Quality of life characteristics inpatients with cervical cancer

European Journal of Cancer (2012) 48, 3009– 3018

Available at www.sciencedirect.com

journal homepage: www.ejcancer.info

Quality of life characteristics inpatients with cervical cancer Vesna Bjelic-Radisic a,⇑,h, Pernille T. Jensen b,h, Karin Kuljanic Vlasic c,h, Ann-Charlotte Waldenstrom d,h, Susanne Singer e,h, Weichu Chie f,h, Andy Nordin g,h, Elfriede Greimel a,h a

Department of Obstetrics and Gynecology, Medical University of Graz, Auenbruggerplatz 14, 8036 Graz, Austria Department of Obstetrics and Gynecology, Herlev University Hospital, Copenhagen, Denmark c Department of Gynecology and Obstetrics, University Hospital Center Rijeka, Rijeka, Croatia d Department of Oncology, Sahlgrenska University Hospital, Goteborg, Sweden e Department of Social Medicine, University of Leipzig, Leipzig, Germany f Department of Public Health and Institute of Preventative Medicine, National Taiwan University, Taipei, Taiwan g East Kent Gynaecological Oncology Centre, Queen Elizabeth the Queen Mother Hospital, Margate, United Kingdom b

Available online 7 June 2012

KEYWORDS Quality of life Cervical cancer Patient-reported outcome

Aim: Annually about 500,000 women worldwide are diagnosed with cervical cancer. For many patients, young age at the time of diagnosis and a good prognosis regarding the disease imply a long life with the side-effects and sequels of various treatment options. The present study investigated the extent to which different quality of life (QoL) domains in patients during and after treatment for cervical cancer are affected according to menopausal status, treatment status and treatment modality. Methods: QoL data from 346 cervical cancer patients from 14 countries who were included in a cervical cancer module validation study of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of life Group were analysed according to menopausal status, treatment status and treatment modality. QOL was assessed using the EORTC Quality of life Questionnaire (QLQ)-C30 and the QLQ-CX24 module. Statistical analyses were performed using descriptive statistics and analysis of covariance. Results: Active treatment had the strongest negative impact on 13 different QoL domains: physical, role, emotional, cognitive, social functioning, global health/QoL, fatigue, nausea and emesis, pain, appetite loss, constipation, symptom experience and sexual enjoyment. Irradiation alone ± other therapy was associated with most symptoms of diarrhoea. Age had the most negative impact on sexual activity and the strongest positive effect on sexual worry. Abstract

⇑ Corresponding author: Tel.: +43 316 385 80504; fax: +43 316 385 13061. h

On behalf of the EORTC QoL Group.

0959-8049/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ejca.2012.05.011

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Conclusion: Our results revealed that patients with cervical carcinoma had different sideeffects with different impacts on QOL depending on the menopausal status and therapy modalities. Patients should be informed about the possibility that therapy may have a negative impact on QoL. Ó 2012 Elsevier Ltd. All rights reserved.

1. Introduction Annually, about 500,000 women worldwide are diagnosed with cervical cancer.1 Due to early detection and effective therapy the 1-year and 5-year survival rates for early disease are 87% and 71%, respectively.1–5 Treatment choices depend on tumour stage, age, comorbidities, side-effects of the therapies, patient preferences and quality of life (QoL) considerations. For many patients, young age at the time of diagnosis implies a long life with side-effects and sequels of treatment.2 Lower self-esteem, poorer body image due to the removal of uterus in young women who had not completed childbearing and negative impact on sexuality were found in several studies.6–11 Some studies show more late sequels after radiation than after surgery, namely abdomen pain, sexual and bladder problems.3 Chemotherapy in combination with other modalities improves survival rates but increases the risk of additional side-effects.3–5,12 Some studies have shown a persistent negative effect on physical and psychosocial functioning.6,7,13 Thus, discussions and planning of primary treatment should address QoL aspects. Nearly all of these studies assessed QoL without a specific QoL cervical cancer questionnaire. The present study investigated QoL in patients with cervical cancer according to menopausal status, treatment status and treatment modality using the questionnaire specific to cervical cancer patients developed by the European Organisation for Research and Treatment of Cancer Quality of life Group (EORTC QLG) EORTC Quality of life Questionnaire (QLQ)-CX24.2–14 Based on previous research we hypothesised that younger women (premenopausal and treatment-related postmenopausal patients) have lower self-esteem reflected in more sexual difficulties than postmenopausal women; that patients treated with radiotherapy have more negative impact on QoL than patients treated without radiotherapy; and that isolated surgery has the least negative impact on QoL. 2. Patients and methods

Table 1 Sociodemographic and clinical characteristics of patients (N = 346). Variable

No. of patients

Age (mean ± SD)

49.7 ± 13.28

Education Compulsory or less Postcompulsory school University level Unknown Employment Full/part/time Homemaker Unemployed Self-employed Retired Other/unknown

%

140 154 47 5

40.5 44.5 13.6 1.4

143 73 25 10 68 27

41.4 21.1 7.2 2.9 19.6 7.8

Living Alone With partner or family With others Unknown

49 277 12 8

14.2 80.0 3.5 2.3

Sexual partner Yes No Unknown

227 97 22

65.6 28.0 6.4

The International Federation of Gynecology and Obstetrics (FIGO) disease stage Stage I Stage II Stage III Stage IV Unknown

177 102 53 8 6

51.1 29.6 15.3 2.3 1.7

Treatment* Surgery Chemotherapy Radiochemotherapy Brachytherapy External beam radiation Hyperthermia

227 134 57 148 106 10

65.6 38.7 16.5 42.8 30.6 2.9

*

Some patients had more than one treatment.

phase III and phase IV of the study, sociodemographic variables and clinical characteristics were collected (Table 1).

2.1. Patients 2.2. QoL assessment Between 2003 and 2005, a total of 346 patients from 14 countries with various stages of cervical cancer were included in a cervical cancer module validation study of the European Organisation for Research and Treatment of Cancer Quality of life Group (EORTC QLG).14 In

QOL was assessed using the EORTC QLQ-C30 and the QLQ-CX24module.14,15 The EORTC QLQ-C30 (Version 3.0) consists of 30 items measuring functioning (physical, role, emotional,

V. Bjelic-Radisic et al. / European Journal of Cancer 48 (2012) 3009–3018

cognitive, and social functioning and a global health/ QoL scale) and symptoms (fatigue, nausea and emesis, pain, dyspnea, insomnia, appetite loss, constipation, diarrhoea, financial difficulties). All scales and single items range from 0 to 100. A high score for all functioning and global health/QoL scales represents a high/ healthy level of functioning/high QoL, whereas a high score for a symptom scale/item represents a high level of symptoms/problems.15 The EORTC QoL measurement strategy is to supplement the generic QLQ-C30 with disease-specific modules. In line with this strategy all patients additionally completed the EORTC QLQ-CX24 questionnaire specific to cervical cancer patients.14 The QLQ-CX24 contains 24 items summarised in three scales: symptoms experience, body image and sexual/vaginal functioning and six single items: lymphoedema, peripheral neuropa-

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thy, menopausal symptoms, sexual worry, sexual activity and sexual enjoyment.14 For the multi-item scales and single items (except for item sexual activity and sexual enjoyment) a high score is equivalent to more symptoms/problems. For the items sexual activity and sexual enjoyment, a higher score indicates fewer problems. 2.3. Statistical analysis Statistical analyses were performed using descriptive statistics and analysis of covariance. For the analysis, the patients were divided in groups according to menopausal status (premenopausal, postmenopausal, treatment-related postmenopausal), according to treatment status (on treatment, off treatment), and treatment modality: (a) surgery only, surgery + radiotherapy/ chemotherapy, no surgery, and (b) irradiation ± other

Table 2 Quality of life (QoL) score according to menopausal status. Clrel*

Premeno pause

Postmeno pause

Treat rel menopause

p

N = 95

N = 118

N = 123

Across groups

Age (mean ± SD)

41.9 ± 8.7

62.9 ± 9.8

43.2 ± 8.6

<.001

Follow up (years, mean ± SD

1.7 ± 2.5

2.8 ± 3.3

2.9 ± 3.6

.022

Stage FIGO FIGO FIGO FIGO

N (%) 55 (59.1) 26 (28.0) 9 (9.7) 3 (3.2)

53 (44.5) 38 (31.9) 26 (21.8) 2 (1.7)

67 (55.4) 37 (30.6) 14 (11.6) 3 (2.5)

.134

78.2 ± 23.3 67.6 ± 35.0 62.8 ± 27.0 80.6 ± 24.5 70.0 ± 30.9 59.8 ± 24.5

80.2 ± 20.7 73.8 ± 34.3 74.1 ± 28.2 79.1 ± 26.6 83.8 ± 29.0 63.9 ± 26.1

79.9 ± 20.3 77.9 ± 29.9 70.5 ± 27.0 85.3 ± 22.3 77.7 ± 29.7 64.0 ± 24.6

.215 .164 .358 .107 .129 .619

.168 .816 .097 .324 .393 .380

.467 .046 .032 .215 .048 .286

.012 .004 .089 .624 .004 .007

No No No No No No

42.1 ± 28.9 14.1 ± 23.6 23.7 ± 28.6

32.4 ± 29.5 10.5 ± 22.8 20.5 ± 27.0

34.4 ± 27.9 9.7 ± 19.4 23.5 ± 29.4

.360 .558 .913

.319 .994 .410

.066 .034 .514

.032 .068 .001

No No No

18.4 ± 28.9 30.2 ± 33.6 29.4 ± 34.3 19.2 ± 30.2 15.7 ± 28.0 32.5 ± 37.8

11.8 ± 22.8 27.0 ± 35.7 17.9 ± 31.2 18.5 ± 30.0 18.3 ± 32.9 12.8 ± 26.8

11.5 ± 21.9 29.4 ± 31.9 16.1 ± 28.5 15.8 ± 26.8 16.0 ± 27.7 17.4 ± 29.7

.128 .684 .040 .734 .426 .003

.702 .665 .680 .853 .206 .361

.574 .084 <.001 .844 .055 .348

.012 .356 .009 .955 .013 .001

No No Yes No No Yes

18.8 ± 13.4 29.3 ± 32.6 18.7 ± 22.1

15.1 ± 11.4 19.8 ± 24.1 24.0 ± 29.8

16.3 ± 13.7 25.4 ± 28.8 31.8 ± 27.8

.091 .480 .044

.433 .155 .515

.227 .492 .054

.006 .151 .437

No No Yes

14.5 ± 28.8 17.6 ± 29.4 29.4 ± 34.3 36.9 ± 40.1 31.8 ± 35.2 60.0 ± 36.0

13.3 ± 27.7 13.8 ± 22.3 22.4 ± 28.6 12.4 ± 26.1 9.0 ± 21.9 33.3 ± 28.4

29.1 ± 35.2 22.6 ± 28.9 31.4 ± 34.3 35.4 ± 35.9 27.3 ± 29.0 62.2 ± 31.2

<.001 .033 .392 .139 .405 .281

.256 .433 .799 .007 <.001 .057

.472 .002 .955 .631 .433 .132

.739 .010 .582 .021 .112 .804

Yes No No No No No

I II III IV

EORTC QLQ-C30 (mean ± SD) Functioning scales Physical functioning Role functioning Emotional functioning Cognitive functioning Social functioning Global health/QoL Symptoms scales Fatigue Nausea and emesis Pain Single item scales Dyspnea Insomnia Appetite loss Constipation Diarrhoea Financial Difficulties EORTC QLQ-C24 Multiitem scales Symptom experience Body image Sexual/vaginal functioning Single item scales Lymphoedema Peripheral Neuropathy Menopausal Symptoms Sexual worry Sexual Activity Sexual enjoyment *

Clinical relevance P10 points differences.

Age

Time

Stage

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treatment, no irradiation. Age, follow up time (years) and tumour stage were considered as potential confounders. Differences in age and follow up time between the groups were analysed by means of t-test or analysis of variance, respectively. Differences in stage between the groups were analysed by means of a exact chi-square test. In addition, an analysis of covariance was performed with all three group factors and age, follow-up and tumour stage as covariates; this analysis considered only main effects and covariates, not interaction terms. This was done to find out which of these factors or covariates have the strongest impact on QoL. We also tested how statistically significant results were expressed in terms of clinical relevance (difference of > 10 points).16 The institutional review board/ethics committee at the investigators’ hospitals reviewed and approved the study. Patients provided informed consent to participate in the study. 3. Results 3.1. Sample characteristics Table 1 shows clinical and sociodemographic data. The mean follow-up time was 2.5 years (SD 3.2). Patients with different stages of cancer and various therapy options were well represented. The distribution of patients was balanced with regard to menopausal status and treatment status and modality. QoL assessment showed good compliance with <3% missing values (data not shown). The sexual items were completed only by patients who were sexually active (N = 78, 22.7%). 3.2. QoL characteristics of patients according to menopausal status 28.3% of the patients were premenopausal (mean age 41.9, SD 8.7), 35.1% postmenopausal (mean age 62.9, SD 9.8) and 36.6% treatment-related menopausal (mean age 43.2, SD 8.6) (Table 2). Thirty percent of treatment-related postmenopausal women had hormone replacement therapy (HRT) compared with10% of postmenopausal women. Within these three groups, statistically significant differences were found regarding age and follow-up time (p < 0.001; p = 0.022). These two variables were considered in the analyses. Although there was no difference between groups regarding disease stage (p = 0.134), we analysed this variable because of clinical considerations. Few differences were found between the groups regarding QoL issues assessed using the EORTC QLQC30.Statistically significant and clinically relevant differences were found in two scales, appetite loss and financial difficulties with higher scores (more problems) for premenopausal women. Significant differences were more

pronounced within the EORTC QLQ-CX24 in the scales/items: sexual/vaginal functioning, lymphoedema and peripheral neuropathy. Treatment-related menopausal women reported highest scores (most problems) in sexual/vaginal functioning, lymphoedema (statistically significant and clinically relevant) and peripheral neuropathy (statistically significant) (Table 2). 3.3. QoL characteristics of patients according to treatment status At the time of QoL assessment 40.8% of all patients were in active treatment and 59.2% were in follow-up. There were no differences in age and disease stage between these two groups (p = 0.147; p = 0.333). The differences concerning the time of the diagnosis were considered in the analysis. Being in active treatment had a statistically significantly and clinically relevant negative impact on all QoL scales of EORTC QLQ-C30, except physical functioning, cognitive functioning, constipation (statistically significant) and dyspnea (Table 3). QoL data assessed with EORTC QLQ-CX24 showed higher scores for the group in active treatment compared to the followup group in symptoms experience (more symptoms, statistically significant) and sexual enjoyment (less sexual enjoyment, statistically significant and clinically relevant). Sexual/vaginal functioning showed to be better during treatment than during follow-up (statistically significant and clinically relevant). More problems with lymphoedema (statistically significant and clinically relevant) were reported by patients in follow-up (Table 3). 3.4. QoL characteristics of patients according to treatment modalities 3.4.1. Isolated surgery versus surgery plus other treatment versus no surgery About 32.4% of the patients underwent surgery only, 33% were treated with surgery and another treatment, and 34.6% were treated without surgery. Patients undergoing isolated surgery and surgery plus another treatment were statistically significantly younger than the group treated without surgery. Patients with a lower stage were operated more frequently than patients with more advanced disease (Table 4). In the follow-up time there were no differences between the three groups (analysis showed a trend towards significance, p = 0.051).We considered all three co-variables in our analysis. The main impairment on QoL was reported by patients undergoing surgery plus another treatment: negative impact was reported for the physical, cognitive and social functioning (EORTC QLQ-C30) and sexual/vaginal functioning (EORTC QLQ-C24). On the symptom scales, diarrhoea and lymphoedema were most frequently reported by this group of patients. Clinical relevant differences were found in social functioning. The

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Table 3 Quality of life (QoL) score according to treatment status. Clrel*

On treatment

Off treatment

p

N = 133

N = 193

Across groups

Age (mean ± SD)

48.8 ± 12.3

51.0 ± 14.0

Follow up (years, mean ± SD)

1.2 ± 1.6

3.6 ± 3.8

Stage FIGO FIGO FIGO FIGO

N (%) 66 (49.6) 45 (33.8) 18 (13.5) 4 (3)

105 (54.4) 51 (26.4) 34 (17.6) 3 (1.6)

75.1 ± 22.2 63.3 ± 36.6 62.4 ± 28.2 76.7 ± 26.7 68.7 ± 32.3 55.2 ± 24.1

83.2 ± 19.7 81.7 ± 27.2 75.1 ± 25.7 85.8 ± 21.7 84.3 ± 26.2 68.6 ± 23.2

.001 <.001 .001 <.001 <.001 <.001

.476 .565 .261 .030 .942 .898

.518 .793 .017 .651 .012 .436

.125 .041 .289 .835 .041 .061

No Yes Yes No Yes Yes

44.4 ± 29.0 18.2 ± 26.8 28.7 ± 29.5

29.4 ± 26.7 5.7 ± 14.5 17.2 ± 24.4

<.001 <.001 <.001

.416 .609 .436

.107 .881 .227

.168 .291 .021

Yes Yes Yes

14.9 ± 24.1 34.9 ± 33.6 35.2 ± 35.2 23.7 ± 31.3 22.9 ± 35.5 27.7 ± 35.6

11.4 ± 22.6 24.7 ± 33.1 9.4 ± 22.3 13.9 ± 26.6 12.1 ± 23.3 14.2 ± 27.9

.294 .033 <.001 .002 .011 <.001

.706 .411 .117 .435 .307 .291

.902 .993 .190 .715 .620 .001

.100 .571 .014 .669 .040 .005

No Yes Yes No Yes Yes

19.4 ± 11.6 25.2 ± 29.8 12.2 ± 21.5

14.3 ± 12.9 22.7 ± 26.9 31.5 ± 26.4

.001 .522 .001

.773 .738 .567

.571 .015 .505

.039 .396 .298

No No Yes

13.6 ± 25.4 14.1 ± 23.7 27.5 ± 31.4 25.3 ± 34.6 19.3 ± 33.0 42.3 ± 35.8

24.1 ± 35.4 21.5 ± 28.7 27.3 ± 32.8 29.1 ± 36.8 23.9 ± 28.8 63.0 ± 31.5

.012 .110 .998 .236 .106 .013

.648 .029 .842 .844 .817 .683

.269 .172 .079 <.001 <.001 .002

.608 .004 .855 .010 .182 .564

Yes No No No No Yes

I II III IV

EORTC QLQ-C30 (mean ± SD) Functioning scales Physical functioning Role functioning Emotional functioning Cognitive functioning Social functioning Global health/QoL Symptoms scales Fatigue Nausea and emesis Pain Single item scales Dyspnea Insomnia Appetite loss Constipation Diarrhoea Financial difficulties EORTC QLQ-C24 Multiitem scales Symptom experience Body image Sexual/vaginal functioning Single item scales Lymphoedema Peripheral neuropathy Menopausal Symptoms Sexual worry Sexual activity Sexual enjoyment *

Time

Age

Stage

.147 <.001

.333

Clinical relevance P10 points differences.

fewest problems with nausea and emesis (statistically significant), diarrhoea and sexual/vaginal functioning were reported by patients undergoing surgery only (statistically significant and clinically relevant). Patients without surgery reported the least impairments in emotional functioning, pain, menopausal symptoms (statistically significant) and insomnia (statistically significant and clinically relevant) (Table 4). 3.4.2. Irradiation versus no irradiation ± other treatment Overall, 190 (55%) patients underwent irradiation alone ± another treatment (Table 5). These patients were older and had more advanced disease than patients treated without irradiation (p < 0.001, p = 0.01) Followup time was significantly longer in the group without irradiation (p = 0.001). All of these three variables

(age, follow up time, stage) were considered in the analyses (Table 5). Patients treated with irradiation reported a stronger negative impact in emotional functioning, diarrhoea (statistically significant and clinically relevant) and nausea and emesis (EORTC QLQ-C30). These patients also reported statistically significant and clinically relevant more problems in sexual activity and in sexual/vaginal functioning (EORTC QLQ-CX24) compared to patients without irradiation (Table 5). In addition, we analysed which variable had the greatest impact on different domains of EORTC QLQ-C30 and EORTC QLQ-CX24 (Table 6). We included menopausal status, treatment modalities, treatment status, age, follow up time and stage. We found that active treatment had the strongest negative impact on 13 different QoL domains: physical, role, emotional, cognitive, social

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Table 4 QoL score according to surgery versus surgery + another treatment versus no surgery. Clrel*

Surgery

Surgery + other

No surgery

p

N = 110

N = 113

N = 117

Across groups

Age (mean ± SD)

47.1 ± 10.9

47.7 ± 12.1

55.0 ± 15.2

<.001

Follow up (years, mean ± SD)

2.0 ± 3.1

3.0 ± 3.2

2.6 ± 3.3

.051

Stage FIGO FIGO FIGO FIGO

N (%) 96 (87.4) 13 (11.8) 0 (0) 1 (0.9)

57(50.4) 43 (38.1) 8 (7.1) 5 (4.4)

24 (20.5) 46 (39.3) 45 (38.5) 2 (1.7)

<.001

80.8 ± 19.7 75.9 ± 30.9 66.2 ± 27.9 80.9 ± 26.0 80.4 ± 27.6 62.9 ± 24.0

75.7 ± 20.7 69.0 ± 35.4 67.7 ± 29.2 78.3 ± 26.5 71.1 ± 33.0 60.9 ± 24.7

80.7 ± 23.6 75.1 ± 33.0 74.8 ± 25.3 86.3 ± 20.3 81.6 ± 28.9 64.1 ± 26.6

.019 .053 .016 .008 .011 .151

32.8 ± 26.3 6.2 ± 14.6 23.4 ± 29.7

41.1 ± 29.5 14.6 ± 22.8 25.0 ± 27.9

33.7 ± 30.8 11.9 ± 24.8 19.5 ± 27.4

10.3 ± 22.8 34.4 ± 35.8 16.2 ± 26.8 19.2 ± 31.1 9.3 ± 23.4 19.2 ± 31.5

16.0 ± 24.9 32.4 ± 33.0 24.1 ± 33.1 19.2 ± 28.9 21.1 ± 32.3 22.3 ± 33.1

15.5 ± 13.1 22.3 ± 26.9 16.5 ± 26.3 15.8 ± 28.5 15.1 ± 25.0 29.9 ± 32.4 24.4 ± 34.9 29.7 ± 35.4 51.7 ± 38.5

I II III IV

EORTC QLQ-C30 (mean ± SD) Functioning scales Physical functioning Role functioning Emotional functioning Cognitive functioning Social functioning Global health/QoL Symptoms scales Fatigue Nausea and emesis Pain Single item scales Dyspnea Insomnia Appetite loss Constipation Diarrhoea Financial difficulties EORTC QLQ-C24 Multiitem scales Symptom experience Body image Sexual/vaginal functioning Single item scales Lymphoedema Peripheral neuropathy Menopausal symptoms Sexual worry Sexual activity Sexual enjoyment *

Age

Time

Stage

.361 .649 .036 .364 .041 .390

.647 .026 .018 .478 .096 .182

.006 .003 .005 .097 .003 .002

No No No No Yes No

.068 .022 .013

.156 .802 .318

.014 .009 .541

.066 .470 <.001

No No No

13.3 ± 23.8 21.5 ± 31.5 20.6 ± 33.1 15.8 ± 27.9 18.8 ± 30.6 17.6 ± 31.6

.252 <.001 .172 .531 .026 .261

.751 .560 .375 .575 .596 .007

.411 .097 <.001 .649 .012 .801

.017 .006 .045 .759 .194 .001

No Yes No No Yes No

17.2 ± 13.1 28.9 ± 29.9 35.8 ± 26.9

16.8 ± 12.6 21.3 ± 28.1 22.8 ± 20.7

.629 .195 .004

.577 .018 .666

.227 .737 .124

.018 .157 .703

No No Yes

26.9 ± 36.0 21.6 ± 28.1 31.1 ± 33.9 34.6 ± 36.8 20.7 ± 28.1 56.7 ± 32.5

15.8 ± 29.7 18.8 ± 27.9 21.2 ± 29.6 24.2 ± 35.5 16.8 ± 27.3 63.0 ± 29.6

.030 .365 .041 .254 .104 .470

.483 .350 .213 <.001 <.001 <.001

.306 .001 .886 .685 .289 .139

.724 .005 .124 .049 .478 .883

Yes No No No No No

Clinical relevance P10 points differences.

functioning, global health/QoL, fatigue, nausea and emesis, pain, appetite loss, constipation, symptom experience and sexual enjoyment. Postmenopausal patients reported the highest score in dyspnea and treatmentrelated menopausal women the highest score in lymphoedema. Surgery only as treatment option was associated with the highest score on insomnia and treatment with irradiation ± other therapy with the highest score of diarrhoea. Stage of disease had the strongest impact on financial difficulties and peripheral neuropathy. Age had the most negative impact on sexual activity and the strongest positive effect on sexual worry. 4. Discussion The patient sample in our study with an average age of 49.7 years (60% premenopausal) represents the

cervical cancer population very well. In our study premenopausal women reported more financial difficulties. This finding can be explained by the younger age of these patients. These patients spend more time working and are forced to change their work environment due to the disease. Park et al. reported more financial difficulties in these patients compared to the healthy population.6 Klee et al. reported in her study of 118 patients with cervical cancer that one third of all working patients suspended working for 6–24 months after the diagnosis.7 Our results and these of other studies indicate that body image was impaired due to cancer therapy and is related to age.8 Juraskova et al. found lower self-esteem, poorer body image due to the removal of the uterus in women who had not completed childbearing.9 In our study premenopausal and treatment related menopausal

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3015

Table 5 QoL score according to irradiation versus no irradiation. Clrel*

Irradiation

No irrad

p

N = 190

N = 150

Across groups

Age (mean ± SD)

53.0 ± 14.7

46.3 ± 10.4

<.001

Follow up (years, mean ± SD

3.1 ± 3.6

2.0 ± 2.8

.001

Stage FIGO FIGO FIGO FIGO

62 78 46 4

115 24 7 4

.001

78.2 ± 22.7 72.3 ± 33.7 72.7 ± 27.1 81.8 ± 24.6 77.6 ± 30.6 62.7 ± 24.9

80.3 ± 19.9 74.7 ± 32.8 65.7 ± 27.9 82.2 ± 24.4 77.8 ± 29.9 62.6 ± 25.6

.993 .967 .039 .856 .909 .554

37.1 ± 30.3 13.1 ± 23.1 22.3 ± 27.0

34.3 ± 27.5 8.2 ± 19.4 22.9 ± 30.1

14.1 ± 23.5 27.2 ± 33.4 22.4 ± 33.4 16.4 ± 28.0 21.7 ± 32.2 18.2 ± 31.4

I II III IV

EORTC QLQ-C30 (mean ± SD) Functioning scales Physical functioning Role functioning Emotional functioning Cognitive functioning Social functioning Global health/QoL Symptoms scales Fatigue Nausea and emesis Pain Single item scales Dyspnea Insomnia Appetite loss Constipation Diarrhoea Financial difficulties EORTC QLQ-C24 Multiitem scales Symptom experience Body image Sexual/vaginal functioning Single item scales Lymphoedema Peripheral neuropathy Menopausal symptoms Sexual worry Sexual activity Sexual enjoyment *

Age

Time

Stage

.801 .921 .016 .805 .007 .225

.745 .035 .028 .471 .152 .199

.045 .017 .027 .691 .012 .008

No No No No No No

.306 .044 .357

.044 .479 .138

.018 .013 .565

.156 .391 .002

No No No

12.1 ± 24.5 31.8 ± 34.2 17.7 ± 28.4 20.2 ± 30.8 9.6 ± 23.8 21.7 ± 32.9

.967 .194 .142 .251 <.001 .145

.500 .963 .173 .641 .250 .004

.497 .111 <.001 .764 .007 .946

.021 .217 .067 .844 .318 <.001

No No No No Yes No

17.6 ± 12.8 25.1 ± 29.8 33.1 ± 25.8

15.0 ± 12.8 22.9 ± 26.7 17.5 ± 24.7

.183 .410 .004

.345 .004 .854

.168 .721 .118

.060 .366 .886

No No Yes

21.5 ± 33.6 20.1 ± 27.3 25.7 ± 32.4 28.5 ± 36.0 16.6 ± 25.6 57.3 ± 31.7

16.7 ± 29.3 16.4 ± 26.8 29.3 ± 31.9 26.9.4 ± 36.0 29.7 ± 35.2 55.9 ± 36.6

.095 .883 .422 .355 .028 .811

.174 .209 .089 <.001 <.001 <.001

.277 <.001 .831 .639 .274 .121

.353 .009 .501 .070 .653 .407

No No No No Yes No

Clinical relevance P10 points differences.

women reported more sexual worry, and problems with sexual enjoyment compared to the postmenopausal group. Negative impact on sexuality across all cervical patients was found in several studies.6–8,10,11 Wenzel et al. reported that younger cervical cancer patients experience a persistent negative effect on their QoL.17 Their findings and our results underline the importance of discussing these problems, particularly with younger patients. Unsurprisingly, being in active treatment is associated with a negative effect on most QoL domains compared to being in follow-up. All domains except lymphoedema and peripheral neuropathy improved during follow-up. Lymphoedema is a risk after treatment of cervical cancer18,19 but seldom assessed and reported. Cognitive function and peripheral neuropathy worsened with time probably as a late side-effect of therapy,

especially chemotherapy. There is a lack of data in the literature on late toxicity after treatment and this need to be studied further. We found that patients treated with surgery were significantly younger than patients treated without surgery after correcting for disease stage. Reasons could be comorbidity and risk of surgery for older patients and the tendency to undertreat ‘older’ patients.20 After correcting for age and stage, to be treated with surgery plus other therapy is associated with most impairment of QoL. Especially negative effects have been observed in sexual/vaginal functioning for this group of patients. Similar to our results Hawighorst–Knapstein found in her 10-year follow-up study of cervical cancer patients that women receiving therapy in addition to surgery had more physical, sexual and global QoL problems than women who underwent surgery only.21

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Table 6 Impact of all variables on QoL domains.

EORTC QLQ C30 Functioning scales Physical functioning Role functioning Emotional functioning Cognitive functioning Social functioning Global health/QoL Symptoms scales Fatigue Nausea and emesis Pain Single item scales Dyspnea Insomnia Appetite loss Constipation Diarrhoea Financial difficulties EORTC QLQ-C24 Multiitem scales Symptom experience Body image Sexual/vaginal functioning Single item scales Lymphoedema Peripheral neuropathy Menopausal symptoms Sexual worry Sexual activity Sexual enjoyment

Menopause status

treatment status on/off

Treatment ± surgery

Treatment ± irrad

Age

p

p

p

p

p

g2

g2

g2

g2

Time g2

Stage

p

g2

p

g2

.192 .264 .566

.011 .009 .004

.003 .001 .013

.029 .038 .021

.092 .179 .254

.016 .012 .009

.438 .408 .680

.016 .002 .001

.045 .367 .350

.014 .003 .003

.901 .297 .379

<.001 .004 .003

.042 .030 .037

.014 .016 .015

.198

.011

.004

.028

.013

.030

.154

.007

.707

<.001

.023

.018

.316

.003

.116 .938

.015 <.001

.001 <.001

.040 .047

.060 .380

.019 .007

.942 .514

<.001 .001

.899 .886

.<001 <.001

.370 .907

.003 <.001

.023 .032

.018 .016

.390 .518 .629

.006 .005 .003

.002 <.001 .001

.034 .059 .040

.371 .468 .071

.007 .005 .018

.274 .211 .266

.004 .005 .004

.590 .666 .941

.001 .001 <.001

.286 .280 .452

.004 .004 .002

.355 .878 .002

.003 <.001 .032

.045 .552 .100 .912 .629 .013

.021 .004 .016 .001 .003 .030

.736 .059 <.001 .006 .009 .006

<.001 .012 .103 .025 .023 .025

.339 .005 .544 .731 .945 .327

.007 .035 .004 .002 <.001 .008

.585 .438 .199 .297 .008 .381

<.001 .002 .006 .004 .024 .003

.422 .285 .931 .489 .247 .648

.002 .004 <.001 .002 .005 .001

.569 .442 .045 .404 .159 .901

.001 .002 .014 .002 .007 <.001

.140 .031 .124 .929 .511 .002

.007 .016 .008 <.001 .001 .032

.029

.024

.005

.027

.262

.009

.007

.025

.325

.003

.847

<.001

.122

.008

.309 .902

.008 .002

.961 .002

<.001 .082

.150 .026

.013 .060

.240 .334

.005 .008

.260 .441

.004 .005

.854 .874

<.001 <.001

.239 .433

.005 .005

.019 .088

.027 .017

.087 .339

.010 .003

.293 .237

.008 .010

.655 .547

.001 .001

.288 .452

.004 .002

.996 .031

<.001 .016

.660 .003

.001 .029

.528

.004

.925

<.001

.114

.015

.755

<.001

.971

<.001

.798

<.001

.220

.005

.110 .473 .290

.016 .005 .021

.087 .096 .023

.010 .010 .043

.272 . 598 .529

.009 .004 .011

.925 .386 .582

<.001 .003 .003

.009 .<001 .172

.025 .061 .016

.825 .522 .620

<.001 .001 .002

.028 .364 .675

.017 .003 .001

Our finding that patients treated with radiotherapy reported stronger negative effect on sexual activity and sexual/vaginal functioning than patients treated without irradiation is in line with other studies. Jensen et al. reported in a longitudinal study that sexual dysfunction persisted throughout the two years after radiation therapy.10 Schover et al. observed one year post treatment significantly more sexual problems in the radiotherapy group than in the surgery group.22 Bergmark et al. found that a ‘short vagina’ is a specific problem for cervical cancer patients, particularly after radiotherapy.23 Using the same questionnaire in a population-based survey, Korfage et al. reported worse scores for women treated with irradiation in the domains sexual/vaginal functioning than our study does.24 After correcting for age, duration of follow-up and stage of disease, we found more problems in emotional functioning, diarrhoea, nausea and emesis, in patients

treated with radiation ± other therapy compared to the patients treated without radiation. Nausea and emesis, diarrhoea were described by patients themselves as symptoms during and after brachytherapy for gynaecological cancer.7,25 Klee et al. found that diarrhoea may become a chronic symptom during two years after radiotherapy.7 Although not significant, our results are in line with the finding of Korfage et al. indicating that patients treated with radiotherapy generally have more lymphoedema and more peripheral neuropathy than patients treated without radiotherapy.2,24,26 It may be problematic to compare our results with previously published data due to different questionnaires used in other studies. Vistad et al. analysed 23 patientrated QoL studies of long-term survivors of cervical cancer, only eight of which had good methodology and this identified no study using EORTC QLQ-CX24.2

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We found 12published studies which assessed QoL with EORTC QLQ-CX24.6,14,25,27–35 Three of these studies are validation studies14,31,32 and one is a systematic review of questionnaires used in gynaecologic oncology.33 Two studies used the cervical module questionnaire for endometrial cancer patients.34,35 The strength of our study is the large sample size, the multicultural setting, the inclusion of age, duration of follow-up time and disease stage in the analyses. We used validated measures including EORTC QLQ-C30 and the EORTC QLQ-CX24. Despite the sample heterogeneity, the results indicate that the two QOL assessment tools are able to discriminate between groups of cervical cancer patients. The EORTC QLQ-CX24 showed more sensitivity for assessing the impact on QOL of this patient group than the EORTC QLQC30. This confirms the construct validity of the instrument and underlines the necessity of using a disease-specific questionnaire. Clinical relevance is not always identical with statistical significance and could be helpful for assessing various effects of disease and therapy on QoL. A limitation of the study is that we cannot exclude selection bias in that we may have included patients with more problems, or patients with problems may have been more likely to participate. In addition, our study is cross-sectional a without control group (e.g. healthy women). Our results revealed that patients with cervical carcinoma had different side-effects with different impacts on QOL depending on the menopausal status and therapy modalities. Premenopausal patients are an especially vulnerable group concerning their sexuality. Patients treated with multiple therapy had more impairments in their QoL domains than patients treated only with one therapy modality. Since different treatment modalities have different side-effects, the results of our study can be helpful for physicians and patients when planning treatment. Sexual and vaginal problems as short and long-term side-effects have to be discussed with patients before and after primary treatment. Conflict of interest statement None declared. Funding No external funding for this study was received. Acknowledgements We thank the following individuals who took part in various stages of our/the module-development process: V.M. Duric, PhD, (Australia), V. Boyadjian (Russia), T. Conroy (France), CL Graham (United Kingdom

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(UK)), B. Holzner (Austria), K. Kapp (Austria), E. Mautner (Austria), M. Stead (UK), A. Visser (The Netherlands), K. Bergmark (Sweden), C. Creutzberg (The Netherlands), C. DeSouza (Brazil), F. Fehlauer (Germany), L. Incrocci (The Netherlands), J. Routledge (UK), T. Swift (UK), D. Wydra (Poland) and HY Yun (Korea). We also thank F. Daghofer (Austria) for the statistical analyses of the data. Special thanks go to the study participants and recruiting clinicians for their time and effort. The module-development process was supported by a grant from European Organisation for Research and Treatment of Cancer (EORTC) Quality of life Group. References 1. American Cancer Society. Cancer Facts and Figures 2010. Atlanta, GA: American Cancer Society, 2010. Last accessed January 6, 2011. 2. Vistad I, Fossa SD, Dahl AA. A critical review of patient-rated quality of life studies of long-term survivors of cervical cancer. Gynecol Oncol 2006;102:563–72. 3. Peters III WA, Liu PY, Barett RJ, et al. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in highrisk early stage cancer of the cervix. J Clin Oncol 2000;18(8):1606–13. 4. Ryu HS, Chun M, Chang KH, Chang HJ, Lee JP. Postoperative adjuvant concurrent chemoradiotherapy improves survival rates for high-risk, early stage cervical cancer patients. Gynecol Oncol 2005;96:490–5. 5. Eifel PJ, Winter K, Morris M, et al. Pelvic irradiation with concurrent chemotherapy versus pelvic and para-aortic irradiation for high-risk cervical cancer: an update of radiation therapy oncology group trial (RTOG) 90–01. J Clin Oncol 2004;22:872–80. 6. Park SY, Bae DS, Nam JH, et al. Quality of life and sexual problems in disease-free survivors of cervical cancer compared with the general population. Cancer 2007;110:2716–25. 7. Klee M, Thranov I, Machin D. Life after radiotherapy: the psychological and social effects experienced by women treated for advanced stages of cervical cancer. Gynecol Oncol 2000;2000(76): 5–13. 8. Kullmer U, Stenger K, Milch W, et al. Self-concept, body image, and use of unconventional therapies in patients with gynecological malignancies in the state of complete remission and recurrence. Eur J Obst Gynecol Reprod Biol 1999;1999(82):101–6. 9. Juraskova I, Burow P, Robertson R, et al. Post-treatment sexual adjustment following cervical and endometrial cancer: a qualitative insight. Psychooncology 2003;12:267–79. 10. Jensen PT, Groenvold M, Klee MC, et al. Longitudinal study of sexual function and vaginal changes after radiotherapy for cervical cancer. Int J Rad Oncol Biol Phys. 2003;56:937–49. 11. Bergmark K, Avall-Lundq E, Dickman PW, Henningsohn L, Steineck G. Patient-rating of distressful symptoms after treatment for early cervical cancer. Acta Obstet Gynecol Scand 2002;81:443–50. 12. Kirwan JM, Symonds P, Green JA, et al. A systematic review of acute and late toxicity of concomitant chemoradiation for cervical cancer. Radio ther Oncol 2008;68:217–26. 13. Lau MWM, Temperley E, Mehta S, et al. Urinary tract obstruction and nephrostomy drainage in pelvic malignant disease. Br J Urol 1995;76:565–9. 14. Greimel ER, KuljanicVlasic K, Waldenstrom A, et al. The European Organization for Research and Treatment of Cancer

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