Metastatic hormone-sensitive prostate cancer: the decisions you may face
5 treatment settings, 5 with more than one named option. Each section lays out the options the standard of care names, what each is for, the trials behind them with their recorded results, the side effects and cautions on record, and questions to ask. Built from the cancer page's standard-of-care rows; nothing here is advice for your case.
All patients, backbone
Continuous androgen deprivation with a GnRH agonist, GnRH antagonist or orchiectomy; never alone in fit men.
Androgen deprivation lowers testosterone or blocks its receptor, and has been the foundation of prostate cancer treatment since 1941 (Nobel Prize 1966).
- Prolonged disease control
Leuprolide is the injectable that shuts off testosterone production, the foundation of hormone therapy for prostate cancer since the 1980s; it is also used for ovarian suppression in premenopausal breast cancer.
An injectable hormone blocker for prostate cancer that lowers testosterone within days without the initial surge caused by agonists.
Relugolix is the first hormone-suppressing pill for prostate cancer, working within days and wearing off quickly when stopped.
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
- Metabolic and bone toxicity; castration resistance inevitable in metastatic disease
- Between Androgen deprivation & AR pathway inhibitors, Leuprolide (leuprorelin) and GnRH agonists, Degarelix and the other options, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Prostate Cancer), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (all patients, backbone), which of the standard options do you recommend and why?Why: Guideline options include: Continuous androgen deprivation with a GnRH agonist, GnRH antagonist or orchiectomy; never alone in fit men.
- Am I a candidate for Leuprolide (leuprorelin) and GnRH agonists, Degarelix, Relugolix, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Add these to your appointment list, or take the full question set for this cancer.
Doublet therapy
Androgen deprivation plus abiraterone (LATITUDE, STAMPEDE), enzalutamide (ARCHES, ENZAMET), apalutamide (TITAN) or darolutamide (ARANOTE).
Abiraterone is a pill that shuts down testosterone production everywhere, including inside the tumour. Discovered at the Institute of Cancer Research, now generic and used from the first metastatic diagnosis.
Enzalutamide is a second-generation androgen-receptor blocker that stops the receptor binding testosterone, entering the nucleus and switching on genes. It is approved at every stage of advanced prostate cancer, from rising PSA after surgery to castration-resistant disease, and fatigue, falls and memory problems are its main drawbacks.
An AR blocker approved for prostate cancer that has spread and for high-risk disease before it shows on scans.
Darolutamide is an AR blocker that barely enters the brain, so it causes fewer falls and cognitive side effects; it is approved with and without chemotherapy.
- Tests Abiraterone acetateHigh-risk de novo metastatic hormone-sensitive prostate cancer: ADT + abiraterone vs ADT
OS HR 0.66.
Overall survival (months): ADT + abiraterone 53.3 (n=597) vs ADT + placebo 36.5 (n=602) · HR 0.66 · source - Tests Abiraterone acetate, EnzalutamideMulti-arm multi-stage platform in men starting long-term hormone therapy for high-risk locally advanced or metastatic prostate cancer: docetaxel, zoledronic acid, celecoxib, abiraterone, radiotherapy to the prostate, abiraterone with enzalutamide, metformin and transdermal oestradiol added to ADT and compared with ADT alone
Abiraterone + ADT: OS HR 0.63 in mHSPC; docetaxel + ADT: OS HR 0.78. Prostate radiotherapy improved survival in low-volume metastatic disease; abiraterone improved survival in high-risk non-metastatic disease; enzalutamide added to abiraterone, zoledronic acid, celecoxib and metformin did not improve survival.
- Tests EnzalutamideMetastatic hormone-sensitive prostate cancer: ADT + enzalutamide vs ADT
rPFS HR 0.39; OS HR 0.66.
- Take on an empty stomach: food raises exposure up to tenfold and increases toxicity. Prednisone 5 mg covers mineralocorticoid excess.
- Reduce to 250 mg daily in moderate impairment; avoid in severe.
- Seizure risk: caution with drugs that lower the seizure threshold.
- Take with food (exposure roughly doubles).
- Between Abiraterone acetate, Enzalutamide, Apalutamide and the other options, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- How closely do I match the people in LATITUDE and STAMPEDE, and does that change what the results mean for me?Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Prostate Cancer), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (doublet therapy), which of the standard options do you recommend and why?Why: Guideline options include: Androgen deprivation plus abiraterone (LATITUDE, STAMPEDE), enzalutamide (ARCHES, ENZAMET), apalutamide (TITAN) or darolutamide (ARANOTE).
- Am I a candidate for Abiraterone acetate, Enzalutamide, Apalutamide or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of LATITUDE and STAMPEDE apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Add these to your appointment list, or take the full question set for this cancer.
Triplet therapy, high volume, fit for chemotherapy
Androgen deprivation plus docetaxel plus darolutamide (ARASENS) or abiraterone (PEACE-1).
The first chemotherapy to extend life in prostate cancer (2004), now part of triplet therapy at first metastatic diagnosis.
Darolutamide is an AR blocker that barely enters the brain, so it causes fewer falls and cognitive side effects; it is approved with and without chemotherapy.
Abiraterone is a pill that shuts down testosterone production everywhere, including inside the tumour. Discovered at the Institute of Cancer Research, now generic and used from the first metastatic diagnosis.
- Tests Docetaxel, DarolutamideMetastatic hormone-sensitive prostate cancer: ADT + docetaxel + darolutamide vs ADT + docetaxel
OS HR 0.68.
- Tests Docetaxel, Abiraterone acetateDe novo metastatic hormone-sensitive prostate cancer: ADT + docetaxel ± abiraterone ± prostate radiotherapy (2×2 factorial)
OS HR 0.82 in the overall population and HR 0.75 in the ADT plus docetaxel population; HR 0.72 in high-volume disease.
Overall survival, abiraterone vs no abiraterone (with ADT + docetaxel) (months): Abiraterone + ADT + docetaxel 66 vs ADT + docetaxel 52 · HR 0.75 · source - Tests DocetaxelMetastatic hormone-sensitive prostate cancer: ADT + docetaxel vs ADT
OS HR 0.61 overall; high-volume HR 0.63; low-volume no benefit.
- Do not give if bilirubin above ULN, or AST/ALT above 1.5 x ULN with alkaline phosphatase above 2.5 x ULN (treatment-related deaths).
- Take with food (exposure roughly doubles).
- Take on an empty stomach: food raises exposure up to tenfold and increases toxicity. Prednisone 5 mg covers mineralocorticoid excess.
- Reduce to 250 mg daily in moderate impairment; avoid in severe.
- Between Docetaxel, Darolutamide and Abiraterone acetate, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- How closely do I match the people in ARASENS and PEACE-1, and does that change what the results mean for me?Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Prostate Cancer), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (triplet therapy, high volume, fit for chemotherapy), which of the standard options do you recommend and why?Why: Guideline options include: Androgen deprivation plus docetaxel plus darolutamide (ARASENS) or abiraterone (PEACE-1).
- Am I a candidate for Docetaxel, Darolutamide, Abiraterone acetate, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of ARASENS and PEACE-1 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Add these to your appointment list, or take the full question set for this cancer.
Low-volume disease
Doublet therapy plus radiotherapy to the prostate (STAMPEDE); metastasis-directed radiotherapy within trials.
IMRT and IGRT shape the radiation beam to the tumour's outline from multiple angles and check the patient's position with a scan before every session, so surrounding organs receive less dose. Fewer, larger doses are now standard in breast and prostate cancer, but a low-dose bath still spreads across normal tissue.
- Conformal dose, fewer side effects
- Hypofractionation saves visits
Stereotactic body radiotherapy converges multiple beams with sub-millimetre accuracy to deliver tumour-destroying doses in one to five outpatient sessions, doing the job of surgery for inoperable early lung cancer and for metastases in liver, spine and brain. Tumour size and location limit its use, and late toxicity is a concern near the central airways.
- Ablative doses with minimal recovery
- Outpatient
- Multi-arm multi-stage platform in men starting long-term hormone therapy for high-risk locally advanced or metastatic prostate cancer: docetaxel, zoledronic acid, celecoxib, abiraterone, radiotherapy to the prostate, abiraterone with enzalutamide, metformin and transdermal oestradiol added to ADT and compared with ADT alone
Abiraterone + ADT: OS HR 0.63 in mHSPC; docetaxel + ADT: OS HR 0.78. Prostate radiotherapy improved survival in low-volume metastatic disease; abiraterone improved survival in high-risk non-metastatic disease; enzalutamide added to abiraterone, zoledronic acid, celecoxib and metformin did not improve survival.
- Low-dose bath to normal tissue
- Motion management
- Size and location limits
- Late toxicity near central airways
- Between IMRT / IGRT (modern external beam) and SBRT / SABR (stereotactic radiotherapy), which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- How closely do I match the people in STAMPEDE, and does that change what the results mean for me?Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Prostate Cancer), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (low-volume disease), which of the standard options do you recommend and why?Why: Guideline options include: Doublet therapy plus radiotherapy to the prostate (STAMPEDE); metastasis-directed radiotherapy within trials.
- How do the results of STAMPEDE apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Add these to your appointment list, or take the full question set for this cancer.
Biomarker-selected additions (2026)
Capivasertib with abiraterone for PTEN-deficient tumours (CAPItello-281); 177Lu-PSMA-617 with androgen receptor pathway inhibitor for PSMA-positive disease (PSMAddition).
Capivasertib (Truqap) is the first AKT inhibitor, for breast cancer with PI3K-pathway mutations and, since 2026, for prostate cancer with PTEN loss.
A radioactive drug that seeks out PSMA on prostate cancer cells; the best-selling radiopharmaceutical ever.
- Tests CapivasertibDe novo metastatic hormone-sensitive prostate cancer with PTEN deficiency: abiraterone + capivasertib vs abiraterone + placebo
rPFS significantly improved (HR reported at presentation); approved 2026.
Radiographic progression-free survival, PTEN-deficient mHSPC (months): Capivasertib + abiraterone + ADT 40 vs Placebo + abiraterone + ADT 31.7 · HR 0.81 · source - PSMA-positive metastatic hormone-sensitive prostate cancer: 177Lu-PSMA-617 + ADT + ARPI vs ADT + ARPI
rPFS HR 0.72 (updated 0.67); OS HR 0.80 (NS, immature).
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Cutaneous adverse reactions · CAPItello-291 | 56% | 15% |
| Diarrhoea · CAPItello-291 | 77% | 12% |
| Fatigue · CAPItello-291 | 38% | 1.9% |
| Stomatitis · CAPItello-291 | 25% | 1.9% |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Lymphocytes decreased · VISION | 85% | 47% |
| Haemoglobin decreased · VISION | 64% | 15% |
| Platelets decreased · VISION | - | 9% |
| Fatigue · VISION | 48% | - |
- Radiation safety counselling; hydrate and void often. No pharmacokinetic drug interactions; concurrent myelosuppressive therapy adds cytopenia risk.
- Not studied below CrCl 50; renal irradiation is dose-limiting over multiple cycles.
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
- Between Capivasertib and Lutetium-177 vipivotide tetraxetan, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- How closely do I match the people in CAPItello-281 and PSMAddition, and does that change what the results mean for me?Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
- Which side effects of Capivasertib or Lutetium-177 vipivotide tetraxetan are most likely for me, which are reversible, and which would make us stop?Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- For my situation (biomarker-selected additions (2026)), which of the standard options do you recommend and why?Why: Guideline options include: Capivasertib with abiraterone for PTEN-deficient tumours (CAPItello-281); 177Lu-PSMA-617 with androgen receptor pathway inhibitor for PSMA-positive disease (PSMAddition).
- Am I a candidate for Capivasertib, Lutetium-177 vipivotide tetraxetan, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of CAPItello-281 and PSMAddition apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Add these to your appointment list, or take the full question set for this cancer.