J Cancer Surviv DOI 10.1007/s11764-016-0525-8

REVIEW

Ovarian cancer survivors’ quality of life: a systematic review D. Ahmed-Lecheheb 1 & F. Joly 1,2

Received: 12 August 2015 / Accepted: 9 February 2016 # Springer Science+Business Media New York 2016

Abstract Purpose The assessment of quality of life (QOL) among ovarian cancer (OC) patients has mainly focused on the acute phase of treatment. This systematic review examines studies measuring QOL in patients who survived OC after treatment and synthesizes results in order to assess QOL and patientreported outcome (PRO) data at long-term follow-up. Methods Articles published in English between 1990 to November 2014 were identified with the databases MEDLINE and PubMed, using the specific keywords BOC survivors^ combined with the terms, BQOL,^ Bhealth-related QOL,^ and BPROs.^ Data were reviewed for design, time since end of treatment, measurement tools, and outcomes (categorized in three topics: global QOL compared to controls, treatment sequelae, and intervention strategies). Results The initial search strategy provided 148 articles of which 31 were considered eligible. Most studies focused on epithelial OC, and only a few studies investigated survivors of ovarian germ cell tumor. More than 60 instruments of QOL measures were used in the corpus. Despite the persistence of psychological and physical symptoms, treatment sequelae, sexual problems, and fear of recurrence in some survivors, most studies demonstrated that OC survivors generally have good QOL compared to healthy women. Studies proposing interventions are lacking.

* D. Ahmed-Lecheheb [email protected]

1

U1086 INSERM, Cancers and Preventions, Center François Baclesse, 3 Avenue du General Harris, 14076 Caen, France

2

Medical Oncology Department—Clinical Research Department, Center François Baclesse—CHU Côte de nacre, Caen, France

Conclusions and Implications for Cancer Survivor OC survivors experience a wide range of sequelae that may persist for a long time and negatively impact QOL. Further large-scale research is needed to fully understand problems that have significant effects on QOL, in order to develop interventions and treatments suitable for women at need. Keywords Ovarian cancer . Survivors . Patient-reported outcomes . Quality of life

Introduction Ovarian cancer (OC) is the fourth leading cause of cancerrelated death among women in France, with 3140 deaths and new cases of 4615 estimated in 2012 [1]. There is no proven method for the prevention or early detection of ovarian cancers, and it is usually diagnosed at an advanced stage with a high risk of recurrence. Progress has been made towards prolonging patient survival, and OC responds to the new treatment protocols such as targeted therapy, effective chemotherapy, and improvements in surgery. Even though some of the patients relapse, the percentage of women living 5 years or longer after diagnosis is significant and was estimated for all stages at 44 % for patients diagnosed between 2001 and 2004 [2], a figure increasing to more than 70 % for early-stage OC, so there is a growing population of OC survivors. Moreover, OC and its treatment have significant effects on quality of life (QOL) including fatigue and the physical and functional domains [3]. QOL is a broad multidimensional concept that considers a person’s physical, social, and spiritual well-being [4]. Cancer and its treatment may impact QOL negatively in various domains of life. Patient-reported outcomes (PROs) and QOL assessment can identify OC patients most at risk for subsequent health problems. The identification of such patients can

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guide the allocation of supportive care during and after OC treatment. Therefore, PRO and QOL measures in cancer management have become particularly important throughout the different phases of a person’s cancer. Reporting of QOL in cancer-related randomized controlled trials from 1980 to 1997 increased from 1.5 to 8.2 % [5]. The QOL of patients with OC may suffer considerably during and shortly after active cancer treatment, which is why QOL assessment in OC patients has focused largely on the phase of active disease. OC studies focus on women’s symptoms and concern the active phase of treatment, while the needs and issues of long-term survivors have received less attention [6]. Furthermore, the impact of treatment such as the accumulated toxicities of chemotherapy on QOL has not been sufficiently assessed in survivors at long-term follow-up. Studies directly addressing QOL in OCSs are sparse, and little is known about the phase after cancer. A recent review was conducted to measure the social and psychological needs of OCSs including young women between December 2000 and December 2010 [7], but it did not include the other aspects of QOL. The purpose of our systematic review was to examine published literature measuring QOL in patients who survived OC after treatment and to synthesize results of studies in order to assess QOL and PRO data at long-term follow-up. The secondary aims of this review were to identify the impact of cancer and its treatment on QOL of OCSs and to help to improve the quality of QOL research in women after OC treatment. In this research, we include the two principal types of OC: epithelial ovarian cancer (EOC) and the ovarian germ cell tumor (OGCT). EOC is the most common type, representing approximately 90 % of ovarian cancers, usually with poor prognosis; the most frequent systemic treatment is based on extensive surgery combined with chemotherapy including platinum and paclitaxel (and more recently bevacizumab). OGCT is a neoplasm derived from germ cells representing about 5 % of ovarian cancers [8]. OGCT tend to occur in young women and girls (15– 30 years), making up 70 % of the OC seen in that age group. The treatments comprise fertility-sparing, conservative cytoreductive surgery followed by adjuvant chemotherapy. The introduction of combination chemotherapy, including bleomycin, etoposide, and cisplatin, into standard treatment protocols for OGCT has significantly improved the prognosis for patients diagnosed with this disease [9, 10]. Thus, considering the young age and high survival rate of these patients, the assessment of QOL in survivors of OGCT is of great importance.

Meta-analyses) statement [11]. Articles published in English between 1990 to November 2014 were identified by searches on MEDLINE, PubMed, and references from relevant articles using keywords specific to QOL and OC survivorship: Bovarian cancer survivors^ combined with the terms, Bquality of life,^ Bhealth-related quality of life,^ and Bpatient-reported outcomes.^ Inclusion criteria were (1) full-text articles in peerreviewed journals, (2) papers published in English, (3) studies involving gynecological cancer, only if data were presented separately for patients with an OC diagnosis, (4) studies involving OCSs and reporting QOL data collection as part of the study, (5) citations for review with at least one ovarian cancer, one survivor and one QOL term. Exclusion criteria were (1) studies with all patients under active treatment, (2) review articles, abstracts, and case reports from meetings, editorials, study protocols, and preclinical studies. Types of participants Adult women (age ≥ 18 years) diagnosed with ovarian cancer having completed primary treatment (surgery, chemotherapy), all stages of OC, and all types of OC. Data collection and analysis The first author (DA-L) applied the described inclusion criteria in a standardized manner for all articles identified. Studies not meeting the inclusion criteria were excluded. Potentially relevant studies were retrieved in full text and were further reviewed for eligibility by two independent reviewers (DA-L and FJ). Disagreements between the two reviewers were resolved in consensus meetings. Data were then reviewed for design, sample size, date of original data collection, time since end of treatment, method and measurements tools, and outcomes, which were categorized according to three topics: (1) global QOL of OCSs compared to control groups, (2) sequelae of treatment, and (3) intervention strategies. Measurement tools were also identified.

Results Search results

Methods Literature search and selection criteria Our systematic review was performed by the PRISMA (Preferred Reporting Items for Systematic Reviews and

Of the 148 publications that fulfilled the search criteria, 31 articles met our selection criteria and were included in this review, representing 22 unique studies. A flowchart of our selection procedure is shown in Fig. 1 [12]. The highest number of publications (6) was found in 2009. There were no publications between 1990 and 1996.

Included

Eligibility

Screening

Identification

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148 records identified through database searching

148 of records screened 117 of full-text articles excluded, with reasons

148 of full-text articles assessed for eligibility

31 of full-text articles included in systematic synthesis

n=2: Not English n=1: Study protocol n=2: Editorials n=48: Reviews n=3 Preclinical studies n=11: No QOL in article: n=31: Not ovarian cancer n=18: Ovarian cancer not separated n=1: All patients under active treatment

Fig. 1 Flow chart of MEDLINE search strategy and selection process in line with PRISMA guideline [12]

Types of ovarian cancer Most studies focused on EOC and only 5 articles (representing two studies) investigated OGCT [10, 13–16], which [13–16] represented the same study and was conducted among longterm survivors of OGCT (Tables 1 and 2).

Most studies used generic tools or combinations with specific measures to assess the relationship between treatment and specific outcomes. The questionnaires can be divided into four main groups [43, 44]: general health and physical wellbeing, disease-specific measures, symptom-specific measures, and treatment-specific measures. General health and physical well-being measures We identified one generic (SF-36, reported in 8 articles) and two cancer-specific measures: EORTC QLQ-C30, 10 articles and FACT-G, 3 articles. General cancer survivorship QOL was also measured by using the quality of life-cancer survivorship inventory (QOL-CS, 41 items, 3 articles) which focuses on the longer-term impact of cancer on QOL [45]. Disease-specific measures We identified two EORTC and FACIT ovarian cancer diseasespecific modules: the EORTC QLQ-OV 28 (reported in 7 articles) and the FACT-O (3 articles). A questionnaire developed by Ferell et al. [40] was also identified in 3 publications, the 45-item City of Hope QOL Ovarian Cancer Tool (QOLOVCA), which was initially derived from qualitative data analysis.

Study characteristics Symptom-specific measures EOC Study designs were cross-sectional (19 articles), case control (1), cohort (2), qualitative analysis (2), randomized parallel group (1), and longitudinal prospective (1). Sample sizes ranged from 33 to 1383 participants. Average age of participants ranged from 53 to 65 years. Available date of original data collection ranged from 1988 to 2012. Time since end of treatment was mentioned only in one paper (mean ≈ 2 years) [19]. The majority of articles cited the time since diagnosis of OC, which ranged from 0 to 22 years. OGCT Study designs were cross-sectional (1 article), case control (3), and qualitative description (1). Sample sizes ranged from 109 to 132 participants. Average age of participants was 36 years, and time since end of treatment was >2 years. QOL instruments In addition to collecting sociodemographic data (education, employment, civil status, etc.), the studies used a variety of QOL instruments and interview format that represented more than 60 different measurement tools (Tables 1 and 2).

The FACIT-F, which was developed to assess fatigue and anemia-related concerns in patients with cancer, was used in 4 articles. Other tools designed to measure fatigue such as the MFI-20, the FQ, and the Fatigue Rating Scale were used only once. Sexual function may be regarded as a dimension or aspect of overall QOL for which a number of dimension-specific measures have been developed and validated. There is a wide choice of tools available. The SAQ, which was originally developed to study breast cancer survivors [46], was used in 6 publications. In addition, other questionnaires were used: the CALGB Sexual Functioning Scale (reported in 2 articles) and the Sexual Self-Schema Scale (3 articles). Four articles used the MHI-17 to assess the link between cancer experience and mental health. The MHI-5 short version was used once. Anxiety and depression were assessed with several instruments; the HADS was used in 4 articles, the CES-D Scale in 3, the PTSD in 2, and the Psychological Distress Thermometer, the Stressful Life Events scale and the validated short version of the Centre for Epidemiologic Studies Depression scale only once each. The menopause-specific QOL, the gynecologic symptom scale, the gynecologic concerns abdominal pain scale, and the body image scale also were used only once. None of these questionnaires were specifically developed for ovarian cancer.

Study design

Cohort

Cross-sectional

Cross-sectional, observational

Randomized, parallel group

Longitudinal prospective

Cross-sectional

Population-based, cross-sectional, mailed

Cross-sectional postal

Ezendam et al. (2014) [17]

Teng et al. (2014) [18]

Stavraka et al. (2012) [19]

Paxton et al. (2012) [20]

Greimel et al. (2011) [21]

Mirabeaubeale et al. (2009) [22]

Stevinson et al. (2009) [23]

Stevinson et al. (2009) [24]

359

359

100

33

51

100

102

191

Sample size

Characteristics of studies conducted in OCSs

Study

Table 1

Borderline n = 51 Invasive n = 308

Borderline n = 51 Invasive n = 308

EOC

EOC

EOC

EOC, n = 86

EOC = 80 %

EOC = 95 %

Ovarian cancer type

Time since diagnosis 1.5 since diagnosis

Early-stage OC

Early-stage OC

EOC

56.2

64.6

≥5 since diagnosis

55.3

Mean 5.8 since diagnosis (range 3–15)

>2

57

52.5

57.8

EOCs = 57.8 Controls = 57.8

Median age = 59

60.2

52.1 % ≥ 5 since diagnosis

>1.5 since diagnosis

60.2

Average age of participants (years)

Time since diagnosis 3 since diagnosis (for long-term survivors n = 100)

Time since end of treatment (years)

Involvement in decision making about OC treatment, the use of CAM and about changes in lifestyle health practices is associated with better QOL for cancer survivors

Patients who used massage therapy were significantly less hopeless, as were those with strong faith and well controlled disease symptoms and treatment for adverse effects

emotional, and social well-being comparable to other survivors and controls without cancer. However, 20 % of survivors indicated the presence of long-term treatment side effects

Outcomes

QOL-OVCA

MFI-20, QLQ-C30/OV28, FACT-G. FACT-O. HADS, MAC scale, Social support questionnaire (F-SOZU) QOL-OVCA

Women reported that spirituality helped them discern meaning from their cancer experience and

Significant stressors were identified within all phases of disease. OCSs described both positive and negative effects of disease and frequently demonstrated resourcefulness and perseverance by sharing coping mechanisms and survival strategies

The majority of OCSs suffered from fatigue

FACT-G, FACT-O, FACT/GOG-NTX. The majority of survivors reported a FACIT-F, FACIT-Sp, PTSD, positive impact of cancer on their Checklist-Civilian, Beck's lives and excellent social support. Hopelessness Scale, Sexual 28.9 % of survivors reported needing Problems Related to Cancer, MHI-17, more help than was received Impact of Cancer Scale, MOS Social regarding emotional problems Support Survey, Fear of Relapse, unmet needs QOL-OVCA, Study findings underscore the Psychological Distress importance of developing Thermometer, MUIS, OCPI Final interventions that address the 4 Evaluation Form QOL domains impacted by OC and support initiating a comprehensive psycho-educational intervention earlier in the course of illness

Assessment of involvement in treatment decision making, Demographic questionnaire, CAM use, SF-36

CAM use. Beck’s Hopelessness Scale, FACIT-Sp, MHI-17, EORTC-OV28

pain scale, Impact of Event Scale (IES-R), Likert scale, CES-D scale, CAIS-15, Interpersonal Support Evaluation List, Social well, DUFSS questionnaire, SAQ, ICES, PTGI

Measurements tools (methods)

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QOL is moderately high for OCSs. Qualitative data reflect the complexity of the cancer experience

maintain hope. However, some women may experience a loss of faith after experiences with cancer

Outcomes

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Treatment-specific measures The FACT/GOG-NTX which is a reliable and valid questionnaire that assesses the impact of neuropathy on QOL was used in 6 publications. In addition to validated QOL questionnaires, Swensen et al. used unspecified QOL tools [10]. Furthermore, 5 articles used a non-cancer-specific tool to evaluate spirituality, the FACITSp scale. A Bwell-being thermometer^ for the rapid assessment of the overall subjective health of patients was used in only 1 article.

QOL-CS, a demographic sheet 52.7 Mean 5 since diagnosis OC Cross-sectional Ersek et al. (1997) [42]

152

Study design Study

Table 1 (continued)

Sample size

Ovarian cancer type

Time since end of treatment (years)

Average age of participants (years)

Measurements tools (methods)

Outcomes QOL of OCSs compared with OCSs subgroups or with females free of cancer In a longitudinal prospective study conducted in 33 EOCs, the investigators assessed QOL in long-term survivors (patients free of disease for more than 10 years since diagnosis) compared to short-term survivors (patients deceased within 5 years post-treatment). The QOL of long-term survivors was also compared to that of females from a general population survey without a history of cancer. Long-term survivors showed similar QOL scores but more dyspnea compared to short-term survivors and had QOL scores similar to women without a history of cancer [21]. Another cross-sectional observational study evaluated the physical and psychological symptoms experienced by 100 patients (86 were EOC) following completion of treatment for OC since a mean of ≈2 years. Symptoms reported in questionnaires were compared to those documented in patients’ hospital notes (hospital notes recorded at the time of follow-up visits were reviewed for study patients). Particular discordance was observed over psychological, neurological, hormonal, and sexual symptoms as well as over fatigue, insomnia, frequent urination, and weakness in extremities. In all cases, patients scored more morbidities in their questionnaires than were reported to their physicians or documented in their hospital notes. The authors concluded that the majority of women surveyed experienced persistent psychological and physical symptoms after completion of treatment that did not seem to improve over time and had a negative impact on their QOL [19]. Mirabeau-Beale et al. compared the QOL of 58 early-stage and 42 advanced-stage EOCs: time since diagnosis was >3 years. Results showed that 71 % of early-stage and 64 % of advanced-stage survivors scored above the medical outpatient norm for emotional status. Overall QOL, fatigue, hopelessness, spirituality, social support, and degree to which unmet needs were met, and use of complementary therapy did not differ between the two groups [22]. Another controlled study explored fatigue, QOL, and somatic and mental morbidity in 189 EOCs (mean time since diagnosis 6.3 years). Minimal differences were

Case-control

Case-control

Case-control

Cross-sectional

Qualitative description

Matei et al. (2009) [13]

Monahan et al. (2008) [14]

Gershenson et al. (2007) [15]

Champion et al. (2007) [16]

Swenson et al. (2003) [10]

109

132

132 Survivors 137 controls

132 Survivors 137 Controls

132 Survivors 137 controls

Sample size

OGCT

OGCT

OGCT

OGCT

OGCT

Ovarian cancer type

Mean 9.9 since diagnosis (range 2.7–18.6)

Mean 10.2 since diagnosis (range 2.7–21.3)

Mean 10.2 since diagnosis (range 2.7–21.3)

Mean 10.2 since diagnosis (range 2.7–21.3)

>2

Time since end of treatment (years)

Reproductive Concerns Scale, CAIS, DUFSS questionnaire, Family APGAR scale, SF-36. FACT/GOG-NTX. CES-D scale, PANAS, ICES telephone interview format, Integrative Cancer Experience, Sexual Self-Schema scale, SAQ, DAS, FACIT-Sp, PTGI Telephone interview: narrative responses to four semi-structured questions

35.9

35.4

SAQ. Gynecologic Symptoms Scale, Sexual Self-Schema scale, DAS

Physical well-being, FACT/GOG-NTX, Questions regarding insurance coverage, and frequency with which survivors used physical and mental health care services SF-36, FACIT-Sp. FACT/GOG-NTX, DUFSS questionnaire, IES, Stressful Life Events scale, ICES, DAS, Family APGAR scale. SAQ, Sexual Self-Schema Scale. CES-D scale, PANAS, PTGI

Measurements tools (methods)

Survivors = 35.9 Controls = 35.7

Survivors = 35.9 Controls = 35.7

Survivors = 35.9 Controls = 35.7

Average age of participants (years)

The shared meanings constructed from the narrative data provide a fuller understanding of what aspects of surviving were critically important in the lives of OGCT survivors

Clinicians may want to be especially sensitive to identifying a survivor's social support and confidence (self-efficacy) in handling issues evolving from treatment since these skills may be related to overall QOL outcomes

Women who had fertility-sparing surgery were very likely to retain menstrual function and fertility after chemotherapy. There is some increase in gynecologic symptoms and diminution in sexual pleasure, survivors tended to have stronger, more positive relationships with significant others

Compared to controls, germ cell CSs expressed more reproductive concerns and reported less sexual functioning, but they also experienced greater appreciation of life and more affective (i.e., emotional) social support

In general, OGCT survivors enjoy a healthy life compared to that of controls, despite persistent of few sequelae

Outcomes

ACSM American College of Sports Medicine, AHA American Heart Association, APGAR adaptability, partnership, growth, affection, and resolve, BIS Body Image Scale, CAIS Confidence Adjusting to Illness Scale, CALGB Cancer and Leukemia Group B, CAM complementary and alternative medicine, CES-D Center for Epidemiologic Studies-Depression, DAS Dyadic Adjustment Scale, DUFSS DukeUNC Functional Social Support, EOC epithelial ovarian cancer, EORTC QLQ-C30 European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire, EORTC-OV28 European Organization for the Research and Treatment of Cancer Ovarian Disease-Specific Module, FACIT-F Functional Assessment of Chronic Illness Therapy–Fatigue, FACIT-Sp Functional Assessment for Chronic Illness Therapy Spiritual Well-Being Scale, FACT/GOG-NTX the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group Neurotoxicity questionnaire, FACTG Functional Assessment of Cancer Therapy-General, FACT-O the Functional assessment of Cancer Therapy Ovarian disease-specific module, FOR fear of recurrence, FQ Fatigue questionnaire, FSQOLS Fox Simple Quality of Life Scale, HADS the Hospital Anxiety and Depression Scale, IBM Intimate Bond Measure; ICES Integrative Cancer Experience Scale, IES Impact of Events Scale, LSI Leisure Score Index, MAC Mental Adjustment to Cancer, MHI-17 Mental Health Inventory–17 items, MHI-5 5-item Mental Health Inventory, MOS Medical Outcomes Study, MQOL menopause-specific quality of life, MUIS Mishel Uncertainty in Illness Scale, OGCT ovarian germ cell tumor, PANAS Positive and Negative Affect Scale, PCL-C post-traumatic stress disorder checklist, PTGI Post-Traumatic Growth Inventory scale, PTSD post-traumatic stress disorder, QOL-CS Quality of Life-Cancer Survivorship inventory, QOL-OVCA Quality of Life Ovarian Cancer Tool, SAQ Sexual Adjustment Questionnaire, SF-36 36-item Short Form Survey, TPB theory of planned behavior

Study design

Characteristics of studies conducted in OGCT survivors

Study

Table 2

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observed with regard to somatic and mental morbidity, fatigue and QOL between EOCs with and without relapse, long or short follow-up time, and prognostic index status. Chronic fatigue was found in 22 %, and only body image was significantly associated with chronic fatigue in multivariable analyses. Compared to females free of cancer, EOCs showed significantly more somatic and mental morbidity, somatic complaints, use of medications, and use of healthcare services. The levels of anxiety and fatigue were also significantly higher in EOCs than in women free of cancer, whereas the levels of depression and several QOL dimensions were lower [29]. Other studies investigated QOL in non-epithelial ovarian cancer. In a case-control study, the investigators compared the late effects of treatment on physical well-being and utilization of health care resources between 132 OGCT survivors and 137 age-, race-, and education-matched controls (healthy women), (mean age ≈ 36 years for the two groups). Patients were disease-free for at least 2 years at the time of enrollment. There were no significant differences in health care utilization between the groups, but 15.9 % of survivors reported being denied health insurance versus 4.4 % of controls. These results should provide the reassurance that late toxicity from treatment is infrequent and does not impact the future general health of survivors [13]. In the same population, Monahan et al. compared QOL in long-term OGCT survivors with that of matched controls. There was no difference between survivors and controls on physical function, role performance, mental health, or depression. However, they did differ with regard to sexual and reproductive concerns and OCSs had more neuropathic symptoms. Survivors reported more post-traumatic growth, especially life appreciation, and better emotional social support and dyadic adjustment [14].

experienced a loss of faith after an episode of cancer. The authors concluded that spirituality is an important component of QOL and contributes to the process of deriving meaning from the OC experience [41]. However, a subset of survivors reported needing more help than was received regarding their emotional problems [37]. In a cross-sectional study, Ferrel and colleagues investigated psychological well-being and QOL in OCSs and concluded that healthcare professionals’ awareness of the common psychological stressors throughout the OC trajectory may allow them to identify more readily the need for support, leading to an improvement in overall QOL [40]. Another study underscored the importance of developing interventions that address the four QOL domains (physical, psychological, social, and spiritual) impacted by OC and pointed to the need to undertake a comprehensive psychoeducational intervention earlier in the course of illness [38]. Studies of this sort are important in identifying the types of variables before treatment that could be used to identify women at risk of psychosocial morbidity, given that the majority of women surveyed experienced persistent psychological symptoms following ovarian cancer treatment [19]. Furthermore, a previous study demonstrated that psychological distress was evident in a subset of early-stage OCSs [33]. A recent investigation concluded that clinical factors such as age, stage, and histology did not have any significant impact on QOL, and psychosocial factors have a larger impact on the global QOL of women with ovarian cancer than physical symptoms [18]. Few data are available for survivors of OGCT. Compared to matched controls, long-term survivors of OGCT did not differ on role performance, mental health, or depression, but they reported more post-traumatic growth, especially life appreciation, and better emotional social support and dyadic adjustment [14].

Sequelae Psychological Patients generally experience psychological problems related to cancer and treatment at diagnosis and at recurrence. Only a few studies have investigated QOL in patients who have survived more than 2 years after primary treatment [29, 32]. The first study demonstrated that in general, EOC patients without evidence of disease and with no showed impressive and inspiring resilience reported excellent psychological health and feelings of greater pleasure in life and personal relationships [32]. In contrast, the second investigation found that EOCs had considerably more somatic and mental morbidity, use of medication, and consumption of health services than age-adjusted controls [29]. In a qualitative study assessing meaning of illness and spirituality in OCSs based on 7 years of natural correspondence among OCSs and a support newsletter, analysis was based on the QOL OC instrument. Women reported that spirituality helped them discern meaning from their cancer experience and maintain hope. However, some women may have

Sexual issues and gynecological symptoms Treatments for OC may cause the early onset of menopausal symptoms such as irregular periods, hot flushes, drying, or thinning of vaginal tissues and loss of interest in sex. Problems such as vaginal dryness may become permanent and interfere with sexual activity and satisfaction. Valid questionnaires with established reliability and validity have been used to assess QOL and sexuality. The majority of EOCs experienced sexual inactivity following OC treatment [19]. Regardless of staging, sexual problems are bothersome for some EOCs [22]. In a study conducted among 58 early-stage OCSs including a majority with EOC, survivors reported good physical QOL scores and few unmet needs. However, menopausal symptoms and negative impact on sexuality were reported. Fewer than 10 % of survivors reported either an interest in sex or were sexually active and the majority of survivors reported sexual dysfunction. These results indicate the need for intervention and improved distress screening in the early-stage OC population [33]. Liavaag et al. explored sexual activity and functioning

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in 189 EOCs compared to age-adjusted controls. Among EOCs, 47 % were sexually active compared to 53 % in controls. Findings showed that sexually active EOCs reported lower levels of sexual pleasure and higher levels of sexual discomfort than controls. Sexually active EOCs were significantly more often in a paired relation and showed lower levels of fatigue and better QOL compared to inactive EOCs. Lack of interest and physical problems were significantly more common in sexually inactive EOCs compared to controls. In multivariable analyses of sexually active EOCs, premenopausal oophorectomy, having had chemotherapy, age at survey, mental health, and body image were significantly associated with sexual functioning [28]. Few data are available for patients with non-epithelial OC. In a case control study, 132 malignant OGCT survivors were compared with a matched control group of females on menstrual and reproductive outcomes, sexual functioning, and dyadic adjustment. Survivors who are continuously disease-free with minimum follow-up of 2 years were studied and their responses were compared with a matched group (i.e., age, race, and education) of healthy women. Compared with controls, survivors had significantly greater reproductive concerns, less sexual pleasure, and lower scores on the total Sexual Activity Scale Score. Although there was some increase in gynecologic symptoms and a decrease in sexual pleasure, survivors tended to have stronger, more positive relationships with significant others [15]. Other study findings demonstrated that OGCT survivors compared to controls expressed more reproductive concerns and reported significantly lower sexual functioning, primarily because they reported less sexual pleasure. Whereas survivors were not statistically different on sexual discomfort, they also experienced greater appreciation of life and more affective social support [14]. Specific research of treatment toxicity We identified only 1 recent publication that assessed the prevalence and risk factors of chemotherapy-induced peripheral neuropathy and its impact on QOL of OCSs. Of all 191 patients, 129 women who received chemotherapy more often reported having tingling hands/feet and numbness in fingers/toes; specifically, 51 % reported Ba little^ to Bvery much^ of these symptoms versus about 27 % who did not receive chemotherapy. They also reported more symptoms of fatigue, nausea/vomiting, pain, dyspnea, insomnia, and loss of appetite. The authors concluded that 51 % of OCSs who received chemotherapy experienced neuropathic symptoms that seriously affected their QOL even up to 12 years after the end of treatment [17]. Intervention strategies Physical activity There are a few data on the aspects of physical health that might influence the QOL of OCSs. Of the 31

included articles, 4 publications albeit from the same study investigated physical activity among EOCSs mainly [23–26]. In the first, the authors reported that their investigation was the first to study the association between physical activity and QOL in 359 OCSs. The findings clearly indicated that meeting public health guidelines for physical activity is positively associated with QOL [22]. OCSs who met public health physical activity guidelines reported less fatigue, peripheral neuropathy, depression and anxiety, greater happiness, and better sleep outcomes than those who did not meet them [25]. The majority of OCSs expressed interest in receiving information and participating in physical activity programs. Post-treatment, home-based walking programs were most popular overall but particularly with survivors who were currently inactive and those who were older and less educated. Considering the preferences of OCSs in the design of interventions may optimize adherence and improve outcomes in this population [24]. In their most recent publication, the authors concluded that demographic and medical variables can help identify OCSs at risk for physical inactivity, for example, older age, higher BMI, and shorter time since diagnosis and current disease [23]. Complementary and alternative medicine Complementary and alternative medicine (CAM) is used by some OC patients in the hope of a cure or an improvement in their QOL. Anderson et al. demonstrated that 80 % of 219 participants reported engaging in some form of complementary or alternative medicine since their diagnosis and 45 % reported using some form of CAM substances since their diagnosis. Fortyone percent reported consulting some form of CAM provider such as a naturopathic doctor, an acupuncturist, a chiropractor, or a massage therapist since their diagnosis. The use of CAM was associated with better QOL in cancer survivors [36]. Another study demonstrated that patients who used massage therapy were significantly less hopeless, as were those with strong faith and well-controlled disease symptoms and treatment for adverse effects [35].

Discussion This review identified the state of the research in ovarian cancer survivors’ quality of life. Our search revealed only a few studies that have focused on assessing QOL among OCS, particularly in OGCT survivors. Several studies [13, 14, 21, 22, 26, 32, 34, 37, 42] reported that the majority of OCSs were satisfied with their global QOL, despite persistent psychological and physical symptoms, treatment sequelae, sexual problems, and fear of recurrence for some survivors. Other studies conducted mainly in patients with EOC demonstrated that OCSs experienced a high level of fatigue and depression [19, 30, 33, 39] and had more somatic and mental morbidity,

J Cancer Surviv

poorer QOL, and used more medication and health services than controls [29]. OCSs reported significant QOL concerns across dimensions of physical, psychological, social, and spiritual well-being [31]. Moreover, these studies did not investigate several other factors such as socioeconomic status, ethnicity, and age at diagnosis. Lower socioeconomic status and younger age seem to pose great difficulty for regaining QOL [47, 48]. Survivors diagnosed at an older age tend to have poorer physical functioning, whereas younger age is associated with poorer emotional functioning [49]. In addition, patients who have a history of more invasive and aggressive treatments tend to report poorer QOL in the long term. Furthermore, there is little consensus about the definition of survivors, since some studies have considered as survivors those who had completed their treatment more than 2 years earlier [19], whereas others considered those whose initial diagnosis had been made more than 1 year earlier [27, 28]. The QOL concerns between these groups of patients were different. Since the difficulties experienced by women who had completed treatment some years before were different from those in the acute phase of diagnosis and treatment, these studies are difficult to compare. Studies conducted in patients with OGCT considered long-term survivors as those who had completed their treatment more than 2 years earlier [13–16]. In the research included in this review, the greatest problems needing attention and treatment were physical and psychological symptoms, treatment sequelae, and sexual problems. The physical sequelae of treatment contribute to sexual problems, while hysterectomy and abdominal scarring may distort a woman’s body image [50]. Thus, sexual inactivity and poorer sexual functioning among this population of women should be given more attention in aftercare programs. The need for interventions to prevent or remediate sexual problems in OCSs is evident. Interventions can reduce distress, hasten the resumption of routine activities, and improve social outcomes for patients at high risk of QOL morbidity [51, 52]. Research should therefore focus not only on how OC and its treatment affect the QOL of OCSs but also on developing effective interventions for these women. Research and interventions should target the QOL of OCSs and aim to reduce and alleviate distress, fear of recurrence, and sexual dysfunction [22]. In addition, care provided to patients should not be stopped when the treatment ends because many women continue to experience complaints after their cancer treatment. Some symptoms such as peripheral neuropathy are to a large extent irreversible, while others such as pain, fatigue, digestive disturbances, loss of appetite, insomnia, and psychological and sexual problems can potentially be reversed if identified early. Investigations into the financial and social difficulties are completely lacking, yet financial matters play an important role in cancer-related QOL issues, especially for patients who lose their jobs owing to the effect of cancer and its

treatment. The personal support system also needs to be evaluated. In addition, researchers should pay more attention to OGCT, which is usually diagnosed in young women and is associated with high survival rates. Little is known about the QOL of OGCT survivors and we identified only 5 publications that assessed this type of OC. For these reasons, future research should address the needs of survivors and seek to understand the impact of the disease and its treatment on the QOL of OCSs. In fact, the challenge is to translate the findings obtained in QOL research into clinical practice in order to enhance QOL of these patients, include improving physical activity, nutrition, and the use of support groups and relationships. Some research has explored the ways to improve QOL, including physical activity and the use of CAM. Although intervention groups can address cancer-related issues that enable patients to gain strength from other patients with similar experiences [53], the use of support groups and relationships has not received attention. In the research included in this review, a variety of validated tools were used to measure QOL in OCSs, but they were not always adapted to the specific problems of survivors. The development of questionnaires and scales dedicated for measuring QOL in survivors should be encouraged. The methodological limitations of the current review include the fact that we restricted the search to MEDLINE and confined our interest to articles in English. Publications in other languages were not included in the review. In addition, the pooled information was difficult to evaluate owing to the heterogeneity of patient groups (age, stages, histology, etc.), measurement methods, tools, and differences in design. Common standardized instruments should be used in the future. Furthermore, this review did not aim to assess the quality of the tools for assessing QOL.

Conclusions OCSs experience a wide range of sequelae that may persist for a long time and negatively impact the QOL of these women. Measuring QOL in OCSs is of great importance because knowledge about the impact of OC and its treatment on QOL of cancer survivors can help clinicians to choose an appropriate supportive therapy adjusted to their patients’ needs. Unfortunately, only a few studies have been conducted to assess the impact of cancer and its treatments on QOL in this population, especially for survivors of OGCT. Additionally, the studies to date have suffered from shortcomings. Further large-scale research is thus needed to fully understand QOL issues in survivors and to identify problems that have a significant impact on QOL in order to develop interventions for women at need.

J Cancer Surviv Compliance with ethical standards This article does not contain any studies with human participants or animals performed by any of the authors. Conflict of interest The authors declare that they have no conflict of interest. No significant financial support for this work was received that could have influenced its outcome.

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