- Email: [email protected]
Frequent Use of Complementary Medicine by Prostate Cancer Patients
European Urology
European Urology 43 (2003) 604–608
Frequent Use of Complementary Medicine by Prostate Cancer Patients Anton Ponholzera,b, Gerhard Struhalc, Stephan Madersbachera,b,* a
Department of Urology and Andrology, Donauspital - SMZO, Langobardenstrasse 122, Vienna A-1220, Austria Ludwig Boltzmann Institute of Urological Oncology, Donauspital - SMZO, Langobardenstrasse 122, A-1220 Vienna, Austria c Hartmann-Spital, Vienna, Austria b
Accepted 26 March 2003
Abstract Objectives: To assess the use of complementary and alternative medicine (CAM) by prostate cancer patients and to characterize CAM-users in this population. Methods: Prostate cancer patients who underwent routine follow-up at urological practices completed an anonymous, self-administered questionnaire on lower urinary tract function, sexuality, quality of life and use of CAM. All patients with biopsy proven cancer irrespective of age, stage and therapy were eligible. Results: 822 men (69 8:5 years; range: 45–95) entered this survey. 245 men (29.8%) used at least one form of CAM, most frequent forms were fat-reduced diet (13.3%), selenium (10.8%) and vitamin E (9.3%). CAM-users did not differ regarding age (68.6 vs. 69.2 years), time interval between diagnosis and current evaluation (4.4 vs. 3.8 years) and PSA at diagnosis (24.9 vs. 18.5 ng/ml) from non-users. CAM-use was dependent on primary therapy (radical prostatectomy: 23.3%, radiotherapy: 31.6%, endocrine therapy: 38.8%) and disease progression. CAMusers were generally less satisfied with their treatment and rated health status and quality of life lower than those not using CAM (all p < 0:001). Conclusions: CAM is used by almost 1/3 of prostate cancer patients in Austria, particularly by those with disease progression, impaired quality of life and treatment satisfaction. Urologists have to be aware of this fact and require a detailed knowledge on this issue to provide objective and evidence-based information. # 2003 Elsevier Science B.V. All rights reserved. Keywords: Oncology; Alternative medicine; Prostate; Prevention; Quality of life
1. Introduction Complementary and alternative medicine (CAM) defined as any kind of supportive measures used to complement evidence based treatment is becoming increasingly popular for health preservation, disease prevention and as an adjunct treatment of neoplastic diseases [1,2]. In the USA, the percentage of CAMusers in the general population increased from 34% to 42% between 1990 and 1997 and currently more visits are reported to alternative health practitioners than total visits to all primary care physicians [1,2]. It *
Corresponding author. Tel.: þ43-1-28802-3700; Fax: þ43-1-28802-3780. E-mail addresses: [email protected], [email protected] (S. Madersbacher).
has been estimated that 7–64% of all oncological patients (average 31%) use some form of CAM [3]. For several reasons, prostate cancer is a particularly attractive target for CAM [4–6]. First, because epidemiological data document a 10–100 fold lower incidence in Asia as compared to Europe/USA (despite similar incidences of tumour precursors) suggesting that environmental factors particularly nutrition seem to be important co-factors for prostate cancer development, yet the association between obesity and prostate cancer risk is controversially discussed [7,8]. Secondly, experimental studies have demonstrated an inhibitory effect e.g. of a fat-reduced diet or vitamin E on prostate cancer cells [4–6]. And finally, encouraging data of interventional studies with vitamin E or selenium for prostate cancer risk reduction are available,
0302-2838/03/$ – see front matter # 2003 Elsevier Science B.V. All rights reserved. doi:10.1016/S0302-2838(03)00155-6
A. Ponholzer et al. / European Urology 43 (2003) 604–608
although in two highly popularised studies prostate cancer was not the primary end-point [9,10]. According to our knowledge there exist no descriptive data regarding the use of CAM by prostate cancer patients in Europe. Prompted by this fact and by recent US-data indicating their popularity in prostate cancer patients we assessed the use of CAM by prostate cancer patients in Austria [11–14]. To cover the entire disease spectrum and to present real-life experience, patients with biopsy proven cancer regardless of age, tumour stage and type of therapy seen at urological practices were eligible. 2. Methods Between January and June 2002 we conducted a survey assessing quality of life of men undergoing routine follow-up for prostate cancer at 28 urological practices or outpatient clinics throughout Austria. A consecutive series of patients were invited to complete an anonymous, self-administered questionnaire regardless of age, extent of disease or cancer therapy. Eligible patients all had histologically proven adenocarcinoma of the prostate. The first part of the questionnaire (16 items) covered several aspects of prostate cancer, such as age at diagnosis, diagnostic procedures, presence of symptoms at diagnosis, Prostate specific antigen (PSA) value at diagnosis, time interval between diagnosis and current evaluation, last PSA-value, first/second line treatment and therapy-related side-effects. The second part (13 items) investigated several aspects of lower urinary tract function; these questions were extracted from the International Prostate Symptom Score and the Bristol-LUTS questionnaire [15]. In the third part (8 items), sexual function was assessed by using questions from the International Index of Erectile Function (IIEF-5) [16]; the effect of treatment on sexual function was quantified by three additional questions. Quality of life was covered by 10 items, which were extracted from the SF-36 [17]. In addition, patients were also asked whether they had or are currently using CAM. If yes, patients were asked to specify the form of CAM with the aid of an attached list. 2.1. Statistical analysis Statistical analyses were performed using SPSS, version 10.1 for Windows. Beside descriptive statistics for prevalence rates t-test was used to assess differences between men using CAM or not. All data were tested for their Gaussian distribution. All hypothesis testing was 2-sided with p < 0:05 considered significant.
605
Last available PSA was 3:3 23:0 ng/ml; in 76.6% of patients PSA was less than 0.5 ng/ml (Table 1). As second-line treatment 45.8% received endocrine treatment and 23% external beam radiation within a mean of 3.5 years after first line treatment; hence almost 70% had a combination of at least two standard treatment modalities (Table 1). A total of 245 (29.8%) men have used or are currently using at least one type of CAM. The most frequently used forms were low-fat diet (13.3%), selenium (10.8%), vitamin E (9.3%), mistletoe lectin (8.6%), multivitamins (7.4%) and tomatoes (6.8%). One third of users (33%) consumed only one form of CAM, 25% two, 19% three and 23% four or more different forms. We subsequently compared clinical characteristics between CAM-users (n ¼ 245) and non-users (n ¼ 577) (Table 1). Both groups were comparable (p > 0:05) regarding age, time interval between diagnosis and current evaluation, presence/absence of metastases and PSA at diagnosis and last PSA-value (Table 1). Use of CAM was dependent on primary therapy and—in part—on disease progression. In the radical prostatectomy group 23.3% used CAM, in those who underwent radiotherapy 31.6% and in those who received primary endocrine therapy 38.8%. In the radical prostatectomy group CAM-use was more frequent in those with PSA progression (34.6% vs. 22.9%); such a trend was not demonstrable in the radiotherapy and endocrine-therapy group. In those considered to have stable disease (PSA <0.5 ng/ml) 28.5% used CAM as compared to 38.5% in those with PSA 0.5 ng/ml. Analysis of quality of life and treatment-satisfaction issues revealed that three of the 10 items were different in CAM-users, who were less satisfied with their therapy and rated their physical state and quality of life in general lower (Fig. 1). Please note that a high score in ‘‘treatment satisfaction’’ indicates low satisfaction, these patients took CAM more frequently (Fig. 1); in contrast, high scores for ‘‘physical state’’ and ‘‘quality of life’’ indicate good physical state and quality of life, these patients were less likely to consume CAM (Fig. 1).
4. Discussion 3. Results Within 6 months, 822 patients (698:5 years; mean standard deviation; range: 45–95 years) were recruited. Serum PSA at diagnosis was 20:0 52:0 ng/ml, mean time interval between diagnosis and current evaluation 3:9 3:1 years (Table 1). First-line treatment was radical prostatectomy in 54%, external beam radiation in 11.8% and endocrine treatment in 23.2% (Table 1).
The use of CAM for treatment and prevention of neoplastic diseases continues to receive an increasing level of attention from the medical community, media, support groups and internet [1,2]. Given the increasing public awareness of prostate cancer it would be reasonable to hypothesize that the use of CAM is also increasing among prostate cancer patients [18]. In our unselected sample of 882 patients, 30% have used
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A. Ponholzer et al. / European Urology 43 (2003) 604–608
Table 1 Clinical characteristics of the entire study population as well as CAM-users and non-users Total population (n ¼ 822)
CAM user (n ¼ 245)
No CAM use (n ¼ 577)
Mean-age [years] (SD) (range) <60 years 60–70 years 70–80 years >80 years
69.0 (8.5) (45–95) 16.0% 38.0% 37.0% 9.0%
68.6 (8.9) (50–95) 19.6% 38.4% 32.2% 9.8%
69.2 (8.4) (45–91) 14.3% 38.7% 28.4% 8.6%
Diagnosis known since [years] (SD) (range) <1 years 1–3 years 3–5 years 5–7 years >7 years
3.9 (3.1) (0–30) 2.3% 34.7% 29.5% 21.5% 12.0%
4.4 (3.5) (0–30) 1.3% 31.1% 31.5% 20.6% 15.5%
3.8 (2.9) (0–30) 2.7% 36.6% 29.4% 18.2% 13.1%
11.5% 88.5%
15.0% 85.0%
9.7% 90.3%
Metastases at diagnosis yes no PSA at diagnosis [ng/ml] (SD) (highest) First line treatment radical prostatectomy radiotherapy endocrine treatment others radiotherapy þ endocrine treatment
20.0 (52.0) (843)
24.9 (62) (843)
18.5 (47.0) (739)
54.0% 11.8% 23.2% 3.9% 7.1%
51.2% 12.1% 24.8% 3.4% 8.5%
59.7% 11.6% 19.4% 4.1% 5.2%
Last PSA [ng/ml] (SD) (range) last PSA before (years) <0.5 ng/ml
3.3 (23) (0–491) 0.5 76.6%
4.4 (20.2) (0–195) 0.6 70.9%
2.9 (24.4) (0–491) 0.5 79.2%
23.0% 45.8% 7.7%
26.2% 57.6% 12.6%
20.9% 39.0% 4.5%
Second line treatment external beam radiation hormone treatment analgetic therapy
or are currently using at least one form of CAM. These data, being the first of this kind in Europe, are in line with four recent US studies [11–14]. Nam et al. reported that prostate cancer patients presenting to urology clinics and support groups used CAM in 27% and 39%, respectively [11]. Wilkinson et al. performed a postal survey of 1099 patients attending 6 urology institutions for prostate
cancer management [14]. In this group, 24% and 18% of patients had been or were currently using CAM [14]. Lippert et al. reported that 43% of 190 patients who were treated with a curative intent (surgery or radiotherapy) used CAM [12]; Kao et al. studied 50 consecutive patients undergoing radiation therapy and reported on 37% CAM-users [13].
Fig. 1. CAM-users are less satisfied with their treatment and report on an impaired quality of life and physical state. (A) Overall treatment satisfaction on a 6point scale (1: very satisfied; 6: very unsatisfied). (B) Rating of physical state on a 10-point scale (1: very bad; 10: excellent). (C) Rating of overall quality of life on a 10-point scale (1: very bad; 10: excellent). Mean and standard errors of the mean are given.
A. Ponholzer et al. / European Urology 43 (2003) 604–608
The four most popular forms of CAM in our population were low-fat diet, selenium, vitamin E and mistletoe lectins. This distribution correlates quite well with that of the above-mentioned US-studies. In Nam’s series, vitamin E, garlic, low-fat diet and selenium were the four most popular forms, in Wilkinson’s one it were low-fat diet, multivitamins, green tea and selenium [11,14]. This frequent use of CAM is in clear contrast to the fact that to date no definite proof of a beneficial effect of CAM in prostate cancer has been demonstrated in a clinical study that will withstand rigid scientific scrutiny. However, there is growing evidence, that nutritional factors, especially a low-fat diet, soy-products, vitamin E and selenium have biological effects against prostate cancer [8,19–23]. However, further welldesigned, prospective, randomised, placebo-controlled studies are needed to definitely proof their (chemo)preventive role in prostate cancer; such trials are currently underway [24]. However, the high prevalence of CAM-use in the general population and by prostate cancer patients may pose a challenge in randomising patients for such large-scale trials. According to our study, CAM-use was correlated to the type of primary therapy, disease progression, quality of life and overall satisfaction with prostate cancer treatment. Of those who underwent radical prostatectomy 23.3% used CAM, in the radiotherapy group 31.6% and the primary endocrine group 38.8%. A similar trend, i.e. lowest percentages in the radical prostatectomy group (15.4%) and highest in the endocrine therapy group (31.0%) has been made by Wilkinson et al. [14]. What are the reasons for this frequent use of CAM by prostate cancer patients? Undoubtedly, a number of factors are involved. Prostate cancer patients using CAM believed in 90% that it would them help to live longer and improve quality of life, 60% thought it would relieve symptoms and 47% expected it to cure the disease [14]. In addition, 81% reported feeling more hopeful and 63% thought they had more control over the disease [14]. The greater use by patients with advanced disease and lower quality of life may present a marker for distress or may signal unstated patient needs. Some patients may be seeking a more holistic approach to health care. Sociodemographic factors, such as educational level and income are also involved
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and have a positive association with the use of CAM [13,14]. Finally, patients might be attracted by the good tolerability of CAM. A draw-back of our study is that we did not specifically ask for the reasons for CAM-use, for patient expectations and who recommended the CAM-use. This study was primarily designed to assess quality of life in patients with prostate cancer in general and not to evaluate CAM-use in great detail. However, prompted by our data demonstrating frequent use of CAM by prostate cancer patients in our country, we currently consider to design a large-scale, multicenter study to specifically adress these important issues. The majority of prostate cancer patients using CAM do not discuss or inform their doctors [14]. This might be because patients do not believe that physicians know much about these supplements and that they may be biased against them. Doctors are usually unfamiliar with CAM and may be uncomfortable discussing them with their patients or unable to provide adequate guidance. This bias is rooted in the fact that most physicians have never received training in this area. Interestingly, patients who had a dialogue with their family physician or urologist were significantly less likely to use CAM [14]. It is likely that physicians communicate negative attitudes when discussing CAM, based—in part—on the current lack of evidence-based data [14]. In conclusion this study demonstrates that almost one third of prostate cancer patients in Austria have used or are currently using at least one form of CAM. This observation raises several relevant issues: (i) urologists have to be aware of this fact and require a detailed knowledge on this complex topic; (ii) urologists should ask their patients regarding use of CAM and discuss pros and cons [25]; (iii) the undisclosed use of CAM may interfere with conventional treatment and may even have potential severe side effects (e.g. thrombembolic events with PC-SPES); (iv) the frequent use of CAM raises methodological concerns for prostate cancer trials. The use of CAM might bias study results and should therefore be assessed/excluded at inclusion; (v) further studies on CAM-use in other parts of Europe as well as on patient’s attitudes and motivations for use are required. In addition further studies to characterise CAM-users and to determine the interrelation of CAM with ‘‘conventional’’ evidence-based medicine are urgently needed.
References [1] Eisenberg DM, Kessler RC, Foster C, Norlock FE, Calkins DR, Delbanco TL. Unconventional medicine in the United States. Prevalence, costs and patterns of use. N Engl J Med 1993;328:246–52.
[2] Eisenberg DM, Davis RB, Ettner SL, Appel S, Wilkey S, VanRompay M, et al. Trends in alternative medicine use in the United States, 1990–1997. JAMA 1998;280:1569–75.
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[3] Ernst E, Cassileth BR. The prevalence of complementary alternative medicine in cancer: a systematic review. Cancer 1998;83:777–82. [4] Kelloff GJ, Lieberman R, Steele VE, Boone CW, Lubet RA, Kopelovitch L, et al. Chemoprevention of prostate cancer: concepts and strategies. Eur Urol 1999;35:342–50. [5] Fair WR. Back to the future—The role of complementary medicine in urology. J Urol 1999;162:411–20. [6] Schulman CC, Anderson JB, Bangma CH, Marberger MJ. Prevention and screening. Eur Urol Suppl 2002;1(7):3–9. [7] Hsing AW, Devesa SS. Trends and patterns of prostate cancer: what do they suggest? Epidem Rev 2001;23:3–13. [8] Nomura AM. Body size and prostate cancer. Epidem Rev 2001;23: 126–31. [9] Heinonen OP, Albanes D, Virtamo J, Taylor PR, Huttunen JK, Hartman AM, et al. Prostate cancer and supplementation with atocopherol and b-carotene: incidence and mortality in a controlled trial. J Natl Cancer Inst 1998;90:440–6. [10] Clark LC, Combs Jr GF, Turnbull BW, Slate EH, Chalker DK, Chow J, et al. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin: a randomized controlled clinical trial. JAMA 1996;276:1957–63. [11] Nam RK, Fleshner N, Rakovitch E, Klotz L, Trachtenberg J, Choo R, et al. Prevalence and patterns of the use of complementary therapies among prostate cancer patients: an epidemiological analysis. J Urol 1999;161:1521–4. [12] Lippert MC, McClain R, Boyd JC, Theodorescu D. Alternative medicine use in patients with localized prostate carcinoma treated with curative intent. Cancer 1999;86:2642–8. [13] Kao GD, Devine P. Use of complementary health practices by prostate carcinoma patients undergoing radiation therapy. Cancer 2000;88:615–9. [14] Wilkinson S, Gomella LG, Smith JA, Brawer MK, Dawson NA, Wajsman Z, et al. Attitudes and use of complementary medicine in men with prostate cancer. J Urol 2002;168:2505–9.
[15] Jackson S, Donovan J, Brookes S, Eckford S, Swithinbank L, Abrams P. The Bristol female lower urinay tract symptoms questionnaire: development and psychometric testing. Br J Urol 1996;77:805–12. [16] Rosen RC, Riley A, Wagner G, Osterloh IH, Kirkpatrick J, Mishra A. The International Index of Erectile Function (IIEF): a multidimensional scale for assessment of erectile function. Urology 1997;49: 822–30. [17] Jenkinson C, Coulter A, Wright L. Short Form 36 (SF36) health survey questionnaire: normative data for adults of working age. BMJ 1993;306:1437–40. [18] Zimmerman RA, Thompson Jr IM. Prevalence of complementary medicine in urologic practice. A review of recent studies with emphasis on use among prostate cancer patients. Urol Clin North Am 2002;29:1–9. [19] Giovannucci E, Rimm EB, Colditz GA, Stampfer MJ, Ascherio A, Chute CC, et al. A prospective study of dietary fat and risk of prostate cancer. J Natl Cancer Inst 1993;85:1571–9. [20] Adlercreutz H, Mazur W. Phyto-oestrogens and Western diseases. Ann Med 1997;29:95–120. [21] Moyad MA. Selenium and vitamin E supplements for prostate cancer: evidence or embellishment. Urology 2002;59(Suppl 4A):9–19. [22] Wang Y, Corr JG, Thaler HT, Tao Y, Fair WR, Heston WD. Decreased growth of established human prostate LNCaP tumors in nude mice fed a low-fat diet. J Natl Cancer Inst 1995;87:1456–62. [23] Moyad MA. Fat reduction to prevent prostate cancer: waiting for more evidence? Curr Opin Urol 2001;11:457–61. [24] Klein EC, Thompson IM, Lippman SM, Goodman PJ, Albanes D, Taylor PR, et al. SELECT: the next prostate cancer prevention trial. J Urol 2001;166:1311–5. [25] Weiger WA, Smith M, Boon H, Richardson MA, Kaptchuk TJ, Eisenberg DM. Advising patients who seek complementary and alternative medical therapies for cancer. Ann Intern Med 2002;137: 889–903.
European Urology 43 (2003) 604–608
Frequent Use of Complementary Medicine by Prostate Cancer Patients Anton Ponholzera,b, Gerhard Struhalc, Stephan Madersbachera,b,* a
Department of Urology and Andrology, Donauspital - SMZO, Langobardenstrasse 122, Vienna A-1220, Austria Ludwig Boltzmann Institute of Urological Oncology, Donauspital - SMZO, Langobardenstrasse 122, A-1220 Vienna, Austria c Hartmann-Spital, Vienna, Austria b
Accepted 26 March 2003
Abstract Objectives: To assess the use of complementary and alternative medicine (CAM) by prostate cancer patients and to characterize CAM-users in this population. Methods: Prostate cancer patients who underwent routine follow-up at urological practices completed an anonymous, self-administered questionnaire on lower urinary tract function, sexuality, quality of life and use of CAM. All patients with biopsy proven cancer irrespective of age, stage and therapy were eligible. Results: 822 men (69 8:5 years; range: 45–95) entered this survey. 245 men (29.8%) used at least one form of CAM, most frequent forms were fat-reduced diet (13.3%), selenium (10.8%) and vitamin E (9.3%). CAM-users did not differ regarding age (68.6 vs. 69.2 years), time interval between diagnosis and current evaluation (4.4 vs. 3.8 years) and PSA at diagnosis (24.9 vs. 18.5 ng/ml) from non-users. CAM-use was dependent on primary therapy (radical prostatectomy: 23.3%, radiotherapy: 31.6%, endocrine therapy: 38.8%) and disease progression. CAMusers were generally less satisfied with their treatment and rated health status and quality of life lower than those not using CAM (all p < 0:001). Conclusions: CAM is used by almost 1/3 of prostate cancer patients in Austria, particularly by those with disease progression, impaired quality of life and treatment satisfaction. Urologists have to be aware of this fact and require a detailed knowledge on this issue to provide objective and evidence-based information. # 2003 Elsevier Science B.V. All rights reserved. Keywords: Oncology; Alternative medicine; Prostate; Prevention; Quality of life
1. Introduction Complementary and alternative medicine (CAM) defined as any kind of supportive measures used to complement evidence based treatment is becoming increasingly popular for health preservation, disease prevention and as an adjunct treatment of neoplastic diseases [1,2]. In the USA, the percentage of CAMusers in the general population increased from 34% to 42% between 1990 and 1997 and currently more visits are reported to alternative health practitioners than total visits to all primary care physicians [1,2]. It *
Corresponding author. Tel.: þ43-1-28802-3700; Fax: þ43-1-28802-3780. E-mail addresses: [email protected], [email protected] (S. Madersbacher).
has been estimated that 7–64% of all oncological patients (average 31%) use some form of CAM [3]. For several reasons, prostate cancer is a particularly attractive target for CAM [4–6]. First, because epidemiological data document a 10–100 fold lower incidence in Asia as compared to Europe/USA (despite similar incidences of tumour precursors) suggesting that environmental factors particularly nutrition seem to be important co-factors for prostate cancer development, yet the association between obesity and prostate cancer risk is controversially discussed [7,8]. Secondly, experimental studies have demonstrated an inhibitory effect e.g. of a fat-reduced diet or vitamin E on prostate cancer cells [4–6]. And finally, encouraging data of interventional studies with vitamin E or selenium for prostate cancer risk reduction are available,
0302-2838/03/$ – see front matter # 2003 Elsevier Science B.V. All rights reserved. doi:10.1016/S0302-2838(03)00155-6
A. Ponholzer et al. / European Urology 43 (2003) 604–608
although in two highly popularised studies prostate cancer was not the primary end-point [9,10]. According to our knowledge there exist no descriptive data regarding the use of CAM by prostate cancer patients in Europe. Prompted by this fact and by recent US-data indicating their popularity in prostate cancer patients we assessed the use of CAM by prostate cancer patients in Austria [11–14]. To cover the entire disease spectrum and to present real-life experience, patients with biopsy proven cancer regardless of age, tumour stage and type of therapy seen at urological practices were eligible. 2. Methods Between January and June 2002 we conducted a survey assessing quality of life of men undergoing routine follow-up for prostate cancer at 28 urological practices or outpatient clinics throughout Austria. A consecutive series of patients were invited to complete an anonymous, self-administered questionnaire regardless of age, extent of disease or cancer therapy. Eligible patients all had histologically proven adenocarcinoma of the prostate. The first part of the questionnaire (16 items) covered several aspects of prostate cancer, such as age at diagnosis, diagnostic procedures, presence of symptoms at diagnosis, Prostate specific antigen (PSA) value at diagnosis, time interval between diagnosis and current evaluation, last PSA-value, first/second line treatment and therapy-related side-effects. The second part (13 items) investigated several aspects of lower urinary tract function; these questions were extracted from the International Prostate Symptom Score and the Bristol-LUTS questionnaire [15]. In the third part (8 items), sexual function was assessed by using questions from the International Index of Erectile Function (IIEF-5) [16]; the effect of treatment on sexual function was quantified by three additional questions. Quality of life was covered by 10 items, which were extracted from the SF-36 [17]. In addition, patients were also asked whether they had or are currently using CAM. If yes, patients were asked to specify the form of CAM with the aid of an attached list. 2.1. Statistical analysis Statistical analyses were performed using SPSS, version 10.1 for Windows. Beside descriptive statistics for prevalence rates t-test was used to assess differences between men using CAM or not. All data were tested for their Gaussian distribution. All hypothesis testing was 2-sided with p < 0:05 considered significant.
605
Last available PSA was 3:3 23:0 ng/ml; in 76.6% of patients PSA was less than 0.5 ng/ml (Table 1). As second-line treatment 45.8% received endocrine treatment and 23% external beam radiation within a mean of 3.5 years after first line treatment; hence almost 70% had a combination of at least two standard treatment modalities (Table 1). A total of 245 (29.8%) men have used or are currently using at least one type of CAM. The most frequently used forms were low-fat diet (13.3%), selenium (10.8%), vitamin E (9.3%), mistletoe lectin (8.6%), multivitamins (7.4%) and tomatoes (6.8%). One third of users (33%) consumed only one form of CAM, 25% two, 19% three and 23% four or more different forms. We subsequently compared clinical characteristics between CAM-users (n ¼ 245) and non-users (n ¼ 577) (Table 1). Both groups were comparable (p > 0:05) regarding age, time interval between diagnosis and current evaluation, presence/absence of metastases and PSA at diagnosis and last PSA-value (Table 1). Use of CAM was dependent on primary therapy and—in part—on disease progression. In the radical prostatectomy group 23.3% used CAM, in those who underwent radiotherapy 31.6% and in those who received primary endocrine therapy 38.8%. In the radical prostatectomy group CAM-use was more frequent in those with PSA progression (34.6% vs. 22.9%); such a trend was not demonstrable in the radiotherapy and endocrine-therapy group. In those considered to have stable disease (PSA <0.5 ng/ml) 28.5% used CAM as compared to 38.5% in those with PSA 0.5 ng/ml. Analysis of quality of life and treatment-satisfaction issues revealed that three of the 10 items were different in CAM-users, who were less satisfied with their therapy and rated their physical state and quality of life in general lower (Fig. 1). Please note that a high score in ‘‘treatment satisfaction’’ indicates low satisfaction, these patients took CAM more frequently (Fig. 1); in contrast, high scores for ‘‘physical state’’ and ‘‘quality of life’’ indicate good physical state and quality of life, these patients were less likely to consume CAM (Fig. 1).
4. Discussion 3. Results Within 6 months, 822 patients (698:5 years; mean standard deviation; range: 45–95 years) were recruited. Serum PSA at diagnosis was 20:0 52:0 ng/ml, mean time interval between diagnosis and current evaluation 3:9 3:1 years (Table 1). First-line treatment was radical prostatectomy in 54%, external beam radiation in 11.8% and endocrine treatment in 23.2% (Table 1).
The use of CAM for treatment and prevention of neoplastic diseases continues to receive an increasing level of attention from the medical community, media, support groups and internet [1,2]. Given the increasing public awareness of prostate cancer it would be reasonable to hypothesize that the use of CAM is also increasing among prostate cancer patients [18]. In our unselected sample of 882 patients, 30% have used
606
A. Ponholzer et al. / European Urology 43 (2003) 604–608
Table 1 Clinical characteristics of the entire study population as well as CAM-users and non-users Total population (n ¼ 822)
CAM user (n ¼ 245)
No CAM use (n ¼ 577)
Mean-age [years] (SD) (range) <60 years 60–70 years 70–80 years >80 years
69.0 (8.5) (45–95) 16.0% 38.0% 37.0% 9.0%
68.6 (8.9) (50–95) 19.6% 38.4% 32.2% 9.8%
69.2 (8.4) (45–91) 14.3% 38.7% 28.4% 8.6%
Diagnosis known since [years] (SD) (range) <1 years 1–3 years 3–5 years 5–7 years >7 years
3.9 (3.1) (0–30) 2.3% 34.7% 29.5% 21.5% 12.0%
4.4 (3.5) (0–30) 1.3% 31.1% 31.5% 20.6% 15.5%
3.8 (2.9) (0–30) 2.7% 36.6% 29.4% 18.2% 13.1%
11.5% 88.5%
15.0% 85.0%
9.7% 90.3%
Metastases at diagnosis yes no PSA at diagnosis [ng/ml] (SD) (highest) First line treatment radical prostatectomy radiotherapy endocrine treatment others radiotherapy þ endocrine treatment
20.0 (52.0) (843)
24.9 (62) (843)
18.5 (47.0) (739)
54.0% 11.8% 23.2% 3.9% 7.1%
51.2% 12.1% 24.8% 3.4% 8.5%
59.7% 11.6% 19.4% 4.1% 5.2%
Last PSA [ng/ml] (SD) (range) last PSA before (years) <0.5 ng/ml
3.3 (23) (0–491) 0.5 76.6%
4.4 (20.2) (0–195) 0.6 70.9%
2.9 (24.4) (0–491) 0.5 79.2%
23.0% 45.8% 7.7%
26.2% 57.6% 12.6%
20.9% 39.0% 4.5%
Second line treatment external beam radiation hormone treatment analgetic therapy
or are currently using at least one form of CAM. These data, being the first of this kind in Europe, are in line with four recent US studies [11–14]. Nam et al. reported that prostate cancer patients presenting to urology clinics and support groups used CAM in 27% and 39%, respectively [11]. Wilkinson et al. performed a postal survey of 1099 patients attending 6 urology institutions for prostate
cancer management [14]. In this group, 24% and 18% of patients had been or were currently using CAM [14]. Lippert et al. reported that 43% of 190 patients who were treated with a curative intent (surgery or radiotherapy) used CAM [12]; Kao et al. studied 50 consecutive patients undergoing radiation therapy and reported on 37% CAM-users [13].
Fig. 1. CAM-users are less satisfied with their treatment and report on an impaired quality of life and physical state. (A) Overall treatment satisfaction on a 6point scale (1: very satisfied; 6: very unsatisfied). (B) Rating of physical state on a 10-point scale (1: very bad; 10: excellent). (C) Rating of overall quality of life on a 10-point scale (1: very bad; 10: excellent). Mean and standard errors of the mean are given.
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The four most popular forms of CAM in our population were low-fat diet, selenium, vitamin E and mistletoe lectins. This distribution correlates quite well with that of the above-mentioned US-studies. In Nam’s series, vitamin E, garlic, low-fat diet and selenium were the four most popular forms, in Wilkinson’s one it were low-fat diet, multivitamins, green tea and selenium [11,14]. This frequent use of CAM is in clear contrast to the fact that to date no definite proof of a beneficial effect of CAM in prostate cancer has been demonstrated in a clinical study that will withstand rigid scientific scrutiny. However, there is growing evidence, that nutritional factors, especially a low-fat diet, soy-products, vitamin E and selenium have biological effects against prostate cancer [8,19–23]. However, further welldesigned, prospective, randomised, placebo-controlled studies are needed to definitely proof their (chemo)preventive role in prostate cancer; such trials are currently underway [24]. However, the high prevalence of CAM-use in the general population and by prostate cancer patients may pose a challenge in randomising patients for such large-scale trials. According to our study, CAM-use was correlated to the type of primary therapy, disease progression, quality of life and overall satisfaction with prostate cancer treatment. Of those who underwent radical prostatectomy 23.3% used CAM, in the radiotherapy group 31.6% and the primary endocrine group 38.8%. A similar trend, i.e. lowest percentages in the radical prostatectomy group (15.4%) and highest in the endocrine therapy group (31.0%) has been made by Wilkinson et al. [14]. What are the reasons for this frequent use of CAM by prostate cancer patients? Undoubtedly, a number of factors are involved. Prostate cancer patients using CAM believed in 90% that it would them help to live longer and improve quality of life, 60% thought it would relieve symptoms and 47% expected it to cure the disease [14]. In addition, 81% reported feeling more hopeful and 63% thought they had more control over the disease [14]. The greater use by patients with advanced disease and lower quality of life may present a marker for distress or may signal unstated patient needs. Some patients may be seeking a more holistic approach to health care. Sociodemographic factors, such as educational level and income are also involved
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and have a positive association with the use of CAM [13,14]. Finally, patients might be attracted by the good tolerability of CAM. A draw-back of our study is that we did not specifically ask for the reasons for CAM-use, for patient expectations and who recommended the CAM-use. This study was primarily designed to assess quality of life in patients with prostate cancer in general and not to evaluate CAM-use in great detail. However, prompted by our data demonstrating frequent use of CAM by prostate cancer patients in our country, we currently consider to design a large-scale, multicenter study to specifically adress these important issues. The majority of prostate cancer patients using CAM do not discuss or inform their doctors [14]. This might be because patients do not believe that physicians know much about these supplements and that they may be biased against them. Doctors are usually unfamiliar with CAM and may be uncomfortable discussing them with their patients or unable to provide adequate guidance. This bias is rooted in the fact that most physicians have never received training in this area. Interestingly, patients who had a dialogue with their family physician or urologist were significantly less likely to use CAM [14]. It is likely that physicians communicate negative attitudes when discussing CAM, based—in part—on the current lack of evidence-based data [14]. In conclusion this study demonstrates that almost one third of prostate cancer patients in Austria have used or are currently using at least one form of CAM. This observation raises several relevant issues: (i) urologists have to be aware of this fact and require a detailed knowledge on this complex topic; (ii) urologists should ask their patients regarding use of CAM and discuss pros and cons [25]; (iii) the undisclosed use of CAM may interfere with conventional treatment and may even have potential severe side effects (e.g. thrombembolic events with PC-SPES); (iv) the frequent use of CAM raises methodological concerns for prostate cancer trials. The use of CAM might bias study results and should therefore be assessed/excluded at inclusion; (v) further studies on CAM-use in other parts of Europe as well as on patient’s attitudes and motivations for use are required. In addition further studies to characterise CAM-users and to determine the interrelation of CAM with ‘‘conventional’’ evidence-based medicine are urgently needed.
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