Prostate Cancer Patients' Preferences for Intermittent vs. Continuous Androgen Deprivation—A Pilot Institutional Study

Journal of Medical Imaging and Radiation Sciences

Journal of Medical Imaging and Radiation Sciences xx (2015) 1-5

Journal de l’imagerie médicale et des sciences de la radiation

www.elsevier.com/locate/jmir

Research Article

Prostate Cancer Patients’ Preferences for Intermittent vs. Continuous Androgen DeprivationdA Pilot Institutional Study David Chun-Leung Chau, BSca, David Wang, BScb, Alissa Tedesco, BScb, Merrylee McGuffin, MRT(T)c, Lisa Di Prospero, MRT(T) BSc, MScde, Margaret Fitch, RN, PhDb, Xingshan Cao, PhDf, Deb Feldman-Stewart, PhDg, Janet Ellis, MDh and Ewa Szumacher, MD, FRCP(C), MEDe* a

University of Waterloo, Waterloo, Ontario Faculty of Medicine, University of Toronto, Toronto, Ontario c Department of Radiation Therapy, Sunnybrook Odette Cancer Centre, Toronto, Ontario d Department of Research and Education, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario e Department of Radiation Oncology, University of Toronto, Toronto, Ontario f Department of Evaluative Clinical Science, Sunnybrook Health Sciences Centre, Toronto, Ontario g Department of Oncology, Queen’s University, Kingston, Ontario h Department of Psychiatry, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario b

ABSTRACT Introduction: With locally advanced, recurrent, and metastatic prostate cancer patients, patient preference between intermittent (IAD) and continuous (CAD) androgen deprivation therapy has not been investigated. The goal of the study was to determine patients’ preference for IAD vs. CAD therapy. The secondary aim was to elucidate demographic or treatment variables that may affect a patient’s preference for one type of hormonal treatment. Materials and Methods: Using a tradeoff model that demonstrates the difference in outcome between IAD and CAD, a survey questionnaire was developed and administered to prostate cancer patients at the Odette Cancer Centre at Sunnybrook Health Sciences Centre in Toronto, Ontario, Canada. Only patients who had (1) locally advanced prostate cancer, (2) been previously treated for prostate cancer with relapsing prostate-specific antigen, or (3) slow metastatic disease were asked to participate. Data related to patients’ demographic information and their decisional preference factors were collected. Results and Conclusions: Overall, 36 of 53 (68%) patients completed the survey. Most patients favoured IAD (n ¼ 32) over CAD (n ¼ 4). Patients currently on radical treatment (adjuvant hormone therapy and radiation therapy) preferred CAD compared with patients who were not on radical treatment (P ¼ .044). Patients with high (>20 ng/L) pretreatment prostate-specific antigen showed preference for CAD; however, this was not statistically significant (P ¼ 0.07). Patients from both groups viewed quality of life as the strongest influence on their treatment preference, but had diverging opinions on side effects and general well being. The results of this pilot study could serve as a guide for future studies; a larger study combined with qualitative methodology may better address patients’ needs and minimize any regret over their hormonal treatment.



RESUM E Introduction : Chez les patients pr
esentant un cancer de la prostate localement avanc
e, r
ecurrent et m
etastatique, Il n’existe pas d’
etudes sur les pr
ef
erences des patients entre la th
erapie de privation androg
enique intermittente (PAI) ou permanente (PAP). Le but de l’
etude est de d
eterminer la pr
ef
erence des patients pour la th
erapie PAI ou PAP. L’objectif secondaire est de d
eterminer les variables d
emographiques ou de traitement susceptibles d’avoir une incidence sur la pr
ef
erence du patient pour un type de traitement hormonal. Mat
eriel et m
ethodologie : En utilisant un modele de compromis qui permet d’
etablir la diff
erence de r
esultat entre la PAI et la PAP, un questionnaire a
et
e
elabor
e et administr
e aux patients atteints d’un cancer de la prostate au Centre de canc
erologie Odette du Centre des sciences de la sant
e Sunnybrook de Toronto, en Ontario, Canada. Seuls les patients pr
esentant (1): un cancer de la prostate localement avanc
e; (2): ayant d
eja
et
e trait
es pour un cancer de la prostate avec APS r
ecurrent, ou (3): une maladie m
etastatique lente ont
et
e invit
es a participer a l’
etude. Les donn
ees d
emographiques des patients et les facteurs ayant une incidence sur leur pr
ef
erence ont
et
e recueillis. R
esultats et conclusions : Au total, 36 patients sur 53 (68 %) ont r
epondu au questionnaire. La majorit
e des patients favorisent la PAI (n¼32) plut^ot que la PAP (n¼4). Les patients pr
esentement soumis a un traitement radical (traitement hormonal adjuvant et radioth
erapie) sont plus susceptibles de pr
ef
erer la PAP que les patients qui ne suivent pas un traitement radical (p¼0,044). Les patients pr
esentant un APS
elev
e (>20 ng/L) avant le traitement montrent une pr
ef
erence pour la PAP, bien que cette donn
ee ne soit pas statistiquement significative (p¼0,07). Les patients des deux groupes considerent que la qualit
e de vie est le facteur qui a la plus grande influence

This research was presented at the 2014 International Cancer Education Conference in Clearwater, Florida, 22–25 October 2014. * Corresponding author: Ewa Szumacher, MD, FRCP(C), MEd, Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, Canada M4N 3M5. E-mail address: [email protected] (E. Szumacher). 1939-8654/$ - see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jmir.2015.09.005

sur leur choix de traitement, mais ont des opinions divergentes sur les effets secondaires et le bien-^etre g
en
eral. Les r
esultats de cette
etude-pilote pourraient servir de guide pour des
etudes futures; une plus grande
etude combin
ee

a une m
ethodologie qualitative pourrait mieux r
epondre aux besoins des patients et minimiser leurs regrets, s’il y a lie, face au choix de traitement hormonal.

Keywords: Patients preferences; prostate cancer; hormonal treatment

Introduction Prostate cancer is the sixth leading cause of death among North American men, accounting for 10% of all cancer mortality in 2013 [1]. In addition, prostate cancer is the secondmost commonly diagnosed cancer in North American men, accounting for 24% of all new cancer diagnoses and has a lifetime prevalence of 13% [1]. With the growing occurrence of prostate cancer, the number of available treatment options also increases, which makes the process of treatment decision making challenging for health care providers, patients, and their families. A variety of treatment options can be recommended for prostate cancer patients based on patients’ risk categories [2]: active surveillance; different forms of radiotherapy, such as intensity-modulated radiotherapy (IMRT) or brachytherapy; or surgery and hormonal treatment (HT), which can be given as a monotherapy or combined with other modalities. HT consists of androgen deprivation therapy (ADT), which can be instituted as a continuous or intermittent approach [2–4]. ADT is administered to patients as a hormonal injection typically as a luteinizing hormone–releasing hormone (LHRH) agonist to inhibit androgen synthesis, suppressing their systemic androgen levels [2]. The aim of ADT was to prolong patients’ survival, delay disease progression, and control patients’ symptoms. Continuous androgen deprivation therapy (CAD) is administered at regular intervals, usually every 3 months [5, 6]. Intermittent androgen deprivation (IAD) is administered during an initial on-treatment phase and withheld when a predefined prostate-specific antigen (PSA) level is achieved, at which PSA surveillance follows [6, 7]. The PSA level and its changes serve as indicators to a patient’s response to his initial or ongoing treatment, which is emphasized in the on-treatment and/or off-treatment cycles of IAD. After cessation of initial treatment, IAD continues with the off-treatment phase until clinical parameters (a predefined PSA level) dictate reinitiation of the next on-treatment phase [6]. ADT may be added to the salvage treatment to those patients who developed biochemical failure after prostatectomy and/or radiation therapy. It can be given as an adjuvant treatment to high-risk patients with prostate cancer, to whom radiation therapy and ADT are often concurrently administered to improve the effectiveness of the treatment. Patients’ choice between CAD and IAD therapy is influenced by a variety of factors; the choice often depends on the patient’s survival gains, overall quality of life, sexual function, fatigue, urinary function, and other side effects [8–10]. In addition, social and economic factors such as the 2

patient’s income and treatment and transportation costs, may also impact a patient’s preference of IAD or CAD [2, 4, 5, 7]. For example, in the province of Ontario, Canada, ADT for prostate cancer patients aged younger than 65 years is not covered by the provincial Ontario Health Insurance Plan. Because of the substantial costs of the HT, patients may not be able to afford their treatments and would be forced to go with the IAD treatment. Practitioners must be aware of the varying factors affecting patients’ treatment decisions and respect patients’ choices. Cancer patients’ satisfaction with their treatment is extremely important and their input into treatment decisions will lead them to choose the best option for their situation and to accept treatmentinduced complications [11–14]. ADT is associated with a variety of side effects which decrease a patient’s quality of life. The meta-analysis of nine randomized controlled trials by Nirula had compared IAD and CAD treatment in 5,508 patients (who met the criteria) and showed no significant differences in time-to-event outcomes between the two groups in any of the studies [7]. Patients treated with IAD had a superior quality of life over patients treated with CAD. Choosing CAD over IAD resulted in higher treatment costs, inconvenience, and potential increased toxicities [7, 15]. That meta-analysis provided fair evidence to recommend the use of IAD over CAD for the treatment of men with relapsing, locally advanced or metastatic prostate cancer who achieve a good initial response to androgen deprivation. However, practitioners continue to disagree over the best ADT treatment option for patients in this study’s population. There are a variety of items that affect practitioners and their particular opinions. Congruently, patients may also prefer certain treatments based on their own values [8]. As such, there is a need to further understand factors that influence patients’ decision between CAD and IAD, and the benefits of increasing the patient’s role in a shared decision-making process [4]. The objectives of this study were to better understand prostate patients’ preferences about what type of HT (IAD vs. CAD) they would prefer and reasons why one treatment may be favoured over another and to identify factors that patients are willing to tradeoff when making their treatment choice between IAD and CAD. Methods Survey Development The survey questionnaire was developed in several steps, which included a comprehensive literature review related to

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CAD and IAD and prostate cancer patients’ treatment decision making. The draft questionnaire was presented to the steering committee for feedback and comments. This committee was multidisciplinary and consisted of a radiation therapist, nurse, urologist, radiation oncologist, medical oncologist nurse, statistician, and cognitive psychologist. The survey consisted of (1) patient demographics, (2) a tradeoff table between IAD and CAD, and (3) a list of the factors that were mentioned in the tradeoff table, representing the factors that patients took into consideration when choosing between IAD and CAD (see Appendix 1). Based on the value placed on the factors in the tradeoff table, the patient was asked to rate each factor using a four-point Likert scale of categories (one, most important; two, very important; three, somewhat important; and four, not at all important). Basic demographic data were collected to determine if certain factors correlated with a specific treatment preference. These included age, ethnicity, education, distance from home to the treatment centre, employment, insurance coverage, culture, income and social status, sexual activity, comorbidities, and whether the patient had received surgery and/or radiation therapy. As a pilot test, five patients with prostate cancer tested the questionnaire for length, readability, and clarity. Feedback and suggestions from the steering committee and five patients were incorporated into the final survey. Study Participants All patients with prostate cancer at the Odette Cancer Centre at Sunnybrook Health Science Centre attending one of the genitourinary clinics were invited to participate in this study, provided that they met the inclusion criteria. Inclusion Criteria (1) Patients with locally advanced or recurrent prostate cancer treated with radical prostatectomy who were postradiotherapy with a relapsing PSA or who had any form of radical radiotherapy (external beam radiation [IMRT] and brachytherapy). (2) Patients with high-risk prostate cancer who have received adjuvant hormone therapy (CAD only) along with radiation therapy. (3) Patients with metastatic prostate cancer (stable, slow progressing, and bone metastases). (4) Patients who were able to speak and understand English well enough to complete the survey. (5) Patients who provided written consent for completing the survey. Procedure The clinical research assistant approached the eligible participants and introduced the study. Patients who were interested in participating in the study were provided with a package containing the study information, consent form, tradeoff table, and the questionnaire. If the patient could not complete the questionnaire at the clinic, he was provided

with the appropriate stamped envelopes to mail them back to the treatment centre. Patients who required support or clarification regarding the material in the survey were able to contact the clinical research assistant or the study principal investigator as outlined in the study informed consent form. On completion of the study materials, all the participants received a five-dollar gift card to Tim Hortons as outlined in the consent form. Sample Size It was estimated that a convenience sample of 36 was required to analyze the results. Fifty-three patients were accrued, and the 36 surveys that were returned were analyzed. Ethics Approval The study was approved by the Sunnybrook Health Sciences Centre Ethics Board. All patients gave written consent to be involved in the project. Results Survey Results From February 7 to June 19, 2014, 53 patients were recruited, of whom 36 (68%) returned their surveys. The surveys showed that patients’ preferences between the two treatment groups were unbalanced, with 32 patients preferring IAD and four preferring CAD (see Table 1 in Appendix 2). Demographics Descriptive statistics of the two preference groups (IAD and CAD) with different demographic and treatment variables was conducted. Subsequently, using the chi-square test and Fisher exact test, it was examined whether the patient preference (IAD or CAD) was associated with any demographic or treatment variables. Because of the small sample size for patients preferring CAD (n ¼ 4), only statistically significant associations (P < 0.05) found from Fisher exact tests were reported. The demographics are presented in Table 1 in Appendix 2. Although there was a statistically significant difference between treatment choices, where most patients preferred IAD over CAD, there were no statistically significant differences between any of the demographic variables and HT choice. Preference of Patients between IAD and CAD The preferences of the tradeoff table between IAD and CAD revealed a similar ranking pattern of the most important concerns (see Table 2 in Appendix 2). All the differences were categorized by one group rating a factor as ‘‘most important’’ more often and having a lower average rating on the fourpoint Likert scale used in the survey (one, most important; to four, not at all important).

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Discussion The uncertainty from the patients’ and physicians’ perspectives between choosing IAD or CAD is a barrier to optimizing the use of ADT for prostate cancer patients. Niraula et al [7] examined the same population and also found conflicting literature. In accordance with previous studies, these results show that male patients prefer IAD to CAD. This study examined some factors that could affect patient preferences of IAD or CAD. The knowledge of demographics and treatment factors can be used to develop an approach to better address patients’ needs when choosing their treatment. The survey provided further insight into factors of high priority for patients to arrive at their HT decision. The results appear to suggest that patients view quality of life as the most important factor. The prioritization of other factors starts to diverge between IAD- and CAD-preferring patients. Chances of cancer return and overall lifespan were highly prioritized by both groups, but more so by CAD-preferring patients, who also rated risk of death from prostate cancer as more important than IAD-preferring patients. Conversely, general well being was also prioritized by all patients, but more so by IAD-preferring patients. Side effects, such as urinary function, sexual dysfunction, hot flashes, physical function, fatigue, and cardiovascular disease risk, were more influential to IADpreferring patients (see Table 2 in Appendix 2). The results from the present study suggest that patients with locally advanced or recurrent prostate cancer value quality of life the most, regardless of treatment preference, but vary in defining the quality of life. That trend is consistent with a number of trials on health-related quality-of-life tradeoffs with survival benefits [16–19]. King et al demonstrated that loss of libido and urinary incontinence influenced patients’ choices in choosing HT. Patients would rather accept the decrease in overall survival around four months to be able to preserve their sexual function and be urinary continent [17]. Conversely, the results of this study showed that patients who preferred CAD placed a higher importance on overall survival and chances of cancer return and risk of death from prostate cancer. Perhaps patients who prefer CAD value the potential for cancer survival over the quality of that postcancer life. Sexual dysfunction, which was shown in previous literature to have a significant influence on the decisional preference of IAD over CAD, was found to be one of the least important factors for patients in this study [16–17]. This contradictory result may reflect the demographics of this particular patient population, as most of them (69%) reported to be sexually inactive. The patient’s age also appears to have an influence on his decisional preferences, as most patients were aged older than 65 years (81%), and therefore, eligible under Ontario Health Insurance Plan to have the cost of their LHRH agonist injections covered. Therefore, despite a relatively low annual household income among patients and the high cost of LHRH agonist injections (around $300–$400 per month

4

for those under CAD), the free access to HT under the provincial health care plan eliminates cost as a significant factor in treatment decisions. The findings of this pilot study show that patients have varied opinions on how they approach their decision making toward HT. The distinctions revealed in the results underline the importance of better facilitating the decision-making process for locally advanced and recurrent prostate cancer patients. Overall, the study highlights key influences in specific decisional preferences that encourage further exploration in subsequent studies to simulate the decision-making process and help tailor HT decisional preferences to the patient. Limitations Future studies can improve on this pilot study because it was relatively restricted in research design. The pilot had a sample size of 36 patients, and of those, only four had selected CAD. As a result, even statistically significant differences in the data between patient preferences could only indicate divergence of opinions among them, rather than highlight truly significant conclusions that could be made from future studies with a larger patient sample size. Furthermore, the questionnaire and the survey based on the four-point Likert scale both served as quantitative assessments of patients. Inclusion of qualitative methodology can more accurately simulate the interactive environment in which patients’ decision making takes place, including the use of focus groups or direct interviews with the patients. Incomplete understanding of the questionnaire and survey on the patient’s part may lead to the inability to uncover reliable trends in their preferences. Because all eligible patients under this study understood English, this largely Caucasian, English-speaking cohort may have an advantage in language comprehension, whereas patients of other demographics may experience difficulty understanding the same questions [20–21]. Another limitation is that patients were approached from a single oncologist clinic by either a Determinants of Community Health-2 (DOCH-2) student or a research assistant; the lack of variation in location may serve to hide or exaggerate discrepancies found in the results. In addition, patients may have been biased by their current or past treatment. Future studies may benefit by using a larger proportion of patients in each subgroup and increasing the variety in their demographic, and including more-recently diagnosed patients. Conclusion Overall, the results from the pilot study show that patients largely prefer IAD over CAD. There are variations in patient opinions leading to their preferences, such that a larger study will more accurately generalize these results and uncover possible significances that lead to the divergence in preference between different patients. The varying views among patients indicate that a tailored approach to patients’ HT choice may better address their individual needs, which a more thorough

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process involving the patient and set clinical guidelines will help achieve. Acknowledgments The authors thank all the patients who participated in this research project and Ewa Stewart for editorial assistance. References [1] Canadian Cancer Society’s Advisory Committee on Cancer Statistics (2014). Canadian Cancer Statistics 2014. Toronto, ON: Canadian Cancer Society. [2] Hussain, M., Tangen, C. M., & Hingano, C. S., et al. (2013). Intermittent versus continuous androgen deprivation in hormone sensitive metastatic prostate cancer. N Engl J Med 368, 1314–1325. [3] Mottet, N., Damme, J. V., Salim, L., Russel, C., Leitenberger, A., & Wolff, J. M. (2012). Intermittent hormonal therapy in the treatment of metastatic prostate cancer: a randomized trial. BJU International 10, 1262–1269. [4] Salonen, A. J., Taari, K., Ala-Opas, M., Viitanen, J., Lundstedt, S., & Tammela, T. L. J. (2013). Advanced prostate cancer treated with intermittent or continuous androgen deprivation in the randomised FinnProstate Study VII: quality of life and adverse effects. Eur Urol 63(1), 111–120. [5] Klotz, L. (2013). Intermittent versus continuous androgen deprivation therapy in advanced prostate cancer. Curr Urol Rep 14(3), 159–167. [6] Kuo, K. F., Hunter-Merrill, R., & Gulati, R., et al. (2015). Relationships between times to testosterone and prostate-specific antigen rises during the first ‘‘off treatment’’ interval of intermittent androgen deprivation are prognostic for castration-resistance in men with nonmetastatic prostate cancer. Clinical Genitourinary Cancer 13(1), 10–16. [7] Niraula, S., Le, L. W., & Tannock, I. F. (2013). Treatment of prostate cancer with intermittent versus continuous androgen deprivation: a systematic review of randomized trials. J Clin Oncol 31, 1–9. [8] Davison, B. J., Gleave, M. E., Goldenberg, S. L., Degner, L. F., Hoffart, D., & Berkowitz, J. (2002). Assessing information and decision preferences of men with prostate cancer and their partners. Cancer Nurs 25(1), 42–49. [9] Everett, R. A., Packer, A. M., & Kuang, Y. (2014). Can mathematical models predict the outcomes of prostate cancer patients undergoing intermittent androgen deprivation therapy? Biophys. Rev. Lett 09, 173–191.

[10] Sommers, B. D., Beard, C. J., & D’Amico, A. V., et al. (2007). Decision analysis using individual patient preferences to determine optimal treatment for localized prostate cancer. Cancer 110(10), 2210–2217. [11] Resnick, M. J., Guzzo, T. J., Cowan, J. E., Knight, S. J., Carroll, P. R., & Penson, D. F. (2013). Factors associated with satisfaction with prostate cancer care: results from Cancer of the Prostate Strategic Urologic Research Endeavour (CaPSURE). BJU Int 111(2), 213–220. [12] Lloyd, A., Penson, D., Dewilde, S., & Kleinman, L. (2007). Eliciting patient preferences for hormonal therapy options in the treatment of metastatic prostate cancer. Prostate cancer and prostatic diseases 11(2), 153–159. [13] Aning, J. J., Wassersug, R. J., & Goldenberg, S. L. (2012). Patient preference and the impact of decision-making aids on prostate cancer treatment choices and post-intervention regret. Curr Oncol 19(Suppl 3), S37–S44. [14] Sanda, M. G., Dunn, R. L., & Michalski, J., et al. (2008). Quality of life and satisfaction with outcome among prostate-cancer survivors. N Engl J Med 358(12), 1250–1261. [15] Botrel, T. E., Clark, O., & dos Reis, R. B., et al. (2014). Intermittent versus continuous androgen deprivation for locally advanced, recurrent or metastatic prostate cancer: a systematic review and meta-analysis. BMC Urol 14, 9. [16] De Bekker-Grob, E. W., Bliemer, M. C. J., & Donkers, B., et al. (2013). Patients’ and urologists’ preferences for prostate cancer treatment: a discrete choice experiment. Br J Cancer 109(3), 633–640. [17] King, M. T., Viney, R., & Smith, D. P., et al. (2012). Survival gains needed to offset persistent adverse treatment effects in localised prostate cancer. Br J Cancer 106(4), 638–645. [18] Helgason, A. R., Adolfsson, J., Dickman, P., Fredrikson, M., Arver, S., & Steineck, G. (1996). Waning sexual function–the most important disease-specific distress for patients with prostate cancer. Br J Cancer 73(11), 1417–1421. [19] Wilke, D. R., Krahn, M., Tomlinson, G., Bezjak, A., Rutledge, R., & Warde, P. (2010). Sex or survival: short-term versus long-term androgen deprivation in patients with locally advanced prostate cancer treated with radiotherapy. Cancer 116(8), 1909–1917. [20] Knight, S. J., Siston, A. K., & Chmiel, J. S., et al. (2004). Ethnic variation in localized prostate cancer: a pilot study of preferences, optimism, and quality of life among black and white veterans. Clin Prostate 3(1), 31–37. [21] Hosain, G. M. M., Sanderson, M., Du, X. L., Chan, W., & Strom, S. S. (2012). Racial/ethnic differences in treatment discussed, preferred, and received for prostate cancer in a tri-ethnic population. Am J Mens Health 6(3), 249–257.

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(continued)

Appendix 1 Tradeoff Table between Intermittent Androgen Deprivation (IAD) and Continuous Androgen Deprivation (CAD) Therapy

Demographics

Very Quite A Little Not at all Important Important Important Important

Demographics

IAD

CAD

2

3

4

Similar Similar

Similar Similar

1

2

3

4

Higher overall risk in studies although not statistically significant Lower overall risk in studies although not statistically significant Better

Lower overall risk in studies although not statistically significant Higher overall risk in studies although not statistically significant Worse

1

2

3

4

1 1 1 1

2 2 2 2

3 3 3 3

4 4 4 4

Lower

Higher

1 1 1 1

2 2 2 2

3 3 3 3

4 4 4 4

Lower Better Better Lower

Higher Worse Worse Higher

The risk of dying from other causes Quality of life Side effects Sexual dysfunction and libido Hot flashes Urinary function Physical function Fatigue Other factors Cost Cardiovascular disease risk Activities of daily living General well being Other factors not included in this questionnaire (please specify):

1

Overall lifespan Chances of the cancer returning The risk of dying from prostate cancer

Lower Same

Higher Same

Better Better

Worse Worse

The risk of dying from other causes

Quality of life Side effects Sexual dysfunction and libido Hot flashes Urinary function Physical function Fatigue Other factors Cost Cardiovascular disease risk Activities of daily living General well being

Appendix 2 Table 1 Survey Demographics for Patients Choosing between IAD and CAD Demographics

Summary Both treatment options have the ‘‘same’’ overall lifespan, chance of the cancer returning, and cardiovascular risk, ‘‘but the differences’’ in these treatments include: B CAD has a lower likelihood of death related to prostate cancer than IAD; B CAD has a higher likelihood of deaths not related to prostate cancer; B CAD is related to lower quality of life scores than IAD; B CAD has more severe side effects (sexual dysfunction, hot flashes, urinary function, impaired physical function, and fatigue); B CAD costs more than IAD. Given these similarities and differences, which treatment plan would you prefer? Intermittent Androgen Deprivation OR Continuous Androgen Deprivation. How did you arrive at this decision? If you were in this situation, tell us how important the following factors were in making your decision. Demographics Overall lifespan Chances of the cancer returning The risk of dying from prostate cancer

Very Quite A Little Not at all Important Important Important Important 1 1

2 2

3 3

4 4

1

2

3

4

Average age (y) Treatment* Salvage HT (3-step HT, after failed treatment) Adjuvant HT (HT þ RT, for high-risk patients) HT for metastatic cancer patients Previous HT Injection Injection þ pill None Marital status Married Single Distance to OCC <10 km >10 km Comorbidities None 1þ chronic condition 2þ chronic conditions Highest level education Elementary High school Employment Employed Retired or unemployed Health insurance Fully insured Partially insured None

IAD (n ¼ 32)

CAD (n ¼ 4)

n

n

72.97

D. Chun-Leung Chau et al./Journal of Medical Imaging and Radiation Sciences

% Of Total CAD

71

18

56.25

0

0

10

31.25

4

100.00

4

12.5

0

0

26 5 1

81.25 15.63 3.13

3 1 0

75.00 25.00 0

28 4

87.50 12.50

2 2

50.00 50.00

9 23

28.13 71.88

1 3

25.00 75.00

8 16 8

25.00 50.00 25.00

2 2 0

50.00 50.00 0

5 27

15.63 84.38

1 3

25.00 75.00

6 26

18.75 81.25

2 2

50.00 50.00

25 5 2

78.13 15.63 6.25

3 0 1

75.00 0 25.00

(continued on next page)

(continued)

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% Of Total IAD

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Table 1 (continued ) Demographics

Annual household income <40K >40K Decline to disclose Sexual activity Yes No Decline to disclose Pretreatment PSAy <10 >10 Radiation RT only RT with surgery

IAD (n ¼ 32)

CAD (n ¼ 4)

n

n

% Of Total IAD

% Of Total CAD

7 19 6

21.88 59.38 18.75

0 3 1

0 75.00 25.00

6 23 3

18.75 21.88 6.25

1 2 1

25.00 50.00 25.00

23 9

71.88 28.12

2 2

50.00 50.00

21 11

65.63 34.38

3 1

75.00 25.00

CAD, continuous androgen deprivation therapy; IAD, intermittent androgen deprivation therapy; HT, hormonal treatment; PSA, prostatespecific antigen; OCC, Odette Cancer Centre; RT, radiotherapy. * Fisher test indicated a significant difference (P ¼ .044) associated with IAD vs. CAD. y Fisher test indicated marginal significant difference (P ¼ .0705) associated with IAD vs. CAD.

Table 2 Tradeoff Survey for Patients Choosing between IAD and CAD Factors

Overall lifespan Chances of return Risk of death from prostate cancer Risk of death from other causes Quality of life Sexual dysfunction Hot flashes Urinary function Physical function Fatigue CVD risk Activities of daily living General well being

IAD (n ¼ 32)

CAD (n ¼ 4)

n

% Rated with Most Importance

Mean Rating Value

n

% Rated with Most Importance

Mean Rating Value

21 25 18

65.6 78.1 56.3

1.500 1.406 1.719

4 4 3

100.0 100.0 75.0

1.000 1.000 1.750

11

34.4

2.156

1

25.0

2.750

27 12 11 19 18 17 17 18

84.4 37.5 34.4 59.4 56.3 53.1 53.1 56.3

1.156 2.129 2.156 1.500 1.563 1.594 1.781 1.531

4 1 1 2 1 1 1 2

100.0 25.0 25.0 50.0 25.0 25.0 25.0 50.0

1.000 2.750 2.500 2.000 2.750 2.250 2.250 2.000

22

68.8

1.375

3

75.0

1.500

CAD, continuous androgen deprivation therapy; CVD, cardiovascular diseases; IAD, intermittent androgen deprivation therapy.

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