Preferences of Healthy Men for Two Different Endocrine Treatment Options Offered for Locally Advanced Prostate Cancer*
By Jenkins, V; Fallowfield, L; Edginton, T; Payne, H; Hamilton, E
Key words: LHRHa – Locally advanced prostate cancer – NSAA – Patient choice
ABSTRACT
Objective:The aim of this study was to determine whether healthy men would prefer either luteinizing hormone releasing hormone analogues (LHRHa) or non-steroidal anti-androgen therapy (NSAA) should they hypothetically develop locally advanced prostate cancer.
Participants and methods: A representative sample of 180 men without prostate cancer (68% over 65 years of age, range 50-90 years), read two scenarios describing LHRHa or NSAA treatments for locally advanced prostate cancer. Participants chose which drug treatment they hypothetically would prefer, gave a reason for their choice and indicated the degree to which they wanted to avoid side effects specific to each drug.
Results: Eighty-six per cent (156/180) of the men chose NSAA therapy, 7% (12/180) chose LHRHa therapy and 7% (12/180) could not decide. The main reason men chose LHRHa therapy was because of the method of administration (9/12) whereas those who chose NSAA therapy cited avoidance of the side effects associated with LHRHa treatment (115/156). The side effects, ranked in order of importance, that men who chose NSAA therapy most wanted to avoid included risk of potential fractures (85%), reduced physical strength (76%), decreased sexual interest (56%), impotence (51%), hot flushes (49%), breast enlargement (17%) and breast tenderness (13%).
Conclusion: Although this project was a hypothetical study, several important issues emerged from the data that are relevant to patient choice. Men should be fully informed about the side-effect profiles of different endocrine treatments, involved in decision making and allowed to choose therapies less likely to cause side effects they would prefer to avoid.
Introduction
Prostate cancer is now the most common male cancer in the UK1 and the majority of oncology healthcare professionals believe that patients with cancer should be involved in making informed treatment choices, but there is often a difference in opinion regarding the type and amount of information that is required2. Several recent studies exploring information needs and quality of life issues in patients with prostate cancer have shown that men want an active or collaborative role in decision making with their physician and that the areas where they want clear information are prognosis, stage of disease, treatments and side effects3.
The desire for more information emerged as a key area in a study of 115 men receiving hormonal manipulation therapy (HMT) for prostate cancer. Results revealed that men receiving HMT had a knowledge deficit with regards to their disease and treatment. Only 34% of men knew the location of the prostate, 34% the name of the treatment they were receiving and 13% that the treatment worked by hormonal manipulation. Men perceived the most useful information given was that related to diagnosis (61%) and investigative tests (48%), however, the majority (82%) complained of a lack of information particularly with reference to the side effects of treatment and how they might be eased4.
It appears that clinicians remain undecided as to which therapies are best for locally advanced prostate cancer in terms of enhancing both quality and quantity of life. In the UK the most widely used hormonal treatment for men with locally advanced prostate cancer is luteinizing hormone releasing hormone analogue (LHRHa) sometimes combined with a non-steroidal anti-androgen. Management and treatment regimes differ between clinicians; some prefer to give neo- adjuvant LHRHa therapy prior to radiotherapy for effective tumour shrinkage and/or prescribe adjuvant hormonal therapy post- radiotherapy; in addition clinicians may either administer LHRHa therapy followed by NSAA treatment at progression or prescribe simultaneous LHRHa therapy and NSAA treatment to achieve maximal androgen blockade3. The rationale for these decisions tends to be based on clinician experience and assumptions as to which potential side effects patients would most prefer to avoid.
There is an emerging trend to prescribe anti-androgens as monotherapy in men with locally advanced disease6. The use of anti- androgens as monotherapy is predicted on the presumed quality of life compared with treatment by LHRH analogues. Equal efficacy, in terms of equivalent risk of progression and time to survival, has been demonstrated for castration (mainly LHRHa) and nonsteroidal anti-androgen (NSAA) monotherapy7. Moreover, in locally advanced disease NSAA monotherapy gives a significant reduction in the risk of progression and a trend towards improved survival when compared with placebo8. This creates a further viable treatment option for patients particularly as the side effect profiles and route of administration differ for both treatments.
LHRHa therapy is usually given by monthly or three monthly injections in the UK at a health centre/GP surgery or hospital, whereas anti-androgen treatment is an oral preparation that requires the patient to take at least one tablet daily. There are side effects common to both treatments albeit to differing degrees, for example impotence, loss of libido, hot flushes and weight gain. While nine out of ten men on LHRHa could experience impotence and loss of libido9,10, the rate is much lower in men treated with NSAA monotherapy11-13. In addition an increased risk of fractures and loss of physical strength are specific to LHRHa treatment14-17, whereas gynaecomastia and breast tenderness (7/10 men) are commonly associated with NSAA treatments18. The impact of these associated side effects will vary from patient to patient and some may challenge the stereotypical image men have of themselves and the male sense of identity. For example one study reported that men with non-metastatic prostate cancer were willing to trade off some life expectancy to be relieved of the burden of troublesome side effects such as limitations in physical energy19. These results underline how important it is that patients are given adequate information about different treatment options and how these impact upon quality of life. Particularly as it is recognised that patients with cancer who are better informed tend to have better psychosocial outcomes and are better equipped to cope20.
The study reported here assessed the preferences of a group of healthy men for either LHRHa or NSAA should they hypothetically develop locally advanced prostate cancer. Reasons why healthy men chose or rejected treatments were explored together with any socio demographic variables associated with their choices.
This project did not involve prostate cancer patients, as current or previous experience of endocrine therapy could have produced biased outcomes. It would also have been unethical to have alerted patients to potential side effects of their treatment if these had not been discussed previously with their clinician, before a therapy was chosen.
Method and materials
The methodology used was similar to that utilised successfully in another preference study of breast cancer treatments21. A questionnaire was designed to elicit healthy men’s preferences for one of two endocrine therapies based on their side-effect profiles and route of administration. Scenarios describing LHRHa treatment and NSAA treatment were constructed using published data, information from four experienced prostate cancer consultants, one specialist prostate cancer nurse and cancer charity websites. The scenario explained how each treatment was administered and the associated side effects with each treatment. Table 1 shows the side effects as listed in the scenarios. Care was taken to emphasise that the number and severity of side effects varies from person to person.
Table 1. Treatment and side-effect profiles of two different endocrine treatment options offered for locally advanced prostate cancer
A short questionnaire was designed to gather information about each man’s age, partnership status, educational qualifications, whether anyone close to them had experienced cancer, the type of cancer and any treatment given. The scenarios and questionnaires were pilot tested for clarity and ease of completion on men of different ages and educational backgrounds and modified accordingly.
Sample and data collection of subjects (healthy men)
The target sample comprised 185 men aged between 50 years and above 75 years and who had not had cancer. Healthy men are potential patients who can consider the side effects in relation to their current lifestyle without the immediate threat of illness. The recruitment of men in each age group was stratified broadly to reflect the incidence of prostate cancer in the UK population (Table 2). Men were recruited using a variety of means including: email messages to University staff, colleagues and friends, direct approaches to people in day centres, senior citizen clubs and Age Concern organisations in the South East of England. Approximately 300 questionnaires were distributed and 185 were returned, a response rate of 62%.
Table 2. Recruitment of men stratified broadly to reflect the proportion of prostate cases in the UK population by age group
The presentation order of the treatment side-effect profiles was counterbalanced, so that half the men read the LHRHa profil\e as Drug A and the NSAA profile as Drug B and the for the other half the LHRHa profile was known as Drug B and the NSAA profile as Drug A.
The following paragraph prefaced each scenario:
Imagine you have just been diagnosed with prostate cancer.
The specialist recommends that you should have radiotherapy together with a course of hormone treatment. The specialist offers you the choice of two treatments which have been shown to be equally good at preventing the return of the cancer but they differ in
(a) the way they are taken, and
(b) their side effects.
Which of the two treatments would YOU choose based on the following information?
Each man’s treatment preference was then elicited using three response options Drug A, Drug B or undecided. The primary reasons for their treatment choices were recorded initially by free response then prompts asking which of the following three factors most influenced their choice; the method of taking the drug, the side- effect profile or how often the drug was taken. Finally participants were asked to indicate how much they wanted to avoid each individual side effect on a Likert scale of 0-4 with O = not at all and 4 = very much.
Statistics
All data were analysed using the Statistical Package for the Social Sciences (SPSS) version 11 and included descriptive statistics and χ^sup 2^ analyses.
Results
One hundred and eighty-five questionnaires were completed, five were excluded because they were either incomplete (n = 3) or completed by men who had been previously diagnosed with prostate cancer (n = 2).
Demographics
Education level was assessed by categorising the age of leaving full-time education; 62% (n = 112) of men had left school before the age of 16 years, 14% (n = 26) had remained in full-time education until the age of 18 years and 22% (n = 40), had continued to higher education. There were missing data for two men. In addition 79% (142/ 180) of men knew someone with a diagnosis of cancer and in 54% (98/ 180) of cases it was someone treated for prostate cancer.
Treatment preferences
Figure 1 shows the treatment preferences of the men. It can be seen that significantly more men chose the tablet option (χ^sup 2^, p < 0.0001).
Figure 2. Avoidance of individual side effects in those who chose either drug A or drug B (n = 168) for endocrine treatment for locally advanced prostate cancer
Figure 1. Treatment choice of the healthy men [N = 180) for two different endocrine treatment options offered for locally advanced prostate cancer
Factors relating to preferences
One hundred and fifteen of one hundred and fifty-six men who chose the tablet option indicated that the sideeffect profile was the most important factor for their choice and 28 stated the method of administration. In contrast 9/12 men who preferred the injection option stated that the method of administration was an important factor in making their choice.
When treatment preferences were categorised by age, the majority of the men 10/12 who preferred the injection option were over the age of 65 years. The age of the men who chose the tablet option was less polarised as a third were aged under 65 years.
Avoidance of impotence and loss of libido might be of greater concern to those with a partner, so this issue was examined for both groups. When treatment preferences were categorised by partnership status 124/156 men who preferred the tablet option and only 6/12 men who chose the injection option had partners. This difference was statistically significant (χ^sup 2^, p < 0.05), although this result could be an artefact of so few men choosing the injection option.
When treatment preferences were categorised by experience of knowing someone with prostate cancer, the frequencies were similar with 85/156 (54%) for men who chose the tablet option and 6/12 (50%) for men who chose the injection option.
Individual side effects
Figure 2 shows the percentage of men who indicated that they strongly wanted to avoid specific side effects. These figures were calculated by collapsing together the frequency counts on the Likert scale of 3 'quite a bit' and 4 Very much".
Less than a third of the sample stated that the avoidance of gynaecomastia and breast tenderness was important, irrespective of their treatment preference. However, a higher percentage of men who chose the injection wanted to avoid gynaecomastia and breast pain. Over half of the men who chose the tablet option and a quarter of those who chose the injection option indicated that it was important for them to avoid reduced sexual interest and impotence. However, the side effects that the majority of those who chose the tablet option most wanted to avoid were the potential increased risk of fractures 133/156 (85%) tablet; and loss of physical strength 117/ 156 (75%).
Reasons for preferences
The men were all invited to write unprompted comments or reasons for their treatment preferences. These comments were coded into discrete categories. Of the 156 men who chose the tablet option, 153 men made 166 comments about their choice of treatment. The primary reason for the choice of NSAA therapy given by 43 % men was that they believed that the sideeffect profile was less drastic, with 25% wanting to avoid the specific side effects of loss of physical strength and potential risk of fracture, 20% valued the convenience of taking tablets, 7% wanted to maintain their libido and 5% stated that they did not like injections.
Comments made by men on completion of the study
Several men wrote comments about their desire to avoid loss of physical strength and avoid being at increased risk of fractures if they were to receive the LHRHa treatment. There were more comments concerning these side effects than concern over reduced sexual activity, or breast enlargement and tenderness.
I have an active life - golf, walking, travel - I would not like to risk undermining this ability (69 year old).
Quality of life would be affected by a loss of physical strength (66 year old).
Drug A chosen because drug B specific side effects, i.e. a risk of fractures and physical strength loss would affect my working and sporting activities (69 year old).
I am 77 years old and consequently less agile so the risk of fractures would be a very high concern.
At age 75 years erection is out, despite sexual interest and I would prefer breasts than brittle bones and strength loss!
As I live on my own I should not want the risk of fracturing nor would I welcome reduction in physical strength (78 year old).
I look after my wife who is disabled and would particularly want to avoid a loss of physical strength and be at risk of having a fracture (72 year old).
Discussion
The results from this study show an overwhelming preference by healthy men for NSAA treatment rather than LHRHa were they to develop locally advanced prostate cancer and there was a choice of treatment. The most common reasons for choosing NSAA were that the side-effect profile appeared less severe than for LHRHa treatment. In particular men wanted to avoid the loss of physical strength and the potential increased risk of fractures associated with the LHRHa treatment option. These side effects do not tend to be emphasised by clinicians and are often referred to as general fatigue. Gynaecomastia and breast pain did not rate highly as side effects to be avoided; men who did rate this highly were more likely to choose the LHRHa option.
It was noted when compiling the profile of side effects table that there was considerable variation in the clinical studies of the reported incidence of side effects. The published clinical data studies rarely mention the severity or impact the symptoms had for the patients, in terms of quality of life, except when toxicity led to a withdrawal of treatments. In particular the incidence of reduced sexual functioning and sexual interest in men receiving either anti-androgen or LHRH therapy varied considerably. The figures appeared to depend on the type of questionnaire used in the study and whether there were data available on men's current sexual interest and activity prior to receiving treatment. Although the scenarios were designed with the best evidence based data we could find after considerable searching of the literature, we acknowledge that the side effect descriptions offered could be challenged. Some clinicians may disagree and quote quite different figures in discussions with their patients - either more optimistic or pessimistic, yet according to patient surveys this conversation rarely occurs3,22,23. Research suggests that although both patients and oncologists seem willing to discuss a wide range of health related quality of life issues, many physicians do not initiate discussion of certain psychosocial issues24. Patients may feel reluctant or too embarrassed to bring some subjects up themselves hence the true burden or impact of treatment can be unrecognised.
In an ideal world we would like to think that patients make a thoughtful logical appraisal of the facts provided by their doctor and other resources, then make a rational decision about treatments. The ideal decision maker is one who assembles all possible information from many different sources, weighs up the costs/ benefits of different treatments and makes a rational decision. Yet often in reality this is not the case, patients come to the consultation with expectations, are often anxious and find it difficult to assimilate information provided to them. They are quite likely to use minimal heuristics to simplify their understanding of the treatments and side effects, use many unreliable sources of information and make decisions that may look irrational to the observer. In addition treatments may be accepted or rejected on the basis of the way in which they are framed and the information provided by health care professionals is extremely variable. Patients with locally advanced prostate cancer may take hormonaltherapy for many years and the long-term burden of some of the side effects may not be appreciated by the patient at the time that treatment is initiated.
Studies of clinicians' communication skills reveal an emphasis on closed, leading and multiple questioning styles during consultations with health professionals avoiding describing variables that are important to patient decision making but difficult to measure e.g. quality of life25.
Conclusion
This project has all the limitations of a hypothetical study because it was conducted on a sample of men without cancer who were asked to consider treatment options that might be on offer for locally advanced prostate cancer. However, several important issues emerged from the data. One is that potential patients make judgments about treatment options based upon the side effects that they believe will exert the greatest impact on their life over a period of time. The choice will differ according to each individual but the important message is that in this age of collaborative decision making about treatments and side effects, it is surely a requirement that clinicians and specialist nurses provide more information about all available treatment options tailored to an individual's needs. This highlights a pressing need for a more robust collection of patient recorded outcomes about severity of side effects and their temporal nature to assist both the patient and their healthcare professionals.
Acknowledgements
Declaration of interest: The study was supported by an unrestricted educational grant from AstraZeneca (AZ).
Professor Lesley Fallowfield acts as a consultant adviser on quality of life to AZ, Dr Heather Payne is a paid consultant to AZ and Dr Elizabeth Hamilton is an employee of the company, which markets two products used in prostate cancer.
We gratefully acknowledge the assistance of Dr Bloomfield, Dr Deutsch, Dr Harland and research nurse Sarah Henderson. Lesley Fallowfield and Valerie Jenkins are funded by Cancer Research UK.
Co-ordination of the study, all analysis and interpretation of the data were conducted independently of the funders by the named authors.
* Some of this material was presented at the British Association of Urological Surgeons, Manchester, November 2004
References
1. Cancer Research UK. Scientific Yearbook; 2004
2. Feldman-Stewart D, Brundage MD, Hayter C, et al. What prostate cancer patients should know: variation in professionals' opinions. Radiother Oncol 1998;49:111-23
3. Davison BJ, Parker PA, Goldenberg SL. Patients' preferences for communicating a prostate cancer diagnosis and participating in medical decision-making. Br J Urol Int 2004;93:47-51
4. Templeton H, Coates V. Informational needs of men with prostate cancer on hormonal manipulation therapy. Patient Educ Couns 2003;49:243-56
5. Boccardo F, Barichello M, Battaglia M, et al. Bicalutamide monotherapy versus flutamide plus goserelin in prostate cancer: updated results of a multicentric trial. Eur Urol 2002;42:481-90
6. Carroll PR, Kantoff PW, Balk SP, et al. Overview consensus statement. Newer approaches to androgen deprivation therapy in prostate cancer. Urology 2002;60(3 Suppl l):l-6
7. Iversen P, Tyrrell CJ, Kaisary AV, et al. Bicalutamide monotherapy compared with castration in patients with nonmetastatic locally advanced prostate cancer: 6.3 years of follow-up. J Urol 2000;164:1579-82
8. Wirth MP, see WA, McLeod DG, Iversen P, Morris T, Carroll K. Bicalutamide 150 mg in addition to standard care in patients with localized or locally advanced prostate cancer: results from the second analysis of the early prostate cancer program at median follow-up of 5.4 years. J Urol 2004; 172:1865-70
9. Boccardo F, Rubagotti A, Barichello M, et al. Bicalutamide monotherapy versus flutamide plus goserelin in prostate cancer patients: results of an Italian Prostate Cancer Project study. J Clin Oncol 1999; 17:2027-38
10. Scholz M, Lamb R. Antiandrogen monotherapy. Available from: www.prostateoncology.com; 2004 [last accessed February 2005]
11. Migliari R, Muscas G, Usai E. Effect of Casodex on sleep- related erections in patients with advanced prostate cancer. J Urol 1992;148:338-41
12. Iversen P, Tammela TL, Vaage S, et al. A randomised comparison of bicalutamide (‘Casodex’} 150mg versus placebo as immediate therapy either alone or as adjuvant to standard care for early nonmetastatic prostate cancer. First report from the Scandinavian Prostatic Cancer Group Study No. 6. Eur Urol 2002;42:204-11
13. Tyrrell CJ, Payne H, Tammela TL, et al. Prophylactic breast irradiation with a single dose of electron beam radiotherapy (10Gy) significantly reduces the incidence of bicalutamideinduced gynecomastia. Int J Radit Oncol Biol Phys 2004;60: 476-83
14. Smith MR, Goode M, Zietman AL, McGovern FJ, Lee H, Finkelstein JS. Bicalutamide monotherapy versus leuprolide monotherapy for prostate cancer: effects on bone mineral density and body composition. J Clin Oncol 2004;22:2546-53
15. Daniell HW, Dunn SR, Ferguson DW, Lomas G, Niazi Z, Stratte PT. Progressive osteoporosis during androgen deprivation therapy for prostate cancer. J Urol 2000; 163:181-6
16. Basaria S, lieb 2nd J, Tang AM, et al. Long-term effects of androgen deprivation therapy in prostate cancer patients. Clin Endocrinol (Oxf) 2002;56:779-86
17. ShahinianVB, Kuo YF, Freeman JL, GoodwinJS. Risk of fracture after androgen deprivation for prostate cancer. New Engl J Med 2005;352:154-64
18. Iversen P. Bicalutamide monotherapy for early stage prostate cancer: an update. J Urol 2003; 170:548-52 [discussion S52-4]
19. Sculpher M, Bryan S, Fry P, de Winter P, Payne H, Emberton M. Patients’ preferences for the management of non-metastatic prostate cancer: discrete choice experiment. Br Med J 2004;328:382
20. Fallowfield LJ, Hall A, Maguire P, Baum M, A’Hern RP. Psychological effects of being offered choice of surgery for breast cancer. Br Med J 1994;309:448
21. Fallowfield L, McGurk R, Dixon M. Same gain, less pain: potential patient preferences for adjuvant treatment in premenopausal women with early breast cancer. Eur J Cancer 2004;40:2403-10
22. Feldman-Stewart D, Brundage MD, Nickel JC, MacKillop WJ. The information required by patients with early-stage prostate cancer in choosing their treatment. Br J Urol Int 2001 ;87: 218-23
23. Jonker-Pool G, Hoekstra HJ, van Imhoff GW, et al. Male sexuality after cancer treatment – needs for information and support: testicular cancer compared to malignant lymphoma. Patient Educ Couns 2004; 52:143-50
24. Detmar SB, Aaronson NK, Wever LD, Muller M, Schornagel JH. How are you feeling? Who wants to know? Patients’ and oncologists’ preferences for discussing health-related quality-of-life issues. J CHn Oncol 2000; 18:3295-301
25. Fallowfield L, Jenkins V. Effective communication skills are the key to good cancer care. Eur J Cancer 1999;35:1592-7
26. Metz R, Namer M, Adenis L, et al. Zoladex as primary therapy in advanced prostatic cancer. A French cooperative trial. Am J Clin Oncol 1988;ll(SuPP12):S112-4
27. Clark JA, Wray NP, Ashton CM. Living with treatment decisions: regrets and quality of life among men treated for metastatic prostate cancer. J Clin Oncol 2001;19:72-80
28. Wei JT, Gross M, Jaffe CA, et al. Androgen deprivation therapy for prostate cancer results in significant loss of bone density. Urology 1999;54:607-11
CrossRef links are available in the online published version of this paper: http://www.cmrojournal.com
Paper CMRO-3066_2, Accepted for publication: 30 June 2005
Published Online: 19 July 2005
doi: 10.1185/030079905X59058
V. Jenkins(a), L. Fallowfield(a), T. Edginton(a), H Payne(b) and E. Hamilton(c)
a Cancer Research UK, Psychosocial Oncology Group, Brighton & Sussex Medical School, University of Sussex, Palmer, UK
b Myerstein Institute of Oncology, Middlesex Hospital, London, UK
c AstraZeneca UK Ltd, Luton, UK
Address for correspondence: Dr V. Jenkins, DPhil, Cancer Research UK, Psychosocial Oncology Group, Brighton & Sussex Medical School, University of Sussex, Palmer, Brighton BN1 9QG, UK. Tel.: +44 1273 873016; Fax: +44 1273 873022; email: val@sussex.ac.uk
Copyright Librapharm Sep 2005