Cancer Research UK : Prostate Cancer symptoms and treatment

Prostate Cancer symptoms and treatment

The prostate gland lies at the base of the bladder surrounding the upper part of the urethra – Figure 6.1.1

Figure 6.1: The prostate gland

Enlargement of the prostate gland often causes urinary tract obstruction. The symptoms for localised prostate cancer may be the same as those for BPH, namely difficulty in urinating, more frequent micturation and occasionally blood in the urine.

However, localised prostate cancer is often asymptomatic and men with more advanced disease may present with pain from widespread skeletal metastases, especially back pain.

Prostate cancer stage and grade

Tumours are usually staged using the TNM system.2-3

In brief, T1 and T2 tumours are confined within the prostatic capsule and are called ‘early’ disease. When the tumour has spread beyond the prostate gland into the surrounding tissue but not to other parts of the body, it is staged as T3/T4 and is known as ‘locally advanced’ disease.

Tumours are also graded according to the histology of the malignant cells – the most widely used grading system is the Gleason system.4 In transrectal ultrasound-guided biopsies, there is insufficient tissue architecture to reliably identify Gleason scores ≤2 and in these samples Gleason grading is usually only assessed when between 6 (well differentiated), 7 (moderately differentiated) and ≥8 (poorly differentiated). The biopsy results are used to estimate the size of the tumour, which also has a bearing on prognosis.

Treatment of prostate cancer

At present, there is no consensus as to the best treatment for early prostate cancer.

Treatment of localised prostate cancer

For early, localised disease, there are two curative treatment options: radical prostatectomy or radical radiotherapy. Alternatively, ‘watchful waiting’ may be recommended.

‘Watchful waiting’ is based on the premise that many patients are elderly with a relatively short life expectancy and that their prostate cancer is likely to progress very slowly, may not cause symptoms and will not be their cause of death. Hormone therapy may also be used with all these treatments.

Ten-year survival is high for all three approaches: 80–90% for radical prostatectomy, 65–90% for radical radiotherapy and 70–90% for ‘watchful waiting’,5 although the results of a recent randomised trial, comparing radical prostatectomy with ‘watchful waiting’ in early stage prostate cancer, reported that after ten years treated men had a significantly reduced risk ratio of death from prostate cancer (0.56), and for metastases (0.6).6

The management of early prostate cancer is still controversial and patients need to be fully informed as to the options available to them. The intent and drawbacks for the three approaches to early localised cancer are summarised in Table 6.1.7-9 Table 6.1:Treatment options for localised prostate cancer

Download this table (15kb)

Active surveillance is a fourth option, which aims to follow early localised prostate cancer to determine its biological aggressiveness with a possibility of offering curative treatment if significant disease progression occurs, based on PSA testing, digital rectal examination (DRE) and repeat biopsy.

In general, ‘watchful waiting’ for a patient under 60 is not advised, but best practice for men aged between 60 and 70 is unclear. British urologists seem to favour radical treatment for patients under 70.10

To help answer these uncertainties, men should be considered for entry into clinical trials whenever possible, but difficulties in recruitment to randomised trials have been reported.11-12

The Prostate Testing for Cancer and Treatment (ProtecT) trial has been set up in the UK to evaluate the effectiveness of treatment (‘active monitoring or surveillance’, radical surgery/radiotherapy) for clinically localised prostate cancer. Recruitment began in 2001, and will continue until May 2008, with follow-up planned for 10–15 years.13

Other trials investigating the merits of treating early prostate cancer diagnosed through screening include the European Randomised Study of Screening for Prostate Cancer, the Prostate Cancer Intervention Versus Observation trial and the Prostate, Lung, Colon, and Ovarian cancer screening trial.14-16

New improvements in both surgery and radiotherapy may reduce side-effects and increase effectiveness.

Conformal radiotherapy delivers higher, more effective doses of radiation to the tumour while minimising damage to the healthy surrounding tissue, and a more sophisticated version of conformal radiotherapy known as intensity modulated radiotherapy (IMRT) is now under development.

Brachytherapy using radioactive prostatic implants is an alternative to external beam radiation, but it is only available in a few centres. This localised radiotherapy may result in a lower incidence of rectal and neurovascular side-effects (such as impotence) than external beam radiotherapy, although urinary side-effects may be higher.8

Dissatisfaction with the complications of radical prostatectomy has encouraged surgeons to look for better ways of performing the operation. Two developments are underway. The first is a laparoscopic (keyhole) approach to radical prostatectomy, which can be carried out with the assistance of a robotic device (robotic-assisted laparoscopic prostatectomy).

Laparoscopic prostatectomy has been shown to result in less blood loss during surgery than during open surgery and results indicate that there may be reduced urinary incontinence and erectile dysfunction than with conventional techniques.17

The second method is intra-operative nerve stimulation, which can assess damage to the nerves surrounding the prostate during surgery and predict the likelihood of side-effects of impotence or erectile dysfunction.

Treatment of locally advanced prostate cancer

These patients may receive radiotherapy or hormone therapy.

Randomised trials have established roles for both neoadjuvant (initial) and adjuvant hormonal therapy in addition to radiotherapy, but it is uncertain whether similar results could be obtained by hormonal therapy alone.

An international trial (MRC PRO718) addressing this problem completed recruitment in 2005.

For patients who are up-staged after radical prostatectomy, immediate adjuvant antiandrogen treatment with hormones or bilateral orchidectomy appears to confer a survival advantage.19 Results from a recent trial show that for patients who are at high risk of local recurrence, adjuvant radiotherapy after prostatectomy improves PSA relapse-free survival at five years.20

Treatment of metastatic prostate cancer

Despite the fact that there is an increasing trend towards early detection of prostate cancer, many patients throughout the world still present with metastatic disease, for which there is no curative option. Instead, hormone treatment is used to lower the levels of androgens, principally testosterone, in the body, which gives good short-term control of the cancer.

In the past, surgical castration (bilateral orchidectomy) was used to achieve this but new more acceptable methods of androgen deprivation have been developed using luteinising hormone-releasing hormone (LH-RH) analogues and/or antiandrogens.

The addition of antiandrogens to medical or surgical castration has been investigated and shows no clinically useful benefit.21-23

Androgen deprivation achieves an overall median survival time of approximately two and a half years and around 80% of patients have symptomatic relief.24

In almost all cases, advanced prostate cancer treated with hormone therapy eventually begins to grow again.

Chemotherapy may then be used, particularly for younger, fitter patients. The role of chemotherapy is being evaluated in clinical trials and its benefits have to be weighed against the associated toxicity. Previously,mitoxantrone has been shown to have palliative benefits only; recent studies using docetaxel suggest that this latter agent gives a small but statistically significant survival benefit.25-26

This has been backed up by more recent trials.27-28 Oestrogens and drugs that inhibit growth factors may benefit patients with hormone resistant disease and these are also being evaluated in clinical trials.

Bone pain is the biggest problem for patients with metastatic disease in whom hormone therapy is no longer effective, and is best treated by a multi-disciplinary team.

There is evidence to suggest that some patients with bone metastases may benefit from treatment with bisphosphonates, which suppress bone reabsorption and demineralisation and provide pain relief.

Zoledronic acid is licensed to treat prostate cancer, and has been shown to reduce skeletal related events in men with advanced prostate cancer, but there is no overall improvement in survival with this treatment.29

External-beam radiotherapy or intravenous administration of a radionuclide provides effective pain relief. If a patient has suffered bone fractures, surgery may be recommended before radiotherapy.

Other palliative treatments include pain relief progressing from paracetamol and non-steroidal anti-inflammatory drugs to opioids.30

Future treatments for prostate cancer

Clinical trials for gene therapy and immunotherapy are in progress.

Non-invasive treatment using magnetic resonance imaging (MRI) to pinpoint the cancer and high-intensity focused ultrasound or intensity modulated radiotherapy to ablate localised disease, are also being tested.

References

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