Secondary Care Diagnosis and Management of Prostate Cancer

Overview

This specialist Guidelines summary covers the diagnosis and management of prostate cancer in secondary care, including information on the best way to diagnose and identify different stages of the disease, and how to manage adverse effects of treatment. It also includes recommendations on follow up in primary care for people diagnosed with prostate cancer. This summary is intended for the use of secondary care professionals in oncology.

Please refer to the full guideline for information on the benefits and harms of treatment options.

This guideline replaces CG175, DG17, and ESNM30.

This guideline is the basis of QS91.

A table of NHS England interim treatment regimens gives possible alternative treatment options for use during the COVID-19 pandemic to reduce infection risk. This may affect decisions for patients with prostate cancer. See the COVID-19 rapid guideline: delivery of systemic anticancer treatments for more details.

Information and Decision Support for People with Prostate Cancer, Their Partners and Carers

Information

• For advice on communication and patient-centred care throughout the patient journey, follow the recommendations in the NICE guidelines on improving outcomes in urological cancers and improving supportive and palliative care for adults with cancer.                     
• Offer people with prostate cancer information tailored to their own needs. This information should be given by a healthcare professional (for example, a consultant or specialist nurse) and may be supported by written and visual media.
• Offer people with prostate cancer advice on how to get information and support from websites, local and national cancer information services, and from cancer support groups.
• Choose or recommend information resources for people with prostate cancer that are clear, reliable and up to date. Ask for feedback from people with prostate cancer and their partners or carers to identify the highest quality information resources.

Decision Support

• Find out the extent to which the person wishes to be involved in their decision making, and ensure that they have sufficient information to do so.
• Use an up-to-date decision aid in all urological cancer multidisciplinary teams (MDTs). Healthcare professionals trained in its use should offer it to people with localised prostate cancer when making treatment decisions.
• Use nomograms together with people with prostate cancer to help:
  • with decision making
  • predict biopsy results
  • predict pathological stage
  • predict risk of treatment failure.
• Explain the reliability, validity and limitations of any predictions made using nomograms.
• Discuss all relevant management options in this guideline with people with prostate cancer and their partners or carers, even if they are not available through their local services.
• Tell people with prostate cancer:
  • about treatment options and their risks and benefits in an objective, unbiased manner and
  • that there is limited evidence for some treatment options.
• Ensure that mechanisms are in place so people with prostate cancer and their primary care providers have access to specialist services throughout the course of their disease.
• Tell people with prostate cancer and their partners or carers about the effects of prostate cancer and the treatment options on their:
  • sexual function
  • physical appearance
  • continence
  • other aspects of masculinity.
    
    Support people and their partners or carers in making treatment decisions, taking into account the effects on quality of life as well as survival.
• Offer people with prostate cancer, and their partners or carers, the opportunity to talk to a healthcare professional experienced in dealing with psychosexual issues at any stage of the condition and its treatment.

Assessment and Diagnosis

MRI and Biopsy

• Do not routinely offer MRI to people with prostate cancer who are not going to be able to have radical treatment.
• Offer multiparametric MRI as the first-line investigation for people with suspected clinically localised prostate cancer. Report the results using a 5-point Likert scale.
• Offer multiparametric MRI-influenced prostate biopsy to people whose Likert score is 3 or more.
• Consider omitting a prostate biopsy for people whose multiparametric MRI Likert score is 1 or 2, but only after discussing the risks and benefits with the person and reaching a shared decision (see box 1). If a person opts to have a biopsy, offer systematic prostate biopsy.

There is more than 1 type of prostate biopsy. The most common approach is transrectal ultrasound-guided (TRUS) biopsy. Please refer to the full guideline for further information.

• Do not offer mapping transperineal template biopsy as part of an initial assessment, unless as part of a clinical trial.
• Help people decide whether to have an MRI or prostate biopsy by discussing:
  • their prostate-specific antigen (PSA) level
  • their digital rectal examination (DRE) findings (including an estimate of prostate size)
  • any comorbidities, together with their risk factors (including increasing age and black African–Caribbean family background)
  • any history of a previous negative prostate biopsy.
    
    Do not automatically offer a prostate biopsy on the basis of serum PSA level alone.
• Give people and their partners or carers information, support and adequate time to decide whether or not they wish to have an MRI or prostate biopsy. Explain the risks (including the increased chance of having to live with the diagnosis of clinically insignificant prostate cancer) and benefits.
• If the clinical suspicion of prostate cancer is high, because of a high PSA value and evidence of bone metastases (identified by a positive isotope bone scan or sclerotic metastases on plain radiographs), do not offer prostate biopsy for histological confirmation unless this is needed as part of a clinical trial.
• Have a core member of the urological cancer MDT review the risk factors of all people who have had a negative first prostate biopsy. Discuss with the person that:
  • there is still a risk that prostate cancer is present and
  • the risk is slightly higher if any of the following risk factors are present:
    • the biopsy showed high-grade prostatic intra-epithelial neoplasia (HGPIN)
    • the biopsy showed atypical small acinar proliferation (ASAP)
    • abnormal DRE.

If the MRI or Biopsy is Negative

• For people with a negative biopsy who have an MRI Likert score of 3 or more, discuss the possibility of significant disease in an MDT meeting with a view to repeating the prostate biopsy.
• For people who have a raised PSA and MRI Likert score of 1 or 2, and who have not had a prostate biopsy, repeat PSA test at 3 to 6 months and:
  • offer prostate biopsy if there is a strong suspicion of prostate cancer (for example, PSA density greater than 0.15 nanogram/ml/ml or PSA velocity greater than 0.75 nanogram/ml/year, or strong family history), taking into account their life expectancy and comorbidities
  • discharge the person to primary care if the level of suspicion is low; advise PSA follow up at 6 months and then every year, and set a PSA level for primary care at which to re-refer based on PSA density (0.15 nanogram/ml/ml) or velocity (0.75 nanogram/ml/year).
• For people who have a raised PSA, an MRI Likert score of 1 or 2 (or a contraindication to MRI), and negative biopsy, repeat PSA at 3 to 6 months and:
  • offer prostate biopsy if there is a strong suspicion of prostate cancer (for example, PSA density greater than 0.15 nanogram/ml/ml or PSA velocity greater than 0.75 nanogram/ml/year, or strong family history), taking into account their life expectancy and comorbidities
  • discharge the person to primary care if the level of suspicion is low; advise PSA follow up every 2 years, and set a PSA level for primary care at which to re-refer, based on PSA density (0.15 nanogram/ml/ml) or velocity (0.75 nanogram/ml/year).
• The PROGENSA® PCA3 (prostate cancer gene 3) assay and the Prostate Health Index is not recommended in people having investigations for suspected prostate cancer who have had a negative or inconclusive prostate biopsy.

Staging

CT for Histologically Proven Prostate Cancer

• Consider CT (computerized tomography) for people with histologically proven prostate cancer for whom MRI is contraindicated if knowledge of the T or N stage could affect management.

Risk Stratification for Localised or Locally Advanced Prostate Cancer

• Urological cancer MDTs should assign a risk category (see table 1) to all people with newly diagnosed localised or locally advanced prostate cancer.

Table 1: Risk Stratification for People Localised or Locally Advanced Prostate Cancer

Bone Scans for Newly Diagnosed Prostate Cancer

• Do not routinely offer isotope bone scans to people with Cambridge Prognostic Group (CPG) 1 or 2 localised prostate cancer.
• Offer isotope bone scans when hormonal therapy is being deferred as part of watchful waiting to asymptomatic people who are at high risk of developing bone complications.

Localised and Locally Advanced Prostate Cancer

• Before radical treatment, explain to people and, if they wish, their partner, that radical treatment for prostate cancer will result in an alteration of sexual experience, and may result in loss of sexual function.
• Explain to people and, if they wish, their partner, about the potential loss of ejaculation and fertility associated with radical treatment for prostate cancer. Offer sperm storage.
• Warn people undergoing radical treatment for prostate cancer of the likely effects of the treatment on their urinary function.
• Offer a urological assessment to people who have troublesome urinary symptoms before treatment.
• People with prostate cancer who are candidates for radical treatment should have the opportunity to discuss the range of treatment modalities and their serious side effects in relation to their treatment options with a specialist surgical oncologist and a specialist clinical oncologist.
• Explain to people that there is a small increase in the risk of colorectal cancer after radical external beam radiotherapy (EBRT) for prostate cancer.

Treatment Options for Localised and Locally Advanced Prostate Cancer

• Please refer to the full guideline for information on the benefits and harms of treatment options.
• 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 (See Multiparametric MRI and protocol for active surveillance, below) for people who choose not to have immediate radical treatment.
• Do not offer active surveillance to people with CPG 4 and 5 localised and locally advanced prostate cancer.
• Offer radical prostatectomy or radical radiotherapy to people with CPG 4 and 5 localised and locally advanced prostate cancer when it is likely the person's cancer can be controlled in the long term.

Multiparametric MRI and Protocol for Active Surveillance

• Offer multiparametric MRI to people having active surveillance who have not had an MRI previously. If the MRI results do not agree with the biopsy findings, offer a new MRI-influenced biopsy.
• Consider using the protocol in table 2 for people who have chosen active surveillance.
• If a person wishes to move from active surveillance to radical treatment at any stage in their care, make a shared decision to do so based on the person's preferences, comorbidities and life expectancy.
• Offer radical treatment to people with localised prostate cancer who had chosen an active surveillance regimen and who now have evidence of disease progression.

Table 2: Protocol for Active Surveillance

Radical Treatment

• Commissioners of urology services should consider providing robotic surgery to treat localised prostate cancer.
• Commissioners should base robotic systems for the surgical treatment of localised prostate cancer in centres that are expected to perform at least 150 robot-assisted laparoscopic radical prostatectomies per year to ensure they are cost effective.
• For people having radical EBRT for localised prostate cancer:
  • offer hypofractionated radiotherapy (60 Gy in 20 fractions) using image-guided intensity modulated radiation therapy (IMRT), unless contraindicated or
  • offer conventional radiotherapy (74 Gy in 37 fractions) to people who cannot have hypofractionated radiotherapy.
• Offer people with localised and locally advanced prostate cancer receiving radical EBRT with curative intent planned treatment techniques that optimise the dose to the tumour while minimising the risks of normal tissue damage.
• 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 6 months of androgen deprivation therapy before, during or after radical EBRT.
• Consider continuing androgen deprivation therapy for up to 3 years for people with CPG 4 and 5 localised or locally advanced prostate cancer, and discuss the benefits and risks of this option with them.
• Consider brachytherapy in combination with EBRT 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.
• Discuss the option of docetaxel chemotherapy with people who have newly diagnosed non-metastatic prostate cancer who:
  • are starting long-term androgen deprivation therapy and
  • have no significant comorbidities and
  • have high-risk disease, as shown by:
    • T3/T4 staging or
    • Gleason score 8 to 10 or
    • PSA greater than 40 microgram/litre.
      Explain the benefits and harms (see box 3) and make a shared decision about whether the person should have this treatment.
      
      In May 2019, this was an off-label use of docetaxel. See NICE's guidance on prescribing medicines for further information.
• For people having docetaxel chemotherapy:
  • start treatment within 12 weeks of starting androgen deprivation therapy
  • use six 3-weekly cycles at a dose of 75 mg/m² (with or without daily prednisolone).
• Do not offer high-intensity focused ultrasound and cryotherapy to people with localised prostate cancer, other than in the context of controlled clinical trials comparing their use with established interventions (please refer to the full guideline for further information).

Watchful Waiting

• People with localised prostate cancer who have chosen watchful waiting and who have evidence of significant disease progression (that is, 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 and who are to receive neoadjuvant hormonal therapy and radical radiotherapy.
• Risk of pelvic node lymph involvement estimated using the Roach formula: %LN risk = 2/3 PSA + (10 × [Gleason score - 6]).
• Do not offer immediate post-operative radiotherapy after radical prostatectomy, even to people with margin-positive disease, other than in the context of a clinical trial.
• Do not offer adjuvant hormonal therapy in addition to radical prostatectomy, even to people with margin-positive disease, other than in the context of a clinical trial.
• Do not offer high-intensity focused ultrasound and cryotherapy to people with locally advanced prostate cancer other than in the context of controlled clinical trials comparing their use with established interventions (please refer to the full guideline for further information).
• Do not offer bisphosphonates for the prevention of bone metastases in people with prostate cancer.

Managing Adverse Effects of Radical Treatment

Sexual Dysfunction

• Offer people who have had radical treatment for prostate cancer access to specialist erectile dysfunction services.
• Offer people with prostate cancer who experience loss of erectile function phosphodiesterase type 5 (PDE5) inhibitors to improve their chance of spontaneous erections.
• If PDE5 inhibitors do not restore erectile function or are contraindicated, offer people vacuum devices, intraurethral inserts or penile injections, or penile prostheses as an alternative.

Urinary Incontinence

• Ensure that people with prostate cancer who have troublesome urinary symptoms after treatment have access to specialist continence services for assessment, diagnosis and conservative treatment. This could include coping strategies, pelvic floor muscle re-education, bladder retraining and pharmacotherapy.
• Refer people with prostate cancer who have intractable stress incontinence to a specialist surgeon for consideration of an artificial urinary sphincter.
• Do not offer injection of bulking agents into the distal urinary sphincter to treat stress incontinence in people with prostate cancer.

Radiation-induced Enteropathy

• Offer people with signs or symptoms of radiation-induced enteropathy care from a team of professionals with expertise in radiation-induced enteropathy (who may include oncologists, gastroenterologists, bowel surgeons, dietitians and specialist nurses).
• Include the nature and treatment of radiation-induced enteropathy in training programmes for oncologists and gastroenterologists.
• Carry out full investigations, including flexible sigmoidoscopy, in people who have symptoms of radiation-induced enteropathy to exclude inflammatory bowel disease or malignancy of the large bowel and to ascertain the nature of the radiation injury. Use caution when performing anterior wall rectal biopsy after brachytherapy because of the risk of fistulation.

Follow Up for People with Localised or Locally Advanced Prostate Cancer Having Radical Treatment or on Watchful Waiting

• A urologist or specialist nurse should discuss the purpose, duration, frequency and location of follow up with each person with localised and locally advanced prostate cancer, and if they wish, their partner or carers.
• A urologist or specialist nurse should advise people with prostate cancer about potential longer-term adverse effects of treatment and when and how to report them.
• Check PSA levels for all people with prostate cancer who are having radical treatment no earlier than 6 weeks after treatment, at least every 6 months for the first 2 years, and then at least once a year after that.
• Do not routinely offer DRE to people with localised prostate cancer who are not on active surveillance while their PSA remains at baseline levels.
• After at least 6 months' initial follow up, consider a remote follow-up strategy for people with a stable PSA who have had no significant treatment complications, unless they are taking part in a clinical trial that needs formal clinic-based follow up.
• Follow up people with prostate cancer who have chosen a watchful waiting regimen with no curative intent in primary care only if protocols for this have been agreed between the local urological cancer MDT and the relevant primary care organisation(s). Measure their PSA at least once a year.

Managing Relapse after Radical Treatment

• Analyse serial PSA levels after radical treatment using the same assay technique as used before.
• Do not offer biopsy of the prostatic bed to people with prostate cancer who have had a radical prostatectomy.
• Only offer biopsy of the prostate after radiotherapy to people with prostate cancer who might have local salvage therapy in the context of a clinical trial.
• For people with evidence of biochemical relapse after radical treatment who are thinking about having radical salvage therapy:
  • do not offer routine MRI scanning before salvage radiotherapy in people with prostate cancer
  • offer an isotope bone scan if symptoms or PSA trends are suggestive of metastases.
• Take into account that biochemical relapse (a rising PSA) alone should not mean an immediate change in treatment is needed.
• Estimate PSA doubling time if biochemical relapse occurs. Base this on a minimum of 3 measurements over at least a 6-month period.
• Offer people with biochemical relapse after radical prostatectomy, with no known metastases, radical radiotherapy to the prostatic bed.
• Consider entry to appropriate clinical trials for people with biochemical relapse.
• Do not routinely offer hormonal therapy to people with prostate cancer who have a biochemical relapse unless they have:
  • symptomatic local disease progression or
  • any proven metastases or
  • a PSA doubling time of less than 3 months.

People Having Hormone Therapy

• Consider intermittent therapy for people having long-term androgen deprivation therapy (not in the adjuvant setting). Discuss with the person (and their partner, family or carers if they wish):
  • the rationale for intermittent therapy
  • the limited evidence for reduction in side effects from intermittent therapy
  • the effect of intermittent therapy on progression of prostate cancer.
• For people who are having intermittent androgen deprivation therapy:
  • measure PSA every 3 months and
  • restart androgen deprivation therapy if PSA is 10 nanogram/ml or above, or if there is symptomatic progression.

Managing Adverse Effects of Hormone Therapy

Hot Flushes

• Offer medroxyprogesterone (20 mg per day), initially for 10 weeks, to manage troublesome hot flushes caused by long-term androgen suppression. Evaluate the effect at the end of the treatment period.

In May 2019, this was an off-label use of medroxyprogesterone. See NICE's guidance on prescribing medicines for further information.

• Consider cyproterone acetate (50 mg twice a day for 4 weeks) to treat troublesome hot flushes if medroxyprogesterone is not effective or not tolerated.
• Tell people that there is no good-quality evidence for the use of complementary therapies to treat troublesome hot flushes.

Sexual Dysfunction

• Before they start androgen deprivation therapy, tell people and, if they wish, their partner, that long-term androgen deprivation will cause a reduction in libido and possible loss of sexual function.
• Advise people and, if they wish, their partner, about the potential loss of ejaculation and fertility associated with long-term androgen deprivation and offer sperm storage.
• Ensure that people starting androgen deprivation therapy have access to specialist erectile dysfunction services.
• Consider referring people who are having long-term androgen deprivation therapy, and their partners, for psychosexual counselling.
• Offer PDE5 inhibitors to people having long-term androgen deprivation therapy who experience loss of erectile function.
• If PDE5 inhibitors fail to restore erectile function or are contraindicated, offer a choice of:
  • intraurethral inserts
  • penile injections
  • penile prostheses
  • vacuum devices.

Osteoporosis

• Do not routinely offer bisphosphonates to prevent osteoporosis in people with prostate cancer having androgen deprivation therapy.
• Consider assessing fracture risk in people with prostate cancer who are having androgen deprivation therapy, in line with the NICE guideline on osteoporosis: assessing the risk of fragility fracture.
• Offer bisphosphonates to people who are having androgen deprivation therapy and have osteoporosis.
• Consider denosumab for people who are having androgen deprivation therapy and have osteoporosis if bisphosphonates are contraindicated or not tolerated.

Gynaecomastia

• For people starting long-term bicalutamide monotherapy (longer than 6 months), offer prophylactic radiotherapy to both breast buds within the first month of treatment. Use a single fraction of 8 Gy using orthovoltage, or electron beam radiotherapy.
• If radiotherapy does not prevent gynaecomastia, consider weekly tamoxifen.

In May 2019, this was an off-label use of tamoxifen. See NICE's guidance on prescribing medicines for further information.

Fatigue

• Tell people who are starting androgen deprivation therapy that fatigue is a recognised side effect of this therapy, and might not be because of their prostate cancer.
• Offer people 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.

Metastatic Prostate Cancer

Information and Support

• Offer people with metastatic prostate cancer tailored information and access to specialist urology and palliative care teams to address their specific needs. Give them the opportunity to discuss any significant changes in their disease status or symptoms as these occur.
• Integrate palliative interventions at any stage into coordinated care, and facilitate any transitions between care settings as smoothly as possible.
• Discuss personal preferences for palliative care as early as possible with people with metastatic prostate cancer, their partners and carers. Tailor treatment/care plans accordingly, and identify the preferred place of care.
• Ensure that palliative care is available when needed and is not limited to the end of life. Care should not be restricted to being associated with hospice care.
• Offer a regular assessment of needs to people with metastatic prostate cancer.

Initial Treatment

• Offer docetaxel chemotherapy to people with newly diagnosed metastatic prostate cancer who do not have significant comorbidities as follows:
  • start treatment within 12 weeks of starting androgen deprivation therapy and
  • use six 3-weekly cycles at a dose of 75 mg/m² (with or without daily prednisolone).

In May 2019, this was an off-label use of docetaxel. See NICE's guidance on prescribing medicines for further information.

• 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 (150 mg).

In May 2019, this was an off-label use of bicalutamide. See NICE's information on prescribing medicines for further information.

• 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.

Hormone-relapsed Metastatic Prostate Cancer

• Please refer to the full guideline for information on bone-targeted and pelvic-targeted therapies.
• Discuss the treatment options for people with prostate cancer who develop biochemical evidence of hormone-relapsed disease at the urological cancer MDT. Seek an oncologist and/or specialist palliative care opinion, as appropriate.
• Docetaxel is recommended, within its licensed indications, as a treatment option for people with hormone-refractory prostate cancer only if their Karnofsky Performance-Status score 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 (0.5 mg daily) 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.
• For advice on treatments for metastatic hormone-relapsed prostate cancer previously treated with docetaxel, including genomic biomarker-based treatment, see the NICE technology appraisal guidance on our topic page on prostate cancer. The point at which to use genomic biomarker-based therapy in solid tumour treatment pathways is uncertain.