Version May 2024
INTRODUCTION — Ovarian cancer is the second most common gynecologic malignancy and the most common cause of gynecologic cancer death in the United States. Epithelial ovarian carcinoma is the most common histologic type of ovarian cancer and is closely related to fallopian tube and peritoneal carcinomas. These will be referred to as a single entity here, as epithelial ovarian carcinoma (EOC).
Five-year survival rates for stage III or IV EOC are approximately 40 and 20 percent, respectively (table 1). However, in 2022 there were almost 247,000 EOC survivors in the United States and there are some long-term survivors of EOC [1].
Issues pertaining to survivorship in EOC are not well-studied. This may be due to the overall poor prognosis of patients with ovarian cancer and smaller populations of affected individuals compared with patients with other cancers (eg, endometrial or breast cancer). Additionally, there are many studies of ovarian cancer survivors and their difficulties, but there are few data to guide management. Nevertheless, survivorship-related issues are important to address in this growing population of patients.
The approach to survivors of EOC will be reviewed here. Related topics are discussed in detail separately, including:
●Overview, diagnosis, and treatment:
•(See "Overview of epithelial carcinoma of the ovary, fallopian tube, and peritoneum".)
•(See "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Clinical features and diagnosis".)
•(See "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Surgical staging".)
•(See "Intraperitoneal chemotherapy for treatment of ovarian cancer".)
●Cancer survivorship:
•(See "Assuring quality of care for cancer survivors: The survivorship care plan".)
•(See "Overview of cancer survivorship care for primary care and oncology providers".)
●Relapsed disease:
OVERVIEW OF TREATMENT — EOC is surgically staged (table 2). Total hysterectomy with bilateral salpingo-oophorectomy, pelvic and para-aortic lymph node dissection, and infracolic or infragastric omentectomy is the standard staging procedure. Bowel resection and/or radical pelvic and upper abdominal surgery may be required.
The approach to treatment depends upon the stage and is discussed in detail elsewhere. (See "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Surgical staging" and "Adjuvant therapy of early-stage (stage I and II) epithelial ovarian, fallopian tube, or peritoneal cancer" and "First-line chemotherapy for advanced (stage III or IV) epithelial ovarian, fallopian tube, and peritoneal cancer".)
Nearly 80 percent of patients with EOC enter remission following primary treatment. The recurrence rates are 25 and 80 percent for patients with early-stage and advanced disease, respectively [2,3].
POST-TREATMENT SURVEILLANCE
Risk of recurrence — Patients treated for EOC are at a high risk of recurrence, and most EOC survivors will not be cured. The approach to patients who relapse and require further treatment is discussed separately. (See "Medical treatment for relapsed epithelial ovarian, fallopian tube, or peritoneal cancer: Platinum-sensitive disease" and "Medical treatment for relapsed epithelial ovarian, fallopian tube, or peritoneal cancer: Platinum-resistant disease".)
We agree with the National Comprehensive Cancer Network (NCCN) guidelines for monitoring patients who have completed treatment for EOC [4]:
●Office visits (including history, general physical, and pelvic examinations) every two to four months for two years, then every three to six months for three years, then annually after five years. For patients with advanced-stage disease at presentation who achieve and maintain a complete response, we continue following for life. For those with early-stage disease with no evidence of recurrence at five years, it is reasonable to return care to the primary care physician or gynecologist.
●Cancer antigen (CA) 125 or other tumor markers at every visit, if these markers were elevated at the initial presentation. The Society of Gynecologic Oncology (SGO) prefers to individualize monitoring by serum CA 125 based on discussions between patients and their clinicians on both the pros and cons of CA 125 measurements [5].
●Other testing (ie, chemistry profile or complete blood count, or imaging), only as clinically indicated (eg, for a rise in CA 125 or new or worsening symptom).
Role of CA 125 surveillance — The role of cancer antigen (CA) 125 in surveillance of EOC remains controversial. In our practice, we check CA 125 levels at every visit, if these markers were elevated at the initial presentation.
An SGO white paper, after reviewing all the relevant data, suggests CA 125 be considered "optional" in the surveillance of patients with EOC [6]. However, in the United States, where care is often driven by shared decision-making between the clinician and patient, CA 125 surveillance remains routine practice [7].
While routine CA 125 surveillance may result in earlier disease recurrence detection (two to five months earlier, in one study [8]), it may not improve overall survival (OS). This lack of impact on OS was shown in the Medical Research Council 05 trial in which 1442 patients had their CA 125 levels checked every three months, with both patients and investigators blinded to the results [9,10]. Patients who remained asymptomatic but whose CA 125 levels exceeded twice the upper limit of normal (527 patients) were randomly assigned to immediate treatment or to continued blinding of the CA 125 results with treatment delayed until the time of a clinical or symptomatic recurrence. Patients who developed symptoms or signs of a recurrence were removed from the study. The main results of this study were as follows:
●Second-line chemotherapy was started a median of five months earlier in the immediate treatment arm.
●At a median follow-up of 57 months from randomization, there was no improvement in OS with immediate compared with delayed treatment (hazard ratio [HR] for death 0.98, 95% CI 0.80-1.20).
●Immediate treatment was not associated with a longer remission duration following the detection of recurrence. However, it resulted in an adverse impact on quality of life.
In addition, while an early rise in CA 125 may allow a patient to be identified for surgery earlier in the recurrent disease course, and thus be more likely to achieve an optimal secondary cytoreduction, secondary cytoreduction may be associated with worse outcomes. In a study of 74 patients with recurrent EOC who underwent secondary cytoreduction, patients who had an optimal cytoreduction had a shorter time interval between their initial rise in CA 125 compared with those who had a suboptimal cytoreduction (5 versus 16 weeks; HR 1.03, 95% CI 1.01-1.06), suggesting that acting expeditiously upon a rising CA 125 level may improve surgical outcomes [11]. However, the randomized trial conducted by the Gynecologic Oncology Group (GOG 213) demonstrated no survival benefit to secondary cytoreduction; in fact, those patients who underwent surgery had a worse survival outcome compared with those who were randomized to the no surgery group.
No role for routine imaging — Standard imaging techniques, including ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET), have limited sensitivity to detect recurrent EOC [12]. There are some data to support the use of PET/CT to detect early recurrent disease, but in the absence of data to suggest this improves survival, we do not perform imaging studies in otherwise asymptomatic patients as part of surveillance.
As an example, the role of PET/CT imaging was evaluated in a 2013 meta-analysis that included 29 trials (n = 1651) [12]. PET/CT had a sensitivity and specificity of 89 and 90 percent, respectively, and the positive and negative likelihood ratios were 6.1 (95% CI 3.9-9.5) and 0.12 (95% CI 0.08-0.19), respectively. However, all studies were observational and the recurrent disease was not uniformly confirmed histologically; the analysis included studies in which recurrence was based solely on repeat imaging at six months. Whether earlier detection of recurrent EOC by PET/CT expanded treatment options or improved survival was not reported.
Therefore, PET/CT should not be used as part of routine surveillance for patients treated for EOC. On the other hand, PET/CT may be useful in the evaluation of a rising CA 125 to assess for extent of disease, anticipating further discussion regarding the role of surgery and timing of treatment, pending the results.
Breast cancer risk management in BRCA mutation carriers with EOC — Patients who have been treated for EOC should be counseled about genetic testing if it has not already been done. Patients with an inherited germline mutation in breast cancer susceptibility gene 1 (BRCA1) or breast cancer susceptibility gene 2 (BRCA2) are at increased risk of developing breast cancer, regardless of whether they have had EOC. However, there is no consensus on the most appropriate management of breast cancer risk in these patients. While prophylactic mastectomy is a reasonable option for these patients, surveillance with MRI, mammography, and clinical examination may be a reasonable alternative, particularly for those patients diagnosed with advanced-stage EOC in whom the risk of EOC recurrence is greatest. (See "Cancer risks and management of BRCA1/2 carriers without cancer", section on 'Breast cancer screening'.)
COORDINATION OF CARE — Following treatment of EOC, in general, follow-up care is usually provided by a gynecologic oncologist, regardless of the length of remission. However, as is the case of other patients with a history of cancer, follow-up care may also be provided by a medical oncologist, general gynecologist, or primary care provider. (See "Overview of cancer survivorship care for primary care and oncology providers", section on 'Coordination of care'.)
QUALITY OF LIFE AMONG SURVIVORS — The combination of aggressive surgical cytoreduction and taxane plus platinum-based chemotherapy leads to long-lasting side effects in multiple domains that have been shown to decrease overall quality of life (QOL) in ovarian cancer survivors compared with age-matched healthy controls [13].
While there are no direct data to suggest that QOL has an impact on disease-specific survival, there are data suggesting that QOL is associated with overall survival (OS).
●Observational data have shown that a lower midtreatment QOL score was associated with a higher death rate in patients undergoing secondary cytoreductive surgery [14].
●A similar study in patients undergoing primary therapy concluded that physical well-being was associated with OS: patients who reported baseline physical well-being scores in the lowest quartile had decreased OS when compared with patients in the highest quartile (hazard ratio 1.81, 95% CI 1.20-2.72) [15].
These data are hypothesis-generating regarding the impact of QOL on OS in a disease where recurrence and the need for future treatment are likely.
LONG-TERM PHYSICAL EFFECTS — Following treatment, most ovarian cancer patients have short-term side effects (typically up to 12 months) such as neuropathy, problems with memory and concentration, and fatigue. Some patients will have long-term irreversible peripheral neuropathy as a result of paclitaxel and platinum-based therapy. Anxiety and fatigue may also be long-lasting. The so-called "chemo-brain" or cognitive dysfunction usually lasts for 12 months and in most patients will resolve, but some patients will have long-term cognitive dysfunction as a result of chemotherapy [16].
Neurologic effects
Neurotoxicity — Persistent neurotoxicity is an important quality of life (QOL) issue for long-term survivors and is most commonly due to the adverse effects of chemotherapy [17,18]. The treatment approach to chemotherapy-induced neurotoxicity is discussed separately. (See "Prevention and treatment of chemotherapy-induced peripheral neuropathy", section on 'Treatment'.)
In one study of 49 EOC survivors (all with early-stage disease), the incidences of neurotoxicities were as follows [17]:
●Muscle cramps (39 percent)
●Ringing in ears or trouble hearing (29 to 35 percent)
●Discomfort in feet (29 percent)
●Upper extremity discomfort (23 percent)
●Trouble walking (16 percent)
●Numbness and weakness in the hands (10 percent)
A separate registry-based study of ovarian cancer survivors (who were diagnosed with stage I through IV disease) suggested that neuropathy, specifically tingling in the hands/feet and numbness in fingers/toes, was experienced by 51 percent of patients with ovarian cancer who received chemotherapy even up to 12 years after the end of treatment. Neuropathy was also associated with lower levels of overall functioning and QOL [19].
Gynecologic Oncology Group study 218 reported 71 percent of patients developed grade 1 or higher neurotoxicity during the study, with 31 percent being grade 2 or higher. Older patients and those with worse baseline QOL were more likely to experience neurotoxicity [20].
Neurotoxicity is often underestimated by clinicians. In a study from the ICON7 group, investigators compared neuropathy greater than grade 2 as reported by clinicians versus patients: 28 versus 67 percent. Agreement between clinicians and patients was poor [21].
These figures highlight the importance of longitudinal assessment of neurologic function for EOC survivors. In addition to obtaining a history and performing a neurologic exam, neurotoxicity can be evaluated with standardized questionnaires, such as the Functional Assessment of Cancer Therapy group (FACT) and Gynecologic Oncology Group (GOG) neurotoxicity questionnaire (FACT/GOG-NTX), which consists of 11 items that assess sensory, motor, and hearing as well as functional impact [22]. This measure is currently being utilized prospectively in clinical trials evaluating new regimens for EOC.
Cognitive dysfunction — Few studies have evaluated the cognitive function in patients with ovarian cancer, and their findings have been inconsistent [23-27]. In addition, it is not clear to what extent the disease itself, chemotherapy, or other factors contribute to the risk for cognitive dysfunction. In one small study, 18 patients with ovarian cancer (one to four months after completing first-line taxane/platinum chemotherapy) and 18 controls underwent structural and functional magnetic resonance imaging (MRI) and completed neuropsychologic tests of attention, memory, and executive function. Results showed both structural and functional alterations in the frontal and parietal regions of the brain in patients relative to healthy controls [28].
The GOG reported a prospective longitudinal study of cognitive dysfunction in 231 patients with ovarian cancer entered on chemotherapy protocols. At the postcycle and six-month follow-up time points, 21 and 17 percent of patients, respectively, demonstrated impairment in at least one domain of cognitive function [29].
A small randomized controlled trial of a cognitive behavioral therapy called Memory and Attention Adaptation Training (MAAT) has been reported in a series of 47 breast cancer patients. MAAT participants made improvements in perceived cognitive impairments and neuropsychological processing speed compared with supportive therapy controls [30]. There was also improvement with regard to anxiety concerning cognitive dysfunction.
Although agents being evaluated for pharmacologic intervention include neurostimulants and antioxidants, at this time there are insufficient data to recommend their use [31].
Fatigue — Fatigue occurs in almost all patients with EOC [32-34] and may persist after completion of chemotherapy [35]. Fatigue can be an obstacle to daily functioning and has a negative impact on emotional functioning and overall QOL [18,36]. For patients with EOC, fatigue is moderately distressing and can be difficult to control [37]. The approach to and treatment of fatigue mirrors the approach to fatigue in other patients with cancer.
In one small study, patients with gynecologic cancers were randomized to a physical activity and behavioral change intervention versus standard care. The intervention group experienced a small improvement in fatigue as measured by the Multidimensional Fatigue Symptom Inventory-Short Form [38]. Larger studies specific to ovarian cancer patients are needed to confirm these findings in this population.
The GINECO group reported a case-control study of ovarian cancer survivors and age-matched healthy controls focusing on long-term fatigue and QOL. They used validated questionnaires to assess fatigue, neurotoxicity, anxiety/depression, sleep disturbance, and physical activity. The cancer survivors reported more severe long-term fatigue (26 versus 13 percent), poorer sleep quality (63 versus 47 percent), and more depression (22 versus 13 percent). In multivariate analyses, survivors with high levels of depression, neurotoxicity, and sleep disturbance had an increased risk of developing severe long-term fatigue [39].
Cancer-related fatigue may benefit from lifestyle intervention. One study assessed the feasibility of a nurse-led, home-based exercise and cognitive behavioral therapy program for ovarian cancer patients with cancer-related fatigue. After the intervention, total fatigue scores were significantly reduced in the experimental group with no change in the comparison group. Additionally, after the intervention, the experimental group had lower symptoms of depression. Sleep duration, sleep dysfunction, daytime dysfunction, and total sleep quality all significantly improved [40].
A pilot study that queried ovarian cancer survivors using European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaires reported that the areas that should be given the highest priority for research include fatigue, along with areas involving task completion, memory, concentration, and anxiety [41]. (See "Cancer-related fatigue: Prevalence, screening, and clinical assessment" and "Cancer-related fatigue: Treatment".)
Gastrointestinal toxicity — Patients treated for EOC may have long-term issues with their gastrointestinal (GI) system as a result of the previous disease, surgical treatment, and medical therapy. Most patients with EOC experienced GI symptoms with their initial presentation; in many cases, these symptoms were present for months before the correct diagnosis was made. For this reason, many patients worry that subsequent GI symptoms indicate disease recurrence.
A survey study of patients with all stages of ovarian cancer from the Netherlands noted that 25 percent of patients reported high-level GI symptoms; regression analysis showed that the presence of high-level GI symptoms during survivorship was associated with lower functioning in almost all health care QOL domains, more symptoms, and higher levels of distress [42]. In another study, the presence of GI symptoms correlated with lower QOL, worse emotional status, less spirituality, and greater fear of recurrence [18].
Patients with EOC who experience new GI symptoms should be evaluated for disease recurrence, using history, physical exam, and imaging studies. In most situations, the authors and editors prefer computed tomography (CT) imaging, but other imaging modalities (including MRI or positron emission tomography [PET]/CT) may be performed according to patient and provider preferences.
Surgical complications — Although the GI tract is often involved at the time of diagnosis of EOC [43,44], the onset of symptoms in EOC survivors can herald the diagnosis of recurrence or represent long-term complications of primary surgery. The symptoms include abdominal bloating, cramping, pain, nausea, and vomiting, and they can lead to poor nutrition, fatigue, and overall deconditioning.
In addition, patients treated for EOC are at risk of a bowel obstruction, which can be caused by intraabdominal adhesions secondary to prior surgery or may herald recurrent disease. The management of bowel obstruction is discussed separately. (See "Management of small bowel obstruction in adults".)
Medical complications — Although not a common manifestation, long-term GI complications can be due to medical treatment [45], including the intraperitoneal administration of chemotherapy [2] or the use of medications to manage symptoms (eg, narcotics for pain control). Although some agents (eg, bevacizumab) may be associated with GI complications, these tend to resolve after treatment is discontinued [46]. (See "Intraperitoneal chemotherapy for treatment of ovarian cancer", section on 'Complications' and "Non-cardiovascular toxicities of molecularly targeted antiangiogenic agents", section on 'Gastrointestinal toxicities' and "Prevention and management of side effects in patients receiving opioids for chronic pain", section on 'Opioid bowel dysfunction'.)
Unrelated causes — As with patients without cancer, EOC survivors can also have symptoms due to an unrelated reason (eg, irritable bowel syndrome) [17,47-49]. A medical evaluation should be initiated in the woman with specific GI symptoms (eg, diarrhea, pain, or constipation) who otherwise appears to be in continued remission. (See "Approach to the adult with chronic diarrhea in resource-abundant settings" and "Approach to the adult with acute diarrhea in resource-abundant settings" and "Constipation in the older adult" and "Causes of abdominal pain in adults" and "Evaluation of the adult with abdominal pain".)
Gynecologic effects
Loss of fertility — Up to 17 percent of patients with EOC are less than 40 years of age at diagnosis [50-52]. Ovarian cancer staging includes hysterectomy and bilateral salpingo-oophorectomy and results in loss of fertility in reproductive-age females. A small proportion of patients have early-stage disease, and may be candidates for fertility preservation.
Clinicians should recognize fertility loss as a potential issue early in the diagnosis and treatment process and counsel patients. This is a key feature in helping patients to make decisions and to adjust emotionally. We concur with guidance from the American Society of Clinical Oncology and refer these patients to a fertility specialist as soon as possible following diagnosis. (See "Fertility and reproductive hormone preservation: Overview of care prior to gonadotoxic therapy or surgery" and "Overview of infertility and pregnancy outcome in cancer survivors".)
Sexual dysfunction — Sexual function issues are common among EOC survivors [53]. Patients with ovarian cancer report higher rates of sexual dysfunction and sexual distress and lower levels of relationship satisfaction when compared with the general population.
Sexual problems may be secondary to effects of surgery, chemotherapy, or menopause, or may be due to a partner's sexual issues or relationship problems. Patients may complain of dyspareunia, loss of desire, or other sexual dysfunction [54]. The limited data suggest that sexual dysfunction in ovarian cancer survivors is associated with poorer QOL, emotional health, spirituality, and higher fear of recurrence [18,55].
Sexual dysfunction is reported by many patients with EOC, and many report absent or decreased sexual activity. Up to 63 percent of ovarian cancer survivors report that cancer altered their sexual life in a negative way [56-58]. In one study, reduced interest in sex was reported by 54 and 31 percent of survivors with early- and late-stage EOC, respectively [18]. In addition, 41 and 46 percent reported decreased sexual activity. Reasons for sexual inactivity were evaluated in a study of 232 patients with EOC, and included physical problems in 23 percent and fatigue in 11 percent [56]. Partner factors were also identified. In one study, sexually active survivors reported significantly lower levels of sexual pleasure and a higher level of discomfort despite use of menopausal hormonal therapy [57].
Sexual health after ovarian cancer may be approached by asking patients about sexual health issues, including dyspareunia, libido, or orgasm function, and treatment or referral for symptoms. Some cancer centers have sexual health programs for survivors, or patients may be referred to a gynecologist, internist, mental health professional, or pelvic physical therapist with experience treating sexual issues; another source of referrals is sexual health organizations.
Treatment options include treatment of vulvovaginal atrophy or other etiologies of dyspareunia, addressing loss of libido, and/or addressing partner sexual function or relationship issues. As an example, a study of a psychoeducational intervention for sexual dysfunction after ovarian cancer involving both group therapy and an individualized treatment plan showed significant improvement postintervention [59]. (See "Overview of sexual dysfunction in females: Epidemiology, risk factors, and evaluation" and "Overview of sexual dysfunction in females: Management".)
Sexual issues in female cancer survivors are discussed in detail separately. (See "Overview of sexual dysfunction in female cancer survivors".)
Menopause — The average age at diagnosis of EOC is 63 years, and most patients are postmenopausal. However, EOC survivors that are premenopausal or perimenopausal are candidates for hormone therapy (HT). Treatment of EOC includes hysterectomy for most patients, and thus systemic HT is usually estrogen alone. Patients with genitourinary syndrome of menopause (vulvovaginal atrophy) are candidates for vaginal estrogen therapy. Patients who prefer to avoid hormones may be managed expectantly or with nonhormonal therapies [60,61]. Studies of ovarian cancer always include cases of primary fallopian tube and peritoneal carcinoma, and thus, it is also reasonable to use HT for patients with these cancers.
Systemic menopausal symptoms or effects — Menopause may be accompanied by bothersome symptoms that impact QOL, including vasomotor symptoms, mood changes, sleep disturbance, and other symptoms. Symptoms may be addressed with HT or nonhormonal therapy. Patients should be counseled about the benefits and risks of HT before initiating therapy. (See "Menopausal hormone therapy: Benefits and risks" and "Preparations for menopausal hormone therapy".)
Patients with EOC who have bothersome menopausal symptoms can be counseled in the same manner as the general population:
●HT is used to treat bothersome symptoms in patients who are within 10 years of menopause or younger than age 60 and who do not have contraindications to HT (such as a history of breast cancer, coronary heart disease [CHD], a previous venous thromboembolic event or stroke, or active liver disease). In our practice, we also apply this approach to patients over the age of 60, recognizing the limitations in available data.
●Risk of breast cancer should be considered, particularly for patients with breast cancer susceptibility gene (BRCA) mutations.
●Most patients with EOC have undergone hysterectomy, and HT will consist of estrogen alone. A progestin is required if the uterus has been conserved to offset risks of endometrial cancer.
●Concerns have been raised about estrogen receptor (ER) expression in EOC, but we do not view this as a contraindication to treatment with HT. While this expression has been associated with an improved response to tamoxifen or aromatase inhibitors (AIs) in patients with recurrent disease [62,63], there is no evidence that ER expression is associated with an increased risk of recurrence with the use of HT, with the theoretical exception of the endometrioid subtype. While one study found that estrogen-only HT increased the risk of developing endometrioid ovarian cancer over other histologies, there are no data to suggest that HT after an ovarian cancer diagnosis increases the risk of cancer recurrence in this particular histologic subtype [64]. In our opinion, it is likely safe to use HT in well-informed, symptomatic patients with a history of endometrioid-type ovarian cancer. In addition, there is no role for hormone receptor testing in EOC, either prior to treating with tamoxifen or an AI or for using HT following diagnosis. ER-positive testing does not influence the use of HT if the patient has bothersome menopausal symptoms and HT is the best treatment option [65]. (See "Medical treatment for relapsed epithelial ovarian, fallopian tube, or peritoneal cancer: Platinum-resistant disease", section on 'Endocrine therapy'.)
Ovarian cancer survivors treated with HT do not appear to have an increase in the risk of recurrence or a decrease in overall survival (OS). A meta-analysis of three studies including 350 patients demonstrated that HT compared with no HT after surgery for EOC may improve OS, but made no difference in progression-free survival, incidence of breast cancer, cerebrovascular accident, transient ischemic attack, and myocardial infarction [66]. The largest study in this meta-analysis included a multinational, randomized, nonblinded trial of 150 patients with EOC assigned to HT versus no HT [67]. The majority of participants were treated with estradiol or conjugated estrogens alone, and 14 patients received conjugated estrogens with norgestrel (the authors did not report if these patients did not undergo hysterectomy). The median HT duration was 1.14 years (interquartile range, 0.46 to 5.08 years). Long-term OS was superior in the HT group (risk of death at 20 years: adjusted hazard ratio [HR] 0.45, 95% CI 0.44-0.90). Recurrence-free survival was also superior in the HT group (risk of recurrence at 20 years: HR 0.67, 95% CI 0.47-0.97). The patients taking HT had fewer deaths due to ovarian cancer (67 versus 75 percent) as well as other causes (4 versus 16 percent), including CHD and thromboembolic disease.
These findings are consistent with other systematic reviews and observational studies that suggest the use of HT after surgery in ovarian cancer patients may have a role in treating menopause symptoms [68-71].
Genitourinary syndrome of menopause — EOC survivors with symptoms of genitourinary syndrome of menopause (vulvovaginal atrophy) are candidates for vaginal estrogen therapy, with the exception of those with endometrioid histology that involved the vagina at diagnosis. No studies have studied this therapy in this patient population; however, concerns regarding recurrence are low with this low dose and limited serum absorption, based on the data from systemic HT discussed in the previous section. (See "Genitourinary syndrome of menopause (vulvovaginal atrophy): Treatment".)
PSYCHIATRIC AND PSYCHOSOCIAL ISSUES — Most patients with EOC experience some level of ongoing psychological distress throughout the course of their disease [54,72]. Depression and anxiety are common in ovarian cancer survivors.
Clinicians should ask about psychiatric symptoms and psychosocial issues at follow-up visits. Treatment of depression and anxiety is generally the same in EOC survivors as in other patients. (See "Overview of psychosocial issues in the adult cancer survivor" and "Patients with cancer: Overview of the clinical features and diagnosis of psychiatric disorders" and "Management of psychiatric disorders in patients with cancer".)
Interventions for psychosocial issues are discussed in detail separately. (See "Overview of psychosocial issues in the adult cancer survivor", section on 'Interventions'.)
Depression — Depression can be a persistent issue for survivors of EOC. In one study, up to 15 percent of ovarian cancer survivors met the diagnostic criteria for major depression [73]. In another study, depressive symptoms and higher degrees of social impairment were more common in patients with EOC compared with a cohort with a diagnosed psychiatric illness (but without a history of cancer) [74,75].
Sleep disorders may also contribute to depression. One study demonstrated that in the first year of diagnosis after ovarian cancer, sleep disturbances are common and were associated with depression [76]. In this study, pharmacologic treatment alone was not successful for these patients.
Depression in cancer survivors is discussed in detail separately. (See "Patients with cancer: Overview of the clinical features and diagnosis of psychiatric disorders", section on 'Depressive disorders'.)
Anxiety — Although the data are limited, anxiety may be more problematic than depression for EOC survivors [18,77-81]. In one prospective study, anxiety levels increased three months following completion of chemotherapy, while depression levels decreased [78].
Symptoms may manifest as post-traumatic stress disorder (PTSD), which was diagnosed in up to 7 percent of patients with early-stage disease [18,79,80], or the occurrence of cancer-specific intrusive or avoidant thoughts [81]. An Australian study of ovarian cancer patients specifically queried patients with respect to PTSD in the survivorship period. Among this group, 9.3, 5.6, and 14 percent experienced clinically significant PTSD, depression, and anxiety, respectively [82]. (See "Posttraumatic stress disorder in adults: Epidemiology, pathophysiology, clinical features, assessment, and diagnosis", section on 'Diagnosis'.)
In addition, anxiety may be manifest in two specific ways in EOC survivors:
●Fear of recurrence – More than half of survivors report a fear of disease recurrence, which may persist over time [18,54,73,83,84]. This may be associated with other concerns, including hopelessness and/or a worry about dying [73].
●Preoccupation with cancer antigen (CA) 125 values – Most survivors report anxiety regarding CA 125 testing, even in cases where they have been disease-free for several years [18]. This is particularly true for patients in whom a recurrence is suspected [85,86]. (See 'Role of CA 125 surveillance' above.)
Anxiety in cancer survivors is discussed in detail separately. (See "Patients with cancer: Overview of the clinical features and diagnosis of psychiatric disorders", section on 'Anxiety disorders'.)
Other issues — Ovarian cancer survivors experience many of the same psychosocial issues as other cancer survivors. These may include:
●Cancer-related distress – This includes fear of recurrence and increased awareness of health vulnerability.
●Guilt – Survivors of EOC may have guilt related to a number of issues:
•Guilt due to delay in diagnosis – The symptoms that herald a diagnosis of ovarian cancer are nonspecific. Despite this, some patients suffer from guilt when they are diagnosed with EOC (especially advanced-stage disease) because the lack of recognition of "early" symptoms may have resulted in a delay in diagnosis [87]. (See "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Clinical features and diagnosis", section on 'Clinical presentation'.)
•Familial guilt – Survivors with a breast cancer susceptibility gene (BRCA) mutation sometimes express feelings of guilt due to transmission of the genetic mutation to their children or if they developed EOC after opting against prophylactic surgery [54].
•Survivors’ guilt – Survivors’ guilt can occur in some long-term survivors who have witnessed others with similar disease stage experience recurrence and then succumb to the disease.
●Poor body image – Poor body image has been significantly associated with fatigue and poor sexual functioning, particularly among patients who were premenopausal at diagnosis [34,57]. Poor body image is primarily due to long-term effects of prior surgical treatment, including: surgical scars, loss of the uterus and/or ovaries, presence of an ostomy, and wound complications (eg, infection, incisional breakdown, enterocutaneous fistulas).
●Social well-being – EOC affects the survivor’s daily life as well as that of her family by impacting the roles she plays (eg, as mother, wife, sister, friend, coworker) [88,89]. In general, 75 percent of early-stage survivors reported excellent social wellbeing; however, 23 percent of them were at or below the 25th percentile in social functioning [17]. Beyond the potential inability to perform household chores or socialize with friends, the loss of ability to work and financial concerns may be important concerns to the survivor of EOC [88,89]. These figures underscore the importance of evaluating patients for social adjustment after treatment for EOC has completed.
PROMOTING A HEALTHY LIFESTYLE — There are limited data on the impact of lifestyle interventions for survivors of EOC. In the absence of data specific to this population, general guidelines for cancer survivors should also apply to patients treated for EOC, including consumption of a healthy diet, physical activity, and limited alcohol intake.
Regarding physical activity, one study showed that ovarian cancer survivors who either maintained or increased their physical activity after cancer diagnosis had significantly better mean depression and quality of life scores than patients who decreased physical activity or remained inactive [90]. In addition, among patients who received chemotherapy shortly prior to completing the lifestyle questionnaire, high physical activity was significantly associated with significantly lower mean depression scores during both periods of treatment and nontreatment when compared with low or medium physical activity [90].
The roles of diet, physical activity, and body weight for cancer survivors are discussed separately. (See "The roles of diet, physical activity, and body weight in cancer survivors".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Ovarian, fallopian tube, and peritoneal cancer".)
SUMMARY AND RECOMMENDATIONS
●Clinical significance – Ovarian cancer is the second most common gynecologic malignancy and the most common cause of gynecologic cancer death in the United States. Epithelial ovarian carcinoma (EOC) is closely related to fallopian tube and peritoneal carcinomas. Five-year survival rates for stage III or IV EOC are approximately 40 percent and 20 percent, respectively (table 1); however, in 2022 there were almost 247,000 EOC survivors in the United States. (See 'Introduction' above.)
●Overview of treatment – Ovarian, fallopian tube, and peritoneal carcinoma are surgically staged, including total hysterectomy with bilateral salpingo-oophorectomy, pelvic and para-aortic lymph node dissection, and omentectomy (table 2). Most patients are diagnosed with stage III or IV disease and will undergo surgical staging followed by combination chemotherapy consisting of a platinum salt (carboplatin or cisplatin) plus a taxane (paclitaxel or docetaxel). New maintenance therapies are being studied and may add to both short- and long-term toxicity. (See 'Overview of treatment' above.)
●Post-treatment surveillance – Follow-up office visits (including history, general physical, and pelvic examinations) should occur every two to four months for two years, then every three to six months for three years, then annually after five years. The role of cancer antigen (CA) 125 (or other tumor markers) in surveillance is controversial; in our practice, we check CA 125 levels at every visit, if these markers were elevated at the initial presentation. Other testing (ie, chemistry profile or complete blood count, or imaging) should be pursued only if clinically indicated (eg, for a rise in CA 125 or new or worsening symptom). (See 'Post-treatment surveillance' above.)
●Long-term effects
•Neuropathy – Persistent neurotoxicity is an important quality of life (QOL) issue for long-term survivors and is most commonly due to the adverse effects of chemotherapy [17,18]. The treatment approach to chemotherapy-induced neurotoxicity is discussed separately. (See "Prevention and treatment of chemotherapy-induced peripheral neuropathy", section on 'Treatment'.)
•Fatigue – Fatigue is an obstacle to daily functioning and a contributor to decreased QOL. In patients with EOC, fatigue may persist after completion of chemotherapy and can be moderately distressing and difficult to control. (See 'Fatigue' above.)
•GI symptoms – Ovarian cancer survivors often suffer from significant bowel function disorders, including constipation and diarrhea, both during and after primary therapy. Gastrointestinal (GI) symptoms correlate with poorer QOL in EOC survivors. Patients with EOC who experience new GI symptoms should be evaluated for disease recurrence, using history, physical exam, and imaging studies (eg, abdominal/pelvic computed tomography [CT], magnetic resonance imaging [MRI], positron emission tomography [PET]/CT, or PET). (See 'Gastrointestinal toxicity' above.)
•Sexual dysfunction – Sexual function issues are common among EOC survivors. Sexual problems may be secondary to effects of surgery, chemotherapy, or menopause, or may be due to a partner’s sexual issues or relationship problems. Patients may complain of dyspareunia, loss of desire, or other sexual dysfunction. (See 'Sexual dysfunction' above.)
•Menopausal symptoms – For patients with EOC who have bothersome menopausal symptoms, we offer nonhormonal options as a first-line measure. However, for those who have failed or declined nonhormonal treatments, we suggest hormone therapy rather than no treatment or further lines of nonhormonal therapy (Grade 2C). In general, while studies have typically included patients who are within 10 years of menopause or under 60 years of age, we also apply this approach to ovarian cancer survivors over the age of 60, recognizing the limitations in available data. (See 'Systemic menopausal symptoms or effects' above.)
•Psychosocial issues – Most patients with EOC experience some level of ongoing psychological distress. These emotional challenges may persist for years after diagnosis. Depression and anxiety are common in ovarian cancer survivors. (See 'Psychiatric and psychosocial issues' above.)
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