Professional Reference articles are designed for health professionals to use. They are written by UK doctors and based on research evidence, UK and European Guidelines. You may find the Prostate Cancer article more useful, or one of our other health articles.
Treatment of almost all medical conditions has been affected by the COVID-19 pandemic. NICE has issued rapid update guidelines in relation to many of these. This guidance is changing frequently. Please visit https://www.nice.org.uk/covid-19 to see if there is temporary guidance issued by NICE in relation to the management of this condition, which may vary from the information given below.
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 is the most common cancer in men and makes up 26% of all male cancer diagnoses in the UK.
- The age-standardised incidence of prostate cancer in England in 2016 was 173.7 per 100,000 in 2016.
- It was estimated that the lifetime risk of being diagnosed with prostate cancer is 1 in 6 for men in the UK.
- Globally, prostate cancer accounts for 15% of male cancers, 70% of them occur in developed countries.
- Subclinical prostate cancer is common in men aged over 50.
The three well-established risk factors for prostate cancer are increasing age, ethnic origin and genetic predisposition.
- Increasing age is the most important risk factor for developing prostate cancer. 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 Caucasian men.
- 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.
- 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.
See also the separate Prostate Specific Antigen (PSA) article.
A 2015 review by the UK Screening Committee concluded that despite the likelihood that a national screening programme would reduce mortality by at least 21%, the widespread use of PSA in asymptomatic men who had not had a digital rectal examination would increase the risks of overdiagnosing and overtreating clinically insignificant prostate cancers. Men with indolent disease would unnecessarily be exposed to the side-effects of radical treatment, including sexual dysfunction and urinary problems. There is also, in extreme cases, the risk of death.
This position has been confirmed by the ProtecT trial, which demonstrated that there was no difference in 10-year survival rates between men with low-risk localised prostate cancer who were allocated to active surveillance and those who chose radical treatment. This was supported by the CAP trial of UK general practices, the findings of which did not support single PSA testing for population-based screening.
To complicate matters further, genetic factors (abnormalities of the KLK3 gene) can cause abnormally low PSA readings, resulting in false negatives in some patients[.
There is no organised screening programme for prostate cancer in the UK but 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 test.
- Prostate cancer is only one of several causes of a raised PSA test.
- Three out of four men with a raised PSA will not have cancer cells in their biopsy. Therefore, having the test may lead to unnecessary worry and exposure to the risks of further investigations. The most common problems after biopsy are infection and bleeding. However, if they do not have the test they will have an increased risk of presenting only when they have symptoms, which can increase the chance of prostate cancer remaining undiagnosed until it is advanced and incurable.
- 15% of men with prostate cancer have a normal PSA. Normal results can be falsely reassuring. However, men who do not have the test will miss the chance of early diagnosis and treatment.
- The test cannot distinguish between aggressive and slow-growing cancers and may detect tumours that would not otherwise become evident in the patient's lifetime.
- Potential treatments can include surgery, radiotherapy and hormone therapy. Side-effects can include problems with erections, loss of fertility, and incontinence. Not having the PSA test will mean that treatment will not be required unless symptoms develop, so these risks will be avoided. However, the patient will miss the chance of early detection, as outlined above.
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 referral.
See also the separate Genitourinary History and Examination (Male) article.
Prostate cancer is usually suspected on the basis of DRE and/or PSA levels.
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 LUTS.
- Local disease:
- Raised PSA on screening.
- 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.
- Perineal and suprapubic pain.
- Obstruction of ureters, causing loin pain, anuria, symptoms of acute kidney injury or chronic kidney disease.
- 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.
- Advanced disease: 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.
- 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.
- Lack of mobility - adhesion to surrounding tissue.
- Palpable seminal vesicles.
- All other causes of haematuria (eg, urinary tract infection) and urinary tract obstruction.
- Benign prostatic hyperplasia.
- Bladder tumours.
- The PSA Test is dealt with in the separate Prostate Specific Antigen (PSA) article.
- PCA3 urine test: 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 shown.
- 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.
- 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 biopsies.
- TRUS: the classic picture of a hypoechoic area in the peripheral zone of the prostate 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 useful.
- Uroflow measurement, measurement of postmicturition residual urine, cystoscopy and imaging of the upper urinary tract (if suspect upper tract dilatation or bladder outlet obstruction).
- Multiparametric MRI has been recommended in draft guidance issued by the National Institute for Health and Care Excellence (NICE)as a first-line investigation for patients suspected clinically of having localised prostatic cancer.
- 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 complications.
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 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 prostate.
- 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).
- There are several systems for grading the 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 reporting.
- 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 cancer
Several factors have been shown to predict the risk of recurrence after treatment of localised prostate cancer:
- Low risk: PSA <10 ng/ml and Gleason score 6 or below and clinical stage T1-T2a.
- Intermediate risk: PSA 10-20 ng/mL, or Gleason score 7, or clinical stage T2b.
- High risk: PSA >20 ng/ml, or Gleason score 8-10, or clinical stage ≥T2c.
Dr Sarah Jarvis, 18th May 2019.
New NICE Quality Standards on care of men with prostate cancer.
NICE has issued quality standards relating to the care of men being followed up in primary care for prostate cancer, as well as those referred to secondary care with suspected or confirmed prostate cancer.
The five quality statements are:
- People should have a named nurse specialist with whom to discuss options and possible adverse effects of treatment.
- People should be offered a choice between active surveillance, radical prostatectomy or radical radiotherapy if they have low-risk localised prostate cancer and are suitable for radical treatment.
- If they have been diagnosed with intermediate‑ or high‑risk localised prostate cancer, any non-surgical radical treatment should include the offer of combined androgen deprivation treatment and radical radiotherapy.
- People who have adverse effects of treatment should be referred to specialist services.
- The treatment options for people with hormone‑relapsed metastatic prostate cancer should be discussed at the urological cancer MDT.
- Men and their partners should be made aware of the effects of prostate cancer and its treatment, including sexual dysfunction, urinary incontinence and radiation-induced enteropathy.
- Palliative care services should be offered when needed and not reserved for the time of hospice care or at the end of life.
NICE referral guidelines for suspected cancer state:
- Refer men using a suspected cancer pathway referral (for an appointment within two weeks) for prostate cancer if their prostate feels malignant on DRE examination.
- Consider 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.
- Visible haematuria.
- Refer men aged between 50-69 using a suspected cancer pathway if their PSA level is 3.0 ng/ml or higher.
Treatment options for non-metastatic disease
Treatment options for clinically localised prostate cancer include watchful waiting or observation, active surveillance, radical prostatectomy, external beam radiation therapy, interstitial radiation implants (brachytherapy), cryoablation, androgen deprivation therapy, high-intensity focused ultrasound (HIFU) and focal therapy.
Deferred treatment (active surveillance/watchful waiting)
Active surveillance is defined as regular monitoring of patients who might benefit from curative treatment in the future. Watchful waiting refers to the conservative management of patients deemed unsuitable for curative treatment from the outset.
Mortality from untreated screen-detected PCa in patients with ISUP grade 1-2 might be as low as 7% at fifteen years 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.
- 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 dissection.
- 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 gainedHowever, improving diagnostic techniques means that the picture is forever changing.
- Laparoscopic radical prostatectomy is indicated for localised prostate cancer with no evidence of spread beyond the prostate or distant metastases. 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[25, 26].
- 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 outcomes.
- 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):
- 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[27, 28].
- Cryotherapy may be considered as a treatment for patients with localised or locally advanced prostate cancer.
- Cryotherapy may also be considered to treat locally recurrent carcinoma of the prostate that has been refractory to other treatments, such as radiotherapy or hormone therapy.
- Docetaxel is recommended for men with metastatic castrate-resistant prostate cancer[4, 31].
- 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 chemotherapy.
- 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 indicated.
- 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 indicated.
- 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 chemotherapy.
High-intensity focused ultrasound (HIFU)
NICE recommends using HIFU to treat carcinoma of the prostate, either as a primary or as a salvage therapy. However, the European Association of Urology (EUA) guidelines recommend that, due to lack of evidence, it should only be used within a clinical trial setting.
Low-risk localised prostate cancer
- Active surveillance is an option to men with low-risk localised prostate cancer for whom radical prostatectomy or radical radiotherapy is suitable. NICE recommends the following protocol:
- At enrolment in active surveillance: multiparametric MRI if not previously performed:
- Year 1 of active surveillance: measure PSA every 3-4 months, DRE every 6-12 months, prostate re-biopsy at 12 months.
- Years 2-4 of active surveillance: measure PSA every 3-6 months, DRE every 6-12 months.
- Year 5 and every year thereafter until active surveillance ends: measure PSA every 6 months, DRE every 12 months.
- Throughout active surveillance: monitor PSA kinetics (may include PSA doubling time and velocity).
- If there is concern about clinical or PSA changes at any time during active surveillance, reassess with multiparametric MRI and/or re-biopsy.
- At enrolment in active surveillance: multiparametric MRI if not previously performed:
- Radical treatment:
- The decision to proceed from an active surveillance regimen to radical treatment should be made in the light of the individual man's personal preferences, comorbidities and life expectancy.
- Radical treatment should be offered to men with localised prostate cancer who have chosen an active surveillance regimen and who have evidence of disease progression.
Intermediate-risk and high-risk localised prostate cancer
- Active surveillance should be considered for men with intermediate-risk localised prostate cancer who do not wish to have immediate radical prostatectomy or radical radiotherapy.
- Active surveillance should not be offered to men with high-risk localised prostate cancer.
- Radical treatment:
- Radical prostatectomy or radical radiotherapy should be offered to men with intermediate-risk localised prostate cancer, and to men with high-risk localised prostate cancer when there is a realistic prospect of long-term disease control.
- Men with intermediate-risk and high-risk localised prostate cancer should be offered a combination of radical radiotherapy and androgen deprivation therapy, rather than radical radiotherapy or androgen deprivation therapy alone.
- Men with intermediate-risk and high-risk localised prostate cancer should be offered six months of androgen deprivation therapy before, during or after radical external beam radiotherapy.
- Continuing androgen deprivation therapy for up to three years should be considered for men with high-risk localised prostate cancer.
- High-dose-rate brachytherapy in combination with external-beam radiotherapy should be considered for men with intermediate-risk and high-risk localised prostate cancer. Brachytherapy alone should not be offered to men with high-risk localised prostate cancer.
Locally advanced prostate cancer
- Pelvic radiotherapy should be considered for locally advanced prostate cancer if there is a higher than 15% risk of pelvic lymph node involvement and if neoadjuvant hormonal therapy and radical radiotherapy are to be provided.
- Immediate postoperative radiotherapy after radical prostatectomy should not be offered, even to men with margin-positive disease.
- Adjuvant hormonal therapy in addition to radical prostatectomy should not be offered, even to men with margin-positive disease.
Managing relapse after radical treatment
- Analyse serial PSA levels after radical treatment, using the same assay technique.
- Biopsy of the prostatic bed should not be offered to men with prostate cancer who have had a radical prostatectomy. Biopsy of the prostate after radiotherapy should only be offered to men with prostate cancer who are being considered for local salvage therapy in the context of a clinical trial.
- For men with evidence of biochemical relapse following radical treatment and who are considering radical salvage therapy:
- Routine MRI scanning prior to salvage radiotherapy should not be offered to men with prostate cancer
- An isotope bone scan should be offered if symptoms or PSA trends are suggestive of metastases.
- Biochemical relapse (a rising PSA) alone should not necessarily prompt an immediate change in treatment. Biochemical relapse should trigger an estimate of PSA doubling time, based on a minimum of three measurements over at least a six-month period.
- Men with biochemical relapse after radical prostatectomy, with no known metastases, should be offered radical radiotherapy to the prostatic bed.
- Hormonal therapy should not routinely be offered to men with prostate cancer who have a biochemical relapse unless they have symptomatic local disease progression, any proven metastases, or a PSA doubling time of less than three months.
Metastatic prostate cancer
- Bilateral orchidectomy should be offered to all men with metastatic prostate cancer as an alternative to continuous luteinising hormone-releasing hormone (LHRH) agonist therapy.
- Combined androgen blockade should not be offered as a first-line treatment for metastatic prostate cancer.
- For men with metastatic prostate cancer who are willing to accept the adverse impact on overall survival and gynaecomastia in the hope of retaining sexual function, anti-androgen monotherapy with bicalutamide can be used.
- Androgen deprivation therapy (see below) should be started and bicalutamide stopped for men with metastatic prostate cancer who are taking bicalutamide monotherapy and who do not maintain satisfactory sexual function.
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-androgens.
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 treatment.
- 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).
- Newer drugs: other forms of androgen deprivation treatment include LHRH antagonists, such as degarelix, which binds competitively to pituitary LHRH receptors, rapidly reducing luteinising hormone and testosterone levels without the initial testosterone flare.
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).
For men receiving intermittent androgen deprivation therapy: measure PSA every three months and restart androgen deprivation therapy if PSA is 10 ng/mL or above, or if there is symptomatic progression.
Managing adverse effects of hormone therapy
- Flare phenomenon
- LHRH agonists have become the 'standard of care' in hormonal therapy. The main concern is the 'flare phenomenon' in advanced disease.
- 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: medroxyprogesterone, initially for 10 weeks. Consider cyproterone acetate to treat troublesome hot flushes if medroxyprogesterone is not effective or not tolerated. Megesterol acetate is no longer recommended as it is not available in the UK in the dose needed (amended 2015).
- 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. Offer bisphosphonates to men who are having androgen deprivation therapy and have osteoporosis. Consider denosumab for men who are having androgen deprivation therapy and have osteoporosis if bisphosphonates are contra-indicated or not tolerated.
- Gynaecomastia: for men starting long-term bicalutamide monotherapy (longer than six months), offer prophylactic radiotherapy to both breast buds within the first month of treatment. If radiotherapy is unsuccessful in preventing gynaecomastia, weekly tamoxifen should be considered.
- Fatigue: this is a recognised side-effect. Offer men who are starting or having androgen deprivation therapy, supervised resistance and aerobic exercise at least twice a week for 12 weeks to reduce fatigue and improve quality of life.
Hormone-relapsed metastatic prostate cancer
- Docetaxel is recommended, within its licensed indications, as a treatment option for men with hormone-refractory prostate cancer only if their Karnofsky performance-status score (a measure of the ability to perform daily tasks) 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.
- Offer a corticosteroid such as dexamethasone as third-line hormonal therapy after androgen deprivation therapy and anti-androgen therapy to men with hormone-relapsed prostate cancer.
- Offer spinal MRI to men with hormone-relapsed prostate cancer shown to have extensive metastases in the spine (eg, on a bone scan) if they develop any spinal-related symptoms. Do not routinely offer spinal MRI to all men with hormone-relapsed prostate cancer and known bone metastases.
- Do not offer bisphosphonates to prevent or reduce the complications of bone metastases in men with hormone-relapsed prostate cancer.
- Bisphosphonates for pain relief may be considered for men with hormone-relapsed prostate cancer when other treatments (including analgesics and palliative radiotherapy) have failed.
- Strontium-89 should be considered for men with hormone-relapsed prostate cancer and painful bone metastases, especially those men who are unlikely to receive myelosuppressive chemotherapy.
- Offer decompression of the upper urinary tract by percutaneous nephrostomy or by insertion of a double J stent to men with obstructive uropathy secondary to hormone-relapsed prostate cancer.
- The option of no intervention should also be discussed with men with obstructive uropathy secondary to hormone-relapsed prostate cancer.
- 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.
- 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.
- Survival from prostate cancer is strongly related to the stage of the disease at diagnosis.
- In males in the UK, prostate cancer is the second most common cause of cancer death, with 11,631 deaths in 2016. 74% of prostate cancer deaths in the UK each year are in males aged 75 years and over. Mortality rates for prostate cancer in the UK are highest in males aged over 90 years.
- Since the early 1970s, prostate cancer mortality rates in males have increased by 19% in the UK. However, over the past decade prostate cancer mortality rates in males have decreased by 12% in the UK.
Further reading and references
Prostate Cancer Treatment; National Cancer Institute
Prostate cancer; NICE Quality Standard, June 2015
Nevedomskaya E, Baumgart SJ, Haendler B; Recent Advances in Prostate Cancer Treatment and Drug Discovery. Int J Mol Sci. 2018 May 419(5). pii: ijms19051359. doi: 10.3390/ijms19051359.
Wade CA, Kyprianou N; Profiling Prostate Cancer Therapeutic Resistance. Int J Mol Sci. 2018 Mar 1919(3). pii: ijms19030904. doi: 10.3390/ijms19030904.
Prostate cancer statistics; Cancer Research UK
Cancer registration statistics, England: 2016; Office for National Statistics
Taitt HE; Global Trends and Prostate Cancer: A Review of Incidence, Detection, and Mortality as Influenced by Race, Ethnicity, and Geographic Location. Am J Mens Health. 2018 Nov12(6):1807-1823. doi: 10.1177/1557988318798279. Epub 2018 Sep 11.
Cancer of the prostate: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up; European Society for Medical Oncology (2015)
Merriel SWD, Funston G, Hamilton W; Prostate Cancer in Primary Care. Adv Ther. 2018 Sep35(9):1285-1294. doi: 10.1007/s12325-018-0766-1. Epub 2018 Aug 10.
Wilt TJ, Ahmed HU; Prostate cancer screening and the management of clinically localized disease. BMJ. 2013 Jan 29346:f325. doi: 10.1136/bmj.f325.
Prostate cancer: diagnosis and treatment; NICE Clinical Guideline (January 2014)
Guidelines on Prostate Cancer; European Association of Urologists (2018)
Hamdy FC, Donovan JL, Lane JA, et al; 10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer. N Engl J Med. 2016 Oct 13375(15):1415-1424. doi: 10.1056/NEJMoa1606220. Epub 2016 Sep 14.
Aizer AA, Chen MH, Hattangadi J, et al; Initial management of prostate-specific antigen-detected, low-risk prostate cancer and the risk of death from prostate cancer. BJU Int. 2014 Jan113(1):43-50. doi: 10.1111/j.1464-410X.2012.11789.x. Epub 2013 Mar 8.
Rodriguez S, Al-Ghamdi OA, Guthrie PA, et al; Frequency of KLK3 gene deletions in the general population. Ann Clin Biochem. 2017 Jul54(4):472-480. doi: 10.1177/0004563216666999. Epub 2016 Aug 23.
Prostate cancer risk management programme: overview; Public Health England
Prostate cancer risk management programme (PCRMP): benefits and risks of PSA testing; Public Health England, 2016
Advising well men aged 50 and over about the PSA test for prostate cancer: information for GPs; Public Health England, 2016
PHE; PSA testing and prostate cancer: advice for well men aged 50 and over, 2016.
Jones D, Friend C, Dreher A, et al; The diagnostic test accuracy of rectal examination for prostate cancer diagnosis in symptomatic patients: a systematic review. BMC Fam Pract. 2018 Jun 219(1):79. doi: 10.1186/s12875-018-0765-y.
Prostate cancer; NICE CKS, October 2017 (UK access only)
Chunhua L, Zhao H, Zhao H, et al; Clinical Significance of Peripheral Blood PCA3 Gene Expression in Early Diagnosis of Prostate Cancer. Transl Oncol. 2018 Jun11(3):628-632. doi: 10.1016/j.tranon.2018.02.019. Epub 2018 Mar 22.
Transperineal template biopsy of the prostate; NICE Interventional Procedure Guidance, October 2010
NICE recommends non-invasive MRI scan for prostate cancer; NICE, December 2018
Suspected cancer: recognition and referral; NICE Clinical Guideline (2015 - last updated January 2021)
Bill-Axelson A, Holmberg L, Garmo H, et al; Radical Prostatectomy or Watchful Waiting in Prostate Cancer - 29-Year Follow-up. N Engl J Med. 2018 Dec 13379(24):2319-2329. doi: 10.1056/NEJMoa1807801.
Laparoscopic radical prostatectomy; NICE Interventional Procedure Guidance, November 2006
Ilic D, Evans SM, Allan CA, et al; Laparoscopic and robotic-assisted versus open radical prostatectomy for the treatment of localised prostate cancer. Cochrane Database Syst Rev. 2017 Sep 129:CD009625. doi: 10.1002/14651858.CD009625.pub2.
Huynh LM, Ahlering TE; Robot-Assisted Radical Prostatectomy: A Step-by-Step Guide. J Endourol. 2018 May32(S1):S28-S32. doi: 10.1089/end.2017.0723.
High dose rate brachytherapy in combination with external-beam radiotherapy for localised prostate cancer; NICE Interventional Procedure Guidance, May 2006
Low dose rate brachytherapy for localised prostate cancer; NICE Interventional Procedure Guidance, July 2005
Cryotherapy as a primary treatment for prostate cancer; NICE Interventional Procedure Guidance, November 2005
Cryotherapy for recurrent prostate cancer; NICE Interventional Procedure Guidance, May 2005
Docetaxel for the treatment of hormone refractory prostate cancer; NICE Technology Appraisal Guidance, June 2006
Cabazitaxel for hormone-relapsed metastatic prostate cancer treated with docetaxel; NICE Technology Appraisal Guidance, May 2016
Abiraterone for treating metastatic hormone-relapsed prostate cancer before chemotherapy is indicated; NICE Technology Appraisal Guidance, April 2016
Enzalutamide for metastatic hormone‑relapsed prostate cancer previously treated with a docetaxel‑containing regimen; NICE Technology Appraisal Guidance, July 2014
High-intensity focused ultrasound for prostate cancer; NICE Interventional Procedure Guidance, March 2005
Thomas BC, Neal DE; Androgen deprivation treatment in prostate cancer. BMJ. 2013 Jan 8346:e8555. doi: 10.1136/bmj.e8555.