Prostate cancer overview. Part 2: metastatic prostate ...

oncology

Prostate cancer overview. Part 2: metastatic prostate cancer Lawrence Drudge-Coates and Bruce Turner

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lthough advances in the diagnosis and treatment of prostate cancer have improved survival rates, more than 10 721 men die from prostate cancer each year in the UK; approximately 20–30% of men have bone metastasis when they are diagnosed with prostate cancer (Cancer Research UK, 2011). Skeletal-related events are commonly associated with bone metastases, often causing severe pain, increasing mortality and reducing quality of life, as well as imposing a burden on healthcare resources. Metastatic prostate cancer is incurable, so the aim is to control disease progression, reduce associated symptoms and optimise patients’ quality of life; treatment remains a significant clinical challenge. This is the second of two articles; it looks at metastatic prostate cancer. It aims to give an overview of the key treatment approaches, the challenges, emerging therapies and nursing roles.

Diagnosis In prostate cancer, bone is the most common site of spread (Hatoum et al, 2008). Bone metastases can be diagnosed with imaging such as x-ray, computerised tomography (CT) and magnetic resonance imaging (MRI). In prostate cancer, the gold-standard approach is by bone scan, also known as bone scintigraphy (Heidenreich et al, 2012) (Figure 1). Scintigraphy involves a radioactive tracer being given intravenously. The tracer has an affinity for bone and abnormal bone activity, and a subsequent bone scan allows for abnormal bone activity to be identified. Such a scan is often carried out as an initial assessment where metastases are suspected and in men with prostate cancer who develop signs and symptoms of metastases further on in their cancer pathway, such as a rise in prostate-specific antigen (PSA) despite treatment or bone pain.

Treatments Hormone therapy Prostate cells are physiologically dependent on male hormones or androgens to stimulate growth, function and proliferation; testosterone is essential for the growth and Lawrence Drudge-Coates is Urology Oncology Clinical Nurse Specialist and Honorary Lecturer, King’s College Hospital NHS Foundation Trust, London; Bruce Turner is Uro-oncology Nurse Practitioner, Homerton University Hospital and Barts Health NHS Trust, London. Accepted for publication: October 2012

British Journal of Nursing, 2012 (Urology Supplement), Vol 21, No 18

Abstract

Advances in diagnosis mean that prostate cancer can be detected in the early stages, when options such as surgery and radiotherapy offer curative approaches and active surveillance is appropriate. However, advanced or metastatic disease continues to challenge medical management, which offers only palliative approaches. With such a prognosis, effective treatment of metastatic and metastatic castrate-resistant prostate cancer (mCRPC) is an important element of the management of these patients. The second article of this twopart series focuses on the main management approaches, emerging therapies and nursing roles. Key words: Metastatic prostate cancer n Castrate-resistant prostate cancer n Skeletal-related events n Nursing role n Patient support. perpetuation of prostate cancer cells (Walsh, 1975).The testes are the source of most androgens, with 5–10% of androgens being produced by the adrenal glands. If prostate cells are deprived of androgen stimulation, they undergo apoptosis (programmed cell death). Any treatment that results in the suppression of androgen activity is referred to as androgen deprivation therapy (ADT). Androgen deprivation can be achieved either surgically by the removal of the testes (orchidectomy) or by medical castration with luteinising hormone-releasing hormone (LHRH) analogues and antagonists. ADT is the first-line treatment for metastatic prostate cancer, but it does not offer a curative approach. Commonly used LHRH agonists include leuprolide, goserelin and triptorelin. They stop the testicles from producing testosterone, which in turn stops the production of luteinising hormone in the pituitary gland. LHRH agonists, after an initial phase of stimulation, lead to the suppression of luteinizing hormone and testosterone production. To reduce the risk of initial phase of testosterone stimulating the prostate cancer cells—referred to as the ‘flare-up’ phenomenon—short-term administration of an antiandrogen is required (Heidenreich et al, 2012). In contrast to LHRH agonists, LHRH antagonists, such as degarelix, bind immediately and competitively to LHRH receptors in the pituitary gland. The effect is a rapid decrease in luteinising hormone, follicle-stimulating hormone and testosterone levels, without any flare-ups, so no antiandrogen therapy is required (Klotz et al, 2008) (Figure 2). Importantly for patient care, because they alleviate pain and other symptoms, these rapid and effective hormone therapies play

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Metastases in the spine

Figure 1. Bone scan showing metastases in dark areas (Image courtesy of Lawrence Drudge-Coates, King’s College Hospital NHS Foundation Trust)

an important role in patients with symptomatic metastatic disease, including bone metastases and neurological symptoms due to impending spinal cord compression (Heidenreich et al, 2012). There is still controversy over the most appropriate time to introduce hormonal therapy in patients with metastatic prostate cancer. There is no consensus over whether ADT should be given immediately upon diagnosis of asymptomatic metastatic disease or deferred until there are signs and symptoms of clinical progression. In metastatic disease, initial responses to ADT castration therapy are often favourable, with significant regression of the metastases, reduced pain levels, improvement in quality of life and a rapid decline in PSA levels in 80–90% of patients (Harris et al, 2009). Despite good initial responses, metastatic disease invariably progresses after a median time of 18–24 months of ADT; the time frame varies in individual patients (Eisenberger and Walsh, 1999). The prostate cancer then progresses to what is termed a castration-resistant phase of disease (castrationresistant prostate cancer—CRPC) (Table 1). This term is based on findings suggesting that advancing prostate cancer is not uniformly resistant to further hormonal manipulation. To determine the castration-resistant state, it is imperative that patients have testosterone blood levels measured.

Second-line hormone therapy Many treatment options are available to patients with

progressive disease after ADT. They include antiandrogens (maximal androgen blockade), antiandrogen withdrawal, antiandrogen replacement, oestrogenic compounds, adrenolytic agents and novel approaches. None of them offer a curative approach so it is essential that treatment must therefore be tailored on an individual patient basis. From the most recent reviews and meta-analyses, it appears that, at a follow-up of five years, maximum androgen blockade (MAB) with nonsteroidal antiandrogens provides a small but statistically significant survival advantage (50% PSA decrease for a median duration of approximately four months, with the PSA response seen some 4-6 weeks after withdrawal (Sartor et al, 2008). Heidenreich et al (2012) argue, therefore, that androgen withdrawal considered systematically as a first-line modality in patients experiencing relapses, even if its efficacy is limited. Prostate cancer usually expresses oestrogen receptors, which are upregulated after androgen deprivation. Diethylstilboestrol, a synthetic oestrogen, has been shown to a achieved a positive PSA response of between 24% and 80%, with an overall estimated survival of 63% at two years. However, even at low doses of diethylstilboestrol, about one-third (31%) of patients have been found to develop deep venous thrombosis and 7% to experience myocardial infarction (Oh et al, 2004). The adrenal glands, which secrete approximately 10% of androgens, cause some response in prostate cancer cells. These circulating androgens can be decreased by administering ketoconazole (an antifungal agent); when given at a high dose (1 200 mg/day) or low dose (600 mg/day), it resulted in ≥50% PSA reduction in 27%–63% and 27%–46%, of patients respectively (Small et al, 2004). However, it has notable sideeffects including weakness, gastrointestinal complaints such as nausea or vomiting, liver toxicity and skin reactions as well

Box 1. Definition of castration-resistant prostate cancer n Castrate serum levels of testosterone