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National Collaborating Centre for Cancer (UK). Prostate Cancer: Diagnosis and Treatment. Cardiff (UK): National Collaborating Centre for Cancer (UK); 2008 Feb. (NICE Clinical Guidelines, No. 58.)

  • This publication is provided for historical reference only and the information may be out of date.

This publication is provided for historical reference only and the information may be out of date.

7Metastatic prostate cancer

7.1. Introduction

This chapter addresses the clinical needs of men with prostate cancer which has spread beyond the prostate and pelvic lymph nodes. Bone metastases are common and may cause pain and reduced mobility. The majority of men with metastatic prostate cancer will respond well to hormonal therapy which often keeps the disease controlled for several years. Once the disease becomes refractory to hormonal therapy, the control of symptoms and measures that improve quality of life may become as important as treatments that may prolong life.

7.2. Hormonal Therapy

Androgen withdrawal by either surgical or medical castration can typically control the disease for several years. Bilateral orchidectomy has been an effective treatment for metastatic prostate cancer for over 60 years. The use of luteinising hormone-releasing hormone agonists (LHRHa) has been compared with bilateral orchidectomy in several randomised trials.

Advantages of bilateral orchidectomy include improved convenience for the patient and treatment adherence but with the disadvantage that it is an irreversible procedure. Advantages of LHRHa include the possibility of intermittent use (see below). Their disadvantages include the cost, and problems with compliance and administration.

LHRHa may be given alone (after a short period of anti-androgen therapy to prevent tumour flare) or in combination with an anti-androgen as combined androgen blockade. When bilateral orchidectomy or LHRHa monotherapy fails an anti-androgen may be added as second-line hormonal therapy.

Recommendation

Qualifying statement: There are randomised studies which show comparable survival benefit and side effects for bilateral orchidectomy. There is good evidence that bilateral orchidectomy is more cost effective, but the GDG recognised the importance of patient preference in this issue.

7.3. Androgen Withdrawal Versus Combined Androgen Blockade (CAB)

Androgen withdrawal alone is the standard hormonal therapy for metastatic prostate cancer. It has been postulated that the addition of an oral anti-androgen to androgen withdrawal therapy could improve treatment efficacy and a large number of randomised controlled trials have studied the effect on survival.

Recommendation

Qualifying statement: Evidence shows only a modest survival benefit for combined androgen blockade and high costs.

7.4. Anti-androgen Monotherapy

Anti-androgen monotherapy has been studied in the hope that it would be less toxic than androgen withdrawal but with comparable effectiveness. Several randomised trials have shown that loss of sexual function is less marked with anti-androgen monotherapy than with androgen withdrawal. There is also evidence that anti-androgen monotherapy causes less reduction in bone mineral density (BMD) than androgen withdrawal but the significance of changes in BMD in men is not clear. However anti-androgen monotherapy is associated with increased gynaecomastia and is a less effective treatment for metastatic disease than androgen withdrawal in terms of overall survival. Anti-androgen monotherapy (bicalutamide 150 mg) is therefore licensed for use in locally advanced disease and not for metastatic disease.

Recommendations

Qualifying statement: Evidence from randomised trials confirms the relative protection from loss of sexual function.

Qualifying statement: This recommendation is based on GDG consensus alone.

1

At the time of publication (February 2008) bicalutamide did nothave UK marketing authorisation for this indication. Informed consent should be obtained and documented.

7.5. Intermittent Androgen Withdrawal

The standard approach to hormonal therapy has been continuous treatment. Long-term results from uncontrolled studies of intermittent therapy have shown satisfactory outcomes. Several randomised trials are testing whether intermittent therapy might be less toxic, and whether overall survival is unimpaired or even improved. These trials are not yet mature. Intermittent therapy will probably be cheaper than continuous therapy despite the need for closer monitoring.

Recommendation

Qualifying statement: This recommendation is based on GDG consensus in the light of the results of uncontrolled studies.

Clinical Evidence

Orchidectomy versus LHRHa’s

Evidence came from a systematic review of thirteen randomised trials of hormonal monotherapy in prostate cancer (Seidenfeld et al. 2000; Seidenfeld et al 2001). Meta-analysis suggested comparable overall survival benefit between orchidectomy and LHRHa’s. The evidence about adverse effects was less reliable due to reporting inconsistencies between trials, although adverse event rates appeared similar in orchidectomy and LHRHa treatment groups.

Health Economic Evaluation

The literature review identified 183 potentially relevant economic evaluations. Ten papers were obtained, but only 2 were considered to be full economic evaluations and reviewed in full. One of these papers was published in Japanese, but an English summary was available.

Bayoumi et al (2000) conducted the first evaluation in 2000, as part of a US Agency for Health Care Research (AHRQ) research project. The evaluation represents an extremely comprehensive evaluation that compared 6 different treatment strategies for the first-line choice of hormone treatment for advanced prostate cancer: 1) diethylstilbestrol [DES] 2) bilateral orchiedctomy 3) non steroidal antiandrogen [NSAA] 4) LHRH monotherapy 5) NSAA in combination with a LHRH and 6) NSAA and bilateral orchidectomy. The economic evaluation was underpinned by a systematic review of appropriate randomised controlled trials (RCTs) and a meta-analysis. A Markov model was also constructed, which took into account the progression of the patients underlying prostate cancer and the side effects due to individual treatments. The framework used for the analysis was a cost-utility analysis from a health services perspective. A cost-effectiveness analysis, using survival as the outcome measure, was also conducted.

The results showed that it cost an extra £6100 and £7500 per additional life-year and QALY gained, respectively, if orchidectomy was used instead of DES. All other treatment options, including LHRH monotherapy, were dominated by orchidectomy (i.e. they were more costly and less effective). These results were robust to most alternative assumptions, except when different utility values were assumed. This finding is important, as the analysis did not take into account patients’ preferences for different courses of action, for example, surgical or medical castration. Nonetheless, the authors concluded that orchidectomy was the most cost-effective treatment option.

The second evaluation, by Fujikawa et al. (2003) was published in Japanese, but an English summary was available for review. The evaluation was similar to Bayoumi et al. in so much that it was based on a review of the literature, meta-analysis and Markov modelling exercise. It also compared a number of different options as first-line hormonal therapies for advanced prostate cancer: 1) DES 2) orchidectomy 3) orchidectomy and NSAA 4) LHRH monotherapy and 5) LHRH monotherapy and NSAA. However, an important difference between the two evaluations is that Fujikawa et al (2003) attempted to allow for individual preferences (for medical versus surgical castration) by multiplying the health state utilities of orchidectomy by 0.94 – although a justification for this value is not provided. Thus health outcomes associated with orchidectomy were considered to be of ‘less value’ compared to purely medical alternatives. The overall quality of the evaluation was judged to be good.

The baseline results from the analysis showed that compared to orchidectomy, LHRH monotherapy cost approximately £17 500 per additional QALY gained. However, it is unclear what the incremental cost-effectiveness ratio would have been if the 0.94 weighting had been removed. It is also unclear whether future health benefits were discounted (in Bayoumi et al (2000) they were discounted at 3% per annum). Indeed, minimal sensitivity analysis means that it is difficult to assess the robustness of the results to alternative assumptions.

Clinical Evidence

LHRHa’s versus CAB

Evidence from 27 randomised trials, summarised in two systematic reviews (Prostate Cancer Trialists 2000; Seidenfeld et al. 2001), shows a small survival advantage with combined androgen blockade using non-steroidal anti-androgens. The estimate of five year overall survival from meta-analysis was 28% for men treated with combined androgen blockade compared with 25% for those treated with androgen withdrawal alone (Prostate Cancer Trialists 2000). Using the rate of treatment withdrawal as a index of treatment toxicity, Samson, Seidenfeld and co-workers (Samson et al. 2002; Seidenfeld et al. 2001) reported that men treated with LHRHa alone withdrew from therapy at a rate of 4% or less compared with a rate of 8% or more in men receiving CAB.

Anti-androgen monotherapy

Meta-analysis of thirteen randomised trials of hormonal monotherapy (Seidenfeld et al. 2000; Seidenfeld et al. 2001) showed a trend towards poorer overall survival with anti-androgen monotherapy than with castration. The two therapies had different toxicity profiles. Gynaecomastia was more likely with non-steroidal anti-androgens, whereas hot flushes and reduced sexual function were more likely with androgen withdrawal. The proportion withdrawing from anti-androgen monotherapy and LHRHa treatment was similar, however, suggesting comparable tolerability (Seidenfeld et al. 2000; Seidenfeld et al. 2001).

Intermittent androgen withdrawal

The literature search identified no reliable evidence about the impact of intermittent androgen withdrawal on survival. In their systematic review of five small randomised trials, Conti and co-workers (Conti et al. 2007) concluded that the available information suggests that intermittent androgen deprivation therapy may have a slightly reduced risk of adverse events when compared with continuous androgen deprivation.

7.6. Managing the Complications of Hormonal Therapy

Randomised trials of interventions for complications of hormonal therapy are limited to the management of hot flushes, gynaecomastia and tiredness. Our recommendations are therefore limited to the evidence available.

The interventions for hot flushes that have been studied are diethylstilboestrol, cyproterone acetate, megestrol acetate, clonidine, and oestrogen patches. Since the severity and frequency of hot flushes can improve spontaneously over time, non-randomised studies are of uncertain value. Interventions that have been used for hot flushes, but have not been studied in randomised trials, include selective serotonin reuptake inhibitors (SSRIs), sage, black cohosh and acupuncture.

Gynaecomastia is a common, troublesome complication of long-term bicalutamide monotherapy. Randomised trials have studied the use of tamoxifen and of prophylactic radiotherapy to the breast buds. Although tamoxifen was shown to be an effective treatment of bicalutamide induced gynaecomastia, there is a theoretical concern that, as an anti-oestrogen, it could have an adverse effect on prostate cancer control.

Recommendations

  • Synthetic progestogens (administered orally or parenterally) are recommended as first-line therapy for the management of troublesome hot flushes. If oral therapy is used, it should be given for 2 weeks, and re-started, if effective, on recurrence of symptoms.
  • Men starting long-term bicalutamide monotherapy (> 6 months) should receive prophylactic radiotherapy to both breast buds within the first month of treatment. A single fraction of 8 Gy using orthovoltage or electron beam radiotherapy is recommended.
  • If radiotherapy is unsuccessful in preventing gynaecomastia, weekly tamoxifen should be considered.
  • Inform men starting androgen withdrawal therapy that regular resistance exercise reduces fatigue and improves quality of life.

Qualifying statement: These recommendations are based on GDG consensus, informed by several small RCTs.

Clinical Evidence

Hot flushes

Placebo controlled randomised trials have demonstrated that diethylstilbestrol (Atala et al. 1992) and megestrol acetate (Loprinzi et al. 1994) are effective in the treatment of hot flushes in men treated with hormonal therapy. Very small randomised trials have shown beneficial results from the use of oestrogen patches (Gerber et al. 2000) and cyproterone acetate (Eaton & McGuire 1983). A small case series (Langenstroer et al. 2005) suggested that intramuscular medroxyprogesterone acetate reduced the frequency and severity of hot flushes.

Gynaecomastia

A systematic review (Di Lorenzo et al. 2005) considered evidence from randomised trials of radiotherapy or tamoxifen for the prevention and treatment of gynaecomastia and breast pain associated with anti-androgens. A narrative review of the evidence supported the effectiveness of both radiotherapy and tamoxifen, although there were theoretical concerns that, as an anti-oestrogen, tamoxifen could reduce the effectiveness of hormonal therapy.

Health Economic Evaluation

The GDG did not rate this topic as a health economic priority; therefore the cost-effectiveness literature on this topic has not been reviewed.

7.7. Hormone-Refractory Prostate Cancer

There is no universally accepted definition of hormone refractory disease. The disease can be considered to be hormone refractory when androgen withdrawal therapy or combined androgen blockade are no longer controlling the prostate specific antigen (PSA) or the symptoms of the disease, or when there is radiological evidence of progression. However hormone refractory disease, so defined, may still respond to agents such as oestrogens or corticosteroids that probably work via the androgen receptor. Even when the disease becomes hormone refractory the androgen receptor on the cancer cells can remain active and LHRHa therapy is usually continued.

There is no known curative therapy for hormone refractory disease and so the goals of treatment are to improve survival and quality of life and to control symptoms.

Recommendation

  • When men with prostate cancer develop biochemical evidence of hormone-refractory disease, their treatment options should be discussed by the urological cancer multidisciplinary team (MDT) with a view to seeking an oncological and/or specialist palliative care opinion as appropriate.

Qualifying statement: There was GDG consensus that the management of these men is not usually discussed at MDT meetings despite the recommendations in the NICE cancer service guidance ‘Improving outcomes in urological cancers’ (NICE 2002).

7.8. Chemotherapy

Chemotherapy is usually given to men with symptomatic progression but asymptomatic men with metastatic disease and a rapidly rising PSA may also benefit from chemotherapy.

The combination of docetaxel and prednisolone is the only chemotherapy regime licensed for use in hormone-refractory prostate cancer. The side effects of this combination can be substantial and it may not be possible to use docetaxel if the disease has progressed to a stage where it is causing significant symptoms. Men with poor performance status who may not tolerate docetaxel are usually treated with the combination of mitoxantrone and prednisolone.

Several trials are investigating the use of docetaxel earlier in the course of the disease.

It is not clear whether there is a significant benefit from second line treatment with mitoxantrone or newer chemotherapy drugs for men who have failed docetaxel.

New chemotherapy regimens, targeted therapies and cancer vaccines are currently in clinical trial in prostate cancer.

Recommendations (from NICE technology appraisal guidance 101)

  • Docetaxel is recommended, within its licensed indications, as a treatment option for men with hormone-refractory metastatic prostate cancer only if their Karnofsky performance-status score is 60% or more.
  • It is recommended that treatment with docetaxel should be stopped:

    at the completion of planned treatment of up to 10 cycles, or

    if severe adverse events occur, or

    in the presence of progression of disease as evidenced by clinical or laboratory criteria, or by imaging studies.

  • Repeat cycles of treatment with docetaxel are not recommended if the disease recurs after completion of the planned course of chemotherapy.

Qualifying statement: These recommendations are from ‘Docetaxel for the treatment of hormone-refractory metastatic prostate cancer’, NICE technology appraisal guidance 101 (2006). It has been incorporated into this guideline in line with NICE procedures for developing clinical guidelines.

7.9. Oestrogens and Steroids

Diethylstilboestrol is a synthetic oestrogen that can reduce the PSA level in men with hormone refractory disease. There is also research interest in the use of transdermal oestrogens as an alternative to LHRHa’s in newly diagnosed prostate cancer.

Corticosteroids can be very useful in men with hormone-refractory prostate cancer. Low dose steroids can reduce the production of adrenal androgens in men on androgen withdrawal by suppressing adrenocorticotropic hormone (ACTH) secretion from the pituitary. This effect can be achieved by physiological doses of corticosteroids such as dexamethasone, prednisolone or hydrocortisone. Other mechanisms of action have also been postulated to explain the fall in PSA that has been reported with corticosteroids. Higher dose steroids can have an anti-inflammatory effect on bone metastases.

Recommendation

Qualifying statement: There is evidence from several case series to support this recommendation.

Clinical Evidence

Evidence, from observational studies, suggests a PSA response rate of 50% or more with low dose dexamethasone therapy in men with castration refractory prostate cancer, compared with 21–34% for prednisolone and 21.5% for hydrocortisone.

Health Economic Evaluation

The GDG did not rate this topic as a health economic priority; therefore the cost-effectiveness literature on this topic has not been reviewed.

7.10. Imaging

The natural history of clinically occult spinal cord compression in prostate cancer is unknown and there is little published data on the use of spinal magnetic resonance imaging (MRI) in this clinical setting. The value of prophylactic irradiation for asymptomatic cord compression is unclear. NICE is currently developing a clinical guideline on metastatic spinal cord compression which may expand these recommendations.

Recommendations

  • Men with hormone-refractory prostate cancer shown to have extensive metastases in the spine (for example, on a bone scan) should have spinal MRI if they develop any spinal related symptoms.

Qualifying statement: There was strong GDG consensus that it was important to try to identify spinal cord compression in high-risk men as early as possible to enable them to receive the necessary treatment.

  • The routine use of spinal MRI for all men with hormone-refractory prostate cancer and known bone metastases is not recommended.

Qualifying statement: There is no evidence to support routine use of MRI in this situation.

Clinical Evidence

Bayley and co-workers (Bayley et al. 2001) reported a prospective study using MRI to screen for sub-clinical spinal cord compression in a group of men with vertebral bone metastases from prostate cancer but without symptoms of spinal cord compression. 32% of the group had sub-clinical spinal cord compression on MRI. Another series (Venkitaraman et al 2007) reported the results of spinal MRI in men with prostate cancer considered at high risk of developing spinal cord compression, but without functional neurological deficit. Radiological spinal canal compromise was seen in 27% of these men. Neither of the studies reported outcomes following MRI screening for spinal cord compression.

Risk factors for radiological spinal cord compression in men with metastatic prostate cancer were extensive bone metastasis (Bayley et al. 2001; Venkitaraman et al 2007), duration of hormonal therapy (Bayley et al. 2001) and back pain (Venkitaraman et al. 2007).

Health Economic Evaluation

The GDG did not rate this topic as a health economic priority; therefore the cost-effectiveness literature on this topic has not been reviewed.

7.11. Bone Targeted Therapies

Men with prostate cancer may benefit from bone targeted therapies such as bisphosphonates and Strontium-89, either as treatment for symptomatic bone metastases as a preventive measure to delay or suppress the metastases or as treatment for the osteoporosis caused by hormonal therapy.

Bisphosphonates are also used to treat cancer-related hypercalcaemia.

Androgen withdrawal therapy is a risk factor for the development of osteoporosis.

Recommendations

  • The use of bisphosphonates to prevent or reduce the complications of bone metastases in men with hormone-refractory prostate cancer is not recommended.

Qualifying statement: There is inconsistent evidence, from several RCTs, of the effectiveness of bisphosphonates in preventing or reducing complications of bone metastases.

  • Bisphosphonates for pain relief may be considered for men with hormone-refractory prostate cancer when other treatments (including analgesics and palliative radiotherapy) have failed. The oral or intravenous route of administration should be chosen according to convenience, tolerability and cost.

Qualifying statement: A systematic review supports this recommendation.

Clinical Evidence

Evidence came from a systematic review of ten randomised trials (Yuen et al. 2006). Meta-analysis showed a trend favouring bisphosphonates over placebo for the relief of pain from bone metastases in men with prostate cancer. There was no significant difference, however, between the analgesic consumption of bisphosphonate and placebo groups. Meta-analysis showed a modest reduction in skeletal events with bisphosphonate treatment (using trial authors’ definitions of skeletal events). The estimated rates for skeletal events were 37.8% and 43.0% for the bisphosphonate and placebo groups respectively: an absolute risk difference of 5.2%.

There was inconsistent evidence about the effect of bisphosphonates on the rate of pathological fractures. The rates of spinal cord compression, bone surgery and bone radiotherapy did not differ significantly between bisphosphonate and placebo groups. There were no significant group differences in overall survival or in quality of life.

Health Economic Evaluation

The literature review identified 153 potentially relevant papers, but none were obtained for appraisal as they did not include any economic evaluations. The GDG considered there to be insufficient clinical information available to enable robust economic modelling.

Recommendation

Qualifying statement: This recommendation is based on a lack of evidence that the incidence of bone fractures is reduced.

Clinical Evidence

There was consistent evidence from randomised trials (Diamond et al. 2001; Greenspan et al. 2007; Michaelson et al. 2007; Ryan 2006; Magno et al. 2005; Smith et al. 2001; Smith et al. 2003), that treatment with bisphosphonates increases the bone mineral density of the lumbar spine in men receiving hormonal therapy for prostate cancer. However, there was no evidence about the effect of bisphosphonates on the rate of symptomatic fractures: the single trial reporting this outcome had insufficient follow-up (Smith et al. 2003). There was no significant difference in the rate of severe adverse effects in bisphosphonate and placebo arms in three trials that reported this outcome (Ryan 2006; Greenspan et al. 2007; Smith et al. 2003).

Health Economic Evaluation

The literature review identified 153 potentially relevant papers, but none were obtained for appraisal as they did not include any economic evaluations. No economic modelling was undertaken as the GDG concluded evidence from one available RCT showed that bisphosphonates did not reduce or delay the development of symptomatic factures.

External Beam Radiotherapy

External beam radiotherapy is an effective way of improving pain from bone metastases and is useful as treatment for spinal cord compression caused by bone metastases in the vertebrae.

Bone-seeking Radio-isotopes

Strontium-89 (Sr-89) is a beta-emitting radioactive isotope which is given intravenously and is taken up preferentially in bone metastases. In comparison with standard care, Sr-89 has been shown, in systematic reviews of randomised trials, to improve pain control, and prevent new sites of pain. It has a favourable toxicity profile, but may compromise ability to deliver subsequent myelosuppressive chemotherapy. Samarium-153 has also shown effectiveness in metastatic prostate cancer but has a shorter half-life than Sr-89 and is more complicated to administer. Rhenium-186 is given linked to a bisphosphonate (etidronate) to increase uptake in bone. Radium-223 is an alpha emitter that has shown encouraging results in early studies in prostate cancer and further studies are planned.

Recommendation

  • Strontium-89 should be considered for men with hormone-refractory prostate cancer and painful bone metastases, especially those men who are unlikely to receive myelosuppressive chemotherapy.

Qualifying statement: The evidence of cost effectiveness is weak. However there was GDG consensus that the recommendation should be made based on several RCTs, which demonstrated the clinical benefit of Sr-89.

Clinical Evidence

Systematic reviews of placebo controlled randomised trials (Bauman et al. 2005; Brundage et al. 1998; Figuls et al. 2003; Finlay et al. 2005; Loblaw et al. 2003; McQuay et al. 1999) suggest that strontium-89 (89Sr-chloride) and samarium-153 (153Sm-EDTMP) are effective for the control of pain from bony metastases in men with prostate cancer. There was no evidence of an overall survival benefit for men treated with radioisotopes. Adverse events associated with radioisotope therapy were usually limited to mild myelosuppression. A systematic review of four studies comparing strontium-89 with samarium-153 or rhenium-188 found no significant differences in pain response rate or treatment toxicity (Finlay et al. 2005).

Health Economic Evaluation

The literature review on Sr-89 identified 50 potentially relevant papers. Nineteen of these papers were obtained for appraisal of which 2 were identified and reviewed (McEwan et al 1994; Malmberg 1997). None contained full economic evaluations, only cost comparisons. All three evaluations compared the costs of providing Sr-89 as an adjunct to radiotherapy to patients with hormone-refractory prostate cancer and bone metastases compared with radiotherapy alone.

The study by McEwan et al. (1994) was based on a small Canadian (CAN$) RCT (n=29), although the costing was undertaken retrospectively. All patients were followed-up until death, which was at a median of 30–34 weeks depending on the treatment arm. The study demonstrated a number of clinical benefits including an improvement in quality of life indices. No price year for the costing was provided. The authors stated that the mean treatment cost per patient for the strontium group was Can$16,570 and Can$23,688 for placebo (approximately £7,700–£11,000). However, evidence from within the manuscript suggests that these costs are incorrect, and that the placebo arm was less costly than the strontium-89 arm. No sensitivity analysis was performed, and the evaluation was generally considered to be of poor quality.

The evaluation by Malmberg et al. (1997) also evaluated the costs of external radiotherapy alone versus external radiotherapy with Sr-89, from a Swedish societal perspective (that is, both direct healthcare and indirect costs were included). The analysis was based on a single RCT, but longer terms costs were estimated. That is, the time horizon for the analysis was a patient’s lifetime. The costs relating to radiotherapy included the costs of skeletal scintigraphy, outpatient visits, inpatients days, and travel to the treatment centre. The costs for Sr-89 included the costs of its administration. Costs were reported in 1993 Swedish prices.

The authors reported that the total additional lifetime cost of Sr-89 treatment were more than offset by cost savings from the postponed external radiotherapy treatments. Reported cost savings were approximately between SEK 3,000–11,000 (approximately £200–£800). However, the main limitation with the analysis was that very few details of the methods were reported. Thus it was difficult to determine the quality of the study. In summary, the overall evidence base to support the use of Sr-89 in this setting was considered to be weak.

7.12. Pelvic Targeted Therapies

Management of Obstructive Uropathy

Prostate cancer may result in unilateral or bilateral obstruction of the ureters resulting in impaired renal function.

The development of obstructive uropathy in men with hormone-refractory prostate cancer is a frequent, potentially fatal, event.

Decompression may allow a return to baseline renal function, palliate symptoms of uraemia and improve quality of life. It may also lead to an earlier discharge from hospital. However it is unlikely to significantly prolong survival, with the average life expectancy of this group of men remaining around 6–12 months.

The most common choices for decompression lie between external placement of a nephrostomy tube under local anaesthetic or the internal insertion of a double J stent from the bladder to the kidney under general anaesthetic. Decompression does have an associated complication rate and long term morbidity. Medical intervention such as high-dose steroids have also shown promise.

Recommendations

Qualifying statement: These recommendations are based on observational evidence of effectiveness and GDG consensus.

Clinical Evidence

Evidence about urinary tract decompression in men with ureteric obstruction and hormone-refractory prostate cancer came from case series. Most studies concluded that urinary tract decompression, with nephrostomy or ureteral stents, should be considered (Harris & Speakman 2006; Bordinazzo et al. 1994; Chiou et al. 1990; Sandhu et al. 1992; Fallon et al. 1980). Some, however concluded that, despite any survival benefit, urinary tract decompression was usually not appropriate in this group (Dowling et al. 1991; Paul et al. 1994). There was insufficient evidence about the relative effectiveness of nephrostomy and ureteral stents: no series directly compared different interventions.

Health Economic Evaluation

The GDG did not rate this topic as a health economic priority; therefore the cost-effectiveness literature on this topic has not been reviewed.

Management of Haematuria

Locally advanced prostate cancer can result in haematuria caused by bleeding from the prostatic urethra or base of bladder. Endoscopic control of bleeding points can be performed under general anaesthesia. Palliative radiotherapy to the bladder base and prostate also may be effective.

Management of Bowel Obstruction

Local extension of prostate cancer into the rectum can cause luminal narrowing or complete obstruction. The former can usually be managed by alterations to the diet, the prescription of aperiants and consideration of radiotherapy. Complete obstruction of the lower bowel may require a defunctioning colostomy.

7.13. Palliative Care

The understanding of supportive and palliative care on which this guidance is based originates from work by the National Council for Palliative Care. The recommendations in ‘Improving supportive and palliative care for adults with cancer’ (NICE 2004) apply to men with prostate cancer.

Palliative Care is: “… the active holistic care of patients with advanced, progressive illness. Management of pain and other symptoms and the provision psychological, social and spiritual support is paramount. The goal of palliative care is achievement of the best quality of life for patients and families.” (NICE 2004). Many aspects of palliative care are also applicable earlier in the course of the illness in conjunction with other treatments.

Multidisciplinary Needs of Men with Prostate Cancer

The present provision of palliative care to National Health Service (NHS) patients involves substantial service provision in the independent and charitable sector as well as service within the NHS.

The management of physical symptoms and the psychological needs of men with metastatic prostate cancer needs to draw on the expertise of many healthcare professionals. The day to day management of men with metastatic prostate cancer is the responsibility of the primary care services but in order to achieve optimum care there needs to be close co-operation between primary care, the urology MDT and generic and specialist palliative care staff.

The long natural history of prostate cancer means that specialist care may start with the urologist, transfer to the oncologist and end with palliative care. Often there will be overlap between services but the man and his carers and professionals need to be clear which service is in overall control at each stage of the illness

The palliative care of these men draws on the expertise of primary care, urological surgeons, orthopaedic surgeons, oncologists, neurosurgeons, neurologists, physicians, support services and experts in pain as well as generic and specialist palliative care providers.

The Dying Patient

Some men will die from their prostate cancer but many will die from other diseases whilst they have prostate cancer. It is important to identify when men are close to death and ensure that symptom relief and palliative care is available to all. This may require generic or specialist palliative care.

The effective management of symptoms at the end of life, in all care settings, is supported by the use of appropriate care pathways. The Liverpool Care Pathway for the Dying (http://www.mcpcil.org.uk/liverpool_care_pathway) and the Gold Standards Framework (http://www.goldstandardsframework.nhs.uk/) are models that facilitate the quality of care at the end of life.

Recommendations

  • Men with metastatic prostate cancer should be offered tailored information and access to specialist urology and palliative care teams to address the specific needs of men with metastatic cancer. They should have the opportunity to discuss any significant changes in their disease status or symptoms as these occur.
  • The regular assessment of needs should be applied systematically to men with metastatic prostate cancer2.
  • Palliative interventions at any stage should be integrated into coordinated care, and any transitions between care settings should be facilitated as smoothly as possible.
  • Healthcare professionals should discuss personal preferences for palliative care as early as possible with men with metastatic prostate cancer, their partners and carers. Treatment/care plans should be tailored accordingly and the preferred place of care should be identified.
  • Healthcare professionals should ensure that palliative care is available when needed and is not limited to the end of life. It should not be restricted to being associated with hospice care.

Qualifying statement: There is evidence from qualitative studies and GDG consensus to support these recommendations.

2

’Improving supportive and palliative care for adults with cancer’. NICE cancer service guidance (2004)

Clinical Evidence

Literature searches did not find any studies that compared palliative care settings or models in prostate cancer. Several observational studies described experiences with palliative care in particular settings. Although this shows that care is possible in such settings, without comparative studies there was no evidence about which palliative care model or setting was best.

Several themes emerged: the need for multidisciplinary delivery of palliative care (Palmieri & Waxman 2005; Pienta et al. 1996; Cunliffe 2003; Ok et al. 2005) and the integration of curative and palliative treatment (Ok et al. 2005; Pienta et al. 1996) during the often long course of the disease (Green et al. 2002).

Health Economic Evaluation

The GDG did not rate this topic as a health economic priority; therefore the cost-effectiveness literature on this topic has not been reviewed.

Research Recommendation

  • Further clinical trials should be conducted to determine if there is a role for bisphosphonates in men with prostate cancer.

References

  1. Atala A, Amin M, Harty JI. Diethylstilbestrol in treatment of postorchiectomy vasomotor symptoms and its relationship with serum follicle-stimulating hormone, luteinizing hormone, and testosterone. Urology. 1992;39:108–110. [PubMed: 1736500]
  2. Bauman G, Charette M, Reid R, Sathya J. Radiopharmaceuticals for the palliation of painful bone metastases - A systematic review. Radiotherapy & Oncology. 2005;75:258. [PubMed: 16299924]
  3. Bayley A, Milosevic M, Blend R, Logue J, Gospodarowicz M, Boxen I, Warde P, McLean M, Catton C, Catton P. A prospective study of factors predicting clinically occult spinal cord compression in patients with metastatic prostate carcinoma. Cancer. 2001;92:303–310. [PubMed: 11466683]
  4. Bayoumi AM, et al. Cost-effectiveness of androgen suppression therapies in advanced prostate cancer. Journal of the National Cancer Institute. 2000;92(21):1731–1739. [PubMed: 11058616]
  5. Brundage MD, Crook JM, Lukka H. Use of strontium-89 in endocrine-refractory prostate cancer metastatic to bone. Provincial Genitourinary Cancer Disease Site Group. Cancer Prevention & Control. 1998;2:79–87. [PubMed: 9765768]
  6. Bordinazzo R, Benecchi L, Cazzaniga A, Vercesi A, Privitera O. Ureteral obstruction associated with prostate cancer: the outcome after ultrasonographic percutaneous nephrostomy. Arch Ital. Urol Androl. 1994;66:101–106. [PubMed: 7889041]
  7. Chiou RK, Chang WY, Horan JJ. Ureteral obstruction associated with prostate cancer: the outcome after percutaneous nephrostomy. Journal of Urology. 1990;143(5):957–959. [PubMed: 2329611]
  8. Cunliffe J. Reflections on pain management: a case study. Int J Palliative Nursing. 2003;53 [PubMed: 14593283]
  9. de Leval J, Boca P, Yousef E, Nicolas H, Jeukenne M, Seidel L, Bouffioux C, Coppens L, Bonnet P, Andrianne R, Wlatregny D. Intermittent versus continuous total androgen blockade in the treatment of patients with advanced hormone-naive prostate cancer: results of a prospective randomized multicenter trial. Clinical Prostate Cancer. 2002;1:163–171. [PubMed: 15046691]
  10. Diamond TH, Winters J, Smith A, De SP, Kersley JH, Lynch WJ, Bryant C. The antiosteoporotic efficacy of intravenous pamidronate in men with prostate carcinoma receiving combined androgen blockade: a double blind, randomized, placebo-controlled crossover study. Nature reviews.Cancer. 2001;92:1444–1450. [PubMed: 11745221]
  11. Di Lorenzo G, Autorino R, Perdona S, De PS. Management of gynaecomastia in patients with prostate cancer: A systematic review. Lancet Oncology. 2005;6:972–979. [PubMed: 16321765]
  12. Dowling RA, Carrasco CH, Babaian RJ. Percutaneous urinary diversion in patients with hormone-refractory prostate cancer.[see comment] Urology. 1991;37:89–91. [PubMed: 1992595]
  13. Eaton AC, McGuire N. Cyproterone acetate in treatment of post-orchidectomy hot flushes. Double-blind cross-over trial. Lancet. 1983;2:1336–1337. [PubMed: 6139671]
  14. Fallon B, Olney L, Culp DA. Nephrostomy in cancer patients: To do or not to do? Br J Urol. 1980;52:237–242. [PubMed: 7426987]
  15. Figuls M, Martinez MJ, onso-Coello P, Català E, Garcia JL, Ferrandiz M. Radioisotopes for metastatic bone pain [Cochrane review] Cochrane Database of Systematic Reviews. 2003
  16. Finlay OG, Mason MD, Shelley M. Radioisotopes for the palliation of metastatic bone cancer: a systematic review. Lancet Oncology. 2005;6:392–400. [PubMed: 15925817]
  17. Fujikawa K, et al. Cost-utility analysis of androgen ablation therapy in metastatic prostate cancer. Japanese Journal of Urology. 2003;94(4):503–512. [PubMed: 12795165]
  18. Gerber GS, Zagaja GP, Ray PS, Rukstalis DB. Transdermal estrogen in the treatment of hot flushes in men with prostate cancer. Urology. 2000;55:97–101. [PubMed: 10654902]
  19. Green JS, Trainer A, Hussain M. A study of the comparative use of palliative care services by patients with prostate cancer. J Urol. 2002;167:69–70.
  20. Greenspan SL, Nelson JB, Trump DL, Resnick NM. Effect of once-weekly oral alendronate on bone loss in men receiving androgen deprivation therapy for prostate cancer: a randomized trial.[summary for patients in Ann Intern Med. 2007 Mar 20;146(6):I72; PMID: 17371883] Ann Intern Med. 2007;146:416–424. [PubMed: 17371886]
  21. Harris MR, Speakman MJ. Nephrostomies in obstructive uropathy; how should hormone resistant prostate cancer patients be managed and can we predict who will benefit? Prostate Cancer & Prostatic Diseases. 2006;9:42–44. [PubMed: 16402089]
  22. Langenstroer P, Kramer B, Cutting B, Amling C, Poultan T, Lance R, Thrasher JB. Parenteral medroxyprogesterone for the management of luteinizing hormone releasing hormone induced hot flashes in men with advanced prostate cancer. J Urol. 2005;174:642–645. [PubMed: 16006929]
  23. Loblaw DA, Laperriere NJ, MacKillop WJ. A population-based study of malignant spinal cord compression in Ontario. Clin Oncol (R Coll.Radiol) 2003;15:211–217. [PubMed: 12846501]
  24. Loprinzi CL, Michalak JC, Quella SK, O’Fallon JR, Hatfield AK, Nelimark RA, Dose AM, Fischer T, Johnson C, Klatt NE. Megestrol acetate for the prevention of hot flashes.[see comment] N Engl J Med. 1994b;331:347–352. [PubMed: 8028614]
  25. Magno C, Anastasi G, Morabito N, Gaudio A, Maisano D, Franchina F, Gali A, Frisina N, Melloni D. Preventing bone loss during androgen deprivation therapy for prostate cancer: early experience with neridronate. European Urology. 2005;47:575–580. [PubMed: 15826746]
  26. Malmberg I, et al. Painful bone metastases in hormone-refractory prostate cancer: Economic costs of strontium-89 and/or external radiotherapy. Urology. 1997;50(5):747–753. [PubMed: 9372886]
  27. McEwan AJ, et al. A retrospective analysis of the cost effectiveness of treatment with Metastron (89Sr-chloride) in patients with prostate cancer metastatic to bone. Nuclear Medicine Communications. 1994;15(7):499–504. [PubMed: 7970425]
  28. McQuay HJ, Collins SL, Carroll D, Moore RA. Radiotherapy for the palliation of painful bone metastases [Cochrane review] Cochrane Database of Systematic Reviews. 1999 [PubMed: 10796822]
  29. Michaelson MD, Kaufman DS, Lee H, McGovern FJ, Kantoff PW, Fallon MA, Finkelstein JS, Smith MR. Randomized controlled trial of annual zoledronic acid to prevent gonadotropin-releasing hormone agonist-induced bone loss in men with prostate cancer. J Clin Oncol. 2007;25:1038–1042. [PMC free article: PMC3047397] [PubMed: 17369566]
  30. National Institute for Health and Clinical Excellence. NICE cancer service guidance. London: National Institute for Health and Clinical Excellence; 2002. Improving Outcomes in Urological Cancers.
  31. National Institute for Clinical Excellence. NICE cancer service guidance. London: National Institute for Clinical Excellence; 2004. Improving Supportive and Palliative Care for Adults with Cancer.
  32. National Institute for Health and Clinical Excellence. NICE technology Appraisal 101. London: National Institute for Health and Clinical Excellence; 2006. Docetaxel for the treatment of hormone-refractory metastatic prostate cancer.
  33. Ok JH, Meyers FJ, Evans CP. Medical and surgical palliative care of patients with urological malignancies. [Review] [48 refs] J Urol. 2005;174:1177–1182. [PubMed: 16145365]
  34. Palmieri C, Waxman J. Prostate cancer is best managed by multidisciplinary teams. Pharmacy in Practice. 2005;15:398–404.
  35. Paul AB, Love C, Chisholm GD. The management of bilateral ureteric obstruction and renal failure in advanced prostate cancer. Br J Urol. 1994;74:642–645. [PubMed: 7827817]
  36. Pienta KJ, Esper PS, Naik H, Parzuchowski J, Bellefleur J, Huber ML. The hospice supportive care program: A new “transitionless” model of palliative care for patients with incurable prostate cancer. J Natl Cancer Inst. 1996;88:55–56. [PubMed: 8847729]
  37. Prostate Cancer Trialists. Maximum androgen blockade in advanced prostate cancer: an overview of the randomised trials. Prostate Cancer Trialists’ Collaborative Group. Lancet. 2000;355:1491–1498. [PubMed: 10801170]
  38. Reed SD, Radeva JI, et al. Cost-effectiveness of zoledronic acid for the prevention of skeletal complications in patients with prostate cancer. Journal of Urology. 2004;171(4):1537–1542. [PubMed: 15017215]
  39. Ryan CW. Zoledronic acid initiated during the first year of androgen deprivation therapy increases bone mineral density in patients with prostate cancer. The Journal of urology. 2006;176:972–978. [PubMed: 16890673]
  40. Samson DJ, Seidenfeld J, Schmitt B, Hasselblad V, Albertsen PC, Bennett CL, Wilt TJ, Aronson N. Systematic review and meta-analysis of monotherapy compared with combined androgen blockade for patients with advanced prostate carcinoma. Cancer. 2002;95:361–376. [PubMed: 12124837]
  41. Sandhu DPS, Mayor PE, Sambrook PA, George NJR. Outcome and prognostic factors in patients with advanced prostate cancer and obstructive uropathy. Br J Urol. 1992;70:412–416. [PubMed: 1450851]
  42. Seidenfeld J, Samson DJ, Aronson N, Albertson PC, Bayoumi AM, Bennett C, Brown A, Garber A, Gere M, Has selblad V, Wilt T, Ziegler K. Relative effectiveness and cost-effectiveness of methods of androgen suppression in the treatment of advanced prostate cancer. [Review] [330 refs] Evidence Report: Technology Assessment (Summary) 2001:i–x. [PubMed: 11098244]
  43. Seidenfeld J, Samson DJ, Hasselblad V, Aronson N, Albertsen PC, Bennett CL, Wilt TJ. Single-therapy androgen suppression in men with advanced prostate cancer: A systematic review and meta-analysis. Ann Intern. Med. 2000;132:566–577. [PubMed: 10744594]
  44. Smith MR, Eastham J, Gleason DM, Shasha D, Tchekmedyian S, Zinner N. Randomized controlled trial of zoledronic acid to prevent bone loss in men receiving androgen deprivation therapy for nonmetastatic prostate cancer. The Journal of urology. 2003;169:2008–2012. [PubMed: 12771706]
  45. Smith MR, McGovern FJ, Zietman AL, Fallon MA, Hayden DL, Schoenfeld DA, Kantoff PW, Finkelstein JS. Pamidronate to prevent bone loss during androgen-deprivation therapy for prostate cancer. New England Journal of Medicine. 2001;345:948–955. [PubMed: 11575286]
  46. Venkitaraman R, Sohaib SA, Barbachano Y, Parker CC, Khoo V, Huddart RA, Horwich A, Dearnaley DP. Detection of Occult Spinal Cord Compression with Magnetic Resonance Imaging of the Spine. Clin Oncol (R CollRadiol) 2007 [PubMed: 17499490]
  47. Yuen KK, Shelley M, Sze WM, Wilt T, Mason MD. Bisphosphonates for advanced prostate cancer. [Review] [51 refs] Cochrane Database of Systematic Reviews. 2006:CD006250. [PubMed: 17054286]

At the time of publication (February 2008) bicalutamide did nothave UK marketing authorisation for this indication. Informed consent should be obtained and documented.

’Improving supportive and palliative care for adults with cancer’. NICE cancer service guidance (2004)

Copyright © 2008, National Collaborating Centre for Cancer.

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