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Keywords:

  • bicalutamide;
  • GnRH analogue;
  • orchidectomy;
  • androgen deprivation therapy;
  • prostate cancer

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

OBJECTIVE

To investigate patient preference for three established androgen-deprivation therapies for locally advanced prostate cancer; the patient's capacity to decide his therapy; the reasons for selecting a certain mode of therapy; and patient satisfaction with the chosen therapy 3 months after initiation.

PATIENTS AND METHODS

In all, 150 patients (mean age 75 years, range 57–89) with previously untreated locally advanced prostate cancer from 13 hospitals were consecutively given the chance to choose between the antiandrogenic oral drug bicalutamide, a gonadotrophin-releasing hormone analogue (GnRH) by injection, or surgical orchidectomy. After discussing the nature of their disease the patients took home written information about prostate cancer and the three different treatment options. After 1 week they were assessed using a questionnaire for biographical data, their attitude towards the different treatment alternatives and their choice of therapy. Three months later the patients completed a questionnaire about the treatment they had undergone.

RESULTS

Sixty-three patients (42%) chose bicalutamide, 51 (34%) the GnRH analogue and 36 (24%) orchidectomy; 87% of those choosing bicalutamide, 84% GnRH and 94% orchidectomy, respectively, were sure about their choice but 12%, 17% and 3% of the patients, respectively, had some difficulty in deciding. The most important reasons for the therapy chosen were avoidance of injections and surgery, and a lower risk of impotence (bicalutamide), negative attitude to surgery and tablets (GnRH), and avoidance of injections and tablets (orchidectomy). Almost all patients (98%, 98% and 97%, respectively) were satisfied with their choice after 3 months of treatment.

CONCLUSION

There are three equally effective forms of androgen deprivation for locally advanced prostate cancer without known metastases. There are major differences among these treatments in the mode of application and the likelihood and impact of side-effects. When patients are fully informed and play an active role in the treatment decision they are satisfied with their decision 3 months later.


Abbreviations
ADT

androgen deprivation therapy.

INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

Androgen deprivation therapy (ADT) reduces tumour burden, palliates symptoms and delays clinical progress in advanced prostate cancer. The earliest form of ADT was surgical orchidectomy, which was the standard for more than five decades [1]. Newer methods are the administration of a depot formulation of a GnRH-analogue every 3 months by injection [2] or the androgen-receptor blocker bicalutamide once daily by mouth [3,4].

In locally advanced prostate cancer without known metastases, treatment with orchidectomy, a GnRH analogue or the oral nonsteroidal antiandrogen bicalutamide 150 mg daily are considered equal in terms of antitumour effect [5]. The patient's opinion about the three different treatment options can thus be decisive in choosing therapy. However, the patient's understanding of the treatment characteristics and their impact on quality of life are necessary for decision making [6]. Previous studies analysed patient preference between orchidectomy and treatment with a GnRH analogue and concluded that patients readily take advantage of the opportunity to select the treatment that best suits their requirements [7–9]. Patient preference for the antiandrogen bicalutamide, pharmacological or surgical castration has not been studied so far. We conducted the present trial to determine if it is feasible for the patient to select one of these three treatment options based on standardized written information.

PATIENTS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

In this prospective study, 150 consecutive, previously untreated men (mean age 75 years, range 57–89) with locally advanced prostate cancer (T3–4, NX–NO, MX–M0) [10] were recruited at 13 hospitals in Sweden (Table 1). All patients knew their diagnosis and had no severe pain or mental handicap. According to the clinician, ADT was indicated for all patients. After being informed about the three treatment options the patients were given the chance to choose their treatment and to participate in the study. The patients who accepted participation signed a written consent form and were enrolled. The consent form included information on the procedures and outcome measures; furthermore, they were given written information to take home.

Table 1.  The number of patients, hospital and choice of treatment
VariableBicalutamideGnRHOrchidectomyTotal
Hospital
Söder1210 8 30
Sahlgrenska14 8 3 25
Norrköping 5 7 4 16
Gävle 7 6 1 14
Växjö 1 5 4 10
Linköping 3 2 4  9
Karlskrona 7 1 1  9
Skövde 2 4 3  9
Örebro 4 2 2  8
Karlstad 1 4 2 (1 excl)  7
Karolinska 3 1 2  6
Västerås 2 1 2  5
Halmstad 2 0 0  2
Total635136150

The information given described the prostate gland, its function, prostate cancer and the three forms of treatment. The characteristic side-effects of the three treatment options were mentioned in a comprehensive, unbiased and structured way. To prevent breast tenderness and swelling, low-dose radiation treatment of the breasts before the start of treatment with bicalutamide was described. Orchidectomy was described, with the form of anaesthesia usually administered at the hospital. For orchidectomy and GnRH treatment the risk for decreased sexual desire and potency was highlighted. For patients treated with GnRH, the prevention of ‘flare’ of the disease by administering antiandrogen tablets over a 4-week period was mentioned.

The patients were given time to discuss the different treatment options with their partners and relatives before they made their decision at an appointment 1 week later. On that occasion the men answered four self-assessment questionnaires, one with open questions about biographical data and three with boxes (multiple choices with five alternative answers) concerning circumstances about the choice, sexuality and attitudes towards the three different treatments. Sexual desire, the possibility to have an erection and ability to ejaculate were assessed using six alternative answers. The questionnaires were used previously and were modified for this study [9].

Three months after starting treatment the men once again answered the questionnaire on sexuality and a questionnaire asking about what they felt about the treatment they had received. They were also asked if they would like to change their treatment if that was possible (Table 2). Further details of the trial (information and questionnaires in Swedish) can be accessed at http://www.cancer.nu (AstraZeneca).

Table 2.  Flow chart and allocation of questionnaires
PeriodDetails
StartVerbal and written information about the study, written consent
Written information to take home
1 weekQuestionnaire:
 Choice of treatment
 Biographical data
 Attitude to the different treatments and side-effects
 Sexuality
Start of treatment according to patients’ choice
3 monthsQuestionnaire:
 Attitude to treatment received, perceived side-effects
 Satisfaction with chosen treatment
 Wish to change treatment if possible
 Sexuality

anova was used to test differences in age, Fisher's exact test to assess differences in civil status, and the chi-square test for differences in education among the treatment groups. All other variables were analysed descriptively and the proportion of answers in each treatment group given. The study protocol was approved by the Ethics Committee of each participating hospital.

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

All 150 patients were able to make their own decision about treatment; one, who chose orchidectomy, regretted his choice and received bicalutamide, and was excluded from further evaluation. Sixty-three patients (42%) chose antiandrogen and were treated with bicalutamide 150 mg daily by mouth. Fifty of 63 patients received low-dose radiation to their breasts to prevent tenderness and swelling. Fifty-one patients (34%) chose a GnRH analogue, and were treated with a 3-month depot formulation; bicalutamide 50 mg daily by mouth for 30 days was given to counteract flare of the disease. Thirty-six (24%) men chose orchidectomy; the man who regretted his choice received bicalutamide, so 35 men had orchidectomy. Of the 150 patients, 149 completed the questionnaires at entry and 148 at follow-up. One patient in the orchidectomy group died before answering the questionnaire at 3 months.

There were no significant differences among the treatment groups in age (P > 0.05), civil status (P = 0.1) or education (P = 0.06) (Table 3). Most patients wanted to participate in the choice of treatment. The vast majority discussed the alternatives with partner or relatives. Most patients were sure about their choice (Table 3). The patients’ attitudes to the treatment options and expected side-effects are also summarized in Table 3, with data on the patients’ sexuality .

Table 3.  The patients’ details, attitudes to each treatment and attitude to sexuality
VariableBicalutamideGnRHOrchidectomy
  • *

    The attitudes are to treatment with each method according to whether the chosen method; one patient was excluded from further evaluation by questionnaire.

  • The attitudes and sexuality of the patients treated with each method 3 months after starting treatment are shown in parentheses.

N patients635136
Mean age, years74.377.175.7
Education, %
 Primary school413366
 High school465528
 College1312 6
Civil status
 Stable relationship817874
Choice of treatment
 Wish to participate606770
 Difficult to choose1217 3
 Discussion with other person848697
 Sure about choice878494
Patients’ attitudes*
N patients635135
To bicalutamide,%
One tablet daily laborious 11 (0)3248
Treatment reversible valuable30 (55)19 0
Lower risk of decreased sexual desire/potency valuable67 (64)3027
Lower risk of hot flushes valuable84 (83)5558
Higher risk of breast tenderness/swelling distressing39 (10)4139
To GnRH,%
Visit to nurse/pharmacy laborious10 2 (2)18
Treatment reversible valuable7372 (67)44
Decreased sexual desire/potency distressing44 6 (6) 11
Hot flushes distressing5114 (24)28
Breast tenderness/swelling distressing4727 (6)31
To orchidectomy,%
Hospital care troublesome434014 (6)
Surgery distressing545917 (3)
Risk for bleeding/infection alarming484614 (9)
Decreased sexual desire/potency distressing511210 (3)
Hot flushes distressing512914 (37)
Breast tenderness/swelling distressing513515 (0)
Sexuality, %
 Desire76 (68)61 (37)51 (31)
 Erection60 (52)35 (16)39 (14)
 Ejaculation59 (48)33 (14)34 (9)
Satisfaction 3 months after start of treatment989897

Three months after starting treatment almost all patients were satisfied with the treatment they had received (98% bicalutamide, 98% GnRH, 97% orchidectomy). The decrease in sexual function was less during treatment with bicalutamide than with GnRH or orchidectomy (Table 3). One patient in the GnRH group wanted to change to bicalutamide and one patient in the bicalutamide group wanted to change to GnRH.

The patients’ attitude to the treatment they had received was in general the same after 3 months. There was a greater acceptance of tablets, less distress about breast tenderness and swelling, and a higher rating of the reversibility of treatment in the bicalutamide group; there was greater distress because of hot flushes in the GnRH and orchidectomy group (Table 3).

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

There have been numerous changes in the management of prostate cancer over the last two decades. Consensus has not yet been reached on the best management for each stage of the disease. The treatment of advanced disease centres on different forms of ADT. The most striking change in this field is the move from surgical castration towards pharmacological castration using GnRH analogues; these agents were gradually introduced to the Swedish pharmaceutical market <20 years ago. According to data from the National Prostate Cancer Register in Sweden, the proportion of patients receiving treatment with a GnRH analogue increased from 3% in 1987 to 48% in 1996. The proportion of patients who had orchidectomy decreased during that time from 40% to 16%[11]. Bicalutamide 150 mg orally as alternative to surgical or pharmacological (GnRH) castration in locally advanced prostate cancer without distant metastases was licensed in Sweden in 1999. The latest Swedish data (2002; http://www.roc.se, Kvalitetsregister: Prostatacancer Primärregistrering (tables and figures in English) on ADT in locally advanced disease show the dominating role of GnRH analogues (52%) and that antiandrogen monotherapy and orchidectomy are used to the same extent (24%). Circumstances that influenced these changes are not analysed, but doctor and patient preference seem to be the most important factors. Patient preference may differ from the opinion of their physician [12]. There are also marked geographical differences in the choice of hormonal therapy, e.g. bilateral orchidectomy is rarely used in the USA.

The preferences for treatment options in the present study differ from the actual treatments given to Swedish patients with locally advanced disease. The present results showed that 42% of the patients preferred treatment with bicalutamide, but only 24% actually receive this treatment. In addition, only 34% of the patients preferred treatment with GnRH, but 52% are actually medically castrated. However, the proportion choosing surgical castration seems to be in a good accordance with the actual practice in Sweden. Based on these findings, changing the treatment pattern away from medical castration towards more treatment with bicalutamide can increase the concordance between patients’ preference and received treatment.

The importance of patient preference for surgical or pharmacological castration has previously been investigated. In a British study from Bristol, 46% of patients chose orchidectomy and 54% GnRH [8]. These results tally with results from Sweden, where half of 100 patients given the choice chose orchidectomy and half GnRH [9]. In an American study the distribution was in favour of GnRH, selected by 78% of patients [7].

The present study, in which patients were given the chance to choose among three treatment options, showed a balanced result. Most patients decided in favour of bicalutamide, but there were differences in the distribution among the three treatment options at the different hospitals.

Patients in the bicalutamide group valued the lower risk for hot flushes or impaired sexual life, and the possibility to change treatment. Patients in the GnRH group wanted the possibility to change treatment; they were wary of surgery and considered it simpler to have an injection at 3-month intervals. Patients in the orchidectomy group wanted quick results, considered surgery to be simpler, and wanted to avoid injections and tablets.

The form of treatment (surgery, injection or tablets) and the side-effect profiles seem to be most important when making the choice. The present patients had no problems in choosing for themselves; most chose quickly, were certain about their decision, did not regret it and were satisfied with their decision 3 months later.

Patient attitude had changed in a few details at 3 months after the start of treatment. The patients in the GnRH and orchidectomy groups rated distress about hot flushes higher after 3 months than before the start of treatment. It is possible that the information given at inclusion about hot flushes was not detailed enough, and the possibility of treatment for hot flushes was not mentioned. However, when attention is paid to the discomfort caused by hot flushes, this side-effect is often categorized as most distressing [13]. Patients in the bicalutamide group rated distress about breast tenderness and swelling less at 3 months after starting treatment, probably because they received prophylactic radiation of the breasts before starting treatment. The three treatment options seem to satisfy different subjective needs. When patients chose treatment based on adequate information they are still satisfied with their decision 3 months later, but the satisfaction is not verified over a longer period.

In Sweden, all residents are covered by a tax-financed national health insurance, including costs for medication. There is a low maximum fixed amount of money per year that the patient has to pay. The cost between pharmacological and surgical hormonal treatment is thus, for most patients in Sweden, insignificant, but for patients who are extremely poor, the difference in cost might be a factor which affects their choice of hormonal therapy. In Sweden there is no financial incentive for physicians related to different treatments. The economic factors vary geographically and if this study were carried out in the USA or in the UK, the results might be different.

ACKNOWLEDGEMENTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

We thank the patients who took part and the members of the study group: Söder Hospital: Ulf Norming, Claes R Nyman; Sahlgrenska Hospital: Pär Lodding; Norrköping Hospital: Hans Hjertberg, Eberhard Varenhorst; Gävle Hospital: Torsten Sandin; Växjö Hospital: Lars Adell; Linköping Hospital: Bill Petersson; Karlskrona Hospital: John Johnsen; Skövde Hospital: Hans Hedelin; Örebro Hospital: Swen-Olof Andersson; Karlstad Hospital: Harri Määkinen; Karolinska Hospital Stockholm: Leif Haendler; Västerås Hospital: Gunnar Nyberg; Halmstad Hospital: Magnus Annerstedt.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES