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31st December 2024

Prostate cancer

Overview of prostate cancer

Prostate cancer is the most common cancer in men in the UK, and the second most common cancer in men globally. It represents a spectrum of disease from small well-differentiated tumours which may never become clinically significant to rarer high-grade tumours which are more aggressive and carry high morbidity and mortality.

Risk factors include age (rare in those aged less than 50), ethnicity (more common in Black men, uncommon in Asian men) and family history. There are no well-established links to any modifiable risk factors.

Pathology of prostate cancer

The majority of prostate cancers are adenocarcinomas and arise in the outer zone of the prostate gland, where they are unlikely to produce urinary symptoms. Low-grade (Gleason 6) tumours are less likely to invade through the prostate capsule; high-grade (Gleason 8-10) tumours are more aggressive and more likely to invade through and metastasise. Spread is by direct invasion of the adjacent organs (seminal vesicles, bladder and rectum), infiltration of pelvic lymph nodes, and haematogenous spread to sites of distal metastasis. The most common site of metastasis is bone, where the classical picture is of osteoblastic or sclerotic metastases, although liver and lung may also be affected.

Presentation of prostate cancer

Patients may present symptomatically with lower urinary tract symptoms (LUTS) such as urgency, frequency, hesitancy, nocturia and retention, although LUTS usually indicate coincident benign prostatic hyperplasia. They also may present with systemic symptoms such as weight loss, poor appetite, and fatigue. However, the majority of new diagnoses are entirely asymptomatic, with referral made on the basis of an elevated age-adjusted prostate-specific antigen (PSA) and/or abnormal findings on digital rectal examination (DRE), such as a nodular or irregular prostate. The role of PSA in screening is controversial as it is non-specific to malignancy (may be elevated secondary to DRE, ejaculation, or benign pathology such as prostatitis).

A minority of patients present with symptoms and/or complications of metastatic disease, e.g. bone pain, fragility fractures, obstructive renal failure and rectal bleeding. Metastatic spinal cord compression may be the first presentation of metastatic prostate cancer and is an oncological emergency. Back pain which is new, progressive and/or severe is usually the primary feature and any additional neurological deficit is usually a late sign. Any clinical suspicion warrants urgent investigation with an MRI whole spine.

Diagnosis of prostate cancer

If prostate cancer is clinically suspected on the basis of history and clinical examination, NICE recommends multi-parametric MRI prostate as the first-line investigation. This is to help identify whether biopsy is necessary and, if so, identify potential targets for biopsy. In patients who are too frail or multimorbid for radical prostate cancer treatment (i.e. surgery or radiotherapy) then MRI is not indicated.

Biopsy enables Gleason histological grading and is done under ultrasound guidance either via the rectum (transrectal ultrasound, TRUS) or perineum. The majority of patients experience haematuria and blood in their semen. Less common but more serious complications include sepsis, clot retention, rectal bleeding and severe haematuria.

Further staging with isotope bone scans is not performed routinely but is required for those with high-grade tumours, tumours that have spread outside of the prostate capsule and/or with clinical or biochemical evidence of bone metastases.

Management of prostate cancer

Management of localised prostate cancer

Patients should undergo risk stratification taking into consideration their Gleason grade, PSA, TNM staging and life expectancy (determined by age and comorbidities).

There are two main radical (potentially curative) options which should be considered in patients with localised prostate cancer, particularly in those with greater life expectancy. All radical options carry a risk of loss of sexual function.

  • Radical prostatectomy ± pelvic lymph node dissection
  • Radical radiotherapy, either external beam or brachytherapy

Additional treatments include:

  • Androgen deprivation therapy may also be offered to patients depending on risk stratification
  • Docetaxel may be used in high risk cases, in conjunction with androgen deprivation. The most important side effect to be aware of is neutropenic sepsis

Those with low risk disease, or with a preference to postpone treatment, may be offered active surveillance during which they are monitored for signs of progression and radical treatment is initiated only once such signs arise:

  • PSA every 3-4 months for the first year
  • Digital rectal examination at 1 year
  • Multi-parametric MRI at 12-18 months
  • After the first year, PSA 6 monthly and rectal examination yearly

Contrast this to watchful waiting, which describes cases where a patient does not ever plan to go on to have curative treatment, either out of preference or due to poor performance status and therefore ineligibility. Usually an annual PSA is performed.

In both active surveillance and watchful waiting a rise in PSA or other abnormality triggers further investigation and/or MDT discussion.

Active surveillance Watchful waiting
Strategy aimed at cure – patients with localised prostate cancer, usually very low-risk disease, opt for close monitoring and proceed to curative treatment only if and when their tumour shows signs of progressing Strategy aimed at control but not cure – patients with localised prostate cancer who do not wish to ever have curative treatment opt for androgen-deprivation therapy to be deferred

Management of locally advanced prostate cancer

Patients with tumour fixation to or invasion of adjacent organs are considered curable but are at very high risk of recurrence and/or progression. If fit, they should be offered either:

  • Radical prostatectomy with extended pelvic lymph node dissection; those with positive lymph nodes should be offered adjuvant radiotherapy or androgen-deprivation therapy;
  • OR radical radiotherapy with long-term androgen-deprivation therapy.

Management of metastatic prostate cancer

Prostate cancer with distant metastases is not considered curable and treatment is aimed at controlling disease and maintaining quality of life. Both specialist urological services and palliative care should be involved from the outset to help with symptom control and holistic needs of the patient.

In hormone-naive patients, the first line is androgen-deprivation (hormone) therapy, also described as medical castration. This aims to reduce testosterone levels, helping to shrink the tumour and/or prevent further growth.
Gonadotropin-releasing hormone (GnRH) agonists such as goserelin and leuprorelin provide negative feedback to the hypothalamic-pituitary axis to suppress testosterone levels. Side effects include fatigue, loss of libido, erectile dysfunction, hot flushes, emotional lability and depression. On initiation there is a testosterone surge, which can cause a tumour flare, manifesting clinically as an exacerbation of bone pain and renal failure, and may prove life threatening. Therefore androgen-deprivation therapy should be preceded by initiation of an anti-androgen such as bicalutamide, which produces androgen receptor blockade.

GnRH antagonists are an alternative to GnRH agonists. The only one available in the UK is degarelix. This does not cause tumour flare, so anti-androgen therapy is not required. It is indicated when patients have spinal metastasis.

Bilateral orchiectomy is a surgical option for androgen deprivation therapy that may be considered.

Androgen-deprivation therapy is more effective when taken in combination with other systemic therapies, usually either abiraterone (inhibits adrenal production of testosterone, must be taken in combination with prednisolone) or docetaxel chemotherapy.

This may be followed by several lines of alternative systemic therapies in patients whose disease progresses despite effective castration, described as castration- or hormone-resistant prostate cancer. The details of this are beyond the scope of this chapter. Of note, however, are specific options for patients with bony metastases in hormone-resistant prostate cancer:

  • Palliative radiotherapy, simple analgesia and IV bisphosphonates can help with bone pain. Bisphosphonates can also be used to treat hypercalcaemia of malignancy.
  • Denosumab can be used to prevent skeletal-related events, including pathological fractures and metastatic cord compression.

Management of the side effects of prostate cancer treatments

Radiation enteropathy

Radiation to the pelvis, for example when radiating prostate cancer, can damage nearby structures including the bowel or rectum. It is a common phenomenon: of patients who receive abdominal or pelvic radiotherapy, 60-80% will experience bowel toxicity.

In patients with suspected radiation-induced enteropathy, flexible sigmoidoscopy is the first-line investigation to rule out bowel cancer and inflammatory bowel disease, but also analyse the extent of radiation-induced enteropathy if it is ultimately diagnosed.

If symptoms are experienced in the first 3 months following radiating it is considered acute radiation enteropathy. Acute radiation enteropathy symptoms include diarrhoea, abdominal pain, nausea and vomiting. If loperamide does not work, octreotide can be considered.

Beyond the first 3 months, it is considered delayed. Delayed radiation enteropathy symptoms include dysfunctional absorption of nutrients or abnormal peristalsis. The treatment approach is more complex than for acute symptoms, and must be tailored specifically to the individual. It is a chronic and progressive disorder requiring a multidisciplinary team approach.

Both types of radiation enteropathy have high morbidity, affecting quality of life for cancer patients.

Rectal radiation injury (radiation proctopathy) is common when treating prostate cancer. First-line treatment is sucralfate enemas, which can cause dramatic improvement in symptoms. If radiation proctopathy is hemorrhagic, endoscopic intervention may be required to stop the bleeding.

Radiation-induced cystitis

Radiation to the prostate can cause bladder wall inflammation and scarring, which can be short term or chronic, and can result in cystitis. Conservative management includes good oral intake of water. If symptoms persist despite this, specialised options include intravesical injection of medications such as sodium hyaluronate (brand names Cystistat or iAluRil), or hyperbaric oxygen therapy. Rarely, the bladder may need to be surgically removed to help with symptoms.

Androgen-deprivation therapy side effects

There can unfortunately be many side effects to androgen-deprivation therapy. Some examples with their management are:

  • Hot flushes: medroxyprogesterone is first line.
  • Gynaecomastia: in those starting long-term (planned for at least 6 months) of bicalutamide, prophylactic radiotherapy to the breast buds is first line, and should be offered within the first month of treatment. Second line is tamoxifen.
  • Osteoporosis: is also an issue with long-term deprivation therapy as it can result in fragility fractures. A risk assessment for the individual patient should be calculated e.g. FRAX score. Bisphosphonates are first line or denosumab is second line in patients identified as having osteoporosis and on androgen deprivation treatment.

References

Complete Guide to Clinical Genetics ST3 Application and Recruitment (2027)

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Complete Guide to Clinical Radiology ST3 Application and Recruitment (2027)

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Complete Guide to Paediatric Surgery ST3 Application and Recruitment in United Kingdom (2026)

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Paediatric Surgery ST3
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