Symptom management in advanced prostate cancer

Most diagnoses of prostate cancer are in the older population and 89% of all new prostate cancers diagnosed were in men aged 60 years or over.^1,2  In addition, 20-30% of men have advanced disease at diagnosis meaning that the disease has spread beyond the prostate, most commonly to bone, and carries with it a five-year survival of just 30%.³

Other sites of metastases include lymph nodes, liver and lungs. Symptoms experienced by a patient can be related to the prostate cancer itself or metastases, treatments, or thirdly from other comorbidities unrelated to prostate cancer but are common due to the age group affected by this disease.

Symptom prevalence of prostate cancer

In an outpatient palliative care setting, pain, fatigue and drowsiness were present in over 50% of patients with advanced prostate cancer.⁴ Patients with prostate cancer have described pain as one of the most distressing and dominant symptoms experienced, most commonly described as – in the pelvis or back, localised in spots, and worsening with movement.⁵

A study from the USA concluded that fatigue was ‘the most important symptom expressed’ by both experts and patients, with patients describing their experiences of fatigue differently; ‘I have a lack of energy’, ‘ feel fatigued.’3

Lower urinary tract symptoms including incomplete emptying, frequency, intermittency, urgency, weak stream, straining or nocturia are very common. In some studies they have been shown to affect 97% of patients, although the symptoms were only described as severe in 11%.⁶

Many patients, however, consider urinary symptoms to be part of the ageing process and therefore do not associate them with their prostate cancer and its treatment. Although prevalence is high in patients with advanced prostate cancer, it is similar to that of the general population of men aged over 65 years.⁷

Sexual dysfunction includes both the loss of libido, which is common in many illnesses, and the inability to gain an erection.  Almost 60% of men were impotent 18 months following radical prostatectomy with slight variation depending on whether the procedure was bilateral nerve sparing or non-nerve sparing.⁸

Androgen deprivation is used in some men following radical prostatectomy and this too has significant effects on sexual dysfunction. In one study only 2% of men receiving androgen deprivation therapy following radical prostatectomy reported the ability to have sexual intercourse in the month of study.⁹

Bowel symptoms in advanced prostate cancer are predominantly due to treatment. Radiotherapy to pelvic areas and opioid analgesics commonly affect the function of the bowel.  Symptoms can include frequency, diarrhoea, incontinence or constipation and associated abdominal pain and bloating.  Unlike symptoms such as urinary and sexual dysfunction, bowel symptoms are not associated with increasing age. Assessment of the care needs of men with prostate cancer suggested that between 8€“35% of men, depending on which treatments they had received, had some supportive care needs due to bowel problems.⁶

Anxiety and depression are the main psychological symptoms experienced by patients with prostate cancer. In quality of life studies moderate or extreme anxiety was reported by 30% of men.⁶

Symptom management of prostate cancer

General principles

There are two main principles that guide the management of symptoms. Firstly it is important to assess whether the symptom is caused by a reversible process either by a concurrent illness or the cancer. Where appropriate, attempts should be made to treat and reverse the reversible. The other principle is to maintain an holistic approach.  In many patients with advanced prostate cancer, symptoms do not occur in isolation and the management should not be of each symptom in isolation.

Pain

Pain can be due to localised disease and compression of surrounding structures, which can be difficult to manage, especially if there is nerve involvement. Bone metastases can also cause significant pain and limitation. The mainstay of pain management follows the World Health Organization (WHO) analgesic ladder starting with paracetamol and NSAIDs increasing to weak and then strong opioids.⁵

To minimise tablet burden and if pain is relatively stable, transdermal routes for analgesia may be beneficial in some patients.¹⁰

Adjuvant drugs including gabapentin and pregabalin may be useful to reduce pain and minimise opioid use and associated adverse effects. Doses should be started at the lowest possible level and titrated slowly whilst observing for side effects.11  In addition to pharmacological management, a single fraction of radiotherapy can help reduce pain in approximately 70% of patients.¹² Although prostate cancer usually forms sclerotic bone metastases, pathological fractures do occur and imaging may be necessary with a view to surgical intervention.¹³

Bisphosphonates may be helpful for relief of pain associated with bone metastases. NICE currently only recommends this if analgesics and palliative radiotherapy have failed. The current guidance recommends not using them to prevent skeletal-related events.¹⁴ 

Increasing analgesic requirements may be due to disease progression but patients should be reassessed if pain escalates as it may be a symptom of malignant spinal cord compression or impending fracture.

Malignant spinal cord compression  requires immediate referral to oncology for investigation and treatment.¹⁵

Fatigue

Fatigue may have major effects on a patient’s quality of life and its cause is often multi-factorial. It is not easily treated with drug therapy16 but benefits can be gained from treating a reversible cause.

Anaemia in men with advanced prostate cancer is often due to bone marrow infiltration. Whilst some patients may gain an improvement in their fatigue following blood transfusion, this is often short lived (14 days). The benefits of blood transfusion in palliative care patients has been questioned as a high proportion of patients (23-35%) die within two weeks of their transfusion.¹⁷ 

For patients in whom no reversible cause has been found or who remain fatigued, graded exercise may be helpful.¹⁸

Referral to a physiotherapist or an occupational therapist can assist in this, as well as providing equipment to minimise fatigue when performing everyday tasks.

Corticosteroids have been shown to be beneficial in the short term for the management of fatigue and for their effect on general wellbeing.¹⁹ However there are significant adverse effects and in the long term these can outweigh any benefit. Corticosteroids are also used as third line treatment for men with hormone refractory prostate cancer.¹⁴

Urinary symptoms and sexual dysfunction

In general, the medical management of urinary symptoms can be the same as for patients with non-malignant causes. However, caution is required with anti-cholinergic drugs that may cause urinary retention, and if there is renal or hepatic impairment, drug doses may need to be adjusted accordingly. Surgery, however, may provide less benefit in a palliative setting.²⁰

Sexual dysfunction in association with prostate cancer can be caused by direct effects of the cancer, psychological distress or most commonly by medication or treatments such as prostatectomy. In the management of sexual dysfunction, medications should be reviewed and a trial of alternatives undertaken if possible. If sexual dysfunction is having a major impact referral to a specialist counselling service can help to address the psychological effects.

Bowel symptoms

There are no specific management strategies for bowel symptoms occurring in advanced prostate cancer. Treatment-associated symptoms usually improve after stopping treatment and can be managed with simple anti-diarrhoeals.²¹ Laxatives can be used for the treatment of constipation and modifying diet can also be helpful.

Psychological

Psychological symptoms can vary from a mild adjustment reaction at the time of diagnosis, which in many cases does not require treatment, to severe depression.  Support groups and information may be sufficient to support both the patient and their partners and family.

In some patients antidepressants can be helpful.²²  Screening for and treating depression can also help in the treatment of other symptoms including pain, fatigue and sexual dysfunction.

Oedema

Although oedema is not listed as a common symptom of prostate cancer, there are specific causes and treatments that should be considered. Oedema may be a result of a comorbidity which should be treated in order to improve symptoms or may be related to malignancy. As a result of both the disease process and often an associated reduced oral intake a low albumin level can cause oedema. In these patients dietary support can be beneficial with advice on fortifying foods.  Prostate cancer can cause lymphoedema due to the lymphatic infiltration, local pressure effects of the prostate cancer and enlarged lymph nodes within the pelvis. In most palliative settings there is no scope to decrease tumour bulk within the pelvis and lymphoedema can be managed with massage, gentle exercises and compression bandaging or stockings.²³ 

Good skin care including twice daily application of an emollient is important to prevent associated complications. When assessing and managing a patient with oedema the development of a DVT should be considered as this is potentially treatable and if untreated could be life-threatening.

Conclusion

Patients with advanced prostate cancer can suffer from a variety of symptoms, which impact upon their quality of life. Symptom management involves addressing the cause and treating this, if appropriate, or developing strategies to minimise the impact the symptoms are having on the patient in order to improve their quality of life.

Conflict of interest: none declared

References

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