Prostate cancer

What is prostate cancer?

Most prostate cancers are adenocarcinomas arising in the peripheral zone of the prostate gland. Most prostate cancers are slow-growing but some prostate cancers are aggressive. The most common sites for metastases are bone and lymph nodes.

Prostate cancer epidemiology¹

• 1 in 6 UK males will be diagnosed with prostate cancer (PCa) in their lifetime.

• In males in the UK, prostate cancer is the most common cancer, with around 52,300 new cases every year (2016-2018).

• Prostate cancer accounts for 27% of all new cancer cases in males in the UK (2016-2018).

• Incidence rates for prostate cancer in the UK are highest in males aged 75-79 (2016-2018). Each year around a third (34%) of all new prostate cancer cases in the UK are diagnosed in males aged 75 and over (2016-2018).

• Prostate cancer incidence rates in males in England are 17% lower in the most deprived quintile compared with the least (2013-2017).

• Prostate cancer is most common in Black males, then White males, and least common in Asian males.

• Globally, prostate cancer accounts for 15% of male cancers, 70% of them occurring in developed countries² .

Risk factors for prostate cancer^{3 4}

The three well-established risk factors for prostate cancer are increasing age, ethnic origin and genetic predisposition⁵ .

• Increasing age is the most important risk factor for developing prostate cancer⁶ . However, around 25% of cases occur in men younger than 65 years.

• There is a higher incidence of and mortality from prostate cancer in men of black African-Caribbean family origin compared with white men.

• Obesity and being overweight are associated with advanced prostate cancer. Men have a 15-20% increased risk of dying from prostate cancer with every 5 kg/m² increase in body mass index⁷ .

• If one first-degree relative has prostate cancer, the risk is at least doubled. About 9% of men with prostate cancer have true hereditary prostate cancer. This is defined as three or more affected relatives, or at least two relatives who have developed early-onset disease (before the age of 55 years). Patients with hereditary prostate cancer usually have an onset 6-7 years prior to spontaneous cases but do not differ in any other ways.

• Factors such as food consumption, pattern of sexual behaviour, alcohol consumption, exposure to ultraviolet radiation, chronic inflammation and occupational exposure have all been considered as possible risk factors of prostate cancer.

• There is some evidence to recommend lifestyle changes (lowered intake of animal fat and increased intake of fruit, cereals and vegetables) in order to decrease the risk of prostate cancer.

Prostate cancer screening

See also the separate Prostate Specific Antigen (PSA) article.

Although there is no organised screening programme for prostate cancer in the UK, there is an NHS Prostate Cancer Risk Management Programme. The aim is to provide enough information to primary healthcare professionals to assist asymptomatic men aged 50 and over to make an informed choice about whether or not to have a PSA test⁸ .

One review found that whilst a positive digital rectal examination (DRE) was a good predictor of malignancy, it should not be used as a screening test. 42.3% of patients with prostate abnormality on DRE had the diagnosis confirmed. However, if symptoms suggestive of prostate cancer are present, negative examination should not be a reason to delay urgent referral⁹ .

Prostate cancer symptoms and presentation⁵

See also the separate Genitourinary History and Examination (Male) article.

Prostate cancer is usually suspected on the basis of DRE and/or PSA levels⁴ .

Lower urinary tract symptoms (LUTS) do not particularly raise suspicion of prostate cancer because LUTS are common in older men and are rarely the presenting symptom of prostate cancer. However, locally advanced prostate cancer may cause obstructive LUTS⁷ .

• Local disease:
  

  • Raised PSA on screening.

  • LUTS: weak stream, hesitancy, sensation of incomplete emptying, urinary frequency, urgency, urge incontinence. The severity of urinary symptoms can be assessed with the International Prostate Symptom Score (I-PSS).

  • Urinary tract infection.

• Locally invasive disease:
  

  • Haematuria, dysuria, incontinence.

  • Haematospermia.

  • Perineal and suprapubic pain.

  • Obstruction of ureters, causing loin pain, anuria, symptoms of acute kidney injury or chronic kidney disease.

  • Impotence.

  • Rectal symptoms - eg, tenesmus.

• Metastatic disease:
  

  • Bone pain or sciatica.

  • Paraplegia secondary to spinal cord compression.

  • Lymph node enlargement.

  • Loin pain or anuria due to ureteric obstruction by lymph nodes.

  • Lethargy (anaemia, uraemia).

  • Weight loss, cachexia.

Signs

• Advanced prostate cancer: general malaise, bone pain, anorexia, weight loss, obstructive nephropathy, paralysis due to cord compression.

• Abdominal palpation may demonstrate a palpable bladder due to outflow obstruction.

• Digital rectal examination (DRE) may reveal a hard, irregular prostate gland. Indications of possible prostate cancer are:
  

  • Asymmetry of the gland.

  • A nodule within one lobe.

  • Induration of part or all of the prostate gland.

  • Lack of mobility - adhesion to surrounding tissue.

  • Palpable seminal vesicles.

• NICE recommends considering a prostate-specific antigen (PSA) test and digital rectal examination to assess for prostate cancer in people with¹⁰ :
  

  • Any lower urinary tract symptoms, such as nocturia, urinary frequency, hesitancy, urgency or retention.

  • Erectile dysfunction.

  • Visible haematuria.

Differential diagnosis⁵

• All other causes of haematuria (eg, urinary tract infection) and urinary tract obstruction.

• Benign prostatic hyperplasia.

• Prostatitis.

• Bladder tumours.

Investigations³

NICE recommends consideration of a PSA test and DRE to assess for prostate cancer in men with any LUTS (such as nocturia, urinary frequency, hesitancy, urgency or retention), erectile dysfunction, or visible haematuria¹⁰ .

• The PSA test is dealt with in the separate Prostate Specific Antigen (PSA) article.

• PCA3 urine test:

  • The assay measures the concentration of prostate cancer gene 3 (PCA3) and prostate-specific antigen (PSA) RNA molecules and calculates the ratio of PCA3 RNA molecules to PSA RNA molecules (PCA3 Score).

  • Superior to PSA total, and percent-free PSA in detection of prostate cancer.

  • The main current indication of the PCA3 urine test may be to determine whether a man needs a repeat biopsy after an initially negative biopsy outcome. The test is expensive and its cost-effectiveness remains to be shown¹¹ .

  • NICE states that the PCA3 assay and the Prostate Health Index are not recommended in people having investigations for suspected prostate cancer who have had a negative or inconclusive prostate biopsy.

• Urinalysis to exclude renal and bladder pathology. Urine sent for microscopy, culture and sensitivities.

• Renal function tests to help exclude renal disease.

• Prostate biopsy:
  

  • To help men decide whether to have a prostate biopsy, their PSA level, DRE findings (including an estimate of prostate size), comorbidities, and risk factors (including increasing age and black African-Caribbean family origin) and any history of a previous negative prostate biopsy should be discussed. Prostate biopsy should not be offered just on the basis of serum PSA level alone.

  • Prostate biopsies find fewer than half of the clinically significant prostate cancers that MRI scans miss. However 11-28% of people with a low-risk MRI actually have clinically significant cancer.

  • Men who have had a negative first prostate biopsy still have a risk that prostate cancer is present and the risk is slightly higher if the biopsy showed high-grade prostatic intraepithelial neoplasia, the biopsy showed atypical small acinar proliferation, and DRE is abnormal.

  • Prostate biopsy in patients with suspected prostate cancer is usually carried out by a transrectal needle biopsy.

  • Transrectal ultrasonography (TRUS) and biopsy: in men with a raised concentration of PSA, biopsy will miss 10-30% of clinically significant prostate cancers.

  • Transperineal template biopsy may be used for patients with suspected prostate cancer who have had a negative or inconclusive transrectal biopsy. Other proposed indications for transperineal template biopsy include mapping to determine the location and extent of prostate cancer as a guide to focal treatment (eg, ablation), and as part of active surveillance of low-risk localised prostate cancer with the aim of reducing the number of biopsies¹² .

• TRUS: the classic picture of a hypoechoic area in the peripheral zone of the prostate gland will not always be seen. It is not useful to replace systematic with targeted biopsies of suspect areas, but additional biopsies of suspect areas may be useful⁴ .

• Uroflow measurement, measurement of postmicturition residual urine, cystoscopy and imaging of the upper urinary tract (if suspect upper tract dilatation or bladder outlet obstruction).

• Multi-parametric magnetic resonance imaging (mp-MRI) produces a detailed image of the prostate gland. NICE recommends multiparametric MRI as the first-line investigation for people with suspected clinically localised prostate cancer³ .

• Isotope bone scans should be offered when hormonal therapy is being deferred through watchful waiting to asymptomatic men who are at high risk of developing bone complications³ .

Prostate cancer staging⁴

Prostate cancer can be divided into:

• Non-metastatic: either localised disease confined to the prostate gland or locally advanced disease that has spread outside the capsule of the gland but has not spread to organs, other than the seminal vesicles.

• Metastatic: spread beyond the prostate gland to local, regional, or systemic lymph nodes, or to other body organs - eg, bone, liver, or brain.

Tumour, node, metastases (TNM) staging for prostate cancer

• Primary tumour (T):
  

  • TX: primary tumour cannot be assessed.

  • T0: no evidence of primary tumour.

  • T1: clinically inapparent tumour neither palpable nor visible by imaging.

  • T1a: tumour incidental histological finding in 5% or less of tissue resected.

  • T1b: tumour incidental histological finding in more than 5% of tissue resected.

  • T1c: tumour identified by needle biopsy (eg, because of elevated PSA).

  • T2: tumour confined within the prostate gland.

  • T2a: tumour involves one half of one lobe or less.

  • T2b: tumour involves more than half of one lobe, but not both lobes.

  • T2c: tumour involves both lobes.

  • T3: tumour extends through the prostatic capsule.

  • T3a: extracapsular extension (unilateral or bilateral), including microscopic bladder neck involvement.

  • T3b: tumour invades seminal vesicle(s).

  • T4: tumour is fixed or invades adjacent structures other than seminal vesicles: bladder neck, external sphincter, rectum, levator muscles and/or pelvic wall.

• Regional lymph nodes (N):
  

  • NX: regional lymph nodes cannot be assessed.

  • N0: no regional lymph node metastasis.

  • N1: regional lymph node metastasis.

• Distant metastasis (M); when more than one site of metastasis is present, the most advanced category (pM1c) is used:
  

  • MX: distant metastasis cannot be assessed.

  • M0: no distant metastasis.

  • M1: distant metastasis.

  • M1a: non-regional lymph node(s).

  • M1b: bone(s).

  • M1c: other site(s).
    

Histological grading

• There are several systems for grading prostate cancer histology. The most commonly used is the Gleason grading system. It estimates the grade of prostate cancer according to its differentiation. A score of two is the most well differentiated tumour and 10 is the most poorly differentiated. Higher scores are associated with a worse prognosis than lower scores:
  

  • Grade 1: small, uniform glands with minimal nuclear changes.

  • Grade 2: medium-sized acinii, separated by stromal tissue but more closely arranged.

  • Grade 3: marked variation in glandular size and organisation and infiltration of stromal and neighbouring tissues.

  • Grade 4: marked atypical cytology with extensive infiltration.

  • Grade 5: sheets of undifferentiated cells.

• To assign a Gleason score the two most common types of glandular growth patterns within the tumour biopsy are graded. A grade from the scale is given to each of these two patterns. The two grades are added together to get the total Gleason score. For example, if the grade given to the most common growth pattern is 3 and the grade given to the second most common growth pattern is 4, the total Gleason score is 7 (3 + 4).

• Prostate cancers are often heterogeneous and the Gleason score is the sum of the two most prominent grades.

• The Gleason score has been used as the best prognostic indicator for prostate cancer but other molecular indicators are being evaluated:
  

  • Gleason score of 4 or less: well differentiated; ten-year risk of local progression 25%.

  • Gleason score 5-7: moderately differentiated; ten-year risk of local progression 50%.

  • Gleason score over 7: poorly differentiated; ten-year risk of local progression 75%.

The International Society of Urological Pathology (ISUP)-World Health Organization (WHO) 2014 grade groups were adopted to allow patients to better understand the behaviour of their diagnosed prostate carcinoma, while separating Gleason score 7 adenocarcinoma into two prognostically very distinct categories: grade group 2 for Gleason score 7 (3 + 4) and grade group 3 for Gleason score 7 (4 + 3) (see Table 3). This ISUP-WHO 2014 grade grouping will gradually be introduced into the standard pathology reporting⁴ .

• Grade 1: Gleason score 2-6.

• Grade 2: Gleason score 7 (3 + 4).

• Grade 3: Gleason score 7 (4 + 3).

• Grade 4: Gleason score 8 (4 + 4) or (3 + 5) or (5 + 3).

• Grade 5: Gleason score 9-10.

Risk stratification criteria for men with localised prostate cancer³

NICE recommends risk stratification for all people with newly diagnosed localised or locally advanced prostate cancer:

• Cambridge Prognostic Group 1: Gleason score 6 (grade group 1), and prostate-specific antigen (PSA) less than 10 microgram/litre, and Stages T1-T2.

• Group 2: Gleason score 3 + 4 = 7 (grade group 2) or PSA 10 microgram/litre to 20 microgram/litre, and Stages T1-T2.

• Group 3: Gleason score 3 + 4 = 7 (grade group 2) and PSA 10 microgram/litre to 20 microgram/litre and Stages T1-T2, or Gleason 4 + 3 = 7 (grade group 3) and Stages T1-T2.

• Group 4: one of: Gleason score 8 (grade group 4), PSA more than 20 microgram/litre, Stage T3.

• Group 5: two or more of Gleason score 8 (grade group 4), PSA more than 20 microgram/litre, Stage T3, or Gleason score 9 to 10 (grade group 5), or Stage T4.

Prostate cancer treatment and management^{3 4}

Referral

NICE referral guidelines for suspected prostate cancer state¹⁰ :

• Refer people using a suspected cancer pathway referral (for an appointment within two weeks) for prostate cancer if their prostate feels malignant on digital rectal examination.

• Consider referring people with possible symptoms of prostate cancer, as specified in recommendation 1.6.2, using a suspected cancer pathway referral (for an appointment within two weeks) for prostate cancer if their PSA levels are above the threshold for their age:
  

  • Age below 40: use clinical judgement.

  • Age 40 to 49: PSA more than 2.5 micrograms/litre.

  • Age: 50 to 59: more than 3.5.

  • Age 60 to 69: more than 4.5.

  • Age 70 to 79: more than 6.5

  • Age above 79: use clinical judgement.

Treatment options for non-metastatic prostate cancer

Deferred treatment (active surveillance/watchful waiting)⁴
Mortality from untreated screen-detected PCa in patients with ISUP grade 1-2 might be as low as 7% at 15-year follow-up. This means that many men with localised prostate cancer will not benefit from definitive treatment. 45% of men with PSA-detected prostate cancer are candidates for deferred management. In men with comorbidity and life expectancy less than 10 years, treatment of localised prostate cancer may be deferred to avoid loss of quality of life.

Prostate cancer surgery

• The surgical treatment of prostate cancer consists of radical prostatectomy, which involves removal of the entire prostate gland between the urethra and bladder, and resection of both seminal vesicles, along with sufficient surrounding tissue to obtain a negative margin. The procedure is often accompanied by bilateral pelvic lymph node dissection⁴ .

• The management of early-stage prostate cancer remains controversial, especially for tumours detected with PSA testing. A Swedish study found that men with clinically detected, localised prostate cancer and a long life expectancy benefited from radical prostatectomy, with a mean of 2.9 years of life gained¹³ . However, improving diagnostic techniques mean that the picture is forever changing.

• Laparoscopic radical prostatectomy is indicated for localised prostate cancer with no evidence of spread beyond the prostate gland or distant metastases¹⁴ . Early studies of robot-assisted prostatectomy suggest that this laparoscopic technique may produce results which are as good as conventional laparoscopy and open laparotomy in terms of effectiveness and adverse effects^{15 16} .

Radiotherapy⁴

• Radiotherapy is an important and valid alternative to surgery as the sole form of curative therapy.

• The ProtecT trial found no difference between radical prostatectomy and external beam radiotherapy for all oncological outcomes¹⁷ .

• The consensus is that external irradiation offers the same long-term survival results as surgery and provides a quality of life at least as good as that following surgery.

• Brachytherapy (transperineal implantation of radioactive seeds into the prostate gland):
  

  • A decision to use this technique takes into account several prognostic factors, including Gleason score, PSA level and TNM classification.

  • High-dose rate brachytherapy in combination with external-beam radiotherapy, and low-dose rate brachytherapy are recommended as a treatment option for localised prostate cancer^{18 19} .

Hormonal therapy
Androgen deprivation treatment refers to treatments that act by reducing the effects of testosterone and other androgens, thus inhibiting the progression of prostate cancer. The main treatments used are LHRH agonists and anti-androgens²⁰ .

• LHRH agonists (such as goserelin, leuprorelin, and triptorelin) induce castrate levels of testosterone by binding to their associated receptors in the anterior pituitary gland. The initial stimulation of the receptors may lead to an initial flare-up of testosterone level, lasting up to 10 days. Castrate levels of testosterone are reached within four weeks.

• Anti-androgens act mainly by inhibiting signalling through the androgen receptor, which leads to apoptosis and inhibition of prostate cancer growth. There are two classes of anti-androgens: steroidal (cyproterone acetate) and non-steroidal (bicalutamide, nilutamide and flutamide).

Apalutamide plus androgen deprivation therapy (ADT)
NICE has issued guidance on the use of the above prostate cancer treatment in two clinical scenarios. They conclude that:

• For hormone-sensitive metastatic prostate cancer in adults²¹ , apalutamide plus ADT should be recommended only if docetaxel is not suitable.

• Apalutamide plus ADT is recommended for hormone-relapsed non-metastatic prostate cancer that is at high risk of metastasising (PSA doubled in ≤10 months on continuous ADT)²²

Surgical castration is still considered the 'gold standard' for androgen deprivation therapy. Bilateral orchiectomy (total or subcapsular) is a simple surgical procedure. It is easily performed under local anaesthesia. The main drawback is that it may have a negative psychological effect and it is irreversible and does not allow for intermittent treatment⁴ .

Prostate cancer may regrow after androgen deprivation treatment, despite castrate levels of testosterone (castration-resistant prostate cancer). Newer drugs used in this phase include abiraterone (which inhibits enzymes needed for androgen biosynthesis) and enzalutamide (which inhibits androgen receptor transfer to the nucleus).

Chemotherapy

• Docetaxel is recommended for men with metastatic castrate-resistant prostate cancer^{24 25} .

• Cabazitaxel in combination with prednisone or prednisolone is recommended as an option for treating metastatic hormone-relapsed prostate cancer in people whose disease has progressed during or after docetaxel chemotherapy²⁶ .

Anti-androgen therapy

• Enzalutamide is recommended by NICE as an option for treating metastatic hormone-relapsed prostate cancer in patients who have mild or no symptoms after androgen deprivation therapy has failed, and before chemotherapy is indicated²⁷ .

• Abiraterone in combination with prednisone or prednisolone is recommended by NICE as an option for treating metastatic hormone-relapsed prostate cancer in people who have no or mild symptoms after androgen deprivation therapy has failed, and before chemotherapy is indicated²⁸ .

• Enzalutamide is also recommended by NICE as an option for treating metastatic hormone‑relapsed prostate cancer in adults whose disease has progressed during or after docetaxel-containing chemotherapy²⁹ .

High-intensity focused ultrasound (HIFU) and cryotherapy
NICE recommends that high-intensity focused ultrasound or cryotherapy should not be offered to people with localised prostate cancer.

NICE's interventional procedures guidance on high-intensity focused ultrasound for prostate cancer, cryotherapy for recurrent prostate cancer and cryotherapy as a primary treatment for prostate cancer evaluated the safety and efficacy of cryotherapy and high-intensity focused ultrasound for the treatment of prostate cancer^{32 33} .

Because there was a lack of evidence on quality-of-life benefits and long-term survival, these interventions are not recommended in the NICE clinical guideline. Although there are no major safety concerns, evidence on efficacy is limited in quantity and there is a concern that prostate cancer is commonly multifocal.

Adverse effects of prostate cancer treatment³

The potential side-effects of prostate cancer treatment include urinary and sexual dysfunction, loss of fertility, radiation-induced enteropathy, osteoporosis, gynaecomastia, fatigue and hot flushes.

Intermittent therapy may be considered for patients who are having long-term androgen deprivation therapy to reduce side-effects.

Flare phenomenon⁴
Tumour flare due to an initial surge in testosterone concentrations has been reported in the initial stages of treatment with LHRH agonists. Prophylactic anti-androgen therapy (such as cyproterone acetate) should be considered.

• The flare phenomenon is associated with bone pain, acute bladder outlet obstruction, obstructive acute kidney injury, spinal cord compression, and fatal cardiovascular events due to hypercoagulation status.

• The overall clinical impact of this initial flare is unknown.

• Patients at risk are usually patients with high-volume, symptomatic, bony disease, which account for only 4-10% of M1 patients.

• Concomitant therapy with an anti-androgen decreases the incidence of clinical flare but does not completely suppress the risk.

• Anti-androgens (eg, cyproterone acetate or flutamide) should be started before the LHRH analogue and should be continued for a two-week period.

• Some mini-flares also occur with the long-term use of LHRH agonists. The clinical impact is unknown but a mini-flare may be associated with a negative impact on overall survival.

Hot flushes
Hot flushes are common and bothersome in patients with prostate cancer³⁴ . Medroxyprogesterone acetate can be used, initially for up to 10 weeks, to manage troublesome hot flushes caused by long-term androgen suppression. Cyproterone acetate can be considered as an alternative if medroxyprogesterone acetate is not effective or not tolerated.

Sexual dysfunction
Long-term androgen deprivation will cause a reduction in libido and possible loss of sexual function. Consider referring men who are having long-term androgen deprivation therapy, and their partners, for psychosexual counselling. Offer treatment options for erectile dysfunction.

Osteoporosis
Do not routinely offer bisphosphonates to prevent osteoporosis in men with prostate cancer having androgen deprivation therapy. A bisphosphonate should be offered to men who do have osteoporosis and who are having androgen deprivation therapy. Denosumab is an alternative if bisphosphonates are not appropriate.

Gynaecomastia
Gynaecomastia can occur with long-term (longer than six months) bicalutamide treatment. Prophylactic radiotherapy (within the first month of treatment) should be offered. If radiotherapy is unsuccessful, weekly tamoxifen can be considered.

Fatigue
Fatigue is a recognised side-effect. Patients who are on androgen deprivation therapy should be offered a supervised exercise program (at least twice a week for 12 weeks) to reduce fatigue and improve quality of life.

NICE guidance³

The following is a brief overview of the NICE guidance. You can use the reference link to access the guideline for details of treatment recommendations and management of the adverse effects of treatment.

Localised and locally advanced prostate cancer

• There are three options for treatment: active surveillance, radical prostatectomy and radical radiotherapy.

• The evidence does not show a difference in the number of deaths from prostate cancer among people offered active surveillance, prostatectomy or radical radiotherapy.

• There is good evidence that both prostatectomy and radiotherapy reduce disease progression compared with active surveillance.

• There is good evidence that both prostatectomy and radiotherapy reduce the rate of development of distant metastases compared with active surveillance.

• There is some evidence that urinary function is better for people offered active surveillance or radiotherapy than for those offered prostatectomy.

• There is some limited evidence that sexual function is better for people offered active surveillance or radiotherapy than for those offered prostatectomy.

• There is some evidence that bowel function is better for people offered active surveillance or prostatectomy than for those offered radiotherapy in the short term.

For people with CPG 1 localised prostate cancer:

• Offer active surveillance

• Consider radical prostatectomy or radical radiotherapy if active surveillance is not suitable or acceptable to the person.

For people with CPG 2 localised prostate cancer:

• Offer a choice between active surveillance, radical prostatectomy or radical radiotherapy if radical treatment is suitable.

For people with CPG 3 localised prostate cancer:

• Offer radical prostatectomy or radical radiotherapy; and

• Consider active surveillance for people who choose not to have immediate radical treatment.

For people with CPG 4 and 5 localised and locally advanced prostate cancer:

• Do not offer active surveillance.

• Offer radical prostatectomy or radical radiotherapy when it is likely the person's cancer can be controlled in the long term.

Radical treatment
For people having radical external beam radiotherapy for localised prostate cancer:

• Offer hypofractionated radiotherapy using image-guided intensity modulated radiation therapy (IMRT), or conventional radiotherapy to people who cannot have hypofractionated radiotherapy. Offer people with CPG 2, 3, 4 and 5 localised or locally advanced prostate cancer a combination of radical radiotherapy and androgen deprivation therapy, rather than radical radiotherapy or androgen deprivation therapy alone. Offer people with CPG 2, 3, 4 and 5 localised or locally advanced prostate cancer six months of androgen deprivation therapy before, during or after radical external beam radiotherapy.

• Consider continuing androgen deprivation therapy for up to three years for people with CPG 4 and 5 localised or locally advanced prostate cancer.

• Consider brachytherapy in combination with external beam radiotherapy for people with CPG 2, 3, 4 and 5 localised or locally advanced prostate cancer. Do not offer brachytherapy alone to people with CPG 4 and 5 localised or locally advanced prostate cancer.

Docetaxel
Discuss the option of docetaxel chemotherapy with people who have newly diagnosed non-metastatic prostate cancer who:

• Are starting long-term androgen deprivation therapy, have no significant comorbidities, and have high-risk disease.

• For people having docetaxel chemotherapy: start treatment within 12 weeks of starting androgen deprivation therapy. Use six three-weekly cycles with or without daily prednisolone.

Watchful waiting
People with localised prostate cancer who have chosen watchful waiting and who have evidence of significant disease progression (rapidly rising PSA level or bone pain) should have their situation reviewed by a member of the urological cancer MDT.

Locally advanced prostate cancer
Consider pelvic radiotherapy for people with locally advanced prostate cancer who have a higher than 15% risk of pelvic lymph node involvement (using the Roach formula: %LN risk = 2/3 PSA + (10 × [Gleason score - 6]) and who are to receive neoadjuvant hormonal therapy and radical radiotherapy.

Metastatic prostate cancer

• Offer docetaxel chemotherapy to people with newly diagnosed metastatic prostate cancer who do not have significant comorbidities. Start treatment within 12 weeks of starting androgen deprivation therapy and use six three-weekly cycles, with or without daily prednisolone.

• Offer bilateral orchidectomy to all people with metastatic prostate cancer as an alternative to continuous luteinising hormone-releasing hormone agonist therapy.

• Do not offer combined androgen blockade as a first-line treatment for people with metastatic prostate cancer.

• For people with metastatic prostate cancer who are willing to accept the adverse impact on overall survival and gynaecomastia with the aim of retaining sexual function, offer anti-androgen monotherapy with bicalutamide.

• Begin androgen deprivation therapy and stop bicalutamide treatment in people with metastatic prostate cancer who are taking bicalutamide monotherapy and who do not maintain satisfactory sexual function.

Enzalutamide plus androgen deprivation therapy (ADT) is recommended as an option for treating hormone-sensitive metastatic prostate cancer³⁵ .

Managing relapse after radical treatment

• Analyse serial PSA levels after radical treatment. Biochemical relapse (a rising PSA) alone should not mean an immediate change in treatment is needed.

• Offer an isotope bone scan if symptoms or PSA trends are suggestive of metastases.

• Offer people with biochemical relapse after radical prostatectomy, with no known metastases, radical radiotherapy to the prostatic bed.

• Do not routinely offer hormonal therapy to people with prostate cancer who have a biochemical relapse unless they have:

  • Symptomatic local disease progression.

  • Any proven metastases.

  • A PSA doubling time of less than three months.

• People having hormone therapy:

  • Consider intermittent therapy for people having long-term androgen deprivation therapy (not in the adjuvant setting).

  • For people who are having intermittent androgen deprivation therapy: measure PSA every three months, and restart androgen deprivation therapy if PSA is 10 nanogram/ml or above, or if there is symptomatic progression.

Hormone-relapsed metastatic prostate cancer

• Docetaxel is recommended as a treatment option for people with hormone-refractory prostate cancer only if their Karnofsky Performance-Status score is 60% or more²⁵ .

• Treatment with docetaxel should be stopped at the completion of planned treatment of up to 10 cycles, if severe adverse events occur, or 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.

• Offer a corticosteroid such as dexamethasone as third-line hormonal therapy after androgen deprivation therapy and anti-androgen therapy to people with hormone-relapsed prostate cancer.

• Offer spinal MRI to people with hormone-relapsed prostate cancer shown to have extensive metastases in the spine (for example, on a bone scan) if they develop any spinal-related symptoms. Do not routinely offer spinal MRI to all people with hormone-relapsed prostate cancer and known bone metastases.

• Bone-targeted therapies:

  • For people with hormone-relapsed metastatic prostate cancer, consider zoledronic acid to prevent or reduce skeletal-related events.

  • Consider oral or intravenous bisphosphonates for pain relief for people with hormone-relapsed metastatic prostate cancer when other treatments, including analgesics and palliative radiotherapy, have not given satisfactory pain relief.

• Pelvic-targeted therapies:

  • Offer decompression of the upper urinary tract by percutaneous nephrostomy or by insertion of a double J stent to people with obstructive uropathy secondary to hormone-relapsed prostate cancer.

  • Discuss the option of no intervention as a treatment choice with people with obstructive uropathy secondary to hormone-relapsed prostate cancer.

Enzalutamide is recommended as an option for treating metastatic hormone‑relapsed prostate cancer in people who have no or mild symptoms after androgen deprivation therapy has failed, and before chemotherapy is indicated²⁷ .

Darolutamide with androgen deprivation therapy (ADT) is recommended as an option for treating hormone-relapsed prostate cancer in adults at high risk of developing metastatic disease³⁶ .

Palliative care

See the separate Palliative Care, Pain Control in Palliative Care, End of Life Care, and Looking After People With Cancer articles.

• Bisphosphonates should be considered for patients with skeletal masses, to prevent osseous complications.

• Palliative treatments, such as radionuclides, external-beam radiotherapy and adequate use of analgesics, should be considered early on in the management of painful bone metastases.

• Emergency spinal surgery or decompressive radiotherapy should be considered for patients with neurological symptoms thought to be critical.

Prostate cancer complications

• Urinary tract obstruction, acute kidney injury, chronic kidney disease.

• Sexual dysfunction: erectile dysfunction, loss of libido.

• Metastatic spread: bone pain, pathological fractures, spinal cord compression.

• Complications of hormonal therapy:
  

  • Hot flushes: synthetic progestogens are recommended as first-line therapy for troublesome hot flushes.

  • Gynaecomastia is a common, troublesome complication of long-term bicalutamide monotherapy: men starting long-term bicalutamide monotherapy (>6 months) should receive prophylactic radiotherapy to both breast buds within the first month of treatment.

Prostate cancer prognosis¹

• In males in the UK, prostate cancer is the second most common cause of cancer death, with around 11,900 deaths in 2018. Prostate cancer accounts for 13% of all cancer deaths in males in the UK (2018).

• Mortality rates for prostate cancer in the UK are highest in males aged 90+. However 75% of all prostate cancer deaths in the UK are in males aged 75 and over (2016-2018).

• 96.6% of men diagnosed with prostate cancer in England survive their disease for one year or more (2013-2017).

• 86.6% of men diagnosed with prostate cancer in England survive their disease for five years or more (2013-2017).

• It is predicted that 77.6% of men diagnosed with prostate cancer in England survive their disease for ten years or more (2013-2017).

• Prostate cancer survival in England is higher for men diagnosed aged 60-69 years old, probably because of PSA testing detecting latent, earlier, slow-growing cancers (2009-2013).

• Almost 95% of men in England diagnosed with prostate cancer aged 50-59 or 60-69 survive their disease for five years or more, compared with two thirds of men diagnosed aged 80 and over (2009-2013).

• When diagnosed at its earliest stage, 100% with prostate cancer will survive their disease for one year or more, compared with 88% when the disease is diagnosed at the latest stage.

• When diagnosed at its earliest stage, 100% with prostate cancer will survive their disease for five years or more, compared with around 49% when the disease is diagnosed at the latest stage.

• Prostate cancer survival is improving and has tripled in the last 40 years in the UK, probably because of PSA testing.