Doktorarbeit / Dissertation, 2015, 471 Seiten
Doktorarbeit / Dissertation
LIST OF FIGURES
LIST OF TABLES
GLOSSARY OF TERMS
CHAPTER 1 - Introduction
1.1 Incidence, prognosis and treatment for gynaecological and female anorectal cancers
1.2 Cancer in Australia
1.3 Gynaecological and female anorectal cancers: Incidence, prevalence and aetiology
1.3.1 Gynaecological Cancer (GC)
1.3.2 Female Anorectal Cancers (ARC)
1.4 Treatment for cancers in the pelvic region
1.4.1 Surgery for GC (CC, VC, VUC and EC) and its side effects
1.4.2 Chemotherapy for GC and its side effects
1.4.3 Surgery for RC and AC and its side effects
1.4.4 Chemotherapy for RC and AC and its side effects
1.4.5 Pelvic radiation therapy (PRT) and its side effects
CHAPTER 2 - Vaginal changes and sexual side effects following PRT for gynaecological and female anorectal cancer patients; Psychosexual Information and support needs
2.2.1 Physical changes after pelvic radiation therapy (PRT)
2.2.2 Sexual changes after pelvic radiation therapy (PRT)
2.2.3 Psychological and quality of life (QOL) sequelae of sexual dysfunction post PRT
2.3 Rehabilitation strategies: Vaginal dilators, lubricants and pelvic floor exercises
2.3.1 Vaginal dilators
2.3.2 Other Rehabilitation Strategies: Vaginal Moisturisers, Lubricants and Pelvic Floor Muscle Exercises (Kegel)
2.3.3 Evidence regarding the impact of dilator use
2.4 Information and supportive care needs after PRT
2.4.1 Unmet needs for information and support
2.4.2 Factors impacting on information provision
2.5 Patient-clinician communication about PRT treatment-related sexual issues
2.6 Psychoeducational psychosexual interventions and resources
2.6.1 Printed materials
CHAPTER 3 - Phase I: The development of a pelvic radiation therapy psychosexual rehabilitation information booklet for women with gynaecological and anorectal cancer
3.2 Booklet development
3.2.1 Steps in developing and evaluating the booklet
3.3 Booklet development
3.5 Tailoring and acknowledging the sensitivity of the content
3.4 Ensuring rigour and quality of the booklet
CHAPTER 4 - Phase II: The pilot of the study developed pelvic radiation therapy psychosexual rehabilitation information booklet for women with gynaecological and anorectal cancer
4.2.6 Demographic and Clinical information
4.2.7 Semi- structured Telephone Interview
4.2.8 Sample size
4.2.9 Data analysis
4.3.1 Sample characteristics
4.3.2 Qualitative results
4.4.1 Pilot aims i) and ii)
CHAPTER 5 - Phase III: The randomised controlled trial of the study developed pelvic radiation therapy psychosexual rehabilitation information booklet for women with gynaecological and anorectal cancer
5.1 Aims and Research Design
5.3.2 Ethical considerations
5.3.4 Data Analysis
5.4.2 First Follow-up
5.4.3 Second Follow-up
CHAPTER 6 - Overall discussion of the information booklet randomised controlled trial findings
6.2 Primary and Secondary Outcomes
6.2.1 Primary Outcome: Adherence to rehabilitation strategies
6.3 Strengths and limitations of this study
6.4 Future Research Directions
CHAPTER 7 - Overall study conclusions
7.2 Advantages of mixed methods
7.3 Limitations of the study
7.4 Strengths of the study
7.5 Lessons learned
7.6 Clinical Implications
7.7 Future research
I certify that the work in this thesis has not been submitted for a degree nor has it been submitted as part of requirements for a degree except as fully acknowledged within the text.
I also certify that the thesis has been written by me. Any help that I have received in my research work and the preparation of the thesis itself has been acknowledged.
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Franchelle Pauline Lubotzky
For Gideon, Claire and Ash. You are the loves of my life and inspire me to be the best person I can.
I am deeply grateful, indebted and thankful to all my family, friends, and colleagues. Specifically, I would like to thank the following people:
To my primary supervisor, Dr Ilona Juraskova, thank you for your ongoing belief, encouragement, understanding, support and invaluable supervision of my work. Thank you for introducing me to this area of endeavour which lead me to where I would like to work and my development academically and as a clinician. I have gained so much from your experience and expertise. In equal measure I have learned from the way that you admirably conduct yourself. It has been a pleasure and privilege working with you throughout my candidature.
To my associate supervisor, Professor Phyllis Butow, I am truly indebted to you and grateful for your support. Thank you for your belief and help completing my PhD at critical junctures and for stepping in and providing me with invaluable advice and supervision. You were always available when I really needed you. I am so privileged and honoured to have worked with you and have learned so much in an area which I value and feel proud to be part of. I have benefited greatly from your experience, expertise and professional and caring manner in which you conduct yourself.
To my associate supervisor, Associate Professor Caroline Hunt, thank you for being available and supportive on often such short notice. You experience and expertise was invaluable to me in writing my thesis and kept me in touch with my clinical psychology roots. I thank you for this. I feel privileged to have worked with you and have learned so much from the professional and supportive manner with which you have treated me.
To my friend/research assistant/practice manager, Sue Thorpe, I cannot put in to words how invaluable your support, dedication, passion, belief, commitment, enthusiasm and care of me and this study have been. I could not have done this without you. You listened to me ad infinitum and always gave encouraging, level-headed, positive and helpful advice when I often could not see the wood from the trees. I will always appreciate how you have been and I am so grateful and indebted to you. You have gone above and beyond in your commitment to this research.
To my statistician, Anubhav Tewari, thank you for all the statistical assistance that you have given me. Thank you for your support, patience and encouraging input. Your professionalism and dependability made all the difference at very stressful and difficult times. I am so grateful and indebted to you for all the help you have given me.
To the women on the pilot and the trial, I am so grateful and thankful for your generous participation during what might have been exceedingly difficult times. Where you might not have directly have benefited by your participation. I have so much respect for you all and for everything that you go through and thank you for sharing your experiences with me.
To all the clinicians I met on the pilot and trial that so generously supported the study, thanks you. I learned so much from you and have enormous respect for you and the work that you do.
To my dear friends, Laura and Jeff, your ever present interest, support, belief in me and fun-filled times, where I could have a break from it all, sustained me through this process and through the hardest times. I am truly grateful to you both for your incredible friendship, for patching me up (in Jeff’s case) and feeding me literally and metaphorically (in Laura’s).
To Paula, Tina and David, Heather and Martin, Glenn and Michelle, Tamar and Tammy thank you for your invaluable support and encouragement and for being there through it all, both the good and the bad times.
Mom and George, you are always supportive and caring no matter what. You are so generous of yourselves and so caring and positive, thank you.
To my late father-in-law Benny, thank you for your kindness, generosity and support of me and of my booklet study. You went through so much with your health and were always stoic and dignified in the way you dealt with it. You inspired me to do this work. You were there for me helping me in ways that allowed me to care for my family and undertake my career. I will always be thankful to you for this. I’d also like to thank my mother-in-law Ella for her, generosity and care throughout this process. You have made me understand the meaning of endurance.
To Gav, thank you always listening and supporting me. I am so appreciative of how you are there for me and grateful for our relationship. It is so special to have you in my life. I am so proud of you.
To my darling sister Joyce, thank you for your belief and encouragement through the good and the hardest of times. Your support and care has been invaluable for me. Thank you for giving me the most precious gift, your time. Thanks Marc, Jas and Noa for your encouragement and support.
My darling daughter Claire, I have always known what the others say about you; you truly are an angel. Your amazing support, lack of judgment and selflessness shines through every day. I am so privileged to have you in my life. No words can describe how I feel about you and how grateful I am for our relationship.
My darling daughter Ash, (my Ror), thank you for your unwavering, positive uplifting support and care. Thanks for your understanding, for listening, and for always being there for me through thick and thin. I could not have done this without your backing and belief in me. No words can convey how truly thankful and grateful I am for our relationship. You are so special, kind and loyal.
To my extraordinary partner Gideon, there are no words to describe or convey how thankful I am for your love, care, patience, help, understanding and encouragement. You always believed in me. I am eternally grateful and indebted to you. I am so lucky and blessed to have you as my partner and best friend. You truly are a very special person.
Figure 1: The female reproductive system
Figure 2: EBRT of the pelvis
Figure 3: Vaginal cylinder applicator
Figure 4: Side view of tandem and ovoids placed in a patient
Figure 5: Radiation applicators
Figure 6: Radiation applicators
Figure 7: X-ray of inserted radiation application rods
Figure 8: Lymphoedema post ovarian cancer surgery and lymph node resection
Figure 9: Post- PRT Dilator use Determinants based on the Health Behaviour Model
Figure 10: Replens, an example of a vaginal moisturiser
Figure 11: Sylk an example of personal lubricant
Figure 12: Examples of booklet pages
Figure 13: The Two Recruitment Pathways for the Pilot of the Information Booklet (Phase II of the study)
Figure 14: Randomised Controlled Trial Procedure
Figure 15: Recruitment sample and data collection overview
Figure 16: Prevalence of Selected Psychological Status and Sexual Function Outcomes - Overall Sample
Figure 17: Prevalence of Selected Psychological Status and Sexual Function Outcomes - Control Group
Figure 18: Prevalence of Selected Psychological Status and Sexual Function Outcomes - Intervention Group
Figure 19: Prevalence of Selected Psychological Status and Sexual Function Outcomes - Overall Sample
Figure 20: Prevalence of Selected Psychological Status and Sexual Function Outcomes - Control Group
Figure 21: Prevalence of Selected Psychological Status and Sexual Function Outcomes - Intervention Group
Table 1: International Guidelines on Levels of Evidence for Vaginal Dilation after Pelvic Radiotherapy
Table 2: Identified published resources (see reference list)
Table 3: Proposed components to facilitate effective post-treatment sexual adjustment
Table 4: Practical suggestions to facilitate positive adjustment
Table 5: Structure and Content of the Information Booklet
Table 6: The C.R.E.D.I.B.L.E. criteria (O’Connor et al., 2003, p. 327)
Table 7: Demographic and clinical characteristics and descriptive statistics of the Sample (N = 20)
Table 8: Descriptive statistics of the Sample (N = 20) on the HADS and IES-R
Table 9: Descriptive statistics of the Sample (N = 20) on the FSFI
Table 10: Women’s Knowledge of Information Contained in the Booklet on the Knowledge Scale
Table 11: Women’s Feedback on the Information Booklet on the Feedback Scale
Table 12: Overview of pilot study, RCT baseline and follow up measures
Table 13: Computational details of scores derived from the Adherence Scale
Table 14: Structure of the Adherence Scale Extracted from the Pattern Matrix by Principal Component Analysis with Direct Oblimin Rotation and Kaiser Normalization
Table 15: Conceptual and Operational Definitions of Three Proposed Subscales
Table 16: Pearson’s Correlation Matrix
Table 17: Computational details of the score derived from the Knowledge Scale
Table 18: Computational details of the score derived from the Feedback Scale
Table 19: Avoidance and Intrusion score estimation
Table 20: Demographic Characteristics of Participants (N=82)
Table 21: Clinical Characteristics of Participants (N=82)
Table 22: HADS Scores
Table 23: IES-R Scores
Table 25: SVQ Scores by Group Membership
Table 26: Adherence Scale Responses - Vaginal Dilator Use - First Follow Up
Table 27: Adherence Scale Responses - Vaginal Moisturiser Use - First Follow Up
Table 28: Adherence Scale Responses - Pelvic Floor Muscle Relaxation Exercises Use - First Follow Up
Table 29: Adherence Scale Scores - First Follow Up
Table 30: Knowledge Scale Responses - First Follow Up
Table 31: Knowledge Scale Score - First Follow Up
Table 32: Feedback Scale Responses - First Follow Up
Table 33: Feedback Scale Score - First Follow Up
Table 34: HADS Scores - First Follow Up
Table 35: IES-R Scores - First Follow Up
Table 36: SVQ Scores - First Follow Up
Table 37: SFAGIS Item Responses - First Follow Up
Table 38: Prevalence and Relative Risk of Selected Psychological Status and Sexual Function Outcomes - Overall Sample
Table 39: Prevalence and Relative Risk of Selected Psychological Status and Sexual Function Outcomes - Control Group
Table 40: Prevalence and Relative Risk of Selected Psychological Status and Sexual Function Outcomes - Intervention Group
Table 41: Full Regression Model for Intimacy
Table 42: Final Regression Model for Intimacy
Table 43: Full Regression Model for Sexual Interest
Table 44: Final Regression Model for Sexual Interest
Table 45: Full Regression Model for Worries About Sex Life
Table 46: Final Regression Model for Worries About Sex Life
Table 47: Full Regression Model for Anxiety
Table 48: Final Regression Model for Anxiety
Table 49: Full Regression Model for Depression
Table 50: Final Regression Model for Depression
Table 51: Full Regression Model for IES-R
Table 52: Final Regression Model for IES-R
Table 53: Adherence Scale Responses - Vaginal Dilator Use - Second Follow Up
Table 54: Adherence Scale Responses - Vaginal Moisturiser Use - Second Follow Up
Table 55: Adherence Scale Responses - Pelvic Floor Muscle Relaxation Exercises Use - Second Follow Up
Table 56: Adherence Scale Scores - Second Follow Up
Table 57: Knowledge Scale Responses - Second Follow Up
Table 58: Knowledge Scale Score - Second Follow Up
Table 59: Feedback Scale Responses - Second Follow Up
Table 60: Feedback Scale Score - Second Follow Up
Table 61: HADS Scores - Second Follow Up
Table 62: IES-R Scores - Second Follow Up
Table 63: SVQ Scores - Second Follow Up
Table 64: SFAGIS Item Responses - Second Follow Up
Table 65: Prevalence and Relative Risk of Selected Psychological Status and Sexual Function Outcomes - Overall Sample
Table 66: Prevalence and Relative Risk of Selected Psychological Status and Sexual Function Outcomes - Control Group
Table 67: Prevalence and Relative Risk of Selected Psychological Status and Sexual Function Outcomes - Intervention Group
Table 68: Full Regression Model for Intimacy
Table 69: Final Regression Model for Intimacy
Table 70: Full Regression Model for Sexual Interest
Table 71: Final Regression Model for Sexual Interest
Table 72: Full Regression Model for Anxiety
Table 73: Final Regression Model for Anxiety
Table 74: Full Regression Model for Depression
Table 75: Final Regression Model for Depression
Table 76: Full Regression Model for IES-R
Table 77: Final Regression Model for IES-R
Table 78: Full Regression Model for Use and frequency of use of Dilator Score
Table 79: Final Regression Model for Use and frequency of use of Dilator Score
Table 80: Full Regression Model for Use and frequency of use of Moisturiser Score
Table 81: Final Regression Model for Use and frequency of use of Moisturiser Score
Table 82: Full Regression Model for Use and frequency of use of PFME Score
Table 83: Final Regression Model for Use and frequency of use of PFME Score
Table 84: Full Regression Model for Knowledge Score
Table 85: Final Regression Model for Knowledge Score
Table 86: Full Regression Model for Feedback Score
Table 87: Final Regression Model for Feedback Score
Table 88: Full Regression Model for Intimacy
Table 89: Final Regression Model for Intimacy
Table 90: Full Regression Model for Sexual Interest
Table 91: Final Regression Model for Sexual Interest
Table 92: Full Regression Model for Anxiety
Table 93: Final Regression Model for Anxiety
Table 94: Full Regression Model for Depression
Table 95: Final Regression Model for Depression
Table 96: Full Regression Model for IES-R
Table 97: Final Regression Model for IES-R
Table 98: Comparisons of current findings with those of other studies for posttraumatic stress/psychological distress, anxiety, depression, and sexual activity, function and satisfaction
The present study entailed the development (Phase I), pilot (Phase II) and randomised controlled trial (RCT) (Phase III) of a psychosexual information booklet for women undergoing pelvic radiation therapy (PRT) for gynaecological or anorectal cancer. This was undertaken due to the high prevalence of psychosexual morbidity following PRT, and the lack of existing resources to facilitate recovery and reduce distress.
The psychosexual information booklet was developed based on the literature, input from an expert multi-disciplinary advisory group, and published standards in developing information materials for cancer consumers.
After the booklet development, a mainly qualitative retrospective pilot study was conducted which explored: a) women’s experiences and rehabilitation informational needs following PRT; b) the feasibility and acceptability of providing women with an information booklet about radiation-induced side effects potentially affecting recovery, and especially sexual functioning/vaginal changes; and c) assessed the acceptability of a measurement protocol that would be used in a later RCT. The pilot highlighted many challenges to quality of life faced by women after PRT, and revealed diverse informational needs, particularly regarding sexual rehabilitation. Overall, the pilot findings provided support for the provision of a psycho-educational resource to better support women in physical and psychosexual rehabilitation following PRT, as well as some guidance regarding improving the format of the booklet. The pilot booklet was revised based on participant feedback, as well as the recent Cochrane Review (Johnson & Miles, 2010) findings regarding vaginal dilator use. Given the high levels of acceptability of the pilot psychosexual booklet, its effectiveness was then prospectively evaluated in a multicentre randomised controlled trial (RCT).
The longitudinal quantitative RCT assessed whether the psychosexual booklet improved adherence to recommended rehabilitation strategies (dilator use, vaginal lubrication and pelvic floor muscle exercises), improved knowledge, lowered levels of anxiety, depression and PRT-related psychological distress and improved sexual activity, function and satisfaction post PRT. The RCT demonstrated that the psychosexual booklet improved knowledge and vaginal dilator use. Given that women in the pilot recognised dilator use as a difficult area for them, with many patient-clinician and patient-related barriers inhibiting use, this represents an important outcome.
The clinical and psychosexual significance for women in implementing rehabilitation strategies is potentially far-reaching with regards to facilitating the detection of new and/or recurrent cancer (with dilator use), and to improving sexual and broader relationship outcomes for women, which in turn, could affect their physical and emotional wellbeing. However, the recent Cochrane Review (Miles et al., 2010) highlighted that there is a lack of evidence regarding the efficacy of dilator use which may alter dilator provision practices in the future. Further research is needed and is being undertaken in this area, which remains controversial.
Furthermore, though levels of psychological distress and sexual dysfunction were low in the present study, the booklet failed to further lower levels of PRT-related psychological distress or anxiety and depression, or to improve sexual activity/function/satisfaction. Thus other strategies may be required to improve quality of life, and reduce psychological and sexual/psychosexual morbidity post PRT/treatment for gynaecological and anorectal cancer, particularly in the subset of women who suffer more morbidity in these areas.
In summary, women experience a range of psychosexual challenges after PRT for gynaecological or anal/rectal cancer. The study psychosexual booklet appears to be useful for women in the gynaecological and anorectal post PRT setting. Women in the pilot found it to be helpful and useful and reported that it reduced distress. In the RCT it was shown to improve knowledge and vaginal dilator use. Future work is required to investigate ways in which the impact of the booklet could be enhanced to further improve women’s psychosexual outcomes.
The development, pilot and randomised controlled trial of a psychosexual rehabilitation information booklet for women undergoing pelvic radiation therapy for gynaecological or anorectal cancer
In this chapter international and Australian statistics regarding aetiology, incidence and prevalence of female pelvic cancers (cervical, endometrial, vaginal, vulvar, rectal and anal) relevant to the current study will be presented. Following this section, the treatment of these cancers will be discussed, with presentation of major treatment side effects.
An Australian Institute of Health and Welfare (AIHW, 2012) report identifies cancer as the most important cause of disease in Australia. In 2012, more than 120,700 Australians were diagnosed with cancer, of which 40% were female. This excludes basal carcinoma and carcinomas of squamous cells of the skin. In females, the most frequent cancers reported were: 14560 cases of breast cancer, 7080 cases of bowel cancer, 5070 cases of melanoma of the skin, 4650 cases of lung cancer and 2270 cases of uterine cancer (AIHW, 2012). Bowel and uterine cancers are of relevance to the current study.
The number of Australians who died due to cancer was more than 42800 in 2010. Thus 3 out of every 10 deaths were due to cancer, making cancer the second-most common cause of death after cardiovascular diseases in Australia (AIHW, 2012).
Cancer survival rates in Australia have improved over time. The 5-year survival rate for all cancers combined improved from 47% in 1982–1987 to 66% in 2006–2010. The survival outcome of Australians from cancer is generally better than people living in other countries and regions (AIHW, 2012).
The current study will focus on endometrial cancer (EC), cervical cancer (CC), vaginal cancer (VC) and vulvar cancer (VUC), which are forms of gynaecological cancer (GC). Additionally the study will focus on rectal cancer (RC) - a type of colorectal/bowel cancer (CRC) - and anal cancer (AC). Both RC and AC are cancers affecting the anorectal region and as such are termed anorectal cancers (ARC). These cancers can all be treated with pelvic radiation therapy (PRT). The above terminology will be used throughout the thesis.
Detailed worldwide and Australian incidence, prevalence and aetiology data are presented in the next section for women with gynaecological and anorectal cancer. Data on age-standardised mortality and survival rates, 5-year survival rates, diagnosis by years and burden of disease are also presented.
The term “Gynaecological Cancer“ (GCs) is a common term referring to all cancers of the female reproductive system. Specific names are given according to the organ or part of the body where they first develop. These may be ovary, uterus, cervix, vagina or vulvar. The causes of many GCs are not fully understood. However, there are a number of recognised risk factors linked with the development of one or more types of GC (Cancer Australia, 2014). These are discussed below in the sections on specific cancers.
Comprehensive global cancer estimates are given in the International Agency for Research on Cancer reports. According to its latest report, in 2002, about 19% of the estimated 5.1 million new cancer cases were GCs, and about 13 million women were living with GC up to 5-years since diagnosis across the world (Sankaranarayanan & Ferlay, 2006). GC accounts for 9.4% (4,534) of all new cancers in Australian women (AIHW, 2012). Between 1982 and 2008, there was a 54% increase in new cases of gynaecological cancer in Australia (Cancer Australia, 2012). On average, twelve women were diagnosed per day in 2008. 15,851 women were living following diagnosis in the last 5 years before 2008 (AIHW, 2012).
GC accounts for 8.7% of all cancer deaths in Australian women. Between 1982 and 2007 the mortality rate reduced by 34%; in 2007 risk of dying from GC before 85 years was 1 in 63 which lowered from 1 in 43 in 1982 (Cancer Australia, 2012).
Five-year relative survival from GC has also improved in Australia, from 59.6% in the period 1982 -1987 to 67.3% in the period 2006-2010, for pooled GCs.
Cervical Cancer (CC)
The lower, narrow part of the uterus connected with the top end of the vagina is called the cervix (American Society of Clinical Oncology, 2014).
Human Papilloma viruses (HPVs) have been found to be a causal factor in developing anogenital carcinomas (cervical and anal cancers) (National Cancer Institute, 2013; Moore-Higgs, 2007). The main risk factors for CC include smoking, high parity representing 7 or more full-term pregnancies and long-standing use of oral contraceptives (National Cancer Institute, 2013).
Globally, CC is the third most commonly identified GC and the fourth most common cause of female cancer deaths. About 9% (529, 800) of total new cancer cases and 8% (275, 100) of overall cancer deaths of women in 2008 were CC cases according to GLOBALSCAN (GLOBOCAN 2008, cited in Jemal et al., 2008). In Australia, 778 cases of CC were diagnosed in 2008. CC accounted for 17.2% of all GCs and 1.6% of all cancers and was ranked as the 13th most commonly diagnosed cancer in women.
The estimated figures for mortality from CC in developing countries were 242,000 deaths in 2008. This is more than 85% of all CC cases in the world. This high figure is ascribed to lack of early detection and screening for pre-cancerous and early stage CC, lack of HPV testing and poor access to CC vaccine which can prevent 70% of CCs (Jemal et al., 2011).
With 208 deaths in 2007, CC was the 3rd most common reason for all Australian GC deaths. CC is also ranked 18th in terms of frequency across all cancer deaths among Australian women (Cancer Australia, 2012).
In Australia, between 2006-2010, relative 5-year survival rates for CC were 72% (Cancer Australia, 2012). At the end of 2008, 2286 women suffered from CC over a five-year period (AIHW, 2012).
Uterine / Endometrial Cancer (EC)
Uterine cancer includes all cancers formed in the tissues of the uterus. Two types of uterine cancers occur. Endometrial cancer starts in the uterus linings and is the most common uterine cancer. Uterine sarcoma develops in the muscles or other tissues of the uterus and is a rare cancer. (National Cancer Institute, 2013).
EC mostly affects postmenopausal women. The risk factors of EC are: postmenopausal oestrogen treatment, a high-fat diet, obesity, reproductive factors like nulliparity (never carried a pregnancy to term), polycystic ovarian syndrome, early menarche and late menopause and use of Tamoxifen. In contrast with the general population, markedly higher risk of EC is observed among women with hereditary nonpolyposis colorectal cancer syndrome (National Cancer Institute, 2013).
Estimated new cases worldwide in 2008 were 287,100 (American Cancer Society, 2011). EC is the most common invasive GC in Australia, with the incidence rising with an aging population and growing rates of obesity (Cancer Australia, 2009). In 2010, EC became the most frequently identified cancer in women with a mean of 6 females diagnosed per day (Cancer Australia, 2012). In 2008, EC accounted for 44.5% of all GCs and 4.2% of all cancers in women. (AIHW, 2012). Between 1982-2008 new cases of EC more than doubled and the incidence grew by 22%, with the greatest rise in incidence being in women 50 years and older (ranging from 19-26%)(Cancer Australia, 2012).
With 338 deaths in 2007, EC was ranked the 2nd most common cause of GC death in Australia. Out of all GC deaths, 22.5% was due to EC. Causing 2% of all cancer deaths, EC occupied the 14th rank in all cancer deaths among Australian women.
Between 2006 -2010, relative 5-year survival rate for EC in Australia was 82%, which is the highest of all individual GC types (AIHW, 2012). Overall, improvement in 5-year survival rate was 75% during 1982-1987 to 82% during 2006-2010 (AIHW, 2012). An AIHW report (AIHW, 2012) reported that 7944 of all females living at the end of 2008 were diagnosed with EC in the preceding five years (AIHW, 2012).
Vaginal Cancer (VC)
Any kind of cancer that forms in the tissues of the vagina is considered vaginal cancer (National Cancer Institute, 2014). They are rare tumours as only about 1% of all GC cancers are vaginal cancer. (National Cancer Institute, 2014). There are two primary types of VC. They are squamous-cell carcinoma (85%) and adenocarcinoma (in women 30 years and younger) (5-10%) (National Cancer Institute, 2014). There is an uncommon form of adenocarcinoma, which is related to in utero exposure to Di-Ethyl-Stilbestrol (DES).
Given the rarity of vaginal cancer statistical information is limited. The current available worldwide and Australian data are presented below.
In Australia, there were 70 cases of VC identified in 2008. VC ranked as the 38th most frequently diagnosed cancer in women, accounting for 1.5% of all GCs and .01% of all cancers in females (AIHW, 2012).
VC was the 5th most common cause of Australian GC deaths, with 26 deaths in 2007 (AIHW, 2012). VC is ranked 25th in frequency across all cancer deaths in Australian women (AIHW, 2012).
In Australia, between 2006-2010, relative 5-year survival rates for VC were 45% (AIHW, 2012). At the end of 2008, the 5-year prevalence rate of VC in women was 202 in Australia (AIHW, 2012).
Vulvar Cancer (VUC)
The immediately exterior area of vagina is the vulva. The vulva includes the tissues of the mons pubis, labia, clitoris, Bartholin glands, and perineum (“Vulva”, 2014). The most common vulvar carcinoma is observed in the labia majora, accounting for about 50% of cases. The less frequent occurrence in the labia minora accounts for about 15-20% of vulvar carcinoma cases. The least frequent sites are the clitoris and the Bartholin glands areas (Macnab et al., 1986). Squamous cell cancers are observed in about 90% of vulvar carcinomas (Eifel et al., 1997). The precursors of invasive squamous cell cancers could be some Vulvar Intra-epithelial Neoplasias (VIN) as reported by the National Cancer Institute (2014).
Risk factors for VUC include the following. In many cases VUC is preceded by condyloma (genital warts) or squamous dysplasia (abnormality of development). According to the current evidence, Human Papilloma Virus (HPV) could be strongly associated as a factor for causing many genital tract carcinomas (Hampl et al., 2006). Many common risk factors of cervical cancers are shared by these HPV-linked cancers also. These include: early age sexual intercourse, multiple sex partners, and history of abnormal Pap smears (Schiffman & Kjaer, 2003).
As globally VUC is rare among women (Grulich et al., 2010), there is not much statistical data available. Below the current available worldwide and Australian data are presented.
Developing countries report a higher percentage (approximately 60%) of VUC cases. About 66% of VUCs are reported among women of 70 years or more (Grulich et al., 2010).
In Australia, there were 282 cases of VUC identified in 2008 with VUC placed as the 20th most commonly diagnosed cancer in women, accounting for 6.2% of all GCs and 0.6 % of all cancers (AIHW, 2012).
VUC was the 4th most common cause of Australian GC deaths, with 65 deaths in 2007. VUC in Australia is placed 36th in frequency across all cancer deaths in women (AIHW, 2012).
In Australia, between 2006-2010 relative 5-year survival rates for VUC were 71% (AIHW, 2012). The 5-year prevalence rate at the end of 2008 for women with VUC was 1,034 in Australia (AIHW, 2012).
Colorectal Cancer (CRC)
CRC (which is also known as colon cancer, rectal cancer or bowel cancer) develops in the colon or rectum (parts of the large intestine). Risk of CRC is doubled in cases where CRC was diagnosed in a first-degree relative, especially before 55 years of age. Another significant but weaker risk factor is inflammatory bowel disease. CRC can also occur in persons with genetic pre-disposition like familial adenomatous polyposis and hereditary nonpolyposis coli. However, this accounts for less than 5% of cases (National Cancer Institute, 2014). Other risk factors include: lack of physical activity, overweight, obesity, smoking, consumption of red and processed meat and excessive consumption of alcohol (Ferrari et al., 2007; Giovannucci, 2006 cited in Jemal et al., 2011).
Globally, CRC is second among the most diagnosed cancers in females. The estimated female incidence of CRC is 570,100 or 9.4% of the total global new cancer cases as reported in 2008 (GLOBOCAN, 2008 cited in Jemal et al., 2011). In NSW alone, 3,000 new colon cancer cases and 1,670 rectal cancer cases are identified annually (Cancer Institute NSW, 2013).
Worldwide, there were 288,100 estimated deaths in females from CRC in 2008. CRC death rates have declined in Western countries as a result of improved treatment, increased awareness and early detection/screening (Edwards et al., 2010; Mitry et al., 2002; Sant et al., 2001 cited in Jemal et al., 2011).
In Australia, the one year survival rate for RC is 84% (Coleman, et al., 2011). The 5-year prevalence of CRC in 2004 for females was 18,940 cases, which accounted for 13.4% of all prevalent cases (AIHW and AACR, 2010).
Rectal Cancer (RC)
The rectum is the last section of the large intestine which is nearest to the anus (National Cancer Institute, 2013). RC is a type of colorectal cancer (CRC) that forms in these tissues of rectum.
There are many risk factors for RC. Patients with personal history of CRC, first degree family history and a personal history of ovarian/endometrial/breast cancer constitute the high risk groups accounting for 23% of all CRCs (Oncolink, 2006). Other risk factors for RC are the same as those for CRC described above (National Cancer Institute, 2014).
In terms of international data, cancer of the rectum accounts for approximately 38% of CRCs diagnosed annually in the UK (O’Connor et al., 2010). Among women, CRC is the second most common cancer, of which about one-third occurs in the rectum. In 2006, there were 1,824 cases of RC in Australia, accounting for 4% of all female cancers (ACIM, 2012).
In 2006, there were 541 RC deaths in Australia (ACIM, 2012).
The 5-year survival rate estimated for women with RC for the period 2002-2008 was 66.7% in the USA (Panjari et al., 2012). With improvements in treatment, the number of RC survivors is projected to increase (Roh et al., 2009). There are no Australian data on survival rates from RC, as distinct from CRC.
Anal Cancer (AC)
The anus is the opening of the rectum (i.e. last part of the large intestine) to the outside of the body. AC is formed in tissues of the anus. (National Cancer Institute, 2014).
Human papilloma viruses (HPVs) have been found to be an important factor in developing anal cancers (National Cancer Institute, 2013; Moore-Higgs, 2007). A history of cervical cancer, vulvar or vaginal cancer and immunosuppression after organ transplant or immunosuppression related to human immunodeficiency virus (HIV) have also been linked to the development of AC (Holland, 2007)
AC is a rare cancer in the general population, with annual age-adjusted incidence rates of all types combined of less than 2 per 100,000 worldwide. For reasons only partly understood, AC incidence has been increasing over the past three decades in a number of countries (Aggarwal et al., 2013).
In 2009/2010, 194 females were diagnosed with AC in Australia, accounting for 0.4% of all cancers in females. The Australian incidence of AC has increased significantly, from less than 1 in 100,000 in 1982 to 1.5 in 100,000 in 2005 (Simpson et al., 2012).
There were 37 female deaths from AC in Australia in 2009/2010 (AIHW & AACR, 2012).
Australian 5-year survival rates range from 20% in the case of metastatic disease to 80% in the case of localised anal cancer (Grulich et al., 2010).The five-year relative survival rate increased by nearly 10% from 58.9% to 63.3% over the last 20 years (Jin et al., 2011).
This section describes common treatments administered for endometrial (EC), cervical (CC), vaginal (VC), and vulvar cancer (VC) and female anal (AC) and rectal cancer (RC) patients, with a focus on pelvic radiation therapy (PRT) which is the target treatment in the current study. Side effects of the treatments will be discussed in conjunction with the descriptions of the treatments below. Physical vaginal changes/sexual/psychosexual effects and adjustment/recovery post PRT, which are related to the target treatment for this study, will be the major focus in this section.
Gynaecological (GC) and anorectal cancers (ARC) are primarily treated with surgery, radiotherapy and chemotherapy and with various combinations thereof, for example, surgery and radiotherapy, radiotherapy and chemotherapy (called chemoradiation), or radiation alone. Neoadjuvant therapy may be given before, and adjuvant treatment may be offered after, the primary treatment (e.g. surgery), to target any microscopic disease that cannot be detected by eyesight or scans (Moore-Higgs 2007), in order to improve the outcome of patients at high risk of relapse.
The image below (Figure 1) illustrates the areas of the female reproductive system which are in the pelvic region and can be affected by PRT treatment. Areas like the bladder and rectum are also affected as they lie within the pelvic radiation field area.
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Figure 1: The female reproductive system
Reproduced with permission by Cancer Council Victoria from the booklet ‘Sexuality and Cancer’, 2007, p. 9, with illustrations by Con Stamatis.
1.4.1 Surgery for GC (CC, VC, VUC and EC) and its side effects
Surgical treatment is often the primary treatment offered to GC patients (Audette & Waterman, 2010). The treatment for CC consists of hysterectomy (removal of the whole uterus including part of the vagina) with removal of the lymph nodes if the tumour is found to be invasive. If pathological investigations reveal high risk characteristics in surgery-treated patients, radiation therapy is also done to reduce the risk of relapse (National Cancer Institute, 2013).
EC is a localized disease that can be cured usually by hysterectomy and bilateral salpingo-oophorectomy. Best results are achieved with either of the two standard treatments: hysterectomy or hysterectomy with adjuvant radiation therapy (National Cancer Institute, 2014).
Surgery alone or surgery combined with pelvic radiation is typically used to treat VC (National Cancer Institute, 2014). Stage of tumour is the determining factor of VC treatment options. In early stages, surgery and radiation therapy are more effective, but in more advanced stages, radiation therapy is the main treatment (National Cancer Institute, 2014).
Although the standard primary treatment for VUC is surgery (National Cancer Institute, 2014), high post-surgery complication rates such as wound healing problems, lymphoedema, and functional deficits have, since the 1980’s, driven the tendency towards more restricted surgery, sometimes combined with radiation therapy (Eifel et al., 1997, cited in National Cancer Institute, 2014). More commonly, radiation is an adjuvant to surgery in patients in stages III or IV of the disease (Hacker et al., 1993 cited in National Cancer Institute, 2014).
Side effects of hysterectomy and radical hysterectomy following GC include adverse vaginal changes (Brotto et al., 2008; Bergmark et al., 1999, Audette & Waterman, 2010, Carter et al., 2013) including: shortening of the upper vagina (Corney et al., 1993, Bodurka & Sun, 2006) and damage to pelvic nerves (Andersen et al., 1994; Carter et al., 2013). Sexual short and long-term effects of hysterectomy have been reported by many women (Cull et al., 1993; Lamb, 1990; Pieterse et al., 2006; Carter et al., 2013) and have been found to include: loss of sensitivity and difficulty achieving orgasm (Andersen et al., 1994), dyspareunia and vaginal bleeding (Corney et al., 1993), diminished sexual desire and interest (Greenwald et al., 2008), difficulty becoming sexually stimulated (Weijmar Schultz et al., 1991), reduced vaginal lubrication (Kylstra et al., 1991), diminished sexual satisfaction (Bukovic et al., 2008), and sudden and early menopause (Carter et al., 2011). Patients and partners undergo psychological and physical distress due to post-radical hysterectomy discomfort, which can negatively impact sexual function even though there may not be any effect on the ability to have an orgasm for women (Audette & Waterman, 2010). Infertility is also a consequence of radical hysterectomy (Stead et al., 2007).
Any cancer treatment that damages ovarian function and/or leads to the removal of the ovaries can have adverse effects on vaginal/sexual health due to hormonal deficiency (Carter et al., 2011; 2013; Schover, 2005; Tierney, 2008). Surgical menopause is distressing to deal with, firstly because it is instantaneous and often difficult to manage hormonally since oestrogen is contraindicated especially for EC patients (with ovarian removal common since it is a hormone dependant cancer) (Quinn, 2007). The sudden onset of treatment-induced menopause (also applicable for radiation and chemotherapy patients who lose ovarian function) induces many side effects. The significant effects are hot flushes, labile mood, tiredness, changes in body image, disappearance of desire for sexual acts and enjoyment, vaginal dryness, infertility and scarring (Audette & Waterman, 2010; Carter et al., 2013; Hughes, 2008).
Apart from hysterectomy, the possible other procedures for GC patients are: vulvectomy, pelvic exenteration alone or in combination with radical hysterectomy (Bodurka & Sun, 2006, Audette & Waterman, 2010). Each has its own sexual dysfunction effects. Sexual function is affected post vulvectomy due to the extraction of skin and subcutaneous fat of the labia majora and minora, clitoris, and perineal body and the regional and femoral lymph nodes (Audette & Waterman, 2010; Carter et al., 2013).
Pelvic exenteration, often used to treat recurrent disease such as cervical and vaginal cancers, includes hysterectomy, removal of the bladder, vagina, urethra and rectum and salpingo-oophorectomy, requiring ostomies for bowel and bladder function (Audette & Waterman, 2010, Carter et al., 2013). The surgery related resultant negative sexual affects include striking changes to a woman’s appearance also affecting, for instance, body-image and psychosocial functioning with a long journey to physical and psychological recovery, although often the vagina is reconstructed and the intactness of clitoris and vulva is maintained (Audette & Waterman, 2010).
GC tumours which are larger early stage or late stage are treated using radiation therapy as a pre-surgical or adjuvant treatment, or cisplatin-based chemotherapy plus hysterectomy (Quinn, 2007). Various types of chemotherapy are used in treating GC patients, both definitively and in combination with radiotherapy and surgery (Quinn, 2007). Although sometimes advocated, chemotherapy is not shown to be an effective curative method for advanced VC and there are currently no routine medication schedules for it (National Cancer Institute, 2014). Newer integrated approaches are used with VUC. These include integration of surgery, radiation therapy, and chemotherapy, suitably combined depending upon clinical and pathologic conditions. However, there are varying patterns of practice in combining these treatments (National Cancer Institute, 2014; Shylasree et al., 2011).
Fatigue is the most frequently reported and debilitating side effect of chemotherapy, as well as changes in skin, epilation (hair loss), dry mouth, taste alterations, nausea and vomiting. All these effects can play a part in later development of sexual dysfunction or sexual activity (Quinn, 2007). Other side effects of chemotherapy are anxiety, depression, awareness of changed body image and marital or partner difficulties (Carmack-Taylor et al., 2004).
As discussed in section 1.4.1, premature menopause can be caused by GC treatments, including chemotherapy (Lo Presti et al., 2004; Jensen et al., 2007). Chemically-induced menopause experienced by women, like with surgery, can be more acute and extreme than naturally occurring menopause (Audette & Waterman, 2010). Arousal and vaginal lubrication disruption (Stead et al., 2007) and both sexual desire and excitement problems (Andersen et al., 1992) are linked with premature menopause. These effects have been found to significantly diminish women’s Quality of Life (QOL) (Carter et al., 2011; 2013). Infertility can also be a consequence of chemotherapy treatment if premature menopause occurs (Molassiotis et al., 2002).
For localized RC (i.e. cancer that has not spread), the preferred treatment is complete surgical removal of the tumour with adequate margins, with the attempt of achieving a cure, although radiation and chemotherapy will often be given before or after surgery (National Cancer Institute, 2014). The surgical approach to treatment varies according to the location, stage and presence of high-risk features (e.g. positive margins). Where possible, attempts are made to preserve nerve and sphincter function; however this is not possible for all patients, leaving them with end-colostomy (permanent stoma/bag).
In abdominoperineal resection (APR), incisions are made in the abdomen and perineum and the rectum and part of the sigmoid colon along with the associated (regional) lymph nodes are removed. The last part of the remaining sigmoid colon is brought permanently to the surface of the abdomen as an opening, called a colostomy. As the quality of life generally worsens after APR, the less invasive lower anterior resection (LAR) (“Abdominoperinial resection”, 2014) is generally preferred for RC depending on its surgically feasibility.
Surgery is no longer the treatment of choice for AC (National Cancer Institute, 2014) unless there is recurrence.
In RC, chemotherapy may be used in addition to surgery in certain cases as neoadjunct (before surgery) or adjuvant (after surgery) therapy (“Colorectal cancer”, 2014; National Cancer Institute, 2014). More recently, oncologists are increasingly using an approach combining chemotherapy and radiation treatments, to reduce the necessity of performing the incapacitating AC surgery. This combined approach has increased the preservation of an intact anal sphincter helping to improve the quality of life after definitive treatment for AC patients (National Cancer Institute, 2014; “Anal cancer”, 2014).
There are many side effects of chemotherapy for rectal and anal cancer, including anaemia, bruising and bleeding, tiredness, lowered resistance to infection (neutropenia), nausea and vomiting, sore mouth, hair loss, sore/numb and/or tingling hands and feet, and diarrhea.
In radiation therapy, ionising radiation is used to damage the DNA of the exposed tissue resulting in the death of the cells (“Radiation therapy”, 2014). The success of radiation therapy depends on administering an adequate dose to the entire tumour without causing serious damage to the surrounding tissues, with the goal of achieving the highest probability of local tumour management with the least chance of side effects/toxicity (Moore-Higgs, 2007). Radiation therapy can be delivered with curative or palliative intent (Moore-Higgs, 2007), the former being the focus of the current study.
With particular relevance for the current study, combined treatment modalities (e.g. radiotherapy and chemotherapy) have been associated with not only improved survival rates, but also increases in toxicities which result in significant morbidity (Vogel, 2007; Creutzberg et al., 2000; Greimel et al., 2009).
Provision of information about PRT-induced vaginal changes, sexual acute and late effects/toxicities and available rehabilitation options represents the focus of the current thesis.
External Beam Radiation Therapy (EBRT)
The most common method of radiation therapy is EBRT. Ionising radiation is delivered either using a radioactive source or using an electromagnetic energy from a machine. This is placed at some distance from the tissue to be treated (see Figure 2). It is differentiated from brachytherapy where radioactive sources are implanted or placed internally (i.e. administered internally) (Moore-Higgs, 2007). EBRT equipment is classified according to energy produced and depth of penetration within the intended area (Moore-Higgs, 2007).
In EBRT, the first step is the planning or simulation session. In this session, marks are placed on the body and measurements are taken to direct the radiation beam in the correct position for each treatment. This is followed by a schedule of daily treatment. The patient is placed on a treatment couch and then radiation doses are applied from multiple directions to the pelvis. This allows EBRT to be done on an outpatient basis. Usually, the treatment is delivered five days a week for 4 to 6 weeks. Small amounts of radiation are administered daily rather than using fewer large doses. This enables reduction of tissue damage surrounding the tumour. Normal cells can recover during weekend rests.
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Figure 2: EBRT of the pelvis
(“External beam radiotherapy”, 2014; Health Sciences North, 2013)
Intensity-modulated Radiation Therapy (IMRT)
IMRT is a newer EBRT technique which uses numerous intensity levels via intensity-modulated beams (D’Souza et al., 2012). In these intensity-modulated beams, the direction off any single beam or placement of any single source can be varied (D’Souza et al., 2012). This enables achievement of narrow margins of both dose distributions and dose gradients. This is difficult with conventional and 3-D modes (D’Souza et al., 2012, Light, 2007). Flexibility in dose administration is achievable with IMRT and is seen as a major advance in radiation therapy since it permits higher doses to be given whilst sparing normal tissues (Light, 2007). Intensity of beams is equal irrespective of tumour thickness in conventional therapy. In IMRT, the intensity of the beam can be varied along the treatment field based on the tumour thickness. The beam is stronger where the tumour is thicker and lighter where the tumour is thinner. Thus unnecessary radiation is eliminated (Life Bridge Health, 2014).
The course of treatment in IMRT lasts five to eight weeks at the frequency of five days a week. The patient is in the treatment room for 15-30 minutes for each radiation session. Both EBRT and IMRT are painless (UCFS Medical Centre, 2014).
Further studies are evaluating IMRT for treating gynaecological cancers (D’Souza et al., 2012). IMRT is also used to treat rectal (Ng et al., 2012; Brooks et al., 2013) and anal cancers (Menkarios et al., 2007; Bazan et al., 2011).
Vaginal Brachytherapy (Internal Radiation Therapy)
Brachytherapy (brachy=Greek for short distance), also referred to as internal radiation or implant therapy, refers to the temporary or permanent placing of a radioactive source very close to or in contact with the targeted tissue (Moore-Higgs, 2007). Brachytherapy works by providing a high dose of radiation to a specific tumour volume with a quick decline in dose to bordering normal tissues (Moore-Higgs, 2007).
Brachytherapy can be combined with EBRT, surgery, or chemotherapy if required. It is used for enhancing control of local disease, and to treat high risk tumour recurrence areas, improve comfort with recurrent disease, safeguard vital organ function, and save normal surrounding tissue from damage (Moore-Higgs, 2007).
Either a High Dose Rate (HDR) or a Low Dose Rate (HDR) is possible in Brachytherapy/internal radiation. The radiation can be delivered with a vaginal cylinder applicator (see Figure 3 below and Figures 5, 6 and 7) or an applicator that treats the cervix and the uterus independently (Oncolink, 2006).
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Figure 3: Vaginal cylinder applicator
For the vaginal brachytherapy, women are treated in a lead-lined room. After positioning the cylinder properly, the radiation technician takes x-ray images or CT scans to verify the placement of the cylinder (Oncolink, 2006) (see figure 4). On calculation of the radiation dose by the physicist and radiation therapy technician the treatment machine directs the radioactive sources to the applicators for the required duration. During the process, women may feel vaginal pressure and experience marginal discomfort. If tandems and ovoids (see figures 4, 5 and 6) are used gauze packing is inserted in the vaginal vault to prevent movement of the applicators. In some cases, contrast (barium) may be inserted in the rectum using a small tube. The use of a Foley catheter and the rectal contrast facilitates x-ray examination so that the absorbed radiation dose by the bladder and rectum can be established.
Radiation exposure to others is averted by not allowing anyone into the treatment room. During this time, video cameras and two-way microphones assist monitoring the treatment. The duration of treatment time can vary from 5 to 20 minutes. After achievement of the treatment dose, the source is extracted into the HDR machine. A physicist then checks to ensure that no radioactivity exists in the woman’s body or outside the machine. Then the applicator is removed by the physician (Oncolink, 2006).
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Figure 4: Side view of tandem and ovoids placed in a patient
(Nucletron B.V., 2014)
If HDR is not appropriate, low dose rate (LDR) brachytherapy may be recommended. In LDR brachytherapy, the patient is anesthetised before the insertion of the radioactive material as in the case of HDR. However, this procedure is done under in-patient conditions varying from 2 to 3 days. During the time the radioactive source is placed vaginally, friends and family are not allowed to visit, to avoid their radiation exposure. The duty times of the nurses are also controlled for the same reason (Oncolink, 2006).
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Figure 5: Radiation applicators
(Varian Medical Systems, 2014)
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Figure 6: Radiation applicators
(Mayo Clinic Health Library, 2014)
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Figure 7: X-ray of inserted radiation application rods
(UC San Diego Moores Cancer Center, 2014)
Although radiation therapy by itself is painless, varying degrees of acute side effects are caused by higher radiation doses, usually restricted to the area of treatment. These symptoms may appear during treatment or immediately after, during the first few months or years after the treatment (the long-term or late side effects) or following the re-treatment (cumulative side effects) (Vogel, 2007). These side effects vary in their type, gravity, and permanence depending on the organs receiving the radiation, and treatment and patient factors. The radiation considerations are: type of radiation used, total dose applied and its fractionation and concurrent chemotherapy if used. These side effects can be expected and predicted.
Acute Side Effects of PRT
The main acute side effects of PRT include fatigue and skin irritation. The skin irritation is similar to moderate sunburn in some instances. The irritated skin heals, but in some instances is not as supple as before (“Radiation therapy”, 2014). The fatigue often starts during the course of treatment itself and it can last for weeks, even after the end of the treatment.
Damage to the epithelial surfaces
The area being treated may determine any damage to epithelial surfaces, such as mucosa of the skin and vagina (Incrocci & Jensen, 2013; Johnson & Miles, 2010), bowel and ureter. The renewal rate of epithelial cells determines the speed of damage and time taken for recovery. In typical situations, the skin starts to get painful and go pink many weeks after PRT treatment (“Radiation therapy”, 2014). The effect may reach its zenith during the first week after the end of radiation therapy and lasts another week leading to possible break down of the skin. In spite of the thinning and weeping of skin (moist desquamation) becoming uncomfortable, recovery is usually fast (“Radiation therapy”, 2014). In areas of the skin where there are normal creases in the skin (e.g. the groin), these reactions are worse. Swelling of soft tissues (edema or oedema) is a common inflammation condition. This sometimes causes problems during radiation therapy (“Radiation therapy”, 2014).
Almost all patients show signs of acute enteritis after radiation therapy to any one of abdomen, pelvis, or rectum (National Cancer Institute 2014 – Gastrointestinal complications Health Professional Version: Radiation Enteritis). Enteritis is the term for inflammation of the small intestine and the symptoms include abdominal pain, cramping, diarrhoea, dehydration and fever (Dugdale & Longretch, 2009; MedlinePlus Medical Encyclopedia cited in “Enteritis”, 2014; National Cancer Institute 2014).
Typical intestinal symptoms with radiation treatment to the lower bowel (e.g. in the rectal and anal cancer radiation field) and pelvic structures (e.g. female genital tract)) include diarrhoea, soreness, and nausea (“Radiation therapy”, 2014).
The sensitivity of gonads (ovaries and testicles) to radiation is very high. In women, direct exposure to most commonly applied radiation doses reduces or even stops the capacity of the ovaries to produce ovum (eggs). Therefore, in the design of treatment planning, dose to gonads is excluded or at least minimised if they are not the main treatment areas (“Radiation therapy”, 2014). Saving at least one gonad from radiation can avoid infertility (“Radiation therapy”, 2014).
Late (Post-treatment) Side Effects of PRT
Areas that have been treated may exhibit side effects for periods lasting months to years after treatment, but these side effects are usually limited to the area that has been treated. Such late side effects are mostly attributable to damage caused to blood vessels and to connective tissue cells (“Radiation therapy”, 2014). Fractionating treatment into smaller parts reduces many late effects (“Radiation therapy”, 2014).
Tissues treated with radiation show diffuse scarring which makes the tissues less supple over time (“Radiation therapy”, 2014).
Epilation (hair loss)
High doses of radiation above 1 Gy can cause epilation on any hair bearing skin (“Radiation therapy”, 2014). The absorbed dose is the energy absorbed per unit weight of the organ or the tissue. The unit of expression for this is gray (Gy). Permanent hair loss can be caused by a single dose of 10 Gy; but if the dose is fractionated, permanent hair loss is delayed till the total dose exceeds 45 Gy (“Radiation therapy”, 2014).
Months to years after the completion of treatment, chronic radiation enteritis may be detected. It may also begin as acute enteritis and may continue after treatment ends. The probability of persons treated with radiation to the abdomen developing chronic problems is about 5% to 15% (National Cancer Institute, 2014).
After pelvic radiation, the naturally moist vaginal mucosa may become dry (“Radiation therapy”, 2014).
In lymphoedema, localized fluid retention and tissue swelling occur and are manifested in the radiation area with PRT in the form of swollen legs (see Figure 8). Damage to the lymphatic system during the radiation treatment can lead to this symptom (“Radiation therapy”, 2014).
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Figure 8: Lymphoedema post ovarian cancer surgery and lymph node resection
(Lymphedema Therapy, 2014)
Radiation therapy to pelvic organs may lead to long-term effects on the rectum such as bowel urgency, bleeding and diarrhoea (“Radiation therapy”, 2014). Cystitis (bladder infection) is also known to occur as a result of pelvic radiation therapy when the bladder is affected (“Radiation therapy”, 2014).
In summary, the cancers which are the focus of this study (GC’s, especially EC and CC (VC and VUC relatively rare) and female RC (AC is rare)) are relatively prevalent conditions, with serious consequences, and for which treatment induces serious side-effects. Whilst the overall and general side effects of PRT and other treatments have been briefly described above, the main focus of the current study is on the development and evaluation of a study-designed psychoeducational psychosexual PRT rehabilitation booklet which deals with post PRT physical vaginal and sexual changes for women. Hence an in-depth discussion of the physical and then sexual changes post PRT follows below in Chapter 2.
To inform this chapter, databases were searched including Medline, Web of Science, Science Direct, CINAHL, MEDLINE (PubMed) and PsycINFO. The search terms used were: vulvar cancer, vaginal cancer, cervical cancer, endometrial cancer, female anal and rectal cancers, pelvic radiation treatment, prevalence, incidence, vaginal dilators, sexual side effects, anxiety, depression, posttraumatic stress disorder, psychological adaptation/adjustment, health related quality of life, supportive care needs, and information needs. Other resources were searched such as reference lists of identified papers, reference lists of radiation/oncology books for the relevant cancers, conference abstracts, and the ‘related articles’ feature in databases such as PubMed.
In this chapter, the vaginal and sexual side effects of PRT, which are integral to the present research, will be outlined, along with their impact on quality of life. Leading on from this, the main strategies for addressing the physical side effects of PRT to improve sexual functioning will be presented. The next section will present evidence of women’s psychosexual/ information and supportive care needs, and barriers to effective doctor-patient communication on this topic. The final section of the chapter will discuss the latest research with regards to information resource development and provision in this area. The study aims and hypotheses will conclude this chapter. Kotronoulas et al., (2009) note that all people have a sexual facet which persists through different stages of their cancer passage. As discussed previously, for women with the pelvic cancers being examined in the current study (cervical, endometrial, vaginal, vulvar, rectal and anal), treatment can involve radical pelvic surgery (not current practice for anal cancer) often in conjunction with primary and/or adjuvant radiotherapy and chemotherapy (Schover, 2005; Breukink et al., 2009; Hassan & Cima, 2007). As a result of these invasive therapies, in particular PRT, profound physical changes in the areas of the body with which a woman defines herself sexually can occur. These effects have particular implications for sexual functioning and adjustment post PRT.
The following sections will provide a more detailed overview of: i) post-PRT (a) physical changes, (b) post PRT sexual changes and (c) quality of life and psychological outcomes of sexual dysfunction; ii) physical interventions to improve physical/vaginal and sexual functioning; iii) sexual information needs for women with gynaecological and anorectal cancer; iv) barriers to doctor-patient communication; v) potential interventions/resources to improve psycho-educational information and support to patients, and their barriers/facilitators.
Radiation to the female pelvis can affect sexual function in two ways: damage to the epithelium of the vaginal canal and premature ovarian failure (Shell, 2007). Implications of PRT physical vaginal changes will be discussed separately below only in the instance where they may vary by cancer type.
Epithelium line surfaces and cavities of structures throughout the body. Its function is to protect, secrete, selectively absorb, and for transcellular transport and for detection of sensation. (“Epithelium”, 2014).
Radiation toxicity refers to the health consequences of exposure to high amounts of ionising radiation appearing within 24 hours. The symptoms can begin within one or two hours of radiation and can last for several months (Donnelly et al., 2010; Xiao & Whitnall, 2009). As per its definition, radiation toxicity refers to acute medical problems and does not include the symptoms that evolve after a prolonged period. But similar symptoms may appear within months to years after radiation treatment (Reeves & Ainsworth, 1995). The exact onset and type of symptoms are dependent on the radiation exposure (“Acute radiation syndrome”, 2014).
As noted previously, external pelvic radiotherapy (EBRT) and internal vault/intracavitary brachytherapy can result in significant vaginal changes such as stenosis (narrowing) and agglutination (“glue-like” adhesions resulting from internal scar tissue). If adhesions are not regularly broken down skin tightening and, shortening, narrowing and for some women, entire destruction of the vagina might transpire (Decruze et al., 1999; Gosselin et al., 2000). Vaginal stenosis can prevent adequate pelvic examinations, potentially affecting the ability to detect new cancer and/or recurrence, as well as potentially leading to sexual dysfunction and lowered quality of life (Johnson & Miles, 2010; Bahng et al., 2012; Bergmark et al., 2002). Though vaginal stenosis is a common side effect of PRT for women with gynaecological and colorectal cancer there has been little focus on it in the literature necessitating further study (Wolf, 2006). Wolf (2006) further argues that colorectal patients have received little attention in this regard compared to cervical/gynaecological cancer patients. Wolf (2006) notes this may be as a consequence of PRT being a treatment option for longer in cervical/gynaecological cancer (60 years versus 30 years) and female colorectal patients not being treated by gynaecologists who may focus to a greater degree on sexual/vaginal changes. As will be discussed later in this chapter, whilst this may be the case, the focus on post PRT vaginal/sexual changes is also often not optimal for women with gynaecological cancer either (Bahng et al., 2012, Carter, 2011; 2013).
Although no consensus exists with regards to the definition or a measurement tool for vaginal stenosis (Miles et al., 2012), the International Guidelines for Vaginal Dilation after Pelvic Radiotherapy recommend the following “grade 1-3 in which grade 3 incorporates vaginal narrowing or shortening that interferes with inserting tampons, with sexual activity or physical examination” (Miles et al., 2012, p. 7).
The incidence of vaginal stenosis as a side effect of PRT is reported to range from 1.2% to 88% in gynaecological cancer patients, with a substantial variability due to factors such as type (internal or external and/or combination of both), dose and volume of radiation administered and surgery (Miles et al., 2012, Brand et al., 2006; Sorbe et al., 2012; Nout et al., 2012; Bahng et al., 2012). As noted in the paragraph above there is no consensus on the standards and guidelines for assessing stenosis. The variability in the assessment methods might explain the large variability in the rates of stenosis. By contrast to the above reporting of the incidence of stenosis in gynaecological cancer patients, the number of anal and rectal patients developing post PRT vaginal stenosis is not well documented (Miles et al., 2012). Furthermore, Miles et al. (2012) highlight that there have been extensive modifications in the treatment of rectal and anal cancers, such as, radiation type and dose which potentially confound the measurement and prevalence of vaginal stenosis.
Women’s experiences of vaginal stenosis following PRT are inconsistently reported in the literature. For instance, Nori et al.’s (1994, cited in Miles et al., 2012) study investigated the impact of vaginal stenosis on QOL and reported it being a ‘minor complication’, whilst Andersen et al. (1991, cited in Miles et al., 2012) reported women finding shortening of the vagina to be devastating. Many studies suggest a link between vaginal stenosis, dyspareunia severity and sexual dysfunction (Miles et al., 2012). Miles et al. (2012) note that this is a subjective issue since some women appear to be less disturbed by significant damage to their vagina whilst others are substantially impacted and experience longstanding psychosocial and sexuality-related bereavement from relatively minor damage/vaginal change. Thus, the psychosexual effects of vaginal stenosis/vaginal changes are complex and multifaceted as will be discussed later. Physical changes may not be the only cause of sexual dysfunction for women post PRT for gynaecological and anorectal cancer.
Radiation-induced Sexual Dysfunction
Radiation-induced sexual dysfunction should be contextualised with in sexual dysfunction in women in the general population, which is deemed common (Shifren et al., 2008; Najman et al., 2003). Prevalence rates estimates of 43% have been reported in the U.S. (Addis et al., 2006; Bancroft et al., 2003) and the United Kingdom (Nazareth et al., 2003; Dunn et al., 1998). Prevalence rates of 41% were found in Australia (Dunn et al., 2000). Najman et al.’s (2003) study 60.5% of Australian women reported a symptom of sexual difficulty within the last year, with 19.7% of women reporting more serious sexual dysfunction. In another Australian population based study Richters et al., (2003) found that for women lack of sexual interest and anorgasmia were the most frequent sexual problems. The aforementioned rates of sexual dysfunction in the general population need to be taken into account when discussing the rates of radiation-induced sexual dysfunction, discussed below.
I. Radiation-induced sexual dysfunction in gynaecological cancer patients
In the gynaecological cancer setting, radiation-induced effects contribute to the development of sexual dysfunction in a reported 49-79% of affected women (Munro et al., 1996). Many studies have reported major changes to levels of sexual desire/activity, anorgasmia, and decreased overall satisfaction with sexual life in the months and years following radiotherapy (Frumovitz et al., 2005; Jensen et al., 2004b; Juraskova, 2009; Lindau et al., 2007). In view of upwards of 40% of gynaecological cancer patients reporting chronic post-treatment sexual difficulties, it is likely that sexual and relationship dysfunction persists when other areas of adjustment such as mental health have normalised (Katz, 2005; 2009; Schover, 2005; Wolf, 2006; White, 2008).
For women who are treated for cervical cancer, the effects of PRT have a specific effect on sexuality (Chase et al., 2008). Cervical cancer patients may experience some of these effects to a greater degree, compared to other women undergoing PRT since they are generally younger and premenopausal (Bruheim, 2010a). Jensen et al. (2003) found sexual dysfunction and adverse vaginal changes two years post radiotherapy for cervical cancer. In their findings, more serious sexual dysfunction was observed among women only treated with radiation therapy in contrast to surgery-only patients during a follow-up of 2 years. The effects ranged from 85% of irradiated women reporting no interest in sex, 55% exhibiting dyspareunia, and another 50% exhibiting vaginal shortening. These sexual difficulties were statistically worse compared to women’s pre-treatment sexual function and to age-matched controls (Jensen et al., 2003). Similarly, Frumovitz et al. (2005) found more sexual dysfunction and vaginal problems five years post radiation treatment than in women who had radical hysterectomy and lymph node dissection, in cervical cancer patients. On the other hand, Bergmark et al. (1999) found no differences on the prevalence of vaginal shortness, inelasticity, or lubrication post PRT (internal or external) compared to surgery in early stage cervical cancer patients.
For women with endometrial cancer, high dose brachytherapy can result in extensive sexual problems (Friedman et al., 2011; Greimel et al., 2009; Bahng et al., 2012; Onujiogu et al., 2011), with over a third (Cochran et al., 1987) to a half of patients (Friedman et al., 2011) not resuming sexual activity after treatment. Those who remain sexually active report decreased vaginal lubrication, pain, bleeding and difficulty reaching orgasm, with many women finding intercourse troubling as their vaginas were too reduced in size (Friedman et al., 2011). Of concern, sexual dysfunction in these women may be underreported (Goncalves, 2007), with some finding that these rates are closer to 80% (Damast et al., 2012). Therefore, endometrial cancer survivors, commonly thought to have a low risk, may, in reality suffer from ‘severe’ sexual dysfunction (Onujiogu et al., 2011, p. 356).
Furthermore, PRT combined with surgery has been found to have a greater impact on sexual function than only surgery (Frumovitz et al., 2005, Greimel et al., 2009). In a longitudinal study of postoperative PRT in endometrial carcinoma (PORTEC-1), it was noted that in women who had pelvic EBRT after total abdominal hysterectomy, long-term symptoms of bowel and bladder, reduction in sexual enjoyment and increased vaginal dryness and a negative Health Related Quality Of Life (HRQOL) were observed in comparison to those who had only surgery (Nout et al., 2011).
As vaginal cancer cases are rare, most studies were done with small samples (Hiniker et al., 2013; Tran et al., 2007). Little data are available on late radiation toxicities of the different radiation treatments in this context (Lian et al., 2008; Tran et al., 2007). Lian et al. (2008) found that 68% of women in their study (n=68) had late radiation toxicity of vaginal morbidity, but minimal bladder (4.6%) and bowel toxicity (4.6%). The most frequent vaginal symptom was vaginal stenosis. Of those with stenosis, 30.9% had grade 1, 21.8% grade 2, 5.5% had grade 3 (meaning severely shortened vagina) and 5.5% had grade 4 toxicity (involving either vesico-vaginal fistula or recto-vaginal fistula). In this study vaginal morbidity was highest in the group undergoing both EBRT and brachytherapy (82.1%) and lowest in the brachytherapy alone group (0%). Higher doses of radiation were correlated with more frequent vaginal toxicity in Lian et al.’s (2008) study. Dixit et al.’s study, (1993, cited in Lian et al., 2008) gave some support to these findings with a higher risk of vaginal toxicity, though not statistically significant, in patients undergoing both EBRT and brachytherapy.
Vulvar cancer is relatively rare; as such there is a significant lack of literature on treatment-related side effects (Aerts et al., 2014) and psychosexual outcomes for women (Barlow et al., 2014; Pilger et al., 2012). However, Weijmar Schultz et al. (1990) examined psychosexual functioning longitudinally post radiation treatment for vulvar cancer and found a high risk for vaginal stenosis at the vaginal opening with considerable reduction in genital feeling throughout arousal and orgasm with no symptom diminishment over time. Moreover, Hazewinkel et al. (2012) observed a negative correlation of sexual function of women (n=120), treated for vulvar cancer with age and with adjuvant inguinal (lymph node) radiotherapy. The effect of age was manifested in the decrease of “arousal” and “desire”. However, having a partner had a positive effect on ‘satisfaction’. These authors pointed out that when fibrosis results from adjuvant treatment, there is an increase in local morbidity (Hazewinkel et al., 2012). From multivariate analysis, a negative relationship between adjuvant radiotherapy and orgasm was observed (Hazewinkel et al., 2012). Aerts et al. (2014) citing a van Doorn et al.’s (2006) Cochrane Review, contend that, although vulvar cancer treatment has become more personalised and less extreme, the iatrogenic effects of surgery, such as the impact on nerves and blood vessels related to anal, urinary and sexual function may be more pronounced when combined with radiotherapy. Women with vulvar cancer are at high risk for sexual morbidity given the condition and its treatments (Jefferies & Clifford, 2012; Hazewinkel et al., 2012; Aerts et al., 2014).
II. Radiation-induced sexual dysfunction in anorectal cancer patients
Anal and rectal patients also report significant sexual dysfunction post PRT (Incrocci & Jensen, 2013, Wolf, 2006). Lange et al. (2009) found that 62% of women with rectal cancers noted new or aggravated sexual problems post treatment, whilst rates of sexual activity among these women dropped from 51% pre-treatment to 33% three months post treatment, with a further reduction to 18% two-years post treatment. The only risk factor found for sexual dysfunction was preoperative radiotherapy (Lange et al., 2009). Gervaz et al. (2008) suggest that sexual function in rectal patients does not improve but stabilises over time ranging from 6 months to 2 years (Gervaz et al., 2008). Admittedly, little is known about sexual dysfunction for women with rectal cancer with further research needed in this area (Ho et al., 2011; Incrocci & Jensen, 2013).
In 55% of women with anal cancer, poor sexual function scores were found with respect to inadequate sexual interest, arousal difficulties, incapability to relax and enjoy sex and difficulty in reaching orgasm in Das et al.’s (2010) study. These authors contend that further research is required in female patients with anal cancers for better understanding of the sexual changes that are consequent on radiation to the internal and external genitalia (Das et al., 2010).
Clinicians are inclined to under report anal cancer survivor’s sexuality-related symptoms (Vistad et al., 2008), however, Bentzen et al. (2013) contend that a large number of patients may experience post PRT effects, since the radiation dose is high and the sexual organs and anal sphincter are in the vicinity of the target volume of radiation for patients with anal cancers. Increased awareness of side effects is needed for better management of late effects for anal cancer survivors (Bentzen et al., 2013), who remain a neglected cohort with regards to late PRT effects, and sexual dysfunction in particular (Aggarwal et al., 2013).
Additionally, there is limited understanding of the effects of PRT on sexuality for endometrial cancer patients with rates of sexual dysfunction underestimated and understudied, and similarly for anal cancer patients (Incrocci & Jensen, 2013), which reflects a paucity of research in this area.
Body image, identity disturbance and relationship effects with regards to sexuality post PRT for women with gynaecological cancer and anorectal cancer
Gynaecological and anorectal cancer and its treatment are known to have an extensive impact on body image and sexual self-perception (Incrocci & Jensen, 2013, Carpenter et al., 2009). Some of the factors linked with psychological adaptation and QOL both immediately post-treatment and during survivorship include sexuality and body view issues (Ashing-Giwa et al., 2010, Lindau et al., 2007).
A review of the relevant literature indicates a growing disgruntlement that post cancer sexuality research focuses on the physical effects of gynaecological and female anorectal cancer treatment. Post-treatment effects are experienced not only at a physical but also a psychological level as sexuality is multidimensional; women treated for gynaecological and anorectal cancer experience anxiety, depression (Petersen & Quinlivan, 2002; Dunn et al., 2012), psychological distress (Dunn et al., 2012; Philip et al., 2013), low self-worth (Holmes et al., 2005; Baumann et al., 2013) self-representation, identity and body view breakdown (Carpenter et al., 2009; Gilbert et al., 2011). Furthermore, certain effects may extend beyond the individual patient to involve their partner. These effects may include fear of pain during intercourse; fear that sexual activity will cause recurrence, anxiety relating to bladder and bowel dysfunction whilst having sexual activity, and breakdown in couple communications about sexual closeness (Juraskova et al., 2003; Philip et al., 2013; Gilbert et al., 2011).
Often women find it difficult to perceive themselves to be sexually attractive during the treatment and after. Gynaecological cancer patients have reported a feeling of no longer being a woman, for instance, due to treatment-induced ovarian failure/infertility (Gilbert et al., 2011; Stead et al., 2007). Therefore, the goals of care and rehabilitation should include detection and inclusion of body-image disruption factors (Pilger et al., 2012). Psychological effects of gynaecological cancer and its treatment are primarily related to a range of sexual symptoms. These symptoms include disfavoured body image associated with gaining weight, scars and marking from EBRT radiation beam placement (Gilbert et al., 2011; Burns et al., 2007; Lamb & Sheldon, 1993; Butler et al., 1998), loss of feeling womanlike (Juraskova et al., 2003; Rasmusson et al., 2008), and feeling unattractive (with one woman reporting feeling a ‘monster’) as a result of hair loss (Stead et al., 2007).
Similarly, Panjari et al. (2012) also cited disfavoured body view as a factor affecting sexual dysfunction in female rectal cancer patients along with fatigue, depression, loss of independence, and relationship changes. For instance, couples often experience changes of social roles during treatment which can jeopardise each person’s sense of individuality and worth (National Cancer Institute, 2013). Partner participation in physical care can have negative impact on sexuality. Such effects have been reported in the case of stoma care in colorectal cancer patients (National Cancer Institute, 2013). Younger couples affected by female rectal and anal cancer have been found to be more at risk of problems related to change or new domestic roles associated with treatment. They also report having more concerns about the effects of these on their intimacy and sexual relationship (Das et al., 2010).
There are contradictory findings on the effects due to gynaecological cancer and its treatment in women and their psychosexual/sexual relationships. Some couples report a positive effect on their relationship (Lamb & Sheldon, 1993; Butler et al., 1998) whilst others find that women’s sexual difficulties caused deterioration in the couple’s relationship (Burns et al., 2007; Bergmark et al., 1999). Some negative effects include blaming partners for their cancer, experiencing physical and psychological trauma and emotional detachment related to sexual activity, fear of cancer transmission, and concern of the partner about hurting the woman being translated as rejection or lack of interest (Juraskova et al., 2003).
A major issue with regards to sexual difficulties of post gynaecological cancer cases is communication in couples (Stead et al., 2007; Juraskova et al., 2003). Resumption of intercourse does not necessarily imply satisfaction/enjoyment and may occur without couples explicitly communicating their desire (or non-desire) for resuming intercourse. Some women feel, for instance, a pressure to continue sexual activity to maintain the relationship driven by fear of losing their partners or by feeling markedly dependant on them (Gilbert et al., 2011). Silencing themselves has been noted as a coping mechanism among women and their partners. This may further exacerbate their difficulties particularly due to lack of sexual information and support from clinicians (Stead et al., 2003). Based on this, researchers argue that prioritising sexuality in this setting would legitimise women’s and their partners’ difficulties and improve couples’ communication (Stilos et al., 2008; Weijmar & Schultz et al., 1992).
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