Prostate cancer

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

very low-risk disease

life expectancy <10 years

1st line – observation

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1st line –

observation

For very low-risk disease, the following criteria must be met: cT1c tumour, Grade Group 1, prostate-specific antigen (PSA) <10 micrograms/L (<10 nanograms/mL), <3 prostate biopsy fragments/cores positive, ≤50% cancer in each fragment/core, and PSA density <0.15 micrograms/L/g (<0.15 nanograms/mL/g).[3]

The treatment option for patients with very low-risk disease and a life expectancy <10 years is observation. This involves monitoring the course of the disease with a view to delivering treatment or palliative therapy when symptoms arise or when there is a change in clinical findings that suggest symptoms are imminent.

Observation should include a history and physical examination no more often than every 12 months (without prostate biopsies).[145] If patients become symptomatic, assessment should be performed (including prostate-specific antigen [PSA] and PSA doubling time, life expectancy estimate, and quality-of-life measures) to determine need for, and consideration of, treatment or palliation.[3]

2nd line – androgen deprivation therapy alone (if symptomatic and life expectancy ≤5 years)

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2nd line –

androgen deprivation therapy alone (if symptomatic and life expectancy ≤5 years)

Patients with life expectancy ≤5 years who become symptomatic during observation can receive androgen deprivation therapy alone for palliation (e.g., a luteinising hormone-releasing hormone agonist or antagonist).[3]

See local specialist protocol for dosing guidelines.

Primary options

leuprorelin

goserelin

degarelix

relugolix

Consider – supportive care

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Denosumab (a fully human monoclonal antibody that inhibits RANK ligand) and the bisphosphonates zoledronic acid and alendronic acid are recommended to reduce the risk of bone fractures in patients with non-metastatic disease if they are receiving ADT and have osteoporosis (e.g., T score -2.5 on dual-energy x-ray absorptiometry [DXA] scan) or an increased risk of fractures (e.g., ≥20% for 10-year risk of major osteoporotic fractures, or ≥3% for 10-year risk of hip fractures, based on FRAX® [Fracture Risk Assessment Tool]).[3][360][361] University of Sheffield: FRAX tool Opens in new window

In January 2024, the US Food and Drug Administration (FDA) warned of an increased risk of severe hypocalcaemia in patients with advanced chronic kidney disease who are receiving denosumab (Prolia® 60 mg/mL approved for treatment to increase bone mass in men at high risk for fracture receiving ADT for non-metastatic prostate cancer).[366] Two safety studies showed a significant increase in the risk of severe hypocalcaemia in patients treated with denosumab compared with those treated with bisphosphonates, with the highest risk reported in patients with advanced kidney disease, particularly those on dialysis. Severe hypocalcaemia was more common in those with mineral and bone disorder. Patients with advanced chronic kidney disease taking denosumab are at risk of serious outcomes from severe hypocalcaemia, including hospitalisation and death.

Before prescribing denosumab, healthcare professionals should assess kidney function and calcium levels, and consider other treatment options for patients at risk. During treatment, frequent monitoring and prompt management of hypocalcaemia are essential. The FDA has not issued a warning with respect to the brand of denosumab approved specifically for the prevention of skeletal-related adverse events in malignancy (Xgeva® 120 mg/1.7 mL).

life expectancy ≥10 years

1st line – active surveillance

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1st line –

active surveillance

If life expectancy is ≥10 years, active surveillance is recommended.[3]

Active surveillance involves monitoring the course of the disease (with additional use of prostate biopsies) until symptoms or signs of disease become clinically evident with the expectation to treat with definitive treatment if there is disease progression.

PSA level and digital rectal examination are checked no more often than every 6 and 12 months, respectively, unless clinically indicated.[3][145]

Repeat prostate biopsy and repeat multiparametric magnetic resonance imaging (MRI) are carried out no more often than every 12 months unless clinically indicated.[3] Intensity of active surveillance may be individualised based on patient and tumour factors, risk of progression, and life expectancy. However, most patients should have repeat biopsies every 2-5 years.

Confirmatory testing is recommended before starting active surveillance (within 6-12 months of diagnosis) if prebiopsy multiparametric MRI was not performed prior to diagnostic biopsy.[146] The role of confirmatory testing is to identify those at high risk for future disease upgrading or progression, and to ensure appropriate patients are selected for active surveillance.[146]

Confirmatory testing for active surveillance involves performing a multiparametric MRI (with PSA density calculation), if available, and/or biopsy (systematic and targeted), and/or molecular tumour analysis.[3][102][147] All patients should have a confirmatory prostate biopsy within 1-2 years of initial diagnostic biopsy.[3]

low-risk disease

life expectancy <10 years

1st line – observation

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1st line –

observation

For low-risk disease, patients have all of the following and do not qualify for very low-risk disease: cT1-cT2a tumour, Grade Group 1, and prostate-specific antigen (PSA) <10 micrograms/L (<10 nanograms/mL).[3]

The treatment option for patients with low-risk disease and life expectancy <10 years is observation. This involves monitoring the course of the disease with a view to delivering treatment or palliative therapy when symptoms arise, or when there is a change in clinical findings that suggest symptoms are imminent.[3]

2nd line – androgen deprivation therapy alone (if symptomatic and life expectancy ≤5 years)

Back

2nd line –

androgen deprivation therapy alone (if symptomatic and life expectancy ≤5 years)

See local specialist protocol for dosing guidelines.

Primary options

leuprorelin

goserelin

degarelix

relugolix

Consider – supportive care

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

life expectancy ≥10 years

1st line – active surveillance

Back

1st line –

active surveillance

Patients with low-risk disease and life expectancy ≥10 years can delay definitive treatments (e.g., external beam radiotherapy, brachytherapy, or radical prostatectomy) and undergo active surveillance instead, depending on the patient's wish to avoid treatment-related adverse effects.[166][167][168]

PSA level and digital rectal examination are checked no more often than every 6 and 12 months, respectively, unless clinically indicated.[3][145]

Active surveillance is the preferred approach for most patients with low-risk disease if life expectancy is ≥10 years, but is often under-utilised due to patient preference and lack of adherence.[178][179] Use of standardised patient information, clinician education, and guidelines may improve uptake of and adherence to active surveillance.[178] Decisions about starting treatment should take into account factors that may increase the likelihood of regrading, including high PSA density, ≥3 positive cores, high genomic risk, and/or a known BRCA2 germline mutation.[3]

1st line – brachytherapy

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1st line –

brachytherapy

Brachytherapy is a treatment option for patients with low-risk disease and life expectancy ≥10 years.

Brachytherapy is a definitive treatment. The treatment goal is cure.

Brachytherapy is given as low-dose rate or as high-dose rate.

Low-dose rate brachytherapy involves the permanent transperineal implantation of radioactive sources into the prostate without any incision. The highest radiation dose is confined to the prostate and a small volume of surrounding tissue. The strength of radiation decreases over time, but low levels of radioactivity in the prostate will persist for 4-6 months depending on the half-life of the isotope used. Precautions should be taken in the short term to minimise close contact with pregnant women and small children.

High-dose rate brachytherapy involves the transperineal placement of treatment catheters through which an individual radioactive source is robotically placed temporarily at various dwell positions to achieve a conformal dose of radiation to the prostate. At the end of treatment the catheters are removed. Treatment is repeated up to five times to achieve a curative dose to the prostate.

1st line – external beam radiotherapy

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1st line –

external beam radiotherapy

External beam radiotherapy (EBRT) is a treatment option for patients with low-risk disease and life expectancy ≥10 years.

EBRT is a definitive treatment. The treatment goal is cure.

Conventional fractionated EBRT typically employs daily doses of 1.8 to 2 Gy for 7-9 weeks (excluding weekends) to a total dose of 75.6 to 80 Gy. However, data suggest that hypofractionation (i.e., shorter treatment courses over 4-6 weeks using larger daily doses [>2-4 Gy], but smaller total doses [56-72 Gy]) may yield equivalent results to conventional fractionation.[151][152] [ ]

Hypofractionation is now the preferred approach.[153] Although it shortens treatment duration, it may slightly increase the risk of acute gastrointestinal adverse effects compared with conventional fractionation.[151]

Ultra-hypofractionation may be considered for patients with localised disease, low metastatic burden disease, or oligometastatic disease.[153][154][155][156][157][158][159][160] A commonly used dosing schedule for ultra-hypofractionation is 7.25 Gy given every other day for 2 weeks (excluding weekends) to a total dose of 36.25 Gy.[153] Other ultra-hypofractionation schedules ranging from 4-9 fractions of 5-10 Gy to a total dose of 36.25 to 50 Gy have been reported.[154] Studies suggest comparable biochemical control and toxicity with ultra-hypofractionation versus more protracted fractionation schedules, but higher total doses are associated with a greater risk of severe late genitourinary complications.[154]

Intensity-modulated radiotherapy and image-guided radiotherapy are the standard EBRT techniques because they allow for a highly conformal delivery of radiation that minimises dose to normal tissues (bladder, rectum, and small bowel), thereby potentially decreasing toxicity to these structures. Stereotactic body radiotherapy is the technique used to deliver ultra-hypofractionated radiotherapy.

Biocompatible and biodegradable perirectal spacer materials can be implanted between the prostate and rectum in patients with organ-confined disease to reduce toxicity to the rectum.[3][149][150]

Patients with significant baseline urinary symptoms may not be suitable for EBRT due to increased risk of urinary obstruction.

1st line – radical prostatectomy

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1st line –

radical prostatectomy

Radical prostatectomy is a treatment option for patients with low-risk disease and life expectancy ≥10 years (depending on patient preference and suitability for surgery).

Radical prostatectomy is a definitive treatment. The treatment goal is cure.

Classically, the prostate and prostatic capsule are removed by excision of the urethra at the prostatomembranous junction. The seminal vesicles, ampulla, and vas deferens are also removed. Of the two classic open surgical approaches (retropubic/suprapubic and perineal), the retropubic/suprapubic approach is preferred by many urologists, as this approach facilitates access for pelvic lymph node dissection.

Laparoscopic and robotic-assisted radical prostatectomy are alternative approaches that typically involve five or six small incisions in the abdomen from which the entire prostate is removed, theoretically sparing nerves more easily damaged by a retropubic/suprapubic approach.[162][163] A Cochrane review found that laparoscopic or robotic-assisted radical prostatectomy may result in shorter hospital stays and fewer blood transfusions compared with open surgical radical prostatectomy, but improvements in oncological outcomes (e.g., recurrence or survival) were inconclusive.[164] Complications (e.g., sexual and urinary dysfunction) appear to be similar between these alternative approaches and the open surgical approach.[164][165]

Radical prostatectomy in men with clinically localised prostate cancer that was not detected through PSA screening improves prostate cancer-specific mortality, overall survival, and risk of local disease progression and metastasis, compared with active surveillance.[166][167] These benefits have been shown to continue over the long-term, particularly in those aged ≤65 years.[168][169]

Radical prostatectomy in men with PSA-detected localised prostate cancer does not significantly reduce all-cause mortality or prostate cancer-specific mortality compared with active surveillance or observation.[170][171][172][173] Furthermore, radical prostatectomy is associated with a higher frequency of adverse events than active surveillance and observation.[170][171][172][173][174] [ ]

favourable intermediate-risk disease

life expectancy <10 years

1st line – observation

Back

1st line –

observation

For favourable intermediate-risk disease, patients have no high-risk or very high-risk features and all of the following: one intermediate risk factor (cT2b-c tumour; Grade Group 2; or prostate-specific antigen [PSA] 10-20 micrograms/L [10-20 nanograms/mL]), Grade Group 1 (if not Grade Group 2), and percentage of positive biopsy cores <50%.[3]

Patients with favourable intermediate-risk disease and life expectancy <10 years can delay definitive treatments (e.g., brachytherapy or external beam radiotherapy) and undergo observation instead, depending on the patient's wish to avoid treatment-related adverse effects (e.g., gastrointestinal and genitourinary toxicity).[182][183][184][185]

Observation involves monitoring the course of the disease with a view to delivering treatment or palliative therapy when symptoms arise or when there is a change in clinical findings that suggest symptoms are imminent.[3]

2nd line – androgen deprivation therapy alone (if symptomatic and life expectancy ≤5 years)

Back

2nd line –

androgen deprivation therapy alone (if symptomatic and life expectancy ≤5 years)

See local specialist protocol for dosing guidelines.

Primary options

leuprorelin

goserelin

degarelix

relugolix

Consider – supportive care

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

2nd line – brachytherapy (if life expectancy 5-10 years)

Back

2nd line –

brachytherapy (if life expectancy 5-10 years)

Brachytherapy is a treatment option for patients with favourable intermediate-risk disease and life expectancy 5-10 years (i.e., instead of observation).

Brachytherapy is a definitive treatment. The treatment goal is cure.

Brachytherapy is given as low-dose rate or as high-dose rate.

2nd line – external beam radiotherapy (if life expectancy 5-10 years)

Back

2nd line –

external beam radiotherapy (if life expectancy 5-10 years)

External beam radiotherapy (EBRT) is a treatment option for patients with favourable intermediate-risk disease and life expectancy 5-10 years (i.e., instead of observation).

EBRT is a definitive treatment. The treatment goal is cure.

Biocompatible and biodegradable perirectal spacer materials can be implanted between the prostate and rectum in patients with organ-confined disease to reduce toxicity to the rectum.[3][149][150]

Patients with significant baseline urinary symptoms may not be suitable for EBRT due to increased risk of urinary obstruction.

life expectancy ≥10 years

1st line – active surveillance

Back

1st line –

active surveillance

There is no standard approach to managing patients with intermediate-risk disease. Few randomised trials have compared effectiveness between primary treatments.[180] Adverse effects of treatment may influence treatment choice.[182][183][184][185] Worse urinary incontinence and sexual/erectile dysfunction have been reported in patients who had radical prostatectomy compared with other treatments.[186][187][188][189] Brachytherapy may be associated with worse short-term urinary obstruction and irritation, and external beam radiotherapy (EBRT) with worse bowel function and short-term bowel symptoms.[187][189][190]

Patients with favourable intermediate-risk disease and life expectancy ≥10 years may delay definitive treatments (e.g., brachytherapy, EBRT, or radical prostatectomy) and undergo active surveillance instead, depending on the patient's wish to avoid treatment-related adverse effects.[166][167][168][182][183][184][185]

PSA level and digital rectal examination are checked no more often than every 6 and 12 months unless clinically indicated.[3][145]

1st line – brachytherapy

Back

1st line –

brachytherapy

Brachytherapy is a treatment option for patients with favourable intermediate-risk disease and life expectancy ≥10 years.

Brachytherapy is a definitive treatment. The treatment goal is cure.

Brachytherapy is given as low-dose rate or as high-dose rate.

1st line – external beam radiotherapy

Back

1st line –

external beam radiotherapy

External beam radiotherapy (EBRT) is a treatment option for patients with favourable intermediate-risk disease and life expectancy ≥10 years.

EBRT is a definitive treatment. The treatment goal is cure.

Biocompatible and biodegradable perirectal spacer materials can be implanted between the prostate and rectum in patients with organ-confined disease to reduce toxicity to the rectum.[3][149][150]

Patients with significant baseline urinary symptoms may not be suitable for EBRT due to increased risk of urinary obstruction.

Prophylactic pelvic nodal irradiation may be considered in patients with intermediate-risk disease who are undergoing radiotherapy, but only if further risk assessment (e.g., nomograms, biomarker testing) indicates aggressive disease.[3]

1st line – radical prostatectomy ± lymph node dissection

Back

1st line –

radical prostatectomy ± lymph node dissection

Radical prostatectomy is a treatment option for patients with favourable intermediate-risk disease and life expectancy ≥10 years (depending on patient preference and suitability for surgery). Pelvic lymph node dissection may be carried out (depending on nomogram assessment).

Radical prostatectomy is a definitive treatment. The treatment goal is cure.

Radical prostatectomy in men with PSA-detected localised prostate cancer does not significantly reduce all-cause mortality or prostate cancer-specific mortality, compared with active surveillance or observation.[170][171][172][173] Furthermore, radical prostatectomy is associated with a higher frequency of adverse events than active surveillance and observation.[170][171][172][173][174] [ ]

unfavourable intermediate-risk disease

life expectancy ≤5 years

1st line – observation

Back

1st line –

observation

For unfavourable intermediate-risk disease, patients have no high-risk or very high-risk features and one or more of the following: two or three intermediate risk factors (cT2b-c tumour; Grade Group 2 or 3; and/or prostate-specific antigen [PSA] 10-20 micrograms/L [10-20 nanograms/mL]); and/or Grade Group 3 alone; and/or percentage of positive biopsy cores ≥50%.[3]

The treatment option for patients with unfavourable intermediate-risk disease and life expectancy ≤5 years is observation.

2nd line – androgen deprivation therapy alone (if symptomatic)

Back

2nd line –

androgen deprivation therapy alone (if symptomatic)

See local specialist protocol for dosing guidelines.

Primary options

leuprorelin

goserelin

degarelix

relugolix

Consider – supportive care

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

life expectancy 5-10 years

1st line – observation

Back

1st line –

observation

For unfavourable intermediate-risk disease, patients have no high-risk or very high-risk features and one or more of the following: two or three intermediate risk factors (cT2b-c tumour; Grade Group 2 or 3; and/or prostate-specific antigen [PSA] 10-20 micrograms/L [10-20 nanograms/mL]), and/or Grade Group 3 alone, and/or percentage of positive biopsy cores ≥50%.[3]

There is no standard approach to managing patients with intermediate-risk disease. Few randomised trials have compared effectiveness between primary treatments.[180] Adverse effects of treatment may influence treatment choice.[182][183][184][185] Brachytherapy may be associated with worse short-term urinary obstruction and irritation, and external beam radiotherapy (EBRT) with worse bowel function and short-term bowel symptoms.[187][189][190]

Patients with unfavourable intermediate-risk disease and life expectancy 5-10 years can delay definitive treatments (e.g., EBRT or brachytherapy) and undergo observation instead, depending on the patient's wish to avoid treatment-related adverse effects.[182][183][184][185]

1st line – external beam radiotherapy ± brachytherapy boost

Back

1st line –

external beam radiotherapy ± brachytherapy boost

For unfavourable intermediate-risk disease, patients have no high-risk or very high-risk features and one or more of the following: two or three intermediate risk factors (cT2b-c tumour; Grade Group 2 or 3; and/or prostate-specific antigen [PSA] 10-20 micrograms/L [10-20 nanograms/mL]), and/or Grade Group 3 alone, and/or percentage of positive biopsy cores ≥50%.[3]

External beam radiotherapy (EBRT) with or without brachytherapy boost plus androgen deprivation therapy (ADT) is a treatment option for patients with unfavourable intermediate-risk disease and life expectancy 5-10 years.

EBRT and brachytherapy are definitive treatments. The treatment goal is cure.

Biocompatible and biodegradable perirectal spacer materials can be implanted between the prostate and rectum in patients with organ-confined disease to reduce toxicity to the rectum.[3][149][150]

Patients with significant baseline urinary symptoms may not be suitable for EBRT due to increased risk of urinary obstruction.

Brachytherapy boost may be added to EBRT using either the low-dose rate or high-dose rate approach, if there is concern about the ability to achieve local control with EBRT.[377]

High-dose rate brachytherapy involves the transperineal placement of treatment catheters through which an individual radioactive source is robotically placed temporarily at various dwell positions to achieve a conformal dose of radiation to the prostate. At the end of treatment, the catheters are removed. Treatment is repeated up to five times to achieve a curative dose to the prostate.

High-dose radiation to the prostate and periprostatic tissue is recommended for patients who are candidates for radiotherapy plus ADT.[201][202][203][204][205]

Prophylactic pelvic nodal irradiation may also be considered in highly selected patients with intermediate-risk disease who are undergoing radiotherapy, but only if further risk assessment (e.g., nomograms, biomarker testing) indicates aggressive disease.[3][206]

Plus – androgen deprivation therapy

Back

Plus –

androgen deprivation therapy

Treatment recommended for ALL patients in selected patient group

Androgen deprivation therapy (ADT) (e.g., a luteinising hormone-releasing hormone agonist or antagonist) may be given before, during, and/or after EBRT, for a total of 4-6 months.[3] ADT greater than 6 months duration is not recommended in patients with intermediate-risk disease.[191][192]

ADT may have multiple synergistic effects when combined with radiotherapy, and is associated with significant clinical benefit.[193][194][195][196][197][198][199][200]

See local specialist protocol for dosing guidelines.

Primary options

leuprorelin

goserelin

degarelix

relugolix

Consider – supportive care

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

life expectancy >10 years

1st line – external beam radiotherapy ± brachytherapy boost

Back

1st line –

external beam radiotherapy ± brachytherapy boost

For unfavourable intermediate-risk disease, patients have no high-risk or very high-risk features and one or more of the following: two or three intermediate risk factors (cT2b-c tumour; Grade Group 2 or 3; and/or prostate-specific antigen [PSA] 10-20 micrograms/L [10-20 nanograms/mL]), and/or Grade Group 3 alone, and/or percentage of positive biopsy cores ≥50%.[3]

EBRT and brachytherapy are definitive treatments. The treatment goal is cure.

Biocompatible and biodegradable perirectal spacer materials can be implanted between the prostate and rectum in patients with organ-confined disease to reduce toxicity to the rectum.[3][149][150]

Patients with significant baseline urinary symptoms may not be suitable for EBRT due to increased risk of urinary obstruction.

Brachytherapy boost may be added to EBRT, using either the low-dose rate or high-dose rate approach, if there is concern about the ability to achieve local control with EBRT.[377]

High-dose rate brachytherapy involves the transperineal placement of treatment catheters through which an individual radioactive source is robotically placed temporarily at various dwell positions to achieve a conformal dose of radiation to the prostate. At the end of treatment, the catheters are removed. Treatment is repeated up to five times to achieve a curative dose to the prostate.

High-dose radiation to the prostate and periprostatic tissue is recommended for patients who are candidates for radiotherapy plus ADT.[201][202][203][204][205]

Prophylactic pelvic nodal irradiation may also be considered in patients with intermediate-risk disease who are undergoing radiotherapy, but only if further risk assessment (e.g., nomograms, biomarker testing) indicates aggressive disease.[3][206]

Plus – androgen deprivation therapy

Back

Plus –

androgen deprivation therapy

Treatment recommended for ALL patients in selected patient group

ADT may have multiple synergistic effects when combined with radiotherapy, and is associated with significant clinical benefit.[193][194][195][196][197][198][199][200]

See local specialist protocol for dosing guidelines.

Primary options

leuprorelin

goserelin

degarelix

relugolix

Consider – supportive care

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

1st line – radical prostatectomy + lymph node dissection

Back

1st line –

radical prostatectomy + lymph node dissection

For unfavourable intermediate-risk disease, patients have no high-risk or very high-risk features and one or more of the following: two or three intermediate risk factors (cT2b-c tumour; Grade Group 2 or 3; and/or prostate-specific antigen [PSA] 10-20 micrograms/L [10-20 nanograms/mL]), and/or Grade Group 3 alone, and/or percentage of positive biopsy cores ≥50%.[3]

Radical prostatectomy is a treatment option for patients with unfavourable intermediate-risk disease and life expectancy >10 years (depending on patient preference and suitability for surgery). Pelvic lymph node dissection is also recommended.

Radical prostatectomy is a definitive treatment. The treatment goal is cure.

high-risk or very high-risk disease

asymptomatic and life expectancy ≤5 years

1st line – observation

Back

1st line –

observation

For high-risk disease, patients have no very high-risk features and one of the following high-risk features: cT3a tumour; Grade Group 4 or 5; or prostate-specific antigen (PSA) >20 micrograms/L (>20 nanograms/mL).[3]

For very high-risk (locally advanced) disease, patients have at least one of the following: cT3b-cT4 tumour; primary Gleason pattern 5; ≥2 high-risk features; or >4 cores with Grade Group 4 or 5.[3]

Observation is the usual approach for asymptomatic high-risk and very high-risk patients with life expectancy ≤5 years.[3] However, androgen deprivation therapy or external beam radiotherapy may be considered if symptoms or complications (e.g., hydronephrosis) of untreated disease or metastases are expected within 5 years.

Observation involves monitoring the course of the disease with a view to delivering treatment or palliative therapy when symptoms aris, or when there is a change in clinical findings that suggest symptoms are imminent.[3]

2nd line – androgen deprivation therapy alone

Back

2nd line –

androgen deprivation therapy alone

Androgen deprivation therapy (ADT) alone (e.g., a luteinising hormone-releasing hormone agonist or antagonist) can be considered instead of observation in asymptomatic high-risk and very high-risk patients with life expectancy ≤5 years if symptoms or complications (e.g., hydronephrosis) of untreated disease or metastases are expected within 5 years.[3]

ADT on an intermittent rather than a continuous basis may be considered, although whether this approach has a positive impact on quality of life is controversial.[227][228][229]

See local specialist protocol for dosing guidelines.

Primary options

leuprorelin

goserelin

degarelix

relugolix

Consider – supportive care

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

2nd line – external beam radiotherapy

Back

2nd line –

external beam radiotherapy

External beam radiotherapy (EBRT) can be considered instead of observation in asymptomatic high-risk and very high-risk patients with life expectancy ≤5 years if symptoms or complications (e.g., hydronephrosis) of untreated disease or metastases are expected within 5 years.[3]

EBRT is a definitive treatment. The treatment goal is cure.

Prophylactic pelvic nodal irradiation should also be considered in patients with high-risk or very high-risk disease who are undergoing radiotherapy.[3][206]

Biocompatible and biodegradable perirectal spacer materials can be implanted between the prostate and rectum in patients with organ-confined disease to reduce toxicity to the rectum.[3][149][150]

Patients with significant baseline urinary symptoms may not be suitable for EBRT due to increased risk of urinary obstruction.

symptomatic or life expectancy >5 years

1st line – external beam radiotherapy ± brachytherapy boost

Back

1st line –

external beam radiotherapy ± brachytherapy boost

External beam radiotherapy (EBRT) with or without brachytherapy boost plus androgen deprivation therapy (ADT) is a treatment option for patients with high-risk or very high-risk disease who are symptomatic or have a life expectancy >5 years.

EBRT and brachytherapy are definitive treatments. The treatment goal is cure.

Biocompatible and biodegradable perirectal spacer materials can be implanted between the prostate and rectum in patients with organ-confined disease to reduce toxicity to the rectum.[3][149][150]

Patients with significant baseline urinary symptoms may not be good candidates for EBRT due to increased risk of urinary obstruction.

Brachytherapy boost may be added to EBRT, using either the low-dose rate or high-dose rate approach, if there is concern about the ability to achieve local control with EBRT.[377]

The addition of brachytherapy boost to EBRT (with or without ADT) may provide superior disease control compared with EBRT plus ADT for patients with high-risk or very high-risk disease.[224][225][226]

High-dose rate brachytherapy involves the transperineal placement of treatment catheters through which an individual radioactive source is robotically placed temporarily at various dwell positions to achieve a conformal dose of radiation to the prostate. At the end of treatment, the catheters are removed. Treatment is repeated up to five times to achieve a curative dose to the prostate.

High-dose radiation to the prostate and periprostatic tissue is recommended for patients who are candidates for radiotherapy plus ADT.[201][202][203][204][205]

Prophylactic pelvic nodal irradiation should also be considered in patients with high-risk or very high-risk disease who are undergoing radiotherapy.[3][206]

Plus – androgen deprivation therapy

Back

Plus –

androgen deprivation therapy

Treatment recommended for ALL patients in selected patient group

Androgen deprivation therapy (ADT) (e.g., a luteinising hormone-releasing hormone agonist or antagonist) may be given before, during, and/or after initiation of EBRT, for a total of 1.5 to 3 years.[207][208][209][210][211][212][213][214]

The optimal duration of ADT for these patients remains controversial.[215] A significant improvement in disease-free survival is demonstrated for a longer duration of ADT in patients with high-risk disease.[209][215][216][217]

Use of combined radiotherapy with ADT significantly increases some treatment-related symptoms (e.g., pain with urination and overall urinary and bowel bother), although none are serious. However, given the substantial survival benefit of combined treatment, the increased risk of symptoms seems acceptable and has little extra effect on quality of life after 4 years compared with ADT alone.[218][219][220][221][222][223]

See local specialist protocol for dosing guidelines.

Primary options

leuprorelin

goserelin

degarelix

relugolix

Consider – supportive care

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

1st line – external beam radiotherapy ± brachytherapy boost

Back

1st line –

external beam radiotherapy ± brachytherapy boost

External beam radiotherapy (EBRT) with or without brachytherapy boost combined with 2 years of androgen deprivation therapy (ADT) and abiraterone is recommended for selected patients with very high-risk (non-metastatic) disease (e.g., those with two or more of the following features: cT3 or cT4 tumour, PSA ≥40, and Grade Group 4 or 5).[3]

EBRT and brachytherapy are definitive treatments. The treatment goal is cure.

Conventional fractionated EBRT typically employs daily doses of 1.8 to 2.0 Gy for 7-9 weeks (excluding weekends) to a total dose of 75.6 to 80.0 Gy. However, data suggest that hypofractionation (i.e., shorter treatment courses over 4-6 weeks using larger daily doses [>2-4 Gy], but smaller total doses [56-72 Gy]) may yield equivalent results to conventional fractionation.[151][152] [ ]

Ultra-hypofractionation may be considered for patients with localised disease, low metastatic burden disease, or oligometastatic disease.[153][154][155][156][157][158][159][160] A commonly used dosing schedule for ultra-hypofractionation is 7.25 Gy given every other day for 2 weeks (excluding weekends) to a total dose of 36.25 Gy.[153] Other ultra-hypofractionation schedules ranging from 4-9 fractions of 5-10 Gy to a total dose of 36.25 to 50.00 Gy have been reported.[154] Studies suggest comparable biochemical control and toxicity with ultra-hypofractionation versus more protracted fractionation schedules, but higher total doses are associated with a greater risk of severe late genitourinary complications.[154]

Biocompatible and biodegradable perirectal spacer materials can be implanted between the prostate and rectum in patients with organ-confined disease to reduce toxicity to the rectum.[3][149][150]

Patients with significant baseline urinary symptoms may not be good candidates for EBRT due to increased risk of urinary obstruction.

Brachytherapy boost may be added to EBRT, using either the low-dose rate or high-dose rate approach, if there is concern about the ability to achieve local control with EBRT.[377]

High-dose rate brachytherapy involves the transperineal placement of treatment catheters through which an individual radioactive source is robotically placed temporarily at various dwell positions to achieve a conformal dose of radiation to the prostate. At the end of treatment, the catheters are removed. Treatment is repeated up to five times to achieve a curative dose to the prostate.

High-dose radiation to the prostate and periprostatic tissue is recommended for patients who are candidates for radiotherapy plus ADT.[201][202][203][204][205]

Prophylactic pelvic nodal irradiation should also be considered in patients with high-risk or very high-risk disease who are undergoing radiotherapy.[3][206]

Plus – androgen deprivation therapy + abiraterone (for very high-risk disease)

Back

Plus –

androgen deprivation therapy + abiraterone (for very high-risk disease)

Treatment recommended for ALL patients in selected patient group

Androgen deprivation therapy (ADT) (e.g., a luteinising hormone-releasing hormone [LHRH] agonist or antagonist) may be given before, during, and/or after initiation of EBRT, for a total of 1.5 to 3 years.[207][208][209][210][211][212][213][214]

Abiraterone (a second-generation anti-androgen) is approved for use in metastatic disease. However, off-label use in combination with EBRT and 2 years of ADT (e.g., an LHRH agonist or antagonist) is recommended for selected patients with very high-risk (non-metastatic) disease (e.g., those with two or more of the following features: cT3 or cT4 tumour, PSA ≥40, and Grade Group 4 or 5).[3][230][231]

Abiraterone should not be used concurrently with another anti-androgen (e.g., nilutamide, bicalutamide, flutamide), and it should always be given with prednisolone or methylprednisolone (depending on the formulation of abiraterone).

The addition of abiraterone to primary ADT has been shown to improve overall and failure-free survival in a randomised study of men with locally advanced prostate cancer (radiotherapy was required if node negative, and encouraged if node positive) or metastatic disease.[230] Overall survival data for the subgroup of patients with non-metastatic disease at randomisation are immature.[230] However, there are data showing improved metastasis-free survival in this subgroup.[232]

See local specialist protocol for dosing guidelines.

Primary options

leuprorelin

goserelin

degarelix

relugolix

-- AND --

abiraterone acetate

Consider – supportive care

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

1st line – radical prostatectomy + pelvic lymph node dissection (for fit patients without tumour fixation to the pelvic musculature or skeleton)

Back

1st line –

radical prostatectomy + pelvic lymph node dissection (for fit patients without tumour fixation to the pelvic musculature or skeleton)

Radical prostatectomy with pelvic lymph node dissection is a treatment option for highly selected patients with high-risk or very high-risk disease who are symptomatic or have a life expectancy >5 years (e.g., fit patients without tumour fixation to the pelvic musculature or skeleton), depending on patient preference and suitability for surgery.[3]

Radical prostatectomy is a definitive treatment. The treatment goal is cure.

2nd line – androgen deprivation therapy alone (for patients unsuitable for surgery or radiotherapy)

Back

2nd line –

androgen deprivation therapy alone (for patients unsuitable for surgery or radiotherapy)

Where possible, patients with high-risk or very high-risk disease should receive definitive treatment.[219] However, androgen deprivation therapy (ADT) alone (e.g., a luteinising hormone-releasing hormone agonist or antagonist) may be an option for patients who are unsuitable for definitive treatment due to medical comorbidities (e.g., inflammatory bowel disease or prior pelvic irradiation).[222]

ADT alone is not curative, but it may slow progression and help control symptoms.

ADT on an intermittent rather than a continuous basis may be considered, although whether this approach has a positive impact on quality of life is controversial.[227][228][229]

See local specialist protocol for dosing guidelines.

Primary options

leuprorelin

goserelin

degarelix

relugolix

Consider – supportive care

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

ONGOING

non-metastatic disease: post-radical prostatectomy

with adverse pathological features or detectable PSA and no positive lymph nodes

1st line – monitoring with early salvage external beam radiotherapy

Back

1st line –

monitoring with early salvage external beam radiotherapy

For patients with life expectancy >5 years with adverse pathological or laboratory features (e.g., positive margins, extracapsular extension [pT3 disease], seminal vesicle invasion, or a detectable prostate-specific antigen [PSA]) and no lymph node metastases after radical prostatectomy, options include monitoring with consideration of early salvage external beam radiotherapy (EBRT) for a detectable, rising PSA level or a PSA >0.1 micrograms/L (>0.1 nanograms/mL) (before PSA reaches 0.5 micrograms/L [0.5 nanograms/mL]).[3]

Risk assessment (including use of nomograms) should be carried out to inform decision-making in these patients. The Decipher molecular assay may also be considered to guide decision-making discussions, along with clinical and pathological information, PSA level, and PSA doubling time.[3][234][235][236] Shared decisions about treatment should be based on assessment of potential benefits and harms.[3][146]

Monitoring, with early salvage EBRT performed only when PSA failure is detected, reduces overtreatment with radiotherapy (and associated adverse events) compared with immediate adjuvant EBRT. Monitoring is the preferred option, unless the patient has positive nodes or multiple high-risk features.[3]

Randomised controlled trials have shown that early salvage EBRT results in similar biochemical control and event-free survival rates, and lower genitourinary toxicity, compared with immediate adjuvant EBRT.[239][240][241][242] Systematic reviews of preliminary data support a role for early salvage therapy post-prostatectomy; one review recommends reserving this approach for carefully selected patients with favourable characteristics.[242][243]

PSA failure after radical prostatectomy has no single accepted definition. The American Urological Association defines biochemical recurrence in the post-prostatectomy setting as a rise in PSA ≥0.2 micrograms/L (≥0.2 nanograms/mL) and a confirmatory value of >0.2 micrograms/L (>0.2 nanograms/mL).[233][244] The National Comprehensive Cancer Network defines post-prostatectomy PSA recurrence as undetectable post-prostatectomy PSA with a subsequent detectable PSA that increases on two or more measurements or increases to PSA >0.1 micrograms/L (>0.1 nanograms/mL).[3] Patients receiving early salvage EBRT at lower PSA levels (≥0.1 to 0.2 micrograms/L [≥0.1 to 0.2 nanograms/mL]) have demonstrated better outcomes compared with those receiving salvage EBRT at higher PSA levels.[233][245]

Observation is recommended instead of salvage therapy in patients with life expectancy ≤5 years.[3][238]

1st line – adjuvant external beam radiotherapy

Back

1st line –

adjuvant external beam radiotherapy

For patients with life expectancy >5 years with adverse pathological or laboratory features (e.g., positive margins, extracapsular extension [pT3 disease], seminal vesicle invasion, or a detectable prostate-specific antigen [PSA]) and no lymph node metastases after radical prostatectomy, options include adjuvant external beam radiotherapy (EBRT) with or without androgen deprivation therapy (ADT).[3]

Risk assessment (including use of nomograms) should be carried out to inform adjuvant therapy decisions in these patients.[234][235][236] The Decipher molecular assay may also be considered to guide decision-making discussions, along with clinical and pathological information, PSA level, and PSA doubling time.[3][234][235][236][237] Shared decisions about treatment should be based on assessment of potential benefits and harms.[3][238]

Adjuvant EBRT has been shown to improve progression-free survival, metastasis-free survival, and overall survival in patients with adverse pathological features discovered during radical prostatectomy, compared with no adjuvant therapy.[246][247][248][249]

Observation is recommended instead of adjuvant therapy in patients with life expectancy ≤5 years.[3][238]

Consider – adjuvant androgen deprivation therapy

Back

Consider –

adjuvant androgen deprivation therapy

Additional treatment recommended for SOME patients in selected patient group

The addition of adjuvant androgen deprivation therapy (ADT) (e.g., a luteinising hormone-releasing hormone agonist or antagonist) to external beam radiotherapy (EBRT) may be of benefit in selected patients with negative lymph nodes, such as those with a high Decipher score (e.g., >0.6).[3][250]

See local specialist protocol for dosing guidelines.

Primary options

leuprorelin

goserelin

degarelix

relugolix

Consider – supportive care

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Before prescribing denosumab, healthcare professionals should assess kidney function and calcium levels, and consider other treatment options for patients at risk. During treatment, frequent blood calcium monitoring and prompt management of hypocalcaemia are essential. The FDA has not issued a warning with respect to the brand of denosumab approved specifically for the prevention of skeletal-related adverse events in malignancy (Xgeva® 120 mg/1.7 mL).

with positive lymph nodes

1st line – monitoring with early salvage external beam radiotherapy

Back

1st line –

monitoring with early salvage external beam radiotherapy

For patients with life expectancy >5 years with lymph node metastases after radical prostatectomy, options include monitoring with consideration of early salvage external beam radiotherapy (EBRT) for a detectable, rising prostate-specific antigen (PSA) level or a PSA >0.1 micrograms/L (>0.1 nanograms/mL) (before PSA reaches 0.5 micrograms/L [0.5 nanograms/mL]).[3]

Risk assessment (including use of nomograms) should be carried out to inform decision-making in these patients.The Decipher molecular assay may also be considered to guide decision-making discussions, along with clinical and pathological information, PSA level, and PSA doubling time.[3][234][235][236] Shared decisions about treatment should be based on assessment of potential benefits and harms.[3][146]

Monitoring, with early salvage EBRT performed only when PSA failure is detected, reduces overtreatment with radiotherapy (and associated adverse events) compared with immediate adjuvant EBRT.[3]

PSA failure after radical prostatectomy has no single accepted definition. The American Urological Association defines biochemical recurrence in the post-prostatectomy setting as a rise in PSA ≥0.2 micrograms/L (≥0.2 nanograms/mL) and a confirmatory value of >0.2 micrograms/L (>0.2 nanograms/mL).[233][244] The National Comprehensive Cancer Network defines PSA recurrence as undetectable post-prostatectomy PSA with a subsequent detectable PSA that increases on two or more measurements or increases to PSA >0.1 micrograms/L (>0.1 nanograms/mL).[3] Patients receiving early salvage EBRT at lower PSA levels (≥0.1 to 0.2 micrograms/L [≥0.1 to 0.2 nanograms/mL]) have demonstrated better outcomes compared with those receiving salvage EBRT at higher PSA levels.[233][245]

Observation is recommended instead of salvage therapy in patients with life expectancy ≤5 years.[3][238]

1st line – adjuvant androgen deprivation therapy ± external beam radiotherapy

Back

1st line –

adjuvant androgen deprivation therapy ± external beam radiotherapy

For patients with life expectancy >5 years with lymph node metastases after radical prostatectomy, options include adjuvant androgen deprivation therapy (ADT) (e.g., a luteinising hormone-releasing hormone agonist or antagonist) with or without external beam radiotherapy (EBRT).[3]

Adjuvant ADT (with or without EBRT) initiated immediately in patients with positive nodes (discovered during prostatectomy) has been shown to improve survival compared with deferring adjuvant ADT until disease progression.[251][252][253] Retrospective studies and analysis of data from a US cancer database suggest that adjuvant ADT with EBRT may improve survival compared with ADT alone.[3][254][255]

Observation is recommended instead of adjuvant therapy in patients with life expectancy ≤5 years.[3][238]

See local specialist protocol for dosing guidelines.

Primary options

leuprorelin

goserelin

degarelix

relugolix

Consider – supportive care

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

with PSA persistence or recurrence: negative pelvic nodes and no distant metastases

1st line – salvage external beam radiotherapy (± androgen deprivation therapy) or monitoring

Back

1st line –

salvage external beam radiotherapy (± androgen deprivation therapy) or monitoring

Salvage therapy is indicated for patients with life expectancy >5 years if there is prostate-specific antigen (PSA) persistence (PSA does not fall to undetectable levels) or recurrence (increase of previously undetectable PSA on two or more measurements or to PSA >0.1 micrograms/L [>0.1 nanograms/mL]) after radical prostatectomy.[3][233]

Evaluation for distant metastases should be carried out (e.g., if the patient develops symptoms or PSA is increasing rapidly), which may include bone and soft tissue imaging. Prostate bed biopsy may be helpful, especially if imaging suggests local recurrence.[3]

Risk assessment (including use of nomograms) should be carried out to inform decision-making about salvage therapy. The Decipher molecular assay may also be considered to aid decision-making discussions, along with clinical and pathological information, PSA level, and PSA doubling time.[3][234][235][236][237]

Salvage external beam radiotherapy (EBRT) with or without androgen deprivation therapy (ADT) (e.g., a luteinising hormone-releasing hormone agonist or antagonist) is the main treatment option for postoperative salvage therapy.[3][256][257][258] Salvage therapy is followed by monitoring for progression (physical examination and PSA every 3-6 months, and imaging for symptoms or increasing PSA).

Combining ADT with salvage EBRT reduces the likelihood of progression and may improve survival outcomes compared with salvage EBRT alone, but decisions (including duration of ADT) should be individualised, based on an assessment of potential benefits and harms, and shared decision-making.[256][257][258][259]

Monitoring for progression (physical examination and PSA every 3-6 months, and imaging for symptoms or increasing PSA) with consideration of salvage therapy (EBRT with or without ADT) may be an alternative to salvage therapy in some patients with PSA persistence or recurrence after radical prostatectomy, following a careful review of the balance of risks and benefits.[237] Salvage radiotherapy is more effective when given at lower levels of PSA, and should be considered for local or regional control before PSA levels reach 0.5 micrograms/L (0.5 nanograms/mL).[233]

PSA failure after radical prostatectomy has no single accepted definition, and values between 0.1 and 0.4 micrograms/L (0.1 and 0.4 nanograms/mL) have been used. Guidelines from the American Urological Association, American Society for Radiation Oncology, and Society of Urologic Oncology define biochemical recurrence after radical prostatectomy as PSA ≥0.2 micrograms/L (≥0.2 nanograms/mL).[233] Those receiving salvage EBRT at lower PSA levels (i.e., early salvage) have demonstrated better outcomes compared with those receiving salvage EBRT at higher PSA levels.[233][245]

Observation is recommended instead of salvage therapy in patients with life expectancy ≤5 years.[3][238]

See local specialist protocol for dosing guidelines.

Primary options

leuprorelin

goserelin

degarelix

relugolix

Consider – supportive care

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

with PSA persistence or recurrence: positive pelvic nodes and no distant metastases

1st line – salvage external beam radiotherapy + androgen deprivation therapy ± abiraterone

Back

1st line –

salvage external beam radiotherapy + androgen deprivation therapy ± abiraterone

Risk assessment (including use of nomograms) should be carried out to inform decision making about salvage therapy. The Decipher molecular assay may also be considered to aid decision-making discussions, along with clinical and pathological information, PSA level, and PSA doubling time.[3][234][235][236][237]

Salvage external beam radiotherapy (EBRT) plus androgen deprivation therapy (ADT) (e.g., a luteinising hormone-releasing hormone [LHRH] agonist or antagonist) with or without abiraterone (plus prednisolone or methylprednisolone) is the main treatment option for postoperative salvage therapy in patients with positive pelvic node recurrence.[3][256] Salvage therapy is followed by monitoring for progression (physical examination and PSA every 3-6 months, and imaging for symptoms or increasing PSA).

Combining ADT with salvage EBRT reduces the likelihood of progression and may improve survival outcomes compared with salvage EBRT alone, but decisions (including duration of ADT) should be based on an assessment of potential benefits and harms, and shared decision-making.[256][257][258][259]

Abiraterone (a second-generation anti-androgen) is approved for use in metastatic disease. However, off-label use in combination with EBRT and ADT (e.g., an LHRH agonist or antagonist) for selected patients with positive pelvic node recurrence may be considered.[3][230] Abiraterone should not be used concurrently with another anti-androgen (e.g., nilutamide, bicalutamide, flutamide), and it should always be given with prednisolone or methylprednisolone (depending on the formulation of abiraterone).

PSA failure after radical prostatectomy has no single accepted definition. The American Urological Association defines biochemical recurrence in the post-prostatectomy setting as a rise in PSA ≥0.2 micrograms/L (≥0.2 nanograms/mL) and a confirmatory value of >0.2 micrograms/L (>0.2 nanograms/mL).[233][244] The National Comprehensive Cancer Network defines PSA persistence/recurrence as PSA level that does not fall to undetectable levels (PSA persistence) or undetectable post-prostatectomy PSA with a subsequent detectable PSA that increases on two or more measurements (PSA recurrence) or increases to PSA >0.1 micrograms/L (>0.1 nanograms/mL).[3] Those receiving post-prostatectomy salvage EBRT at lower PSA levels (i.e., early salvage) have demonstrated better outcomes compared with those receiving salvage EBRT at higher PSA levels.[233][245]

Observation is recommended instead of salvage therapy in patients with life expectancy ≤5 years.[3][238]

See local specialist protocol for dosing guidelines.

Primary options

leuprorelin

goserelin

degarelix

relugolix

leuprorelin

goserelin

degarelix

relugolix

-- AND --

abiraterone acetate

Consider – supportive care

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

non-metastatic disease: post-external beam radiotherapy

with PSA recurrence or positive digital rectal examination: negative lymph nodes

1st line – monitoring or androgen deprivation therapy or local secondary therapy

Back

1st line –

monitoring or androgen deprivation therapy or local secondary therapy

Salvage therapy is indicated for patients with life expectancy >5 years if there is prostate-specific antigen (PSA) recurrence or positive digital rectal examination after primary external beam radiotherapy (EBRT). PSA recurrence after EBRT is defined as PSA increase of ≥2 micrograms/L (≥2 nanograms/mL) above the nadir PSA.[260] Evaluation for salvage therapy can also be considered if the PSA is increasing but has not reached 2 micrograms/L (2 nanograms/mL) above nadir.

Treatment decisions should be individualised, guided by risk stratification; PSA density, and bone and soft tissue imaging should be performed, with consideration of prostate/seminal vesicle biopsy if imaging is negative for metastases.[3][261]

If negative for regional lymph nodes and distant metastases, options include: monitoring for progression (with consideration of prostate/seminal vesicle biopsy); androgen deprivation therapy (based on PSA density); local secondary therapy, which may include salvage prostatectomy plus pelvic lymph node dissection, salvage cryotherapy, re-irradiation (low- or high-dose rate brachytherapy, or stereotactic body radiotherapy), high-intensity focused ultrasound.[3][261][262][263][264]

Salvage brachytherapy provides precise treatment for pathologically confirmed (e.g., using magnetic resonance imaging-guided biopsy) locally recurrent disease, therefore minimising toxicity to adjacent organs. Use of salvage prostatectomy and salvage cryotherapy is limited by treatment-related adverse effects (e.g., erectile dysfunction).[264][265][266][267][268][269][270]

Observation is recommended instead of salvage therapy in patients with life expectancy ≤5 years.[3]

with PSA recurrence or positive digital rectal examination: positive lymph nodes

1st line – monitoring or androgen deprivation therapy (± abiraterone) or local secondary therapy (± androgen deprivation therapy)

Back

1st line –

monitoring or androgen deprivation therapy (± abiraterone) or local secondary therapy (± androgen deprivation therapy)

If positive for regional lymph nodes and distant metastases, options include: monitoring for progression (with consideration of prostate/seminal vesicle biopsy); androgen deprivation therapy (ADT) with or without abiraterone (plus prednisolone or methylprednisolone); consideration of local secondary therapy with or without ADT (e.g., pelvic lymph node dissection, pelvic lymph node radiation or re-irradiation [low- or high-dose rate brachytherapy, or stereotactic body radiotherapy]).[3][261][262][263][264]

Abiraterone (a second-generation anti-androgen) is approved for use in metastatic disease. However, off-label use in combination with EBRT and ADT for selected patients with positive pelvic node recurrence may be considered.[3][230] Abiraterone should not be used concurrently with another anti-androgen (e.g., nilutamide, bicalutamide, flutamide), and it should always be given with prednisolone or methylprednisolone (depending on the formulation of abiraterone).

Observation is recommended instead of salvage therapy in patients with life expectancy ≤5 years.[3]

non-metastatic disease: castration-resistant

PSA doubling time >10 months

1st line – continue androgen deprivation therapy + monitoring or secondary hormone therapy

Back

1st line –

continue androgen deprivation therapy + monitoring or secondary hormone therapy

Patients with non-metastatic castration-resistant prostate cancer are those with clinical, radiographic, or biochemical (PSA) progression despite treatment with androgen deprivation therapy (ADT), but who do not have metastases. These patients are at high risk for developing metastases, particularly if PSA doubling time (PSADT) is short (e.g., ≤10 months).

ADT with a luteinising hormone-releasing hormone agonist or antagonist should continue in these patients to maintain castrate serum levels of testosterone, but further hormonal treatment may be added depending on the PSADT.[3]

If PSADT is >10 months, monitoring with continued ADT is the preferred option. A secondary hormone therapy can be added to ADT (if not previously used), although evidence of survival benefit is lacking. Secondary hormone therapy may include: ketoconazole plus hydrocortisone; a first-generation anti-androgen (e.g., nilutamide, bicalutamide, flutamide); or a corticosteroid (e.g., hydrocortisone, prednisolone, dexamethasone).[3] Ketoconazole may cause severe liver injury and adrenal insufficiency. It is contraindicated in patients with liver disease and expert guidance should be sought if used. Liver and adrenal function should be monitored before and during treatment.[274]

See local specialist protocol for dosing guidelines.

Primary options

ketoconazole

and

hydrocortisone

nilutamide

bicalutamide

flutamide

hydrocortisone

prednisolone

dexamethasone

2nd line – continue androgen deprivation therapy + anti-androgen withdrawal

Back

2nd line –

continue androgen deprivation therapy + anti-androgen withdrawal

Anti-androgen withdrawal (i.e., to exclude an anti-androgen withdrawal effect) may be an option for non-metastatic castration-resistant disease.[3][271][272][273]

PSA doubling time ≤10 months

1st line – continue androgen deprivation therapy + second-generation anti-androgen

Back

1st line –

continue androgen deprivation therapy + second-generation anti-androgen

If PSADT is ≤10 months, a second-generation anti-androgen (e.g., apalutamide, darolutamide, or enzalutamide) can be added to ADT.[3]

Randomised studies of second-generation anti-androgens in patients with non-metastatic castration-resistant prostate cancer and PSADT ≤10 months have demonstrated improved overall survival, metastasis-free survival, and time to progression compared with placebo, without compromising quality of life.[275][276][277][278][279][280][281][282][283] It is not known if similar benefit would be achieved in men with a PSADT >10 months.

See local specialist protocol for dosing guidelines.

Primary options

apalutamide

darolutamide

enzalutamide

2nd line – continue androgen deprivation therapy + secondary hormone therapy or anti-androgen withdrawal

Back

2nd line –

continue androgen deprivation therapy + secondary hormone therapy or anti-androgen withdrawal

Alternative options for patients with non-metastatic castration-resistant disease and PSADT ≤10 months include other secondary hormone options or anti-androgen withdrawal (as described for PSADT is >10 months).[3][271][272][273][378]

metastatic disease: castration-sensitive

1st line – androgen deprivation therapy + second-generation anti-androgen ± docetaxel

Back

1st line –

androgen deprivation therapy + second-generation anti-androgen ± docetaxel

The main treatment goals for metastatic disease are prolongation of survival while maintaining quality of life, and palliation of symptoms that may arise from metastatic tumour deposits.

Patients with castration-sensitive metastatic disease include those with metastatic disease at presentation, and those who are not receiving androgen deprivation therapy (ADT) when metastatic disease develops (i.e., castration-naive).

Genetic testing (germline and somatic) should be carried out in all patients with metastatic disease (if not done previously) to inform prognosis and guide treatment decisions, including eligibility for clinical trials and suitability for novel targeted therapies.[284][285] See Diagnosis approach.

Combination therapy with ADT (e.g., a luteinising hormone-releasing hormone [LHRH] agonist or antagonist) plus a second-generation anti-androgen with or without docetaxel is recommended.[230][285][286][287][288][289][290][291][292][293][294][295][296][297]

Specific treatment options include: ADT plus docetaxel and abiraterone or darolutamide; ADT plus abiraterone, apalutamide, or enzalutamide.[3][231][297][300]

Abiraterone should always be given with prednisolone or methylprednisolone (depending on the formulation of abiraterone).

For patients with high-volume disease (i.e., visceral metastases and/or ≥4 bone metastases with ≥1 beyond the vertebral bodies and pelvis) with synchronous metastases, ADT plus a second-generation anti-androgen with or without docetaxel is preferred. For low-volume disease (i.e., non-regional lymph-node-only disease, or presence of <4 bone metastases without visceral/other metastasis) with metachronous metastases, ADT plus a second-generation anti-androgen is preferred.[3][301]

ADT plus docetaxel and abiraterone or darolutamide may improve survival compared with ADT plus docetaxel alone, particularly in those with high-volume castration-sensitive disease.[302][303]

ADT is usually given continuously, but intermittent ADT may be considered if adverse effects occur with continuous ADT.[71][306][307][308][309][310]

A PSA level ≤0.2 micrograms/L (≤0.2 nanograms/mL) after 7 months of ADT is a strong predictor for longer overall survival in patients with castration-sensitive metastatic disease.[311]

ADT alone is not recommended for patients with castration-sensitive metastatic disease unless combination treatment is clearly contraindicated or the patient is asymptomatic and has a life expectancy of ≤5 years.[3]

Surgical castration (bilateral orchiectomy) is an option for patients with castration-sensitive metastatic disease, but is rarely used.

LHRH agonists may cause an increase in testosterone levels during the first week of treatment (testosterone flare), which may exacerbate symptoms in patients with metastatic disease.[367][368][369] An LHRH antagonist (e.g., degarelix, relugolix) should be used for 1 month prior to transitioning to an LHRH agonist if used in the metastatic setting.

See local specialist protocol for dosing guidelines.

Primary options

leuprorelin

goserelin

degarelix

relugolix

-- AND --

abiraterone acetate

apalutamide

enzalutamide

leuprorelin

goserelin

degarelix

relugolix

-- AND --

docetaxel

-- AND --

abiraterone acetate

darolutamide

Secondary options

leuprorelin

goserelin

degarelix

relugolix

Consider – supportive care

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Denosumab (a fully human monoclonal antibody that inhibits RANK ligand) and zoledronic acid (an intravenous bisphosphonate) are recommended to prevent skeletal-related events (e.g., bone fracture, spinal cord compression) in patients with bone metastases.[3][362] [ ] Denosumab is preferred to zoledronic acid due to its superior efficacy.[3][363]

In June 2018, the UK Medicines and Healthcare products Regulatory Agency (MHRA) issued a safety alert following a pooled analysis of four phase 3 studies of denosumab in patients with advanced malignancies involving bone.[365] New primary malignancies were reported more frequently among patients receiving denosumab than those receiving zoledronic acid (cumulative incidence of new primary malignancy at 1 year was 1.1% for denosumab and 0.6% for zoledronic acid). No treatment-related patterns for individual cancers or cancer groupings were identified.

Systemic radiotherapy with the beta-particle emitters strontium-89 or samarium-153 can be considered for palliation in patients with symptomatic bone metastases without visceral metastases. Their use is purely palliative and has largely been superseded by radium-223, which confers a survival advantage.

Radiotherapy in palliative doses can be given to sites of painful bony metastasis. Radiation may include a single treatment or a 1- or 2-week course depending on normal tissue toxicity and patient convenience.[370] Studies do not show a consistent difference between regimens for pain control, but some have reported higher rates of reirradiation in patients receiving single-fraction regimens (although the reason for this is unclear).[370][371][372][373] Stereotactic body radiotherapy (SBRT) may be considered instead of conventional palliative radiotherapy for some patients with painful bony metastases (e.g., with an Eastern Cooperative Oncology Group performance status 0 to 2, without neurological symptoms, and not receiving surgery).[370][374] Radiation may also be given to the pelvis, if previously untreated, in palliative doses to relieve obstructive symptoms or bleeding.

1st line – androgen deprivation therapy + external beam radiotherapy ± abiraterone or docetaxel

Back

1st line –

androgen deprivation therapy + external beam radiotherapy ± abiraterone or docetaxel

The main treatment goals for metastatic disease are prolongation of survival while maintaining quality of life, and palliation of symptoms that may arise from metastatic tumour deposits.

Androgen deprivation therapy (ADT) plus external beam radiotherapy (EBRT) to the primary tumour (with or without abiraterone or docetaxel) may be an option for some patients with castration-sensitive metastatic disease, depending on disease volume and timing of metastases.[3][298][299] Abiraterone should always be given with prednisolone or methylprednisolone (depending on the formulation of abiraterone).

Improved survival has been demonstrated with EBRT plus ADT versus ADT alone in patients with low-volume castration-sensitive disease (i.e., non-regional lymph-node-only disease, or presence of <4 bone metastases without visceral/other metastasis).[158][304][305]

Hypofractionation and ultra-hypofractionation are the preferred approaches for EBRT.[3][158]

Patients with significant baseline urinary symptoms may not be suitable for EBRT due to increased risk of urinary obstruction.

Luteinising hormone-releasing hormone (LHRH) agonists may cause an increase in testosterone levels during the first week of treatment (testosterone flare), which may exacerbate symptoms in patients with metastatic disease.[367][368][369] An LHRH antagonist (e.g., degarelix, relugolix) should be used for 1 month prior to transitioning to an LHRH agonist if used in the metastatic setting.

See local specialist protocol for dosing guidelines.

Primary options

leuprorelin

goserelin

degarelix

relugolix

leuprorelin

goserelin

degarelix

relugolix

-- AND --

abiraterone acetate

docetaxel

Consider – supportive care

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

metastatic disease: castration-resistant

1st line – continue androgen deprivation therapy + docetaxel or second-generation anti-androgen or cabazitaxel

Back

1st line –

continue androgen deprivation therapy + docetaxel or second-generation anti-androgen or cabazitaxel

The main treatment goals for metastatic disease are prolongation of survival while maintaining quality of life, and palliation of symptoms that may arise from metastatic tumour deposits.

Patients with castration-resistant metastatic disease are those who develop metastatic disease despite achieving castrate levels of testosterone with primary androgen deprivation therapy (ADT; e.g., a luteinising hormone-releasing hormone agonist or antagonist).

Genetic testing (germline and somatic) should be carried out in patients with metastatic disease (if not done previously) to inform prognosis and guide treatment decisions, including eligibility for clinical trials and suitability for novel targeted therapies.[284][285] See Diagnosis approach.

Treatment options for patients with castration-resistant metastatic disease have expanded rapidly. Optimal sequencing of drugs following docetaxel-based regimens and/or second-generation anti-androgen therapy is unclear, although studies are ongoing and may help guide decisions.[315][316][317] Treatment decisions should take into account patient goals and preferences, prior treatment exposures, the presence or absence of symptoms, the location of metastases, potential adverse effects, and the presence of certain biomarkers.[3]

ADT should be continued to maintain castrate levels of testosterone in patients with castration-resistant metastatic disease. Patients should be closely monitored for progression, and treatments added sequentially.[3]

For patients with no prior treatment with a second-generation anti-androgen therapy (abiraterone, enzalutamide, darolutamide, or apalutamide), ADT can be combined with one of the following options: abiraterone (with prednisolone or methylprednisolone); enzalutamide; a docetaxel-based regimen (e.g., docetaxel plus prednisolone, if no prior use); or cabazitaxel plus prednisolone (if prior docetaxel).[318][319][320][321][322][323][324][325][326][327][328][329]

For patients with progression following treatment with second-generation anti-androgen therapy and no prior docetaxel treatment, ADT plus a docetaxel-based regimen is recommended.[3]

Cabazitaxel is an option for patients who have had prior docetaxel and prior second-generation anti-androgen treatment.[326][327][328][334] Docetaxel rechallenge is a further option for patients treated previously with docetaxel for castration-sensitive disease.[3]

For patients who are starting to show signs of progression while taking abiraterone plus prednisolone, switching from prednisolone to dexamethasone may be beneficial.[335][336]

See local specialist protocol for dosing guidelines.

Primary options

docetaxel

and

prednisolone

abiraterone acetate

enzalutamide

Secondary options

cabazitaxel

and

prednisolone

Consider – supportive care

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Continue supportive care for possible adverse effects associated with continued androgen deprivation therapy (e.g., testosterone flare).

Radiotherapy in palliative doses can be given to sites of painful bony metastasis. Radiation may include a single treatment or a 1- or 2-week course depending on normal tissue toxicity and patient convenience.[370] Studies do not show a consistent difference between regimens for pain control, but some have reported higher rates of re-irradiation in patients receiving single-fraction regimens (although the reason for this is unclear).[370][371][372][373] Stereotactic body radiotherapy (SBRT) may be considered instead of conventional palliative radiotherapy for some patients with painful bony metastases (e.g., with an Eastern Cooperative Oncology Group performance status 0 to 2, without neurological symptoms, and not receiving surgery).[370][374] Radiation may also be given to the pelvis, if previously untreated, in palliative doses to relieve obstructive symptoms or bleeding.

1st line – continue androgen deprivation therapy + olaparib or rucaparib

Back

1st line –

continue androgen deprivation therapy + olaparib or rucaparib

The main treatment goals for metastatic disease are prolongation of survival while maintaining quality of life, and palliation of symptoms that may arise from metastatic tumour deposits.

For patients with progression following treatment with second-generation anti-androgen therapy (abiraterone, enzalutamide, darolutamide, or apalutamide) and no prior docetaxel treatment, the poly (ADP-ribose) polymerase (PARP) inhibitors olaparib or rucaparib may be considered in this setting if the patient has a BRCA1 or BRCA2 mutation.[330][331][332][333]

Anaemia, fatigue, and nausea are commonly reported with PARP inhibitors. Careful monitoring for anaemia and renal and hepatic function is required.[3]

Primary options

olaparib

rucaparib

Consider – supportive care

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Continue supportive care for possible adverse effects associated with continued androgen deprivation therapy (e.g., testosterone flare).

Radiotherapy in palliative doses can be given to sites of painful bony metastasis. Radiation may include a single treatment or a 1- or 2-week course depending on normal tissue toxicity and patient convenience.[370] Studies do not show a consistent difference between regimens for pain control, but some have reported higher rates of re-irradiation in patients receiving single-fraction regimens (although the reason for this is unclear).[370][371][372][373] Stereotactic body radiotherapy (SBRT) may be considered instead of conventional palliative radiotherapy for some patients with painful bony metastases (e.g., with an Eastern Cooperative Oncology Group performance status 0 to 2, without neurological symptoms, and not receiving surgery).[370][374] Radiation may also be given to the pelvis, if previously untreated, in palliative doses to relieve obstructive symptoms or bleeding.

2nd line – sipuleucel-T

Back

2nd line –

sipuleucel-T

An autologous active cellular immunotherapy, sipuleucel-T may be an option for asymptomatic or minimally symptomatic patients with good functional status (e.g., an Eastern Cooperative Oncology Group performance status of 0 to 1).[3][337][338]

Sipuleucel-T is not recommended for patients with visceral disease and a life expectancy of less than 6 months, or patients with hepatic metastases.[3][337]

See local specialist protocol for dosing guidelines.

Primary options

sipuleucel-T

Consider – supportive care

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Continue supportive care for possible adverse effects associated with continued androgen deprivation therapy (e.g., testosterone flare).

Radiotherapy in palliative doses can be given to sites of painful bony metastasis. Radiation may include a single treatment or a 1- or 2-week course depending on normal tissue toxicity and patient convenience.[370] Studies do not show a consistent difference between regimens for pain control, but some have reported higher rates of re-irradiation in patients receiving single-fraction regimens (although the reason for this is unclear).[370][371][372][373] Stereotactic body radiotherapy (SBRT) may be considered instead of conventional palliative radiotherapy for some patients with painful bony metastases (e.g., with an Eastern Cooperative Oncology Group performance status 0 to 2, without neurological symptoms, and not receiving surgery)[370][374] Evidence is lacking to guide the use of SBRT combined with immunotherapy.[375] Radiation may also be given to the pelvis, if previously untreated, in palliative doses to relieve obstructive symptoms or bleeding.

2nd line – olaparib or rucaparib monotherapy

Back

2nd line –

olaparib or rucaparib monotherapy

Olaparib can be considered for patients with an homologous recombination repair (HRR) gene mutation who have had prior second-generation anti-androgen therapy.[3][231][330][331][332] Efficacy may vary depending on the genes involved; in one study, of patients with an alteration in one of 15 prespecified HRR genes, those with a BRCA1 or BRCA2 mutation appeared to derive the greatest survival benefit.[332]

Rucaparib can be considered for patients with a BRCA1 or BRCA2 mutation who have had prior second-generation anti-androgen therapy.[3][333][339][340] Rucaparib is not recommended for patients without a BRCA1 or BRCA2 mutation.[3][341]

Anaemia, fatigue, and nausea are commonly reported with PARP inhibitors. Careful monitoring for anemia and renal and hepatic function is required.[3]

See local specialist protocol for dosing guidelines.

Primary options

olaparib

rucaparib

Consider – supportive care

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Continue supportive care for possible adverse effects associated with continued androgen deprivation therapy (e.g., testosterone flare).

Radiotherapy in palliative doses can be given to sites of painful bony metastasis. Radiation may include a single treatment or a 1- or 2-week course depending on normal tissue toxicity and patient convenience.[370] Studies do not show a consistent difference between regimens for pain control, but some have reported higher rates of re-irradiation in patients receiving single-fraction regimens (although the reason for this is unclear).[370][371][372][373] Stereotactic body radiotherapy (SBRT) may be considered instead of conventional palliative radiotherapy for some patients with painful bony metastases (e.g., with an Eastern Cooperative Oncology Group performance status 0 to 2, without neurological symptoms, and not receiving surgery).[370][374] Evidence is lacking to guide the use of SBRT combined with immunotherapy.[375] Radiation may also be given to the pelvis, if previously untreated, in palliative doses to relieve obstructive symptoms or bleeding.

2nd line – olaparib or niraparib or talazoparib + second-generation anti-androgen

Back

2nd line –

olaparib or niraparib or talazoparib + second-generation anti-androgen

Olaparib or niraparib may be used in combination with abiraterone (plus prednisolone or methylprednisolone) for patients with a BRCA1 or BRCA2 mutation who have not received prior second-generation anti-androgen therapy.[3][342][343][344]

Talazoparib plus enzalutamide may be an option for patients with an HHR mutation who have had no prior docetaxel therapy.[3][345][346]

Anaemia, fatigue, and nausea are commonly reported with PARP inhibitors. Careful monitoring for anaemia and renal and hepatic function is required.[3]

See local specialist protocol for dosing guidelines.

Primary options

olaparib

niraparib

-- AND --

abiraterone acetate

-- AND --

prednisolone

talazoparib

and

enzalutamide

Consider – supportive care

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Continue supportive care for possible adverse effects associated with continued androgen deprivation therapy (e.g., testosterone flare).

Radiotherapy in palliative doses can be given to sites of painful bony metastasis. Radiation may include a single treatment or a 1- or 2-week course depending on normal tissue toxicity and patient convenience.[370] Studies do not show a consistent difference between regimens for pain control, but some have reported higher rates of re-irradiation in patients receiving single-fraction regimens (although the reason for this is unclear).[370][371][372][373] Stereotactic body radiotherapy (SBRT) may be considered instead of conventional palliative radiotherapy for some patients with painful bony metastases (e.g., with an Eastern Cooperative Oncology Group performance status 0 to 2, without neurological symptoms, and not receiving surgery).[370][374] Evidence is lacking to guide the use of SBRT combined with immunotherapy.[375] Radiation may also be given to the pelvis, if previously untreated, in palliative doses to relieve obstructive symptoms or bleeding.

2nd line – pembrolizumab

Back

2nd line –

pembrolizumab

A programmed death receptor-1 (PD-1)-blocking monoclonal antibody, pembrolizumab may be considered for patients with mismatch repair deficient (dMMR), microsatellite instability-high (MSI-H), or high tumour mutational burden (TMB-H) castration-resistant metastatic prostate cancer.[3][285]

Much of the evidence for this treatment is based on different tumour types; however, early phase trials report antitumour activity among specific subsets of patients with metastatic castration-resistant prostate cancer.[347][348][349][350]

Pembrolizumab may cause severe, life-threatening immune-mediated adverse reactions.[351]

See local specialist protocol for dosing guidelines.

Primary options

pembrolizumab

Consider – supportive care

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Continue supportive care for possible adverse effects associated with continued androgen deprivation therapy (e.g., testosterone flare).

Radiotherapy in palliative doses can be given to sites of painful bony metastasis. Radiation may include a single treatment or a 1- or 2-week course depending on normal tissue toxicity and patient convenience.[370] Studies do not show a consistent difference between regimens for pain control, but some have reported higher rates of re-irradiation in patients receiving single-fraction regimens (although the reason for this is unclear).[370][371][372][373] Stereotactic body radiotherapy (SBRT) may be considered instead of conventional palliative radiotherapy for some patients with painful bony metastases (e.g., with an Eastern Cooperative Oncology Group performance status 0 to 2, without neurological symptoms, and not receiving surgery).[370][374] Evidence is lacking to guide the use of SBRT combined with immunotherapy.[375] Radiation may also be given to the pelvis, if previously untreated, in palliative doses to relieve obstructive symptoms or bleeding.

2nd line – lutetium (Lu-177) vipivotide tetraxetan

Back

2nd line –

lutetium (Lu-177) vipivotide tetraxetan

A radioligand therapeutic agent that delivers beta-radiation to prostate-specific membrane antigen (PSMA)-expressing cells and the surrounding microenvironment. Lu-177 vipivotide tetraxetan can be considered for patients with progression after taxane-based chemotherapy and second-generation anti-androgen therapy who have PSMA-positive castration-resistant metastatic disease.[3][231][285][352][353]

PSMA-PET imaging is required for patient selection. Gallium (Ga-68) PSMA-11, piflufolastat F-18, or flotufolastat F-18 may be used as radiotracers to detect PSMA expression and determine eligibility.[3][352][354]

See local specialist protocol for dosing guidelines.

Primary options

lutetium Lu 177 vipivotide tetraxetan

Consider – supportive care

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Continue supportive care for possible adverse effects associated with continued androgen deprivation therapy (e.g., testosterone flare).

Radiotherapy in palliative doses can be given to sites of painful bony metastasis. Radiation may include a single treatment or a 1- or 2-week course depending on normal tissue toxicity and patient convenience.[370] Studies do not show a consistent difference between regimens for pain control, but some have reported higher rates of re-irradiation in patients receiving single-fraction regimens (although the reason for this is unclear).[370][371][372][373] Stereotactic body radiotherapy (SBRT) may be considered instead of conventional palliative radiotherapy for some patients with painful bony metastases (e.g., with an Eastern Cooperative Oncology Group performance status 0 to 2, without neurological symptoms, and not receiving surgery).[370][374] Radiation may also be given to the pelvis, if previously untreated, in palliative doses to relieve obstructive symptoms or bleeding.

2nd line – mitoxantrone

Back

2nd line –

mitoxantrone

May be considered in combination with prednisolone for palliative treatment of symptomatic patients who have progressed on prior docetaxel and cannot tolerate other therapies. It has not been shown to improve survival.[3][355][356]

See local specialist protocol for dosing guidelines.

Primary options

mitoxantrone

and

prednisolone

Consider – supportive care

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Continue supportive care for possible adverse effects associated with continued androgen deprivation therapy (e.g., testosterone flare).

Radiotherapy in palliative doses can be given to sites of painful bony metastasis. Radiation may include a single treatment or a 1- or 2-week course depending on normal tissue toxicity and patient convenience.[370] Studies do not show a consistent difference between regimens for pain control, but some have reported higher rates of re-irradiation in patients receiving single-fraction regimens (although the reason for this is unclear).[370][371][372][373] Stereotactic body radiotherapy (SBRT) may be considered instead of conventional palliative radiotherapy for some patients with painful bony metastases (e.g., with an Eastern Cooperative Oncology Group performance status 0 to 2, without neurological symptoms, and not receiving surgery).[370][374] Radiation may also be given to the pelvis, if previously untreated, in palliative doses to relieve obstructive symptoms or bleeding.

2nd line – radium-223

Back

2nd line –

radium-223

A calcium mimetic that localises to the bone and delivers radiation directly to bone metastases, radium-223 can be considered for patients with castration-resistant metastatic disease who have symptomatic bone metastases without visceral metastases.[3][357]

Radium-223 is associated with adverse events including anemia, neutropenia, thrombocytopenia, bone pain, and gastrointestinal disorders. There have also been reports of increased risk of fracture and deaths when used in combination with abiraterone plus prednisolone.[358][359]

The European Medicines Agency has restricted the use of radium-223 to symptomatic patients who have received two prior treatments for metastatic prostate cancer, or who cannot receive other treatments. It should not be used with abiraterone and prednisolone or with other systemic cancer therapies (except hormone therapy).[359]

A careful assessment of risk of fractures should be carried out before, during, and after treatment with radium-223.

Bisphosphonates or denosumab are recommended before starting or resuming treatment with radium-223 to increase bone strength.[3][359] For more information, see supportive care.

See local specialist protocol for dosing guidelines.

Consider – supportive care

Back

Consider –

supportive care

Additional treatment recommended for SOME patients in selected patient group

Continue supportive care for possible adverse effects associated with continued androgen deprivation therapy (e.g., testosterone flare).

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Prostate cancer

Treatment algorithm

very low-risk disease

observation

androgen deprivation therapy alone (if symptomatic and life expectancy ≤5 years)

Primary options

supportive care

active surveillance

low-risk disease

observation

androgen deprivation therapy alone (if symptomatic and life expectancy ≤5 years)

Primary options

supportive care

active surveillance

brachytherapy

external beam radiotherapy

radical prostatectomy

favourable intermediate-risk disease

observation

androgen deprivation therapy alone (if symptomatic and life expectancy ≤5 years)

Primary options

supportive care

brachytherapy (if life expectancy 5-10 years)

external beam radiotherapy (if life expectancy 5-10 years)

active surveillance

brachytherapy

external beam radiotherapy

radical prostatectomy ± lymph node dissection

unfavourable intermediate-risk disease

observation

androgen deprivation therapy alone (if symptomatic)

Primary options

supportive care

observation

external beam radiotherapy ± brachytherapy boost

androgen deprivation therapy

Primary options

supportive care

external beam radiotherapy ± brachytherapy boost

androgen deprivation therapy

Primary options

supportive care

radical prostatectomy + lymph node dissection

high-risk or very high-risk disease

observation

androgen deprivation therapy alone

Primary options

supportive care

external beam radiotherapy

external beam radiotherapy ± brachytherapy boost

androgen deprivation therapy

Primary options

supportive care

external beam radiotherapy ± brachytherapy boost

androgen deprivation therapy + abiraterone (for very high-risk disease)

Primary options

supportive care

radical prostatectomy + pelvic lymph node dissection (for fit patients without tumour fixation to the pelvic musculature or skeleton)

androgen deprivation therapy alone (for patients unsuitable for surgery or radiotherapy)

Primary options

supportive care

non-metastatic disease: post-radical prostatectomy

monitoring with early salvage external beam radiotherapy

adjuvant external beam radiotherapy

adjuvant androgen deprivation therapy

Primary options

supportive care

monitoring with early salvage external beam radiotherapy

adjuvant androgen deprivation therapy ± external beam radiotherapy

Primary options

supportive care

salvage external beam radiotherapy (± androgen deprivation therapy) or monitoring

Primary options

supportive care

salvage external beam radiotherapy + androgen deprivation therapy ± abiraterone

Primary options

supportive care

non-metastatic disease: post-external beam radiotherapy

monitoring or androgen deprivation therapy or local secondary therapy

monitoring or androgen deprivation therapy (± abiraterone) or local secondary therapy (± androgen deprivation therapy)