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  Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 58  |  Issue : 2  |  Page : 171-178
 

Quality of life in long term survivors of cervical cancer: A cross sectional study


1 Department of Gynecological Oncology, Tata Memorial Centre, Homi Bhabha National University, Mumbai, Maharashtra, India
2 Department of Biostatistics and Clinical Research Methodology, Tata Memorial Centre, Homi Bhabha National University, Mumbai, Maharashtra, India
3 Department of Radiation Oncology, Tata Memorial Centre, Homi Bhabha National University, Mumbai, Maharashtra, India

Date of Submission31-Oct-2018
Date of Decision11-Mar-2019
Date of Acceptance25-Mar-2020
Date of Web Publication14-May-2021

Correspondence Address:
T S Shylasree
Department of Gynecological Oncology, Tata Memorial Centre, Homi Bhabha National University, Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijc.IJC_712_18

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 » Abstract 


Background: Quality of life (QOL) is an important parameter to evaluate and modify in patients treated for cervical cancer as long-term survival is excellent in early-stage and reasonably good in locally advanced stage compared to other solid cancers. The aim of the study was the cross sectional evaluation of the quality of life in survivors completing at least 3 years of follow-up after curative therapy for cervical cancer at a tertiary cancer institute.
Methods: All patients, following primary curative treatment with no evidence of recurrence and completing at least 3 years follow-up, were assessed for QOL using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-30 and its cervical cancer module (Cx24). Patients were subdivided based on the modality of treatment. Analysis was done using Kruskal-Wallis and Mann-Whitney U test.
Results: One hundred seven patients were analyzed out of the 113 patients initially included. Treated patients showed good global QOL (mean value: 84.07) and functional scores (covering all domains). In the cervical cancer module, sexual activity, sexual enjoyment, and sexual function were low in the majority of the respondents. Chronic lymphedema, symptom experience, and sexual worry were significant across all the treatment arms.
Conclusion: Cervical cancer survivors have an overall good QOL. However, certain concerns related to the sexual quality of life, symptom experience, and chronic lymphedema need to be addressed appropriately.


Keywords: Cervical cancer, long term survivors, quality of life, sexual health
Key Message Long term survivors of cervical cancer continue to largely enjoy good quality of life. However, chronic lymphadema and sexual quality of life needs to be addressed in this group of patients.


How to cite this article:
Shylasree T S, Ranade R, Kattepur AK, Kaur S, Dusane R, Maheshwari A, Mahantshetty U, Chopra S, Engineer R, Kerkar RA. Quality of life in long term survivors of cervical cancer: A cross sectional study. Indian J Cancer 2021;58:171-8

How to cite this URL:
Shylasree T S, Ranade R, Kattepur AK, Kaur S, Dusane R, Maheshwari A, Mahantshetty U, Chopra S, Engineer R, Kerkar RA. Quality of life in long term survivors of cervical cancer: A cross sectional study. Indian J Cancer [serial online] 2021 [cited 2021 Sep 25];58:171-8. Available from: https://www.indianjcancer.com/text.asp?2021/58/2/171/316112





 » Introduction Top


Cervical cancer is the commonest gynecological cancer in India accounting for 6-29% of all cancers in females.[1] Owing to the lack of organized screening programs, it continues to plague women as a major cause of cancer-related mortality. Treatment for cervical cancer depends on the clinical stage at presentation. Surgery and radiotherapy, whether utilized singly or in combination, can be associated with short and long-term side effects including urinary and anorectal symptoms, chronic pelvic pain, lymphedema, and sexual problems (namely dyspareunia, vaginal dryness, and vaginal stenosis).

A number of quality of life (QOL) tools/questionnaires exist for cervical cancer [Table 1]. The most frequently used are the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30) with its cervical cancer module (Cx24) and the Functional Assessment for Cancer Therapy (FACT) questionnaires. The EORTC questionnaire includes five functional scales, three symptom scales, a global health status/QOL scale, and six single-item measures. The multi-item scales and single-item measures are scored from 0 to 100. A high score represents a higher response level: higher the score on the functional scale signifies a high/healthy level of functioning while the same on the symptom scale signifies more symptoms or problems.
Table 1: Quality of life tools and their measurement attribute (domains)

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The aim of our study was to evaluate the QOL in cervical cancer survivors three years post-treatment and to study the effects of the various treatment modalities on QOL in them.


 » Materials and Methods Top


This was a cross-sectional study conducted in the Department of Gynecological Oncology. The study was approved by the institutional research and ethics review board (IRB) and informed consent was taken. Patients with cervical cancer stages I-III who had completed at least 3 years follow-up post therapy with no evidence of disease recurrence were included. Patients were excluded if they didn’t consent for the study or had the recurrent disease at the time of recruitment. Consecutive patients attending the outpatient clinic over 18 months were administered the questionnaire EORTC QLQ-30 and Cx24. The questionnaires were issued in three languages: English, Hindi, and Marathi. For patients who were unable to read, but could speak the language fluently, assistance was obtained from trained social workers to complete the questionnaire. A pilot study involving 10 patients each was done to validate the questionnaire in Hindi and Marathi before study commencement. There was no comparator arm in this study.

All data were tabulated and analyzed using Statistical Package for Social Sciences (SPSS) software ver. 25 (IBM, Armonk, NY; formerly SPSS Inc. Chicago, IL). The analysis was done using Mann–Whitney and Kruskal–Wallis tests and P value < 0.05 was considered significant. For continuous variables, descriptive statistics were used to calculate mean, median, and range. Frequency and percentages were used for categorical variables.


 » Results Top


A total of 113 patients (stages I-III) were initially included in the study. Six patients were excluded as complete information regarding their treatment was not available. The mean age was 50.79 years (range: 40–77 years). The most common histology was squamous cell carcinoma (93.45%). There were four treatment cohorts: radical surgery alone arm: 21 (19.6%) patients, concurrent chemoradiation (CTRT) arm: 53 (49.5%) patients, combined modality I surgery followed by adjuvant therapy arm: 17 (15.9%) patients and neoadjuvant chemotherapy (NACT) followed by radical surgery arm: 16 (15%) patients. The average time taken to complete the questionnaire was 34 minutes. Those who needed assistance took 52 minutes (average) to complete the questionnaire.

The number of women answering each question and the mean scores for each question are tabulated in [Table 2].
Table 2: Mean value of each variable in the questionnaire

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In the Cx24 questionnaire, with regards to sexual activity (Question 49: “Have you been sexually active?”), six women did not answer and 81 said they were not sexually active (having ticked “not at all” in the questionnaire). Therefore, only 20 women were sexually active. However, questions pertaining to sexual/vaginal functioning (CXSV) and sexual enjoyment (CXSXE) were answered by 85% (n = 92-93) with 75 respondents ticking the box “not at all”. In an ideal situation, questions related to CXSV and CXSXE should be answered by women who have been sexually active; interestingly, the majority of the sexually inactive women also attempted these questions.

Each variable in the questionnaire was studied individually across the four treatment arms (stated earlier) and the mean values were calculated [Table 3]. Patients undergoing NACT followed by radical surgery were excluded from further analysis since it is not the standard of care based on a randomized trial published recently.[2]
Table 3: Mean values of variables across the treatment arms (values out of 100)

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Using the Kruskal–Wallis test, the following variables were found to be significant across the treatment arms: Role functioning (RF) (P = 0.034), nausea and vomiting (NV) (P = 0.037), sexual worry (CXSW) (P = 0.039), symptom experience (CXSE) (P = 0.043), and chronic lymphedema (CXLY) (P = 0.001) [Table 4].
Table 4: Kruskal-Wallis test applied for each variable across the three treatment arms

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The above five significant variables obtained were analyzed as group pairs between the three treatment arms using the two-sided test of Mann–Whitney and Wilcoxon rank sum test.

  1. Radical surgery alone versus concurrent chemoradiation: NV (P = 0.039), CXLY (P = 0.001), and CXSW (P = 0.028) showed significance stating that nausea and vomiting, chronic lymphedema, and sexual worry were higher in surgery alone arm [Table 5]
  2. Combined modality therapy versus radical chemoradiation: A trend towards significance was noticed in CXSW (P = 0.054) [Table 6]
  3. Radical surgery alone and combined modality therapy: No variable showed significance [Table 7].
Table 5: Mann-Whitney test between radical surgery alone and chemoradiation arms

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Table 6: Mann-Whitney test between combined modality and radical chemoradiation arms

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Table 7: Mann-Whitney test between surgery alone and combined modality arms

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 » Discussion Top


This study evaluated the QOL in cervical cancer survivors 3-years post treatment using the EORTC questionnaire. Thirty-five studies (which included 5556 patients) have used the EORTC questionnaire for clinical use.[3] Recent studies have validated the same in the South Asian region.[4] Two systematic reviews; one by Tax et al.[3] and the other by Preston et al.[5] have each studied its clinical utility in detail.

The NACT arm was excluded in the study because (a) The overall numbers in the study was small for comparison between different interventions, (b) The study of the role of NACT in cervical cancers published from the same institution (referred to in the paper) did not show benefit in terms of oncological outcomes when this study was being written. So secondary outcomes like QOL takes a back seat when primary outcomes are questionable, like the role of NACT in cervical carcinoma. Hence, we decided not to compare interventions as NACT will not be the current standard of care until further studies prove otherwise.

In our study, all questions were answered satisfactorily by 90–100% of respondents barring question number 29 and 30 related to global QOL (GQOL), which had an 84% response rate. It was probably that patients found it difficult to interpret and quantify GQOL as a single-digit number. Since such questionnaires are often administered and/or answered in outpatient clinics and, knowing that varying degrees of anxiety and apprehension associated with any follow-up cancer clinic visit exists, these factors could plausibly influence the way patients interpret and answer such questions. This is also compounded by the fact that patients often travel long distances, across states to reach tertiary cancer centers, which can be physically and mentally exhausting for them. The timing and place of administering these questionnaires are important components which remain unaccounted for in the analysis in most published QOL papers. Providing sufficient time and explanation before administering the questionnaire can be considered the best clinical practice.

In the cervical cancer module, questions that were supposed to be answered only by sexually active women pertaining to sexual/vaginal functioning and sexual enjoyment were also answered by many who were sexually “inactive”. The cervical module containing 24 questions is divided into two parts: first 17 questions relate to symptoms and body image over the past one week while the remaining seven questions relate to the sexual quality of life over the past four weeks. This difference in time frame could be a source of confusion and oversight when answering but is difficult to prove in this study. This particular time frame is useful in longitudinal studies comparing the effects of treatments/interventions along with primary outcome measures. However, in cross-sectional studies, the main focus caters around identifying residual persistent symptoms and functioning in various domains. Generally, follow- up intervals after three-year recurrence-free status is between 6 and 12 months. So, QOL questions within a time frame of 6 to 12 months will help in identifying the magnitude of problems and help in resource allocation to address the issues.

Many studies have looked at functional variables in the QOL questionnaire. Studies by Pasek et al.,[6] Barnas et al.,[7] and Khalil et al.[8] have shown that role, social, and emotional functioning of patients attain varying peaks and troughs during treatment but generally regain pretreatment status towards the end of treatment completion. In our study, it was found that the functional scores were impressive (mean values of 84–95) and RF remained significantly good (P value) across the various treatment groups.

QOL is also dependent to some extent on the type of treatment received. Lymphedema often serves as a visual hallmark of cancer-related treatment, be it surgery or radiotherapy and can be objectively measured in most cases. Studies have shown that cervical cancer survivors receiving radiotherapy or undergoing surgery appear to be at risk of developing lymphedema with 75% of them being diagnosed within the first year of treatment. Beesley et al.[9] reported that in their cervical cancer patients, 73.6% developed asymptomatic lower limb swelling while 12% had clinically diagnosed lower limb lymphedema. Tada et al.[10] found that 29.8% of their cervical cancer patients developed lymphedema, which was significantly augmented by the use of adjuvant radiation (odds ratio [OR]:1.77). Another study also reported that lower limb lymphedema was proportional to the number of nodes dissected with a higher risk with pelvic nodal dissection. The authors also concluded that pelvic nodal dissection can be the sole cause of lower limb lymphedema.[11] In our study, chronic lymphedema was higher in the radical surgery alone arm in comparison to the concurrent chemoradiation arm. However, the surgical alone arm had fewer patients compared to chemoradiation alone arm. We also compared all patients undergoing surgery (with or without adjuvant therapy) with chemoradiation alone: lymphedema remained higher when surgery component was the part of treatment. Therefore, radical surgery remains one of the most important reasons for developing lymphedema in cervical cancer survivors. There could be various proven and hypothetical explanations for this observation. This may be related to a number of lymph nodes and lymphatics removed completely as a part of pelvic lymphadenectomy. There are, however, various templates published in literature to reduce lymphedema incidence without compromising on oncological outcomes. The second possible explanation is that physical removal of level one lymph nodes (ilio-obturator) along with lymph channels during radical surgery, not only leaves an area in the pelvis with absolutely no lymphatic drainage, it also physically disrupts the adjacent level 2 lymphatic channels (common iliac and lower para-aortic) due to inflammation leading to thrombosis, blockage, and fibrosis of open-ended adjacent lymphatics aggravating the problem. Radiation, on the other hand, leads to blocked lymphatics and lymph node basin but level two nodes are largely not disrupted to the same extent as in surgery. Lymphedema is averted to some extent by the body by the formation of lymphatic collaterals in the area, however, formation of new lymph node basin following removal is not known and also the formation of new lymphatic channels might be a delayed process compared to recanalization of existing channels. The ability to recanalize some of the existing channels along with the formation of new collateral lymphatics might lead to a lower incidence of lymphedema in nonsurgical patients. Lymphedema was higher with combined modality in our study. But it was also higher in the radical surgery group alone. The patients in this study were in a period where radiotherapy techniques offered had improved greatly. Hence, this may have had some impact on reducing lymphedema. This explanation was not explored in this study. It was just observational in nature to the time trends in practices in radiotherapy techniques.

Sexual health and QOL are affected by genital cancers. Loss of vaginal length is an important drawback of surgery in cervical cancer. Lammerlink et al.[12] reported sexual functioning in cervical cancer survivors among 20 studies. There was no difference in the ability to achieve orgasm in treated patients. The survivors had more dyspareunia compared to controls that lasted longer in those treated with radiation. The most common cause identified was a lack of lubrication. In another study by Lind et al.,[13] 34% of the cancer survivors reported ‘absence of vaginal elasticity’ compared to 14% among controls (risk ratio [RR]: 1.8) and ‘deep dyspareunia’ during sexual intercourse occurred in 17% survivors compared to 7% of controls (RR: 3.7), which was not related to the type of treatment modality administered thereby causing 33% of the survivors to have a low frequency of sexual intercourse. In our study, the sexual worry was higher in both the radical surgery alone and combined modality arms (radical surgery followed by CTRT compared to concurrent chemoradiation arm. This implies that the actual removal of the womb and a small length of the vagina might be perceived as a deterrent. Furthermore, in all groups put together, there were low scores in the sexual activity and enjoyment variables with low sexual functioning (may be a cause or effect of the above variables) implying that cancer survivors rarely resumed intercourse post therapy, even though their overall QOL was acceptable. Information on cervical cancer given to patients at the time of diagnosis (verbal or written) contains information on genital human papillomavirus (HPV) as a causative factor and the way it is acquired. Generally, such information states that virus causing it is transmitted sexually but do not contain specific information that cervical cancer is not transmitted sexually. HPV clearance following the treatment of preinvasive and invasive disease is also one of the factors for reducing recurrence. Similarly, persistent HPV infection or acquisition of new high-risk HPV infection might increase the recurrence of cancer. The above gaps in knowledge and fears compounded by the menopausal age group might act as a deterrent to resuming sexual activity even though this study did not address the above issues. However, patients have to be thoroughly counseled during follow-up regarding resumption of sexual activity and probably its benefit in the prevention of vaginal stenosis.[14] The use of vaginal brachytherapy for treatment of cervical cancer can also produce mild to moderate vaginal symptoms within 6 months of therapy ranging from 29% (grade 2) to 89% (grade 1). Severe morbidity is, however, rare (3.6%).[15] In another study, vaginal stenosis has been observed in 33.3% of treated patients.[16] A systematic review by Ye et al.[17] found that anorectal dysfunction, urinary symptoms, and lymphedema were the most common physical symptoms post therapy. Radiotherapy was presumed to be associated with worse QOL and sexual function. They found that treatment-related effects on the vagina were substantial. Younger patients reported being more anxious while elderly patients were more depressed. The domain of the sexual function is complicated and is generally affected by treatment across studies. [Table 8] depicts important cross-sectional studies evaluating QOL in cervical cancer patients.[18],[19], [20,[21],[22],[23],[24],[25],[26],[27],[28],[29],[30],[31],[32],[33]
Table 8: Important conclusions of cross-sectional studies evaluating quality of life in cervical cancer patients

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Sexual QOL scores were low for all modalities of treatment in our study. Only sexual worry was significantly more when surgery was part of the treatment. Surgical removal of the uterus might cause a sense of anxiety/worry and possibly a sense of loss of femininity. However, these theories/explanations were not explored in this study.

Strengths of our study include good compliance in answering the questionnaire, also the first study from India to evaluate QOL in long-term survivors of cervical cancer. Furthermore, standard treatment modalities that are used in day to day clinical practice are compared to one another, making it all the more relevant for QOL-related issues. A cross-sectional study, despite its limitations, may be more cost and clinically effective to assess persistent chronic problems especially in long-term survivors compared to longitudinal studies. The other limitation of the study is the absence of the age-matched control group. In the Indian subcontinent, heterogeneity, barriers, and nuances of the population in a cultural context is difficult to assess and such parameters do make the QOL difficult to measure accurately.


 » Conclusions Top


Patients who undergo treatment for cervical cancer continue to have good QOL 3 years posttreatment irrespective of the type of treatment received. They seem to be well adjusted in all domains of life. However, sexual worry, symptom experience, and chronic lymphedema continue to affect QOL of patients and are more so in women who undergo radical surgery and lymphadenectomy. Qualitative studies that incorporate interviews and thematic analysis might help explore various reasons for sexual worry and reduced sexual health. Optimizing templates for pelvic lymphadenectomy without compromising on overall survival should be looked into. Basic animal research models on surgical removal of lymphatics and lymph node basins as opposed to radiating them might throw light in the future on how recanalization of existing lymphatics and formation of new collateral lymphatics occur.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 » References Top

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]



 

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