Abstract
This article discusses the use of hormone therapy for the treatment of prostate cancer, the most common male cancer. Key to managing this disease is understanding the processes responsible for maintaining prostate growth and hormonal homeostasis in male development. The individual mechanisms of action are outlined and demonstrated for each type of treatment, alongside the effects of these treatments. Each therapeutic option is discussed in conjunction with current key research findings and implications for practice are outlined.
Key words: * Male reproductive system and disorders * Men’s health * Prostate cancer
Prostate cancer is the most common male cancer. It accounts for over 27 000 cases in the UK a year. It is the second most common cause of death from cancer in males after lung cancer, with approximately 10 000 per year. The lifetime risk for being diagnosed is one in 14 and the incidence is rising annually (Cancer Research UK, 2004).
Despite its prevalence, the natural history of the disease is still relatively unknown, with many aspects of its clinical progression being poorly understood (Bono, 2004). However, since the 1940s and the Nobel prizewinning work of Dr Charles Huggins, it is known that prostate cancer responds to manipulation of the male hormone testosterone, either by surgery or pharmacological intervention. Hormonal manipulation has become the prime therapeutic strategy for patients in whom the prostate cancer is not considered curable with local radical therapy (Anderson, 2003).
This article will outline the pathogenesis of the disease, ways in which hormone therapy can be used and issues relating to the impact on the individual’s quality of life. Such treatments will be discussed alongside the role now commonly undertaken by many nurses in its delivery and patient surveillance.
Functions of the prostate gland
The prostate is about the size of a chestnut and lies at the base of the bladder, wrapped around the urethra. Although the prostate gland is known to be involved in stopping retrograde ejaculation, its exact role remains unclear (Emberton and Mundy, 1999). The prostate acts as a secondary sex organ, and its regulation and development are under the control of hormones (androgens).
Similar to breast tissue in females, the prostate gland consists of predominantly three types of cells: basal, epithelial or secretory and smooth muscle cells. Basal cells separate secretory cells from the basement membrane (Newling, 1997). The epithelial or secretory cells of the prostate are responsible for the production of a wide variety of substances, mainly enzymes and nutrients, which help in the mobility, feeding and penetration of the sperm into the female egg. The prostate also produces small concentrations of prostaglandins which may play a role in the stimulation of cellular activities of the gland itself and have an influence on the erectile tissue (Pryor, 1999). The stroma (the supporting fibromuscular connective tissue) of the prostate consists of smooth muscle cells and fibroblasts.
The prostate also has a profuse blood supply, and somatic as well as parasympathetic and sympathetic nerve fibres, an important aspect in prostate surgery when considering the preservation of erectile function in the patient. There are spaces around these nerve fibres called perineural spaces, where prostate cancer cells can migrate. With the migration of prostate cancer cells causing perineural invasion, the cells are able to wrap around nerves and travel through them in the same manner cars travel on a road, as the path of least resistance. Perineural invasion alone, however, does not represent extra prostatic extension, i.e. spread outside the prostate (Bostwick, 1999). It does, however, seem to represent an important predictor of early outcome in patients with organ- confined prostate cancer treated by prostatectomy (Endrizzi and Seay, 2000).
Prostate-specific antigen
One of the most widely known enzymes that is secreted from the cells of the prostate is prostate-specific antigen (PSA). PSA is a glycoprotein which is found in both benign and cancerous conditions of the prostate, and is responsible for the liquefying of seminal fluid to aid its mobility. It is produced almost entirely from the epithelial component of the prostate gland (Belledegrun et al, 1998). In order to measure it a blood sample is taken. Importantly, the PSA test is not a diagnostic test; while PSA is specific to the prostate, it is not specific to prostate cancer; those with an elevated PSA will require a transrectal ultrasoundguided prostate biopsy (TRUS) to obtain tissue on which a diagnosis may be made (NHS Cancer Screening Programmes, 2002). Its discovery in the early 1980s has revolutionized the entire approach to the management of prostate cancer (Brawer and Chetner, 1992).
With the disruption of the prostate gland’s cellular structures and barriers by different dis ease processes, especially prostate cancer, PSA gains access to the systemic bloodstream (Kirby, 2002). While there is no debate that early detection and aggressive treatment is the only way to cure the patient with significant disease, the debate about PSA screening is ongoing, primarily because of the risk of over detection and treatment of clinically insignificant disease (Potter and Emberton, 2003). It must be remembered that despite one-third of men over 50 years and a half of 80 year olds having a small focus of cancer in their prostate glands, only 4% of men will die from the disease (NHS Cancer Screening Programmes, 2002).
Apart from prostate cancer, the PSA levels can also be elevated in other conditions. Prostatitis and urinary-tract infections, trauma to the prostate seen at the time of catheterization, prostatic biopsies, recent ejaculation (within 48 hours) and benign prostatic hyperplasia (BPH) all lead to a rise in the PSA level (Brawer and Kirby, 1999). PSA as a tool to identify prostate cancer is therefore limited by these above confounding factors.
PSA is also limited by its sensitivity, the number of people who have the disease who have an abnormal test result, and specificity, the number of people without the disease who have a normal result (Potter and Emberton, 2003). Various strategies have focused on trying to enhance these parameters, to reduce the number of falsely positive test results, resulting in unnecessary further investigations, anxiety and financial cost (NHS Cancer Screening Programmes, 2002).
Table 1. Age-related reference ranges
Age-related reference ranges
The rationale for establishing age-specific PSA referenced ranges is based on a number of factors. First, PSA levels increase with age, which is more likely owing to the fact that there is greater leakage of PSA from the prostate epithelium with advancing age. second, the incidence of prostate cancer increases with age. Third, it is theorized that using a lower PSA cut-off point in younger men will allow increased sensitivity, while selecting a higher cut-off point in older men will enhance specificity (Brawer and Kirby, 1999).
The prostate cancer risk management programme recommends that the cut-off values in Table ? are used for the PSA test, although there is a single cut off of 4.0 ng/mL used in some areas (Department of Health, 2002). However, within men with a PSA of 4.0-10.0 ng/mL the so called ‘diagnostic gray zone’, the ability of PSA to distinguish prostate cancer from benign conditions, such as BPH and prostatitin’s, is only 18-25% (Catalona et al, 1993). Another emerging issue is the rising incidence of prostate cancer in the low PSA levels (less than 4.0 ng/mL). Studies have reported an incidence of between 24 and 26.3%, when the PSA levels were between 2.5 and 4.0 ng/mL (Djavan et al, 1999;Babaian et al, 2000).
Endocrinology of the prostate gland
The male sex hormone testosterone is the most important androgen in men, responsible for characteristics such as facial hair, sexual development in puberty, deepened voice and increased muscle bulk and bone mass (Marieb, 2003). Testosterone exerts its effects by binding to androgen receptors on target organs such as the prostate gland, and within the prostate it is converted to dihydrotestosterone (DHT) by the enzyme 5-alpha reductase. Testosterone and its more potent metabolite DHT are essential for normal prostate growth and are therefore thought to play a role in the development of prostate cancer (Kirby et al, 2001). Prostate cancer almost never develops in men castrated before puberty, or in individuals deficient in 5- alpha reductase, a syndrome called male pseudohermaphroditism (Brawley, 2003).
The normal function of the prostate gland and its cellular growth is maintained and regulated through a delicate balance by the hypothalamus, the pituitary gland, testes and adrenal glands (Kirby et al, 2001).
Hypothalamic-pituitary-testicular pathway
The hypothalamus caps the top of the brain-stem and is the main control centre of the body. It is vitally important for overall body homeostasis, with few tissues in the body escaping its influence (Marieb, 2003). Its main roles are shown in Table 2.
Table 2. Homeostatic functions of the hypothalamus
Stimulating sexual development and the production of testosterone begins with the hypothalamus and the release of a substance called luteinizing hormone-releasing hormone (LHRH). LHRH is secreted \in a pulsatile fashion by the hypothalamus for a few minutes at a time, once every 1-3 hours (Pryor, 1999). However, there is some disruption as one becomes older to the regularity and time span of the pulses (Keenan and Veldhuis, 2001). Although there is no dramatic reduction in sex steroid production in middle-aged men there is a small reduction in testosterone in the bloodstream, a proportionally larger increase in sex binding hormone globlulin in later life, and so levels of free, biologically active testosterone decline with age (Francis, 1999).
The increase in LHRH stimulates the anterior pituitary to secrete two key hormones: luteinizing hormone (LH) and follicle-stimulating hormone (FSH) responsible for stimulation of the Leydig cells of the testes to produce testosterone and sperm production. Testosterone is then converted into its more potent form DHT, by the enzyme 5-alpha reductase and male oestrogens, in the peripheral tissues and also in the prostate, thus promoting prostate cell growth (Griffiths et al, 1991).
Testosterone circulating throughout the body prevents the release of LHRH from the hypothalamus through negative feedback inhibition. This means that when levels of testosterone fall, LHRH is released in the hypothalamus leading to increased levels of LH and subsequently of testosterone. With a rise in testosterone levels, there is a decrease in the release of LHRH. This pathway is responsible for producing 95% of the testosterone produced daily.
Hypothalamic-pituitary-adrenal pathway
The adrenal glands are the secondary source of androgens. With the stimulation of the pituitary gland conies the release of corticotropin from the adrenal cortex, after stimulation by corticotropin-releasing hormone (CRH) which is secreted by the hypothalamus. Corticotropin is responsible for the regulation of adrenal androgens that are converted to testosterone and DHT and oestrogens in the peripheral tissues and the prostate, which again promote prostate cell growth. The adrenal glands indirectly contribute up to 5% of daily testosterone production.
Figure 1. Endocrine regulation of prostate growth. LHRH = luteinizing hormone-releasing hormone; CRH =corticotropin-releasing hormone; LH = luteinizing hormone; FSH = follicle-stimulating hormone; ACTH = adrenocorticotropic hormone; T-DHT = testosterone- dihydrotestosterone.
While testicular function and production of testosterone is intact, the adrenal androgens are not clinically important (Kirby et al, 1996). They are important, however, when usual testosterone production is inhibited in prostate cancer treatment. The elimination of the testicular androgens by surgical or medical treatment leaves an opportunity for the adrenal androgens instead to stimulate the growth of prostate cancer cells (Newling, 1997). Figure 1 refers to the endocrine regulation of prostate growth.
Hormonal therapy for prostate cancer: therapeutic options
For growth of prostate cancer cells to continue, stimulation is required by androgens. The primary strategy of hormonal therapy is therefore to decrease the production of testosterone by the testes or block the action that testosterone has on the growth of the cells from the adrenal glands and the testes. Hormonal therapy cannot cure prostate cancer, instead it aims to slow down the growth of the prostate cancer and reduce its overall size. Androgen stimulation of prostate cancer growth may be prevented in a number of different ways (Kirby, 2002).
Bilateral orchidectomy
Bilateral orchidectomy is the surgical removal of both of the testes, which are responsible for the production of 95% of the body’s testosterone. Since the testes are the major source of testosterone in the body, Garnick (1993) argues that this procedure is classified as hormonal therapy rather than surgical treatment. The goal of this procedure is to deprive the prostate cancer cells of testosterone, thereby causing the cancer to shrink and/or prevent further growth of the tumour by removing the source on which it depends. It reduces about 95% of circulating testosterone levels and a dramatic tumour response frequently occurs within 24 hours (Shroder et al, 2000). With this procedure the patient will become infertile, unable to produce sperm, and the loss in testosterone will cause erectile dysfunction, loss of libido and hot flushes. It can cause a reduction in bone pain if there is metastatic disease.
LHRH analogues
LHRH analogue injections mimic the action of LHRH and act by occupying a very high proportion of the LHRH receptors on the pituitary gland cell membrane. This initially leads to a rise in LH, resulting in a short-lived increase in testosterone production by the testes which can produce a flare-up of the disease and an increase in the patient’s existing symptoms (phase 1). However, as a result of constant occupation of the LHRH receptors on the pituitary cell by the continuing administration of this drug, a process known as down regulation occurs. This is a reduction in LHRH receptors, with accompanying densensitization, whereby there is a suppression of LHRH synthesis and excretion (Anderson, 2003).
Although new receptors are produced and appear on the cell surface of the pituitary gland, the continuing administration of the treatment causes them to become occupied immediately and to disappear. In this way, LHRH analogue treatment prevents the reappearance of LHRH receptors and constantly inhibits the production of LH and FSH from the pituitary gland and testosterone from the testes (phase 2). Testosterone suppression leads to shrinkage of the prostate tumour as shown in Figure 2. Tumour response is defined by testosterone suppression: usually 2-4 weeks.
With the new development of LHRH antagonists such as abarelix and cetrorelix as injection therapies for the treatment of prostate cancer, additional benefits are already being seen. As antagonists they occupy LHRH receptors, but do not stimulate them; there is therefore an absence of disease flare, rapid down regulation, and no need for combination therapy with an anti-androgen because of its binding, and blocking of the LHRH receptors in the pituitary gland (Weckerman and Harzmann, 2004). Table 3 shows LHRH analogue injections.
Anti-androgens
Anti-androgens are tablet-form treatments that block the effect of testosterone and its more potent form DHT binding to the androgen receptors in the prostate, in the presence of normal or increased levels of testosterone. They do not, however, prevent testosterone production (Griffiths et al, 1991). These orally administered drugs are classified by their chemical structure as either steroidal or non-steroidal (Table 4). Anti-androgens can be used in either combination therapy with LHRH analogue or as primary therapy.
Table 3. LHRH analogue injections
The steroidal anti-androgens have a dual mode of action, being both progestational and anti-androgenic in action (Figure 3). They block androgen receptors in the prostate and exert a negative feedback action on LH secretion, thus lowering the levels of testosterone production and the effect on the cancer cells in the prostate. Consequently, these medications are generally associated with loss of libido and erectile dysfunction (Shroder et al, 2000).
Non-steroidal anti-androgens or ‘pure anti-androgens’ block androgens from binding at the receptor sites of the prostate and also at the level of the hypothalamic-pituitary axis, where androgens normally elicit a negative feedback control on the release of LH (Figure 4). This leads to an increased LH output and a subsequent increase in the synthesis and secretion of testosterone. The increased conversion of testosterone results in an increased level of oestrogens, which have a direct effect on breast tissue, often causing enlargement of the breast, and increased sensitivity and sometimes pain around the nipples (Anderson, 2003). As they do not suppress testosterone synthesis, non-steroidal anti-androgens allow potential preservation of sexual interest and activity (Mason and Moffat, 2003).
Figure 2. Mechanism of action: luteinising hormone-releasing hormone (LHRH) analogues; LH = luteinizing hormone.
Oestrogens
Oestrogens are hormones found in men and women, although they are more widely known to control female sexual development, regulate the menstrual cycle and maintain pregnancy (Marieb, 2003). In prostate cancer they are principally derived from the peripheral conversion of testosterone in the tissues and from secretion by the testes in men with or without prostate cancer (Droller, 1997).
As treatment, they exert their effect by negative feedback, causing a reduction in the secretion of LHRH by the hypothalamus, thereby preventing the release of LH from the pituitary (Figure 5). As a result of non-secretion of LH, there is no action of the Leydig cells of the testes and hence no secretion of testosterone. There is also evidence to suggest that they have a direct cytotoxic effect (either killing the cancer cells or stopping them from multiplying) on the tumour (Kirby et al, 2001).
Indications for hormone therapy
Localized prostate cancer
Localized prostate cancer refers to prostate cancer that is confined within the capsule of the prostate with no evidence of spread. Such tumours are often too small to be palpable on rectal examination and may only be detected by transrectal ultrasound and needle biopsy of the prostate (Anderson, 1999). They may also be diagnosed following histological examination of the prostate ‘chips’ removed during a transurethral resection of the prostate (TURP) for bladder outflow obstruction presumed to be caused by benign prostatic enlargement.
Although the most appropriate management of patients with this disease is controversial, the aim is cure, whether eliminating the cancer or preventing death from it (Anderson, 2003).
Radical prostatectorny and radical radiotherapy
Radical prostatectomy is mostly un\dertaken as a curative procedure and involves the surgical removal of the entire prostate, the seminal vesicles and a variable amount of adjacent tissue. From the point of first-line treatment for localized disease, surgery and radiotherapy are the two principal treatment options alongside PSA surveillance.
Radical radiotherapy as a curative procedure involves a 6-week course of treatment. It offers a particular advantage in patients who are unsuitable for surgery because of co-morbidities, such as heart or lung problems, or evidence of extraprostatic extension of the cancer (Bono, 2004).
A short course (3 months) of hormonal drug therapy may be used before radical prostatectomy or radiation therapy to reduce the size of the prostate cancer (volume reduction). This is called neoadjuvant hormonal therapy.
While hormonal treatment before radical prostatectomy has been shown to reduce prostate cancer tissue volume and the incidence of positive areas of tumour following surgery, the results have not demonstrated any improvement in survival (Soloway et al, 2002).
With radical radiotherapy there is emerging evidence to suggest that the effect of radiotherapy as a curative treatment can be enhanced by 3 months pre-treatment with an LHRH analogue, with a clear improvement in overall survival (Bolla et al, 2002). This also helps to reduce the area to which radiotherapy is given, with a more defined area of treatment, reducing the effects such as diarrhoea and cystitis often seen when both the bladder and bowels are irradiated.
In spite of treatment by radical prostatectomy or radical radiotherapy, cancer cells can recur, suggesting spread of the disease. Patients whose disease recurs after curative treatment are acknowledged as being commonly understaged at diagnosis (Kirby et al, 1996). Subsequently, following restaging of the disease, hormone therapy may be offered after their initial treatment. For example, following failure of initial radiotherapy, defined biochemically as three consecutive increases in PSA levels from the PSA nadir (lowest PSA level) (American Society for Therapeutic Radiology and Oncology (ASTRO) Consensus Panel, 1997). Patients’ long-term outcome may be improved by hormone treatment afterwards, in order to prevent further disease progression such as spread to bone or lymph nodes. This approach is referred to as adjuvant-hormone therapy. However, the optimal duration and timing of adjuvant-hormone therapy remains unresolved (Soloway, 1998).
An additional method of treating prostate cancer which is gaining popularity is a procedure called brachytherapy. ‘Brachy’ (therapy) comes from the Greek -word meaning ‘short’ and is used to describe a treatment where radioactive sources or materials are placed in or close to the tumour. This technique involves placing radioactive ‘seeds’ into the prostate. Evidence from a number of clinical studies suggests that adjuvant hormone therapy with an LHRH may be an advantage only for patients with high risk of disease spread outside the prostate (D’Amico et al, 1998; Merrick et al, 2003). Where the prostate gland is over 60cc in volume, hormone treatment may also be used for 3-6 months to reduce the size of the prostate, making it easier to insert the needles and reduce the number of seeds required (Nag et al, 1999), although it remains unclear as to which form of hormone treatment should be used (Lee, 2002).
Locally advanced prostate cancer
The term ‘locally advanced’ prostate cancer refers to the disease that is no longer confined to the prostate, that has started to invade nearby organs such as the bladder and seminal vesicles, but where there is no evidence of spread either to the lymph nodes or other sites such as bone (Kirby, 2002). For patients with locally advanced disease, the impact on quality of life is likely to be an important consideration as therapy may be continued for several years (Anderson, 2003).
Table 4. Common anti-androgen treatments for prostate cancer
Hormonal treatment followed by surgery
As already discussed in the context of localized prostate cancer, hormone therapy can be used as neoadjuvant or adjuvant, often by the administration of an LHRH analogue together with an anti-androgen to prevent androgen stimulation of the tumour. This treatment has been shown to reduce prostate volume and tumour volume; however, it has not yet been shown to improve overall survival (Bono, 2004).
Radiotherapy followed by hormone treatment
Adjuvant therapy with a LHRH analogue, started at the beginning of external beam radiotherapy treatment and continued for 3 years, has been demonstrated by Bolla et al (1997) to improve overall survival m a clinical trial of patients with locally advanced prostate cancer.
Hormone treatment alone
The development of LHRH analogues and non-steroidal anti- androgens has produced treatments that reduce the intraprostatic concentration of DHT by over 80% (Bono, 2004). This is comparable to the reduction that can be achieved by surgical orchidectomy (Kirby et al, 2001). However, the psychological implications of the removal of both testes must be considered. Many patients find the concept of surgical removal worrisome and distasteful and may prefer treatment with an LHRH analogue to surgery (Kirby et al, 1996).
Figure 3. Mechanism of action – steroidal anti-androgens; LH = luteinizing hormone.
With the use of an LHRH analogue, the initial increase in testosterone can cause a tumour flare phenomenon, which can exacerbate existing symptoms, leading to urinary problems, such as decrease in urinary flow and urinary retention, or spinal cord compression (Coptcoat, 1996). Testosterone levels reach their lowest levels after about 21 days of the LHRH analogue being administered. An anti-androgen should therefore be given before and during the first 2 weeks of therapy to suppress these potential effects (Aus et al, 2003).
Monotherapy with the anti-androgen bicalutamide at 150 mg/day has been shown to be just as effective in locally advanced disease as treatment with orchidectomy or the use of an LHRH analogue (Anderson, 2003). The advantage of this option is that sexual interest and function may be preserved. Some men may understandably opt for the treatment that has a lesser impact on this important aspect of their lives.
Intermittent hormone therapy
There is some evidence to suggest that continuous androgen deprivation therapy may in fact increase the rate of progression of prostate cancer to a point -where it is no longer sensitive to androgen deprivation and therefore the prostate cancer becomes resistant to hormone therapy sooner – this is known as ‘hormone escape’ (Kirby et al, 2001). Attention is now being focused on the use of LHRH analogues for an initial 36 weeks, after which, providing the PSA is within the normal range at 32 weeks, the treatment is discontinued (Kirby et al, 2001). Such a regimen allows serum testosterone levels to return to normal, which renders the cells within the prostate more sensitive to androgen deprivation (Anderson, 2003). Therapy can be reintroduced when the PSA reaches pre-treatment levels. Studies looking at the long-term safety and effectiveness are still under way, and this approach should be regarded as experimental.
Figure 4. Mechanism of action – non-steroidal anti-androgens; LH = luteinizing hormone.
Metastatic prostate cancer
Once cancer has spread to the lymph nodes and to sites, such as bones, it is referred to as metastatic disease (Buck, 1995). Unlike early or locally advanced disease, metastatic prostate cancer is associated with high mortality within 5 years of diagnosis, with as many as 70% of patients dying from, rather than with, prostate cancer (Kirby et al, 1996).
Androgen deprivation, either by orchidectomy or treatment -with LHRH analogues, remains the mainstay of treatment as a palliative approach (Coptcoat, 1996). Patients with metastatic disease typically relapse within 18-24 months on the initiation of hormonal treatment (Anderson, 2003). Comparative trials have shown that the response rates obtained with LHRH analogues are comparable to those after orchidectomy, in terms of time to disease progression and overall survival (Vogelzang et al, 1995). However, despite its comparative effectiveness, orchidectomy, with the combination of the irreversible nature of the procedure, sexual side-effects, and the psychological burden associated with the removal of the testes, has been shown to be less appealing for most patients (Clark et al, 2001). However, this may be indicated for patients with poor compliance to tablets or injections, imminent spinal compression or those who object to regular medication.
Maximal androgen blockade
Although both orchidectomy and LHRH treatment produce good initial responses, it is known that the average time for disease progression is less than 18 months (Prostate Cancer Trialists’ Collaborative Group, 2000). One factor that may contribute to this poor prognosis and outcome is the continuing secretion of adrenal androgens. This has led to the use of both an LHRH analogue and an anti-androgen to provide maximal androgen blockade (MAB). A meta- analysis of 27 studies comparing MAB with LHRH or orchidectomy alone, has shown a small difference in survival favouring MAB (25.4% vs 23.6%) (Prostate Cancer Trialists’ Collaborative Group, 2000). Kirby et al (2001) suggest that such treatment should be considered in younger and fitter patients who are most likely to die from prostate cancer itself rather than from some comorbid condition.
Figure 5. Mechanism of action: oestrogens. LHRH = luteinizing hormone-releasing hormone; LH = luteinizing hormone.
Androgen-independent disease
In almost all cases, advanced prostate cancel-treated by any form of androgen therapy will eventually, when the prostate cancer cells become less sensitive to hormonal control, begin to grow again – a phenomenon known as ‘hormone escape’ or ‘an\drogen independence’ (Bono, 2004). Prostate cancer cells are heterogenous in their sensitivity to androgens. This means that the cells can range from being androgen-dependent, through androgen-sensitive to androgen- independent (Kent and Hussain, 2003). Failure of hormone therapy is detected by a rising PSA, and thus an increase after initial successful androgen treatment almost inevitably indicates disease progression (Aranha and Vaisarnpayan, 2004). Although the prognosis is poor, it is generally accepted that once the cancer has become hormone resistant, treatment to deprive the prostate cancer cells of androgens should be maintained with second-line therapy, to delay disease progression. Paradoxically, patients who have progressed on MAB may have a response if the anti-androgen is withdrawn (Mason and Moffat, 2003).
Table 5. Common effects of hormonal treatment
The synthetic oestrogen diethylstilboestrol (stilboestrol) is used in this manner, but side-effects such as gynaecomastia, deep- vein thrombosis and other cardiac complications, limit its use as first-line therapy (Malkowicz, 2001). This treatment is often used in combination with aspirin to reduce thrombosis and risk of cardiovascular toxicity. Response rates of 30-35% have been seen in reducing disease progression (Newling, 1997).
At this stage of the disease, perhaps more so than at any other time, any treatment is palliative and is an attempt to prolong life. Such treatments must therefore be individualized and be judged in their use against the remaining quality of life of the patient.
The effects of hormone treatment
In response to the treatment of prostate cancer, patients’ reactions will vary considerably. Disturbing the body’s balance of sex hormones can lead to various undesirable and upsetting effects. Patients with advanced disease may often be asymptomatic. It is therefore essential to counsel the patient regarding the potential impact of this therapy on his quality of life. The most common effects of treatment are outlined in Table 5.
Key nursing roles
Men diagnosed with prostate cancer often feel surprised, angry, confused and depressed. Feelings may change from hope and courage to despair and fear, and back again (Kunkel et al, 2000). With increasing numbers of men being diagnosed with this disease, it is essential that they are fully informed about treatments and the inevitable effects on their quality of life. Central to this must be their involvement in the decision-making process to guide them through what may seem a very uncertain and complicated patient journey. Support for the family as a supporting unit is also critical.
With the proliferation of so many nurse-led initiatives emerging in urological cancer care, many nurse specialists are at the forefront of discussing, administering and reviewing the effects of hormone therapy to patients with prostate cancer, as part of their own clinical patient caseloads. It is essential that in this arena, information about the condition and the effects of treatment are discussed with the patient, to empower him to make a decision based on his priorities, the disease, and knowing the potential effects that the treatment may have on his psycho-social-sexual wellbeing. Where treatments may have a lesser effect on erectile function, irrespective of the patient’s age, the potential for these to be used should be discussed.
With many nurse-led clinics reviewing such patients on a continual basis, it is often the nurse who will be more aware of any changes in a patient’s condition, adverse effects of treatment and changes in response to treatment. The nurse is in a key position to assess, plan and implement care to address such issues that may improve the quality of life of the patient. As the disease will invariably progress, the need for palliative care may ensue – the nurse is ideally positioned to discuss such issues -with the patient and his family and to refer patients for ongoing community support, which may lessen the need for repeated and sometimes distressing hospital admissions. There is also a key role to educate other nurses regarding these treatments and how they should be administered.
Conclusion
In prostate cancer, patients may present with many concerns about the effect of treatment on their quality of life, for a condition that may not even be symptomatic. In considering hormone therapy treatment, patients need to be aware of the overall benefits, in terms of survival advantages where the disease is incurable and how the treatment may affect them in the long term. Nurses are in an ideal position to discuss such issues with patients and they should be an integral part of the patient journey from the point of diagnosis.
KEY POINTS
* Prostate cancer is the most common male cancer in the UK with over 27000 cases and over 10 000 deaths per year, with numbers increasing annually.
* Androgens are fundamental to the continuing growth of prostate cancer cells, with treatment strategies aiming to block their effects or decrease their production.
* Patients with prostate cancer may often be asymptomatic.
* The effects of hormone therapy must be discussed and considered with the patient.
* The patient’s journey is often uncertain and key to this is patient empowerment through knowledge and support, to guide him through the decision-making process.
* The nurse is ideally situated to administer hormone therapy, assess the effectiveness of treatment and the patient’s wellbeing when the disease progresses.
Anderson J (1999) Surgery for early prostate cancer. In: Kirk D, ed. International Handbook of Prostate Cancer. Euromed Communications, Haslemere
Anderson J (2003) Treatment of prostate cancer: the role of primary hormonal therapy. Eur Urol 1: 32-9
Aranha O, Vaisarnpayan U (2004) PSA relapse prostate cancer: the importance of tailored therapy. Urol Oncol 22(1): 62-9
ASTRO Consensus Panel (1997) Consensus statement: guidelines for PSA following radiation therapy. Int J Radiat Oncol Biol Phys 37(5): 1035-41
Aus G, Abbou CC, Van Poppel H (2003) EAU Working Group on Oncological Urology: Guidelines on Prostate Cancer. European Association of Urology, Arnhem, the Netherlands
Babaian RJ, Fritsche H, Ayala A, Bhadkamkar V, Johnston DA, Naccarato W, Zhang Z (2000) Performance of a neural network in detecting prostate cancer in the prostate-specific antigen reflex range of 2.5 to 4.0 ng/mL. Urology 56(6): 1000-6
Belledegrun A, Kirby R, Oliver T, eds (1998) New Perspectives in Prostate Cancer. Isis Medical Media, Oxford
Brawley OW (2003) Hormonal prevention of prostate cancer. Urol Oncol 21(1): 67-72
Bolla M, Gonzalez D,Warde P et al (1997) Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserelin. N Engl J Med 337(5): 295-300
Bolla M, Collette L, Blank L (2002) Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer: a phase III randomized trial. Lancet 360: 103-8
Bono AV (2004) Overview of current strategies in prostate cancer. Eur Urol 3: 2-7
Bostwick D (1999) Pathology of prostate cancer. In: Kirk D, ed. International Handbook of Prostate Cancer. Euromed Communications, Haslemere
Brawer MK, Chetner MP (1992) Screening for prostate carcinoma with PSA. J Urol 147: 841-5
Brawer MK, Kirby R (1999) Fast Facts: Prostate Specific Antigen. 2nd edn. Health Press, Oxford
British Medical Association and Royal Pharmaceutical Society of Great Britain (2005) British National Formulary 49. BMA/RPSGB, London
Buck C (1995) Prostate Cancer: Questions and Answers. Merit Publishing, Basingstoke
Cancer Research UK (2004) Cancerstats Monograph: Cancer Incidence, Survival and Mortality in the UK and EU. Cancel-Research UK, London
Catalona WJ, Smith DS, Ratliff TL, Easier JW (1993) Detection of organ-confined prostate cancer is increased through prostate- specific antigen-based screening. JAMA 270(8): 948-54
Clark JA, Wray NP, Ashton CM (2001) Living with treatment decisions: regrets and quality of life among men treated for metastatic prostate cancer. J Clin Oncol 19: 72-80
Coptcoat MJ (1996) The Management of Advanced Prostate Cancer. Blackwell Science, Oxford
D’Amico AV, Whittington R, Malkowica SB (1998) Biochemical outcome after radical prostatectomy, external beam radiotherapy, on interstitial radiation therapy for clinically localised prostate cancer. JAMA 280: 969-74
Department of Health (2002) Referral Guidelines for Suspected Cancer. DoH, London
Djavan B, Zlotta A, Kratzik C, Remzi M, Seitz C, Schulman CC, Marberger M (1999) PSA, PSA density, PSA density of transition zone, free/total PSA ratio, and PSA velocity for early detection of prostate cancer in men with serum PSA 2.5 to 4.0ng/mL. Urology 54(3): 517-22
Droller MJ (1997) Medical approaches in the management of prostatic disease. Br J Urol 79(2): 42-52
Emberton M, Mundy AR (1999) The prostate and benign hyperplasia. In: Mundy AR, Fitzpatrick JM, Neal DE, eds. The Scientific Basis of Urology. Isis Medical Media, Oxford
Endrizzi J, Seay T (2000) The relationship between early biochemical failure and perineural invasion in pathological T2 prostate cancer. BJU Int 85(6): 696-98
Francis RM (1999) The effects of testosterone on osteoporosis in men. Clin Endocrinol 50(4): 411-14
Garnick MB (1993) Prostate cancer: screening, diagnosis, and management. Ann Intern Med 118: 804-18
Griffiths K, Davies P, Eaton CL (1991) Endocrine factors in the initiation, diagnosis and treatment of prostate cancer. In:Voight KD, Knabbe C, eds. Endocrine Tumours. Raven, New York
Keenan D, Veldhuis J (2001) Disruption of the hypothalamic luteinizing hormone pulsing mechanism in ageing men. Am J Physiol Regul Integr Comp Physiol 281(6): R1917-24
Kent E, Hussain M (2003) The patient with hormone-refractory prostate cancer: determining who, when, and how to treat. Urology 62(1): 134-40
Kirby R (2002) The Prostate: Small Gland, B\ig Problem. 2nd edn. Prostate Cancer Research Campaign UK, Health Press, Oxford
Kirby RS, Christinas TJ, Brawer M (1996) Prostate Cancer. Mosby, London
Kirby RS, Brawer MK, Denis LJ (2001) Fast Facts: Prostate Cancer. 3rd edn. Health Press, Oxford
Kunkel EJ, Myers RE, Lartey PL (2000) Communicating effectively with the patient and family about treatment options for prostate cancer. Semin Urol Oncol 18(3): 323-40
Lee R (2002) The role of androgen deprivation therapy combined with prostate brachytherapy. Urology 60(3A): 39-44
Malkowicz S (2001 )The role of diethylstilbestrol in the treatment of prostate cancer. Urology 58(2): 108-14
Marieb EL (2003) Human Anatomy and Physiology. 6th edn. Benjamin Cummings, San Francisco
Mason M, Moffat L (2003) Prostate Cancer: The Facts. Oxford University Press, Oxford
Merrick GS, Butler WM, Galbreath KUV, Lief JH (2003) Does hormonal manipulation in conjunction with permanent interstitial brachytherapy, with or without supplemental external beam irradiation, improve the biochemical outcome with intermediate or high risk prostate cancer? BJU Int 91(1): 23-9
Nag S, Beyer D, Friedland J (1999) American Brachytherapy Society (ABS) recommendations for transperineal permanent brachytherapy of prostate cancer. Int J Radiat Oncol Biol Phys 44(4): 789-99
Newling DWW (1997) Assessment of hormone refractory prostate cancer. Urology 49(4a): 46-53
NHS Cancer Screening Programmes (2002) Prostate Cancer Risk Management. NHS Cancer Screening Programmes, Sheffield (http:// www.cancerscreening.nhs.uk/prostate) (last accessed 30 March 2005)
Potter JM, Emberton M (2003) PSA and PSA Screening: A Guide for Patients, Nurses and Doctors. Euromed, London
Prostate Cancer Trialists’ Collaborative Group (2000) Maximum androgen blockade in advanced prostate cancer: an overview of the randomized trials. Lancet 355: 1491-8
Pryor JP (1999) Male sexual function. In: Mundy AR, Fitzpatrick JM, Neal DE, eds. The Scientific Basis of Urology. Isis Medical Media, Oxford
Shroder FH, Collette L, De Reijke TM (2000) Prostate cancer treated by anti-androgens: is sexual function preserved? Br J Cancer 82: 283-90
Soloway MS (1998) Controversies in the management of clinically localized prostate cancer. In: Belledegrun A, Kirby R, Oliver T, eds. New Perspectives in Prostate Cancer. Isis Medical Media, Oxford
Soloway MS, Pareek K, Sharifi R et al (2002) Lupron Depot Neoadjuvant Prostate Cancer Study Group. Neoadjuvant androgen ablation before radical prostatectomy in cT2bNxMo prostate cancer: 5- year results. J Urol 167: 112-16
Vogelzang NJ, Chodak GW, Soloway MS et al (1995) Goserelin versus orchidectomy in the treatment of advanced prostate cancer: final results of a randomized trial. Zoladex Prostate Study Group. Urology 46: 220-6
Weckerman D, Harzmann R (2004) Hormone therapy in prostate cancer: LHRH antagonists versus LHRH analogues. Bur Urol 46: 279-84
Lawrence Drudge-Coates is Macmillan Urology Clinical Nurse Specialist, Department of Urology, King’s College Hospital, London
Accepted for publication: February 2005
Copyright Mark Allen Publishing Ltd. Apr 14-Apr 27, 2005
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