (metastasize). When the cells of the endometrium begin to mutate and become cancerous, the patient is said to have endometrial cancer.
The American Cancer Society’s estimates for cancer of the uterus in the United States for 2019 are as follows:
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About 61,880 new cases of cancer in the uterine corpus (body of the uterus) will be diagnosed.
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About 12,160 women will die from endometrial cancer.
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Five-year survival rate for Stage I is 95%, Stage II 75%, Stage III 52%, and Stage IV decreases to 25%.
Endometrial cancer is the most common gynecologic malignancy in the United States. It affects mostly postmenopausal women and is classically associated with the symptom of postmenopausal bleeding. The average age that endometrial cancer is diagnosed is 60. It is very unlikely for a woman to be diagnosed under the age of 45 although it does occur especially in the setting of anovulation, hereditary risk such as Lynch syndrome and polycystic ovary syndrome (PCOS). There are a variety of different forms of endometrial cancer, but the most common is an endometrioid tumor. This tumor is typically caught early and associated with a very favorable prognosis. Risk factors include hypertension, anovulation, nulliparity, diabetes mellitus, and obesity.
Another important form of endometrial cancer is serous carcinoma. This form of endometrial cancer is less common and behaves more similar to ovarian carcinoma, with none of the risk factors associated with endometrioid type. Serous carcinoma is grouped in a category of endometrial cancer called high-risk endometrial cancer and most often requires adjuvant chemotherapy and/or radiation therapy after initial surgical staging. Serous carcinomas are more associated with distinctive molecular alteration, while endometrioid tumors are more clearly associated with estrogen imbalance. Genetics may play a role in both of these diagnoses and evaluation for hereditary syndromes is important in every diagnosis of endometrial carcinoma.
Diagnosis and Staging
Endometrial cancer is most commonly diagnosed due to the presence of symptoms. The most common symptom pertaining to endometrial cancer is postmenopausal bleeding as this occurs in 90% of cases. Other less common symptoms associated with endometrial cancer are nonbloody vaginal discharge, pelvic pain, the presence of a mass, and unexpected weight loss. Once a patient presents symptoms such as postmenopausal bleeding, a gynecologist will perform a series of test to obtain the diagnosis, including a transvaginal ultrasound followed by a tissue diagnosis with either and office endometrial biopsy or operative dilatation and curettage. Endometrial biopsy is the most common test in determining endometrial cancer and can be done in the doctor’s office. In an endometrial biopsy a physician will insert a thin flexible tube into the vaginal canal and through the cervix in order to reach the uterus, then using suction the tube will extract a small sample of tissue from the endometrial lining. In some cases, either endometrial biopsy cannot be attained or the results can be inconclusive. If an office biopsy is unsuccessful or not performed, the patient may need to undergo an outpatient procedure called a dilation and curettage. This procedure can be done either with sedation or general anesthesia; the physician will begin by dilating the cervix, then the doctor will scrap endometrial tissue that will be sent to pathology to determine the presence of cancer cells. When endometrial carcinoma is confirmed, the patient will be referred to a gynecologic oncologist for a consultation to plan surgical staging and treatment.
The stage of a cancer is determined using two main systems: the FIGO (International Federation of Gynecology and Obstetrics) system and the American Joint Committee on Cancer TNM staging system. Both of these systems use three main factors to stage :
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The extent (size) of the tumor ( T ): How far has the cancer has grown into the uterus? Has the cancer reached nearby structures or organs?
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The spread to nearby lymph nodes (N): Has the cancer spread to the para-aortic lymph nodes? These are the lymph nodes in the pelvis or around the aorta (the main artery that runs from the heart down the back of the abdomen and pelvis).
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The spread (metastasis) to distant sites (M): Has the cancer spread to distant lymph nodes or distant organs in other parts of the body?
Numbers or letters following T, N, and M provide more detail about each of these factors. Higher numbers mean the cancer is more progressed. Once a person’s T, N, and M categories have been determined, this information is combined in a process called stage grouping to assign an overall stage.
The staging system in Table 18.1 uses the pathological stage. The stage is found by examining tissue removed during an operation. In cases where surgery is not possible right away, the cancer will be given a clinical stage instead. A clinical stage is determined using results from a physical exam, biopsy, and imaging test done prior to surgery.
| Stage | Stage Grouping | FIGO Stage | Stage Description a |
|---|---|---|---|
| I |
| I |
|
| IA |
| IA |
|
| IB |
| IB |
|
| II |
| II |
|
| III |
| III |
|
| IIIA |
| IIIA |
|
| IIIB |
| IIIB |
|
| IIIC1 |
| IIIC1 |
|
| IIIC2 |
| IIIC2 |
|
| IVA |
|
| |
| IVB |
| IVB |
|
a Additional categories that are not described or listed above are as follows:
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TX: Main tumor cannot be assessed due to lack of information.
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T0: No evidence of primary tumor.
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NX: Regional lymph nodes cannot be assessed due to lack of information.
Surgery
The uterus is composed of the uterine corpus and the uterine cervix. The uterine cervix can be described as a supporting structure that allows separation of the vagina and the endometrial cavity and serves to maintain support during pregnancy. The uterus itself is composed of three main layers: endometrium, myometrium, and serosa. The endometrium is the lining of the uterine cavity, which contains a superficial layer consisting of glandular epithelium and stroma. The myometrium is the thickest tissue of the uterus, which is composed of smooth muscle fibers. The final composition of the uterus is the serosa, which is composed of visceral peritoneum. Superior to the uterus hangs the ovaries and fallopian tubes.
The blood supply to the pelvis comes initially from the aorta, which descends down into the abdominal aorta. The ovarian artery forms directly from the aorta and branches off inferiorly to the renal artery. In the pelvis the ovarian artery will then descend to the infundibulopelvic ligament, which supplies the ovary. Following the bifurcation of the ovarian artery, the abdominal aorta will continue and bifurcate again into the common iliac arteries. The common iliac then divides into the external and internal iliac, which provide branches that supply blood to the pelvic organs. The internal iliac artery branches off into anterior and posterior divisions with the anterior division supplying the pelvic organs. The uterine artery travels through the cardinal ligament and is the primary blood supply to the uterus Fig. 18.4 .
Standard treatment for endometrial cancer includes a total hysterectomy, bilateral salpingo-oophorectomy (BSO), and surgical staging. A total hysterectomy includes removal of the uterus and the cervix. A BSO procedure will consist of the physician removing both ovaries and fallopian tubes.
The staging includes a surgical assessment of the lymph nodes (either sentinel or lymphadenectomy) and pelvic washings. To obtain pelvic washings the surgeon will fill the pelvic cavity with saline, then using suction the fluid is collected and sent to pathology for testing of cancer cells. Although this does not change the surgical staging, pelvic washings may be used to provide adjuvant therapy recommendations.
Lymphadenectomy
Pelvic and para-aortic lymphadenectomy is a procedure that is used in intermediate-risk and high-risk endometrial cancers. Lymphadenectomy is a procedure in which the surgeon will remove the lymph nodes that primarily drain the pelvic organs. With endometrial carcinoma the iliac basins are the regional lymph nodes most commonly involved. Factors that are associated with para-aortic lymph node dissemination are advanced stage, high histological grade, deep myometrial involvement, cervical involvement, lympho-vascular space involvement, and pelvic lymph node metastasis. Risks associated with lymph node staging include iatrogenic injury to the vessels, nerves, or ureter during the dissection. Postoperative risks include a higher risk of deep vein thrombosis, lower extremity lymphedema, and musculoskeletal neuropathy. Fortunately with the use of minimally invasive surgery these risks are minimal.
Sentinel Lymph Node Staging
Sentinel lymph nodes are defined as the first lymph nodes in lymphatic drainage from a particular organ. With the widespread adoption of minimally invasive robotic surgery in endometrial cancer, sentinel lymph node staging has become a new standard of care. Multiple sentinel lymph node mapping techniques include the use of dyes such as methylene blue, isosulfan blue, patent blue, and indocyanine green. The injection of these dyes is performed intraoperatively directly into the cervix. The surgeon will then visualize the lymph nodes that turn the color of the dye, which allows for identification of the sentinel lymph node. The benefit of sentinel lymph node staging is to minimize the number and amount of lymph nodes removed to obtain accurate surgical staging. In addition, sentinel lymph nodes are processed differently by the pathologist than a routine lymph node sampling. Sentinel lymph nodes are examined under closer detail called micro-staging and this may allow for the identification of tiny cancer cells that may have otherwise gone undetected.
Fertility preservation
Although endometrial cancer is most often associated with postmenopausal women, it may also be diagnosed in younger women with a desire for fertility. In this setting, progesterone therapy may be used in specific circumstances where the cancer is limited to the endometrial lining, is well-differentiated, and shows no evidence of myometrial invasion by imaging (confirmed by pelvic MRI). This scenario most often occurs in young women with associated risk factors such as PCOS, obesity, and/or diabetes, although this may also occur in young women with no risk factors. It is important for patients in this setting to be counseled thoroughly so that medical management does not have a negative impact on her overall prognosis.
Minimally Invasive Surgery
Laparoscopy and robotic-assisted surgery are the two forms of minimally invasive techniques. Robotic technology introduced 3D vision, precision and dexterity, which has become widely adopted among gynecologic oncologists. Robotic and laparoscopic surgery provides the benefits of enhanced surgical visualization due to the abdominal insufflation and improved clinical outcomes associated with smaller incisions. Patients are routinely able to go home the same or the following day from surgery. From a technical standpoint, during surgery, the patient is securely positioned into a Trendelenburg position which allows gravity to displace the intestines towards the upper abdomen and permits clear visualization of the pelvis during surgery. Prior to placing the patient into the Trendelenburg position, the physician will insert the primary trocar into a 12-mm incision at the umbilicus, avoiding the retroperitoneal vessels and the intestinal tract. CO 2 insufflation is then performed followed by the insertion of the other laparoscopic or robotic trocars. It is important that the uterus is removed intact and is most often accomplished by vaginal extraction after all of the surrounding vessels and attachments have been isolated. When the uterus is too large to be removed vaginally, a separate Pfannenstiel incision may be used for removal of the specimen. Multiple studies have shown the advantages of minimally invasive procedures, including a lower risk of postoperative complications and enhanced postoperative recovery in comparison to traditional open surgery.
Cervical Carcinoma
Introduction and Epidemiology
Cervical cancer was once one of the most common causes of cancer death for American women and continues to be a major cause of death of young women in the developing world. In the United States, the cervical cancer death rate dropped significantly with the increased use of the Pap test that allowed for effective screening of precancerous changes in the cervix. This allowed for earlier interventions and prevention of cancer from developing.
Cervix cancer is one of the most preventable types of cancers if it is detected early, treated correctly, and more recently prevented with HPV vaccinations. However, worldwide cervical cancer remains one of the greatest threats to the lives of women. Globally, one woman dies from cervix cancer every 2 minutes.
The majority of cervical cancer is caused by a virus called human papilloma virus (HPV):
- •
Not all types of HPV cause cervical cancer. Some of them cause genital warts, but other types may not cause any infections.
- •
The diagnosis of cervical cancer is established through a biopsy of the cervix. This may be a result of an abnormal Pap test or of a lesion visualized at the time of a speculum examination. In the setting of an abnormal Pap test, a colposcopy is performed where an examination of the cervix is performed with the use of a colposcope. A colposcope is an instrument that provides a magnification of the cervix to more closely identify the areas of abnormality. When an abnormality is seen, a biopsy is performed using a punch biopsy and/or endocervical curettage. The punch biopsy involves using a sharp tool to pinch off small samples of cervical tissue. Endocervical curettage uses a curet or a thin brush to scrape a tissue sample from the inside of the cervix. In settings where further biopsy tissue is indicated or needed to establish a diagnosis, a LEEP (loop electroexcisional procedure) or cone biopsy may be recommended. A LEEP uses a thin, low-voltage electrified wire to obtain a small tissue sample. Generally, this is done under local anesthesia in the office or an outpatient operating room. A cone biopsy (conization) is similar to a LEEP and is performed with a scalpel, excision of a portion of the cervix. This may be both diagnostic and therapeutic in select cases. This is most often performed in an outpatient surgical setting.
Cervical cancer tends to occur in midlife and is most frequently diagnosed in women between the ages of 35 and 44. It rarely develops in women younger than 20. Many older women do not realize that the risk of developing cervical cancer is still present as they age. More than 15% of cases of cervical cancer are found in women over 65. However, these cancers rarely occur in women who have been getting regular tests to screen for cervical cancer before they were 65.
In the United States, Hispanic women are most likely to get cervical cancer, followed by African-Americans, Asians and Pacific Islanders, and Whites. American-Indians and Alaskan natives have the lowest risk of cervical cancer in this country.
Initial stages of cervical cancer show no signs or symptoms. Signs and side effects of further developed cervical cancer include
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vaginal bleeding after intercourse
- •
abnormal vaginal discharge with foul odor
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pelvic pain during intercourse
Staging
Cervical cancer spreads by direct extension into the parametrium, vagina, uterus, and adjacent organs such as the bladder and rectum. It also spreads through the lymphatics to the pelvic lymph nodes (obturator, external and internal iliac) and the para-aortic region. In advanced or recurrent disease, cervix cancer may also metastasize through hematogenous spread to the liver, lung, and distant organs.
Until recently, cervical cancer staging was limited to the physical examination and limited additional studies when applicable. Tumor size and lymph node involvement remain important prognostic factors for women with cervical cancer and in 2018 the International Federation of Gynecology and Obstetrics (FIGO) published an updated cervical cancer staging system. Among the changes the list of tests and procedures that may be used to assign stage was expanded to include imaging and pathologic findings where available, tumor size criteria for some stages were revised, and lymph node metastases were included in staging.
| International Federation of Gynecology and Obstetrics (FIGO) Staging of Cancer of the Cervix Uteri (2018) | |
| Stage | Description |
| I | The carcinoma is strictly confined to the cervix (extension to the uterine corpus should be disregarded) |
| IA | Invasive carcinoma that can be diagnosed only by microscopy, with maximum depth of invasion <5 mm |
| IA1 | Measured stromal invasion <3 mm in depth |
| IA2 | Measured stromal invasion ≥3 and <5 mm in depth |
| IB | Invasive carcinoma with measured deepest invasion ≥5 mm (greater than Stage IA), lesion limited to the cervix uteri |
| IB1 | Invasive carcinoma ≥5 mm depth of stromal invasion and <2 cm in greatest dimension |
| IB2 | Invasive carcinoma ≥2 and <4 cm in greatest dimension |
| IB3 | Invasive carcinoma ≥4 cm in greatest dimension |
| II | The carcinoma invades beyond the uterus but has not extended onto the lower third of the vagina or to the pelvic wall |
| IIA | Involvement limited to the upper two-thirds of the vagina without parametrial involvement |
| IIA1 | Invasive carcinoma <4 cm in greatest dimension |
| IIA2 | Invasive carcinoma ≥4 cm in greatest dimension |
| IIB | With parametrial involvement but not up to the pelvic wall |
| III | The carcinoma involves the lower third of the vagina and/or extends to the pelvic wall and/or causes hydronephrosis or nonfunctioning kidney and/or involves pelvic and/or para-aortic lymph nodes |
| IIIA | The carcinoma involves the lower third of the vagina, with no extension to the pelvic wall |
| IIIB | Extension to the pelvic wall and/or hydronephrosis or nonfunctioning kidney (unless known to be due to another cause) |
| IIIC | Involvement of pelvic and/or para-aortic lymph nodes, irrespective of tumor size and extent (with r and p notations) |
| IIIC1 | Pelvic lymph node metastasis only |
| IIIC2 | Para-aortic lymph node metastasis |
| IV | The carcinoma has extended beyond the true pelvis or has involved (biopsy proven) the mucosa of the bladder or rectum. (A bullous edema, as such, does not permit a case to be allotted to Stage IV) |
| IVA | Spread to adjacent pelvic organs |
| IVB | Spread to distant organs |
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