, Shannon N. Westin1 and Charlotte C. Sun1
(1)
Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Chapter Overview
Over the past three decades, the number of gynecologic cancer survivors has grown substantially, most notably among women with early-stage disease. Cure of gynecologic cancers is possible with evidence-based and tailored combinations of surgery, chemotherapy, and radiation therapy. The ability to identify genetic predispositions to specific gynecologic malignancies has also positively affected gynecologic cancer survivors. Algorithms have been developed to provide appropriate survivorship care for patients with gynecologic malignancies. Each algorithm is geared toward care of survivors with a specific disease history. Surveillance tests and examinations, as well as risk reduction and early detection strategies, are recommended for survivors of each gynecologic malignancy. Monitoring schedules and testing methods for late effects and psychosocial functioning (including referrals, when appropriate) are also provided. As the field of cancer survivorship develops and the number of gynecologic cancer survivors grows, these algorithms will become increasingly important. Many survivors suffer from long-term cancer- and treatment-related morbidities. We must recognize that the care of survivors extends far past their 5-year survival period, and that some late effects of treatment continue to worsen over time. Additionally, caregiver responsibilities, with subsequent benefits and stressors, must also be further evaluated and supported. The quality of life of each survivor affects and is affected by every member of her team, including her family caregivers.
Introduction
Advances in cancer treatment, especially for women with gynecologic malignancies, have turned this once uniformly fatal illness into a curable disease for some and a chronic illness for many. Today, an estimated one million gynecologic cancer survivors live in the United States. The National Cancer Institute Office of Cancer Survivorship estimates that approximately 9% of female cancer survivors (573,300 women) have uterine cancer; 4% (243,884 women) have cervical, vaginal, or vulvar cancer; and 3% (177,578 women) have ovarian, fallopian tube, or primary peritoneal cancer. Overall survival rates from gynecologic cancers have improved significantly over the past three decades. This improvement is most pronounced among women with early-stage uterine, ovarian, and cervical cancers, for whom cure is possible through administration of tailored combinations of surgery, chemotherapy, and radiation therapy. However, although these treatments have increased overall survival rates, they can lead to myriad health-related concerns for survivors. Addressing these needs is an essential step in the goal of eliminating cancer-related morbidity and mortality in the growing population of gynecologic cancer survivors.
Surveillance
Survivorship monitoring should occur yearly for all women who have survived gynecologic cancer, starting at a specified time point after completion of treatment (see below). If a new primary cancer or recurrent disease is suspected, appropriate cancer treatment algorithms should be consulted for further evaluation and treatment.
Endometrial Cancer
Endometrial cancer is the most common gynecologic cancer, as well as the most curable. Our cancer survivorship algorithm for endometrial cancer divides women into two groups for posttreatment surveillance: low-risk and high-risk. Low-risk endometrial cancer survivors are those who did not receive radiation therapy or chemotherapy as adjuvant treatment after the initial surgery, and survivorship begins three years after treatment is completed and the patient has no evidence of disease. High-risk endometrial cancer survivors are those who received radiation therapy or chemotherapy as adjuvant treatment after the initial surgery, and survivorship begins five years after treatment is completed and the patient has no evidence of disease. Although the posttreatment surveillance begins at different time points for the two groups, all patients, upon reaching that time point, undergo an annual physical examination including a pelvic examination, chest x-ray as clinically indicated, and CA 125 tests if levels were initially elevated (see the endometrial cancer survivorship algorithm presented at the end of this chapter).
Cervical/Vaginal/Vulvar Cancers
The cancer survivorship algorithm for cervical cancer is also used for survivors of vulvar and vaginal cancers. Survivorship begins three years after treatment is completed for women who have a history of vulvar cancer, underwent radiation therapy, and have no evidence of disease, and five years after treatment is completed for women with cervical cancer, vaginal cancer, or vulvar cancer treated with surgery and who have no evidence of disease. Women in both groups undergo a yearly physical examination with a Papanicolaou smear and pelvic examination, and they may also undergo a chest x-ray if clinically indicated (see the cervical cancer survivorship algorithm presented at the end of this chapter).
Ovarian/Fallopian Tube/Primary Peritoneal Cancers
The cancer survivorship algorithm for ovarian cancer is also used for patients with fallopian tube and primary peritoneal cancer, which behave similarly and are therefore treated in the same manner. All patients are examined annually starting five years after treatment for ovarian, fallopian tube, or primary peritoneal cancer is completed and the patient has no evidence of disease. Survivors undergo an annual physical examination, including a pelvic examination. In addition, complete blood count and chemistry profiles are performed as clinically indicated, CA 125 is tested if levels were initially elevated, and a computed tomographic scan of the chest, abdomen, and pelvis is performed as clinically indicated (see the ovarian cancer survivorship algorithm presented at the end of this chapter).
Risk Reduction and Early Detection of Second Primary Cancers
A second primary cancer has been defined as “the occurrence of a new cancer that is biologically independent of the original primary cancer” (Neugut et al. 1999). The precise etiology of a second primary cancer is not always clear. Although many of these cancers are thought to be related to treatment, others are likely caused by environmental exposures. It has long been recognized that an individual who has had cancer in one paired organ is at increased risk of developing a second cancer in the contralateral organ. The underlying premise is that whatever predisposed an individual to develop the first cancer would also predispose that individual to develop a second cancer in the contralateral organ. Gynecologic cancer survivors are at risk for a variety of second primary cancers, many of which are not gynecologic in origin. The risk for second primary malignancies increases with age, and obesity, smoking, human papillomavirus infection, prior chemotherapy, prior radiation treatment, and use of hormonal therapy also increase the risk (Ng and Travis 2008). Early detection strategies include mammography, breast magnetic resonance imaging, fecal occult blood testing, colonoscopy, skin examination, and genetic counseling. Prevention strategies include smoking cessation, sun safety practices, prophylactic surgery, exercise, weight management, and energy balance (i.e., controlled caloric intake).
Endometrial Cancer
Endometrial cancer survivors are at risk for multiple second primary cancers, as illustrated in Table 8.1. The risk of developing a second primary cancer is highest in the breast and colon. The etiology of developing breast cancer after endometrial cancer is not thought to be related to treatment. Rather, the risk of a second primary breast cancer is thought to be related to the same risk factors as those for endometrial cancer. These include nulliparity, an increasing number of years of menstrual cycles, and postmenopausal obesity. Shared genetic factors are still another suspected cause, including hereditary non-polyposis colon cancer (HNPCC).
Table 8.1
Second primary cancers for which gynecologic cancer survivors are at increased risk
Location of second primary cancer | Endometrial cancer survivors | Cervical cancer survivors | Ovarian cancer survivors |
|---|---|---|---|
Bladder | X | X | X |
Breast | X | X | X |
Colon | X | X | |
Colon or rectum | X | ||
Endometrium (uterine lining) | X | ||
Kidney | X | X | |
Leukemia | X | ||
Lung or bronchus | X | X | |
Ovary | X | ||
Pancreas | X | ||
Rectum or anus | X | X | |
Ureter | X | ||
Urethra | X | ||
Uterus | X | ||
Vagina | X | X | |
Vulva | X | X |
Screening efforts are tailored to each individual’s medical history, family history, and prior treatment. Survivors are offered breast and colorectal cancer screening. Skin cancer screening is also offered, owing to the well-documented link between sun exposure and skin cancer. Referrals to the Smoking Cessation Clinic are also available, owing to the link between smoking and lung and oropharyngeal malignancies. Recent data have shown a relationship between obesity and the development of possible malignancies, including breast and colon cancers, as well as between obesity and medical comorbidities such as hypertension, coronary artery disease, and diabetes. Obesity is a well-established risk factor for endometrial cancer. Survivors who are physically inactive after a cancer diagnosis are at increased risk for a variety of problems, including cancer-related fatigue, weight gain, poor quality of life, and declines in physical functioning. Physically inactive survivors are also at an increased risk of developing second cancers and other chronic diseases such as diabetes, cardiovascular disease, and arthritis. Endometrial cancer survivors are more likely to die from diseases such as stroke or heart disease than from cancer.
Treatment with tamoxifen has also been identified as a risk factor for developing endometrial cancer. For women with breast cancer who still have a uterus, an annual gynecologic examination is recommended. Women should also be counseled about the early symptoms of endometrial cancer, including abnormal vaginal spotting, bleeding, or discharge, especially if the woman is postmenopausal. These symptoms should be reported promptly to a health care provider. The endometrium should be sampled and the specimen evaluated by a pathologist for possible malignancy.
Genetic counseling is offered to women who meet the criteria established for increased risk of Lynch syndrome, also called HNPCC, an inherited condition characterized by a mutation in one of the four key mismatch repair genes—MLH1, MSH2, MSH6, and PMS2. Carriers are already known to be at high risk of developing some cancers, particularly colon cancer, and are diagnosed with this cancer at younger ages than the general population. In addition to colon cancer, other cancers known to be associated with Lynch syndrome include uterine, ovarian, renal, stomach, and bladder malignancies. People with this disorder may also have increased risks for breast and pancreatic cancers. Screening criteria include a family member diagnosed with colorectal or endometrial cancer before the age of 50 years, cancer present in two or more generations, and three or more closely related family members with endometrial, colorectal, or other Lynch-associated cancers. These criteria are called the Amsterdam criteria. Not all families that meet the Amsterdam criteria have Lynch syndrome, and families that have Lynch syndrome may not meet all of the Amsterdam criteria. Therefore, an individual concerned about Lynch syndrome in her family should be referred to a genetic counselor for consultation.
Cervical/Vaginal/Vulvar Cancers
All survivors with a history of cervical, vaginal, and vulvar cancers are offered breast cancer screening and colorectal cancer screening as appropriate. Skin cancer screening is also offered. Smoking cessation is of high priority; many studies have shown a relationship between smoking and cervical and vulvar lesions. Diet and weight management assistance, as well as promotion of physical activity, are suggested as described above for endometrial cancer survivors.
Ovarian/Fallopian Tube/Primary Peritoneal Cancers
Each year an estimated 25,000 woman are diagnosed with ovarian cancer. The overall risk of developing a second cancer is approximately 20% greater in women with a history of ovarian cancer who survive at least five years. Risk for a second gynecologic malignancy is low because most women with ovarian cancer have been treated with hysterectomy. Treatment for ovarian cancer usually results in ablation of gonadal function, but this does not necessarily equate to a reduced risk of developing breast cancer. Although the elevated relative risk for a second primary cancer may partly be due to shared risk factors such as early menarche, late menopause, and nulliparity, mutations in the BRCA1 and BRCA2 genes substantially increase the risk of developing breast cancer. Individuals with BRCA1-associated cancers have a 50–80% lifetime risk of developing breast cancer, a 40–60% lifetime risk of developing a second primary breast cancer, and a 20–40% lifetime risk of developing ovarian cancer. Individuals with BRCA2-associated cancers have a 40–80% lifetime risk of developing breast cancer and a 10–25% lifetime risk of developing ovarian cancer. Therefore, survivors with a history of ovarian, fallopian tube, and primary peritoneal cancers are offered breast cancer screening.
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