Key points
- Prostate cancer is the second most common cancer in men worldwide [1].
- Having a PSA test for screening in men aged 55 to 69 is an individual decision that should be made after talking with a doctor about its benefits and harms [2].
- Having an MRI before a biopsy increases the detection of clinically significant cancers and reduces the detection of insignificant ones [5].
- Many low-risk cancers can be followed with active surveillance, without immediate treatment; in the ProtecT trial, deaths from prostate cancer after 15 years were low in all groups [8].
- In advanced disease, adding new-generation hormonal drugs such as abiraterone or enzalutamide to hormone therapy (and, in high-volume disease, docetaxel chemotherapy), chemotherapy and the PARP inhibitor olaparib in castration-resistant disease, and lutetium-177–PSMA radioligand therapy have all improved survival [9, 17, 21, 27, 32].
What is prostate cancer?
The prostate is a small, walnut-sized gland below the bladder in men that makes part of the seminal fluid. Prostate cancer develops when the cells of this gland grow out of control. Almost all cases are adenocarcinomas, and how aggressive they are is measured by Gleason/ISUP grading [7].
Prostate cancer is the second most common cancer in men worldwide [1]. Importantly, the behavior of this disease varies greatly: many tumors grow very slowly and may never cause a problem during a man’s lifetime, while others are aggressive and need active treatment [2]. That is why decisions about screening and treatment should be individual and carefully considered.
Signs and symptoms
In its early stages, prostate cancer usually causes no symptoms, and many men who have it never find out unless they are tested [2]. In more advanced stages, the following symptoms may appear:
- Urinary problems, such as a weak stream, frequent urination or waking up often at night to urinate
- Blood in the urine or semen
- New erectile dysfunction
- Bone pain (especially in the back, hips or ribs), unexplained weight loss or fatigue
Keep in mind that urinary symptoms in older men are more often caused by benign enlargement of the prostate, but they should still be checked by a doctor.
When should I contact my doctor?
Contact your doctor or treatment team without delay in these situations:
- Weakness, numbness or tingling in the legs, difficulty walking or worsening bone pain, especially in the first weeks of hormone therapy; a temporary rise in testosterone during this period can make the symptoms of the disease worse, and pressure on the spinal cord can lead to paralysis [47].
- Blood in the urine or being unable to pass urine [47].
- Chest pain, sudden weakness on one side of the body or difficulty speaking during hormone therapy; an increased risk of heart attack and stroke has been reported with these drugs [47].
- Fever during chemotherapy; take your temperature regularly and report any fever immediately [41].
Risk factors, prevention and screening
The most important risk factors for prostate cancer are:
- Increasing age: the risk rises sharply with age [2].
- Family history: having a father or brother with prostate cancer increases the risk [2].
- Race: Black men of African descent are at higher risk [2].
- Inherited genetic mutations: in particular, a BRCA2 mutation is associated with more aggressive cancer and is taken into account in risk-based screening [4].
No definite way to prevent prostate cancer is known so far; the main focus is therefore on timely detection of significant cancers and on avoiding overtreatment of low-risk cancers [4].
PSA screening and shared decision-making
Prostate-specific antigen (PSA) is a protein measured with a simple blood test. A raised level can be a sign of cancer, but it also rises with benign prostate enlargement or inflammation.
The US Preventive Services Task Force (USPSTF) recommends that the decision to have PSA screening in men aged 55 to 69 be an individual one, made after discussing the benefits and harms with a doctor (grade C recommendation); the task force recommends against screening in men aged 70 and older (grade D recommendation) [2]. Based on trial evidence, screening men aged 55 to 69 may prevent about 1.3 deaths from prostate cancer per 1000 men screened over about 13 years [2].
At 23 years of follow-up in the European ERSPC trial, prostate cancer mortality was 13% lower in the screening group (rate ratio 0.87), and one death was prevented for every 456 men invited to screening [3]. On the other hand, screening brings overdiagnosis (detection of cancers that would never have caused harm), false-positive results and possible treatment complications such as urinary incontinence and erectile dysfunction [2, 3]. The European Association of Urology guideline (EAU, 2026 edition) recommends a risk-based approach: offering a PSA test to well-informed men from age 50, from age 45 for men with a family history of prostate cancer diagnosed before age 60 or of African descent, and from age 40 for BRCA2 mutation carriers; in men with a life expectancy of less than 15 years, a benefit from screening is unlikely [4].
A PSA test is simple, but its result may lead you down a path of further tests and decisions. Ask your doctor: given my age, family history and health, what are the benefits and risks of a PSA test for me? If the result is high, what is the next step? The final decision is yours, and either choice deserves respect as long as it is an informed one [2].
Diagnosis and staging
Diagnostic pathway for prostate cancer
- 1
PSA test and examination
PSA measurement and, if needed, a digital rectal examination of the prostate; a high PSA is usually repeated before any further steps.
- 2
- 3
Targeted biopsy
If MRI shows a suspicious lesion, a targeted biopsy is performed together with samples from around the lesion. The EAU guideline prefers the transperineal route because of its lower risk of infection, and when the MRI is negative and clinical suspicion is low, it suggests forgoing biopsy and monitoring PSA instead [4].
- 4
Gleason score and ISUP grade group
The pathologist determines how aggressive the tumor is using the Gleason score and the ISUP grade group (1 to 5) [7].
- 5
Gleason/ISUP grading and biomarkers
| ISUP grade group | Gleason score | Clinical meaning |
|---|---|---|
| Group 1 | 6 or less (3+3) | Lowest risk; usually suitable for active surveillance [4] |
| Group 2 | 7 (3+4) | Favorable intermediate risk; active surveillance may be considered in selected patients [4] |
| Group 3 | 7 (4+3) | Unfavorable intermediate risk; usually active treatment |
| Group 4 | 8 | High risk |
| Group 5 | 9 and 10 | Most aggressive; requires multimodal treatment |
In metastatic disease, testing for mutations in DNA repair genes (such as BRCA1, BRCA2 and ATM) to select PARP inhibitors [14, 15, 16] and PSMA imaging to select radioligand therapy [17, 18] are important.
Treatment by stage
Active surveillance
For low-risk cancer and some favorable intermediate-risk cases: regular follow-up with PSA, MRI and repeat biopsy, with treatment started only if the disease progresses [4].
Surgery (radical prostatectomy)
Radiation therapy
External-beam radiotherapy or brachytherapy, often combined with a course of hormone therapy in intermediate- and high-risk disease [4]. In high-risk disease without metastases, adding 2 years of abiraterone + prednisolone to 3 years of hormone therapy (usually with radiotherapy) has improved survival [33].
Biochemical recurrence
Metastatic hormone-sensitive disease
Hormone therapy (ADT) plus an androgen receptor pathway inhibitor (ARPI) such as abiraterone, enzalutamide, apalutamide or darolutamide [10, 27, 28, 53]; in high-volume disease and in patients fit for chemotherapy, triplet therapy with ADT + docetaxel + an ARPI [11, 12, 22]. In PSMA-positive patients, adding lutetium-177–PSMA radioligand therapy to ADT + an ARPI has delayed disease progression and received FDA approval in 2026 [36, 46].
Castration-resistant disease
New-generation hormonal drugs (abiraterone or enzalutamide) in patients who have not received them before [25, 26], chemotherapy with docetaxel and then cabazitaxel [31, 32], the PARP inhibitor olaparib alone or with abiraterone in patients with mutations [14, 22, 30], and lutetium-177–PSMA radioligand therapy in PSMA-positive patients [17, 18].
Disease confined to the prostate
Active surveillance, surgery and radiotherapy are all accepted options, and in the ProtecT trial deaths from prostate cancer after 15 years were low with all three approaches [8]. Choosing among them means weighing the benefits against the side effects, together with the patient’s own preferences.
Advanced disease
In metastatic disease, hormone therapy (ADT) is the foundation of treatment, but today it is not enough on its own: it is given together with a new-generation hormonal drug and, in some patients, with chemotherapy as well [22]. When the disease progresses despite a low testosterone level, options are chosen according to previous treatments, the tumor’s genetic profile and PSMA expression [22, 35]; this is why genetic testing is recommended for all patients with castration-resistant disease [22].
What should I do after a diagnosis?
Frequently asked questions
Does a high PSA mean I definitely have cancer?
No. PSA also rises with benign prostate enlargement, inflammation or infection, and many high results are false positives [2]. The test is usually repeated, and an MRI is done if needed [4, 5]. Full answer (Persian)
Why is an MRI done before a biopsy?
If I choose active surveillance, will I miss my chance for treatment?
In the ProtecT trial, after 15 years, deaths from prostate cancer in the active surveillance group did not differ significantly from those in the surgery and radiotherapy groups, although disease spread was more common in the surveillance group [8]. That is why regular, careful follow-up is essential.
What is PSMA PET?
Evidence and recent advances (for physicians)
For physicians
Diagnosis and staging
In PRECISION (500 biopsy-naive patients), MRI ± targeted biopsy was not only non-inferior but superior to systematic TRUS biopsy (adjusted difference of 12 percentage points in the detection of clinically significant cancer) and reduced the detection of clinically insignificant cancer by 13 percentage points [5]. In proPSMA, PET-CT with 68Ga-PSMA-11 had 27% higher accuracy than CT and bone scan in high-risk disease, with lower radiation exposure [6].
Localized disease: active surveillance, surgery or radiotherapy
In the ProtecT trial, 1643 men with PSA-detected localized prostate cancer were assigned to active surveillance, surgery or radiotherapy. After a median follow-up of 15 years, prostate cancer mortality was low and similar in all three groups (3.1% with active surveillance, 2.2% with surgery and 2.9% with radiotherapy) [8]. However, metastases were more frequent in the active surveillance group (9.4% vs 4.7% and 5.0%), and about a quarter of the men in the surveillance group (24.4%) were alive without any treatment at the end of follow-up [8].
High-risk localized disease
In a meta-analysis of two STAMPEDE trials (1974 high-risk non-metastatic patients; 85% with planned radiotherapy), adding abiraterone + prednisolone for 2 years to three-year ADT improved metastasis-free survival (6-year 82% vs 69%; HR 0.53) and increased overall survival (HR 0.60); adding enzalutamide concurrently gave no benefit and only increased toxicity (grade 3 or higher adverse events 58% vs 32%) [33].
High-risk biochemical recurrence
In EMBARK (1068 patients with a PSA doubling time of 9 months or less), enzalutamide + leuprolide increased 5-year metastasis-free survival to 87.3% vs 71.4% (HR 0.42) [13]. In the final analysis, 8-year overall survival was 78.9% vs 69.5% (HR 0.60; P<0.001), whereas enzalutamide monotherapy did not show a significant overall survival advantage (HR 0.83; P=0.19) [19].
mHSPC
In LATITUDE (1199 patients with newly diagnosed mCSPC), abiraterone + prednisone with ADT improved radiographic progression-free survival (33.0 vs 14.8 months; HR 0.47) [23], and in the final analysis (median follow-up 51.8 months) increased median overall survival from 36.5 to 53.3 months (HR 0.66) [27]. In ARCHES (1150 patients with mHSPC), enzalutamide + ADT reduced the risk of radiographic progression or death (HR 0.39), with similar benefit across subgroups by disease volume and prior docetaxel [24], and in the final analysis reduced the risk of death by 34% (HR 0.66) [28]. In CHAARTED, six cycles of docetaxel with ADT increased median overall survival from 47.2 to 57.6 months in the long-term analysis (HR 0.72); the benefit was confined to high-volume disease (51.2 vs 34.4 months; HR 0.63) and was not seen in low-volume disease (HR 1.04) [9]. In TITAN, apalutamide + ADT improved overall survival (HR 0.67; 24-month survival 82.4% vs 73.5%) [10]. In ARANOTE (669 patients with mHSPC; 2:1 randomization), darolutamide + ADT without chemotherapy reduced the risk of radiographic progression or death by 46% (HR 0.54; 95% CI 0.41 to 0.71), with consistent benefit across subgroups, including high- and low-volume disease [53]; on this basis, the FDA has also approved darolutamide without docetaxel for mCSPC, and in the label data the improvement in overall survival was not statistically significant (HR 0.78; 95% CI 0.58 to 1.05) [40]. Two trials support triplet therapy: PEACE-1, in which, in the ADT + docetaxel population, adding abiraterone improved radiographic progression-free survival (HR 0.50) and overall survival (HR 0.75) at the cost of a modest increase in toxicity, mainly hypertension [12], and ARASENS (darolutamide + ADT + docetaxel; HR for death 0.68) [11]. In AMPLITUDE (696 patients with mCSPC and HRR gene alterations), niraparib + abiraterone/prednisone improved radiographic progression-free survival in the BRCA subgroup (HR 0.52) and in the overall population (HR 0.63); overall survival data are still immature, and grade 3–4 adverse events were more frequent (75% vs 59%) [16].
mCRPC
In chemotherapy-naive patients, abiraterone + prednisone in COU-AA-302 increased radiographic progression-free survival from 8.3 to 16.5 months (HR 0.53) [25], and enzalutamide in PREVAIL reduced the risk of death by 29% (HR 0.71) and increased 12-month radiographic progression-free survival to 65% vs 14% [26]. In PROfound (cohort A: BRCA1/2 or ATM), olaparib after progression on an ARPI increased imaging-based progression-free survival to 7.4 vs 3.6 months (HR 0.34) [14], and in the final analysis, despite crossover of 67% of control patients, increased median overall survival from 14.7 to 19.1 months (HR 0.69) [21]. In TAX327, docetaxel every 3 weeks with prednisone reduced the risk of death compared with mitoxantrone (HR 0.76; median 18.9 vs 16.5 months) [31]. In CARD (255 patients previously treated with docetaxel who had progressed within 12 months on an ARPI), cabazitaxel improved imaging-based progression-free survival (8.0 vs 3.7 months; HR 0.54) and overall survival (13.6 vs 11.0 months; HR 0.64) compared with switching to another ARPI [32].
PARP inhibitor plus ARPI in first-line mCRPC
In PROpel (not selected by mutation status), olaparib + abiraterone improved imaging-based progression-free survival (24.8 vs 16.6 months; HR 0.66) [29], but in the final analysis the difference in overall survival was not significant (42.1 vs 34.7 months; HR 0.81; p=0.054), and grade 3–4 anemia occurred in 16% [30]. ESMO 2026 recommends abiraterone–olaparib, enzalutamide–talazoparib or abiraterone–niraparib for patients with BRCA alterations who have not previously received an ARPI [I, A] [22]. In TALAPRO-2, talazoparib + enzalutamide in first-line mCRPC improved radiographic progression-free survival (median not reached vs 21.9 months; HR 0.63); anemia was the most common grade 3–4 adverse event (46%) [15]. In the final analysis (median follow-up 52.5 months), overall survival was also improved (median 45.8 vs 37.0 months; HR 0.80); the benefit was more pronounced in patients with HRR deficiency (HR 0.55) and was not significant in patients without deficiency or with unknown status (HR 0.88) [20].
Radioligand therapy
In VISION (831 PSMA-positive patients after an ARPI and a taxane), lutetium-177–PSMA-617 plus standard care increased both imaging-based progression-free survival (8.7 vs 3.4 months; HR 0.40) and overall survival (15.3 vs 11.3 months; HR 0.62) [17]. In PSMAfore (468 taxane-naive patients who had progressed once on an ARPI), the drug improved radiographic progression-free survival compared with an ARPI switch (updated analysis: 11.60 vs 5.59 months; HR 0.49), with fewer grade 3–5 adverse events (36% vs 48%) [18]; in the final analysis, with 60.3% of control patients crossing over to lutetium, overall survival did not differ significantly (24.48 vs 23.13 months; HR 0.91) [34]. In PSMAddition (1144 patients with PSMA-positive mHSPC), adding lutetium-177–PSMA-617 to ADT + an ARPI improved radiographic progression-free survival (HR 0.72), with more grade ≥3 adverse events (51% vs 43%) [36]. In July 2026, the FDA approved lutetium-177–PSMA-617 with an ARPI for PSMA-positive metastatic prostate cancer that is androgen pathway modulation-naive or -sensitive (mAPMN/S) [46].
Summary of the 2026 ESMO guideline
The new ESMO guideline no longer generally recommends ADT alone or ADT + docetaxel [I, D]; ADT + an ARPI is recommended for low-volume de novo mCSPC [I, A], and triplet therapy for high-volume de novo disease in patients suitable for docetaxel [II, A]. Genomic testing for at least BRCA1, BRCA2, CDK12 and PALB2 is recommended for all patients with CRPC, preferably before the first treatment for mCRPC [III, A] [22]. The second part of the 2026 EAU guideline also highlights the expanding options for metastatic disease, including ARPIs, metastasis-directed therapy, PARP inhibitors and their combinations, and PSMA-based therapy [35].
Treatment regimens and dosing (for physicians)
Treatment regimens and doses: index18 regimens
These notes apply to all the regimens below that contain these drugs; the note of each regimen mentions only what differs.
- Genetic testing before choosing treatment: the choice of a PARP inhibitor depends on identifying alterations in homologous recombination repair genes (especially BRCA1/2) in tumor tissue or in the germline; the greatest benefit in the trials was seen in patients with BRCA mutations [14, 16]. A BRCA2 mutation is also relevant for risk-based screening of relatives [4].
- Abiraterone acetate (for the niraparib/abiraterone combination tablet, see the note of that regimen): moderate hepatic impairment (Child-Pugh B): 250 mg once daily; do not use in Child-Pugh C. ALT, AST and bilirubin before starting, every 2 weeks for the first 3 months and monthly thereafter; blood pressure, potassium and fluid retention at least monthly. If ALT/AST rises above 5 times or bilirubin above 3 times the upper limit of normal, withhold and, after recovery, resume at 750 mg, and at 500 mg if it recurs; ALT above 3 times with bilirubin above 2 times the upper limit of normal: discontinue permanently. Combination with radium-223 is not recommended. With a strong CYP3A4 inducer, give the dose twice daily, only for the duration of concomitant use [37].
- Enzalutamide: for grade 3 or higher adverse reactions, withhold for one week, then resume at the same dose or at 120 or 80 mg; with a strong CYP2C8 inhibitor, 80 mg, and with a strong CYP3A4 inducer, 240 mg. Discontinue permanently if a seizure occurs; assess the risk of falls, fractures and ischemic heart disease [38].
- Darolutamide: for grade 3 or higher adverse reactions, withhold or reduce to 300 mg twice daily (lower doses are not recommended); in severe renal impairment (eGFR 15 to 29, not on dialysis) or moderate hepatic impairment: 300 mg twice daily [40].
- Docetaxel: premedication: oral dexamethasone 8 mg at 12, 3 and 1 hours before the infusion [41, 51]. Give only with neutrophils ≥1500/mm³; do not give if bilirubin is above normal or if AST/ALT is more than 1.5 times with alkaline phosphatase more than 2.5 times the upper limit of normal, and perform liver tests before each cycle. For febrile neutropenia, neutrophils below 500 for more than one week, severe skin reactions or moderate neurosensory symptoms, reduce the dose to 60 mg/m², and discontinue if they recur [41].
- PARP inhibitors: complete blood count before starting and regularly during treatment; the monitoring schedule and discontinuation thresholds for each drug are given in the note of the respective regimen [43, 44, 45].
For physicians
Backbone hormone therapy, high-risk localized disease and biochemical recurrence
ADT (androgen deprivation): GnRH agonist or antagonist
Backbone of treatment for metastatic disease (together with a second agent) and given with radiotherapy in intermediate- and high-risk disease; continued in the castration-resistant phase
Backbone of treatment for metastatic disease (together with a second agent) and given with radiotherapy in intermediate- and high-risk disease; continued in the castration-resistant phase
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Leuprolide depot (Lupron Depot) | 7.5 or 22.5 or 30 or 45 mg | IM | Every 4, 12, 16 or 24 weeks, respectively |
| Subcutaneous leuprolide (Eligard) | 7.5 or 22.5 or 30 or 45 mg | SC | Every 1, 3, 4 or 6 months, respectively |
| Degarelix (GnRH antagonist) | Starting dose 240 mg (two 120-mg injections), then 80 mg | SC, abdomen only | Maintenance dose every 28 days; the first one 28 days after the starting dose |
Radiotherapy + ADT + 2 years of abiraterone (STAMPEDE)
High-risk non-metastatic prostate cancer: nodal involvement, or at least two of T3/T4, Gleason 8 to 10, PSA ≥40 ng/mL (or relapse with high-risk features); WHO performance status 0 to 2Cycle length: Continuous
High-risk non-metastatic prostate cancer: nodal involvement, or at least two of T3/T4, Gleason 8 to 10, PSA ≥40 ng/mL (or relapse with high-risk features); WHO performance status 0 to 2
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| ADT | Per formulation | — | Continuous for 3 years |
| Abiraterone acetate | 1000 mg once daily | Oral, on an empty stomach | Daily for 2 years |
| Prednisolone | 5 mg once daily | Oral | Daily with abiraterone |
| Radiotherapy to the prostate and seminal vesicles | 74 Gy in 37 fractions or a hypofractionated equivalent | External-beam radiotherapy | Mandatory for N0 and recommended for N+ |
STAMPEDE trial regimen; adding enzalutamide concurrently gave no benefit and only increased toxicity [33]. In this regimen, prednisolone 5 mg is given once daily.
Evidence: STAMPEDE (2022), STAMPEDE (2017)
Enzalutamide ± leuprolide (EMBARK)
High-risk biochemical recurrence after prostatectomy and/or radiotherapy: PSA doubling time of 9 months or less, PSA ≥1 ng/mL after prostatectomy or at least 2 above the nadir after radiotherapy alone, no metastases on conventional imaging, and unsuitable for salvage radiotherapyEach drug’s schedule in the table
High-risk biochemical recurrence after prostatectomy and/or radiotherapy: PSA doubling time of 9 months or less, PSA ≥1 ng/mL after prostatectomy or at least 2 above the nadir after radiotherapy alone, no metastases on conventional imaging, and unsuitable for salvage radiotherapy
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Enzalutamide | 160 mg once daily | Oral, with or without food; swallow whole | Daily |
| Leuprolide | 3-month formulation (22.5 mg) | IM or SC | Every 12 weeks |
The FDA label allows enzalutamide in this setting with or without a GnRH analog, but an overall survival advantage was shown only for the combination with leuprolide [13, 19, 38]. If PSA is undetectable after 36 weeks, treatment is suspended and resumed when PSA reaches ≥2.0 ng/mL (after prostatectomy) or ≥5.0 (after primary radiotherapy) [38].
Evidence: EMBARK (2026), EMBARK (2023)
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Metastatic hormone-sensitive disease (mHSPC)
ADT + abiraterone + prednisone (LATITUDE)
mHSPC; in LATITUDE, newly diagnosed disease with at least 2 high-risk factors (Gleason ≥8, ≥3 bone lesions, measurable visceral metastases); ECOG 0 to 2Cycle length: Continuous
mHSPC; in LATITUDE, newly diagnosed disease with at least 2 high-risk factors (Gleason ≥8, ≥3 bone lesions, measurable visceral metastases); ECOG 0 to 2
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Abiraterone acetate | 1000 mg once daily | Oral, fasting (no food for 2 h before and 1 h after the dose); swallow tablets whole | Daily |
| Prednisone | 5 mg once daily | Oral | Daily |
| ADT (GnRH agonist or antagonist, or prior orchiectomy) | Per formulation | — | Continuous |
Evidence: LATITUDE (2019), LATITUDE (2017)
ADT + enzalutamide (ARCHES)
mHSPC regardless of disease volume; prior docetaxel (up to 6 cycles) allowed; ECOG 0 to 1Cycle length: Continuous
mHSPC regardless of disease volume; prior docetaxel (up to 6 cycles) allowed; ECOG 0 to 1
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Enzalutamide | 160 mg once daily | Oral, with or without food | Daily |
| ADT (GnRH agonist or antagonist, or prior orchiectomy) | Per formulation | — | Continuous |
Evidence: ARCHES (2022), ARCHES (2019)
ADT + apalutamide (TITAN)
mHSPC with at least one bone metastasis, high or low volume; ECOG 0 to 1Cycle length: Continuous
mHSPC with at least one bone metastasis, high or low volume; ECOG 0 to 1
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Apalutamide | 240 mg once daily | Oral, with or without food; swallow the tablets whole | Daily |
| ADT (GnRH agonist or antagonist, or prior orchiectomy) | Per formulation | — | Continuous |
Dose per the FDA label and the trial [10, 39]. For grade 3–4 adverse reactions, withhold, then resume at the same dose or at 180 or 120 mg; severe hepatic impairment (Child-Pugh C): 120 mg. Warnings: cardiac and cerebrovascular ischemic events, fractures and falls, seizures (0.4%; discontinue permanently), severe cutaneous reactions (SJS/TEN and DRESS) and pneumonitis [39].
Evidence: TITAN (2019)
ADT + darolutamide (ARANOTE)
mCSPC without docetaxel (FDA label indication); in ARANOTE, consistent benefit in high- and low-volume diseaseCycle length: Continuous
mCSPC without docetaxel (FDA label indication); in ARANOTE, consistent benefit in high- and low-volume disease [40, 53]
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Darolutamide | 600 mg (2 × 300-mg tablets) twice daily | Oral, with food | Daily |
| ADT (GnRH agonist or antagonist, or prior orchiectomy) | Per formulation | — | Continuous |
Triplet therapy: ADT + docetaxel + abiraterone (PEACE-1)
De novo mHSPC (especially high-volume) in patients suitable for docetaxel; ECOG 0 to 1 (or 2 because of bone pain)Each drug’s schedule in the table
De novo mHSPC (especially high-volume) in patients suitable for docetaxel; ECOG 0 to 1 (or 2 because of bone pain)
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Docetaxel | 75 mg/m² | IV | Day 1 every 3 weeks, 6 cycles |
| Abiraterone acetate | 1000 mg once daily | Oral, on an empty stomach | Daily |
| Prednisone | 5 mg twice daily | Oral | Daily |
| ADT (GnRH agonist or antagonist, or prior orchiectomy) | Per formulation | — | Continuous |
Doses from the PEACE-1 trial and its ClinicalTrials.gov registration; in PEACE-1 there was an interval of at least 6 weeks between the start of ADT and the start of docetaxel [12, 52]. Adding abiraterone mainly increased hypertension (grade 3 or higher 22% vs 13%) and did not increase neutropenia or neuropathy [12].
Evidence: PEACE-1 (2022)
Triplet therapy: ADT + docetaxel + darolutamide (ARASENS)
mHSPC (especially high-volume de novo disease) in patients suitable for docetaxel; ECOG 0 to 1; ADT started no more than 12 weeks before treatmentEach drug’s schedule in the table
mHSPC (especially high-volume de novo disease) in patients suitable for docetaxel; ECOG 0 to 1; ADT started no more than 12 weeks before treatment
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Darolutamide | 600 mg (2 × 300-mg tablets) twice daily | Oral, with food | Daily, continuous |
| Docetaxel | 75 mg/m² | IV, 1-h infusion | Day 1 every 21 days; first cycle within 6 weeks after starting darolutamide |
| ADT (GnRH agonist or antagonist, or prior orchiectomy) | Per formulation | — | Continuous |
Per the FDA label and the trial [11, 40]; in ARASENS, prednisone or prednisolone with docetaxel was at the physician’s discretion [11].
Evidence: ARASENS (2022)
Before prescribing, check each dose against the drug label, laboratory tests and the patient’s condition.
Castration-resistant disease (mCRPC): new-generation hormone therapy and chemotherapy
Abiraterone + prednisone (COU-AA-302)
mCRPC with no prior ARPI, before or after docetaxel; in COU-AA-302, asymptomatic or mildly symptomatic, ECOG 0 to 1, no visceral metastasesCycle length: Continuous
mCRPC with no prior ARPI, before or after docetaxel; in COU-AA-302, asymptomatic or mildly symptomatic, ECOG 0 to 1, no visceral metastases
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Abiraterone acetate | 1000 mg once daily | Oral, on an empty stomach | Daily |
| Prednisone | 5 mg twice daily | Oral | Daily |
| ADT (GnRH agonist or antagonist, or prior orchiectomy) | Per formulation | — | Continuous |
Dose per the FDA label and the trial [25, 37]. In mCRPC, prednisone 5 mg is given twice daily (once daily in mCSPC) [37].
Evidence: COU-AA-302 (2013)
Enzalutamide (PREVAIL)
mCRPC with no prior ARPI, before or after docetaxel; visceral metastases allowed; a history of seizures was an exclusion criterion in the trialCycle length: Continuous
mCRPC with no prior ARPI, before or after docetaxel; visceral metastases allowed; a history of seizures was an exclusion criterion in the trial
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Enzalutamide | 160 mg once daily | Oral, with or without food | Daily |
| ADT (GnRH agonist or antagonist, or prior orchiectomy) | Per formulation | — | Continuous |
Evidence: PREVAIL (2014)
Docetaxel + prednisone (TAX327)
mCRPC; in TAX327, Karnofsky performance status 60 or higherEach drug’s schedule in the table
mCRPC; in TAX327, Karnofsky performance status 60 or higher
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Docetaxel | 75 mg/m² | IV, 1-h infusion | Day 1, every 21 days |
| Prednisone | 5 mg twice daily | Oral | Continuous |
| ADT (GnRH agonist or antagonist, or prior orchiectomy) | Per formulation | — | Continuous |
Evidence: TAX 327 (2004)
Cabazitaxel + prednisone (CARD)
mCRPC after docetaxel; in CARD, after progression within 12 months on abiraterone or enzalutamide, it was superior to switching to another ARPIEach drug’s schedule in the table
mCRPC after docetaxel; in CARD, after progression within 12 months on abiraterone or enzalutamide, it was superior to switching to another ARPI
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Cabazitaxel | 20 mg/m² (recommended label dose); 25 mg/m² in CARD and in selected patients | IV, 1-h infusion | Day 1, every 21 days |
| Prednisone | 10 mg once daily | Oral | Continuously throughout treatment |
| ADT (GnRH agonist or antagonist, or prior orchiectomy) | Per formulation | — | Continuous |
Per the FDA label [42] and the CARD trial, which used 25 mg/m² with primary G-CSF prophylaxis [32, 50]. Premedication 30 minutes before each dose (IV): an antihistamine (diphenhydramine 25 mg or equivalent), dexamethasone 8 mg and an H2 antagonist; antiemetic prophylaxis. Primary G-CSF prophylaxis is recommended in high-risk patients and should be considered for all patients at the 25 mg/m² dose. Contraindications: neutrophils ≤1500 and severe hepatic impairment (bilirubin more than 3 times the upper limit of normal); moderate hepatic impairment: 15 mg/m². Weekly blood counts during the first cycle and before each cycle. Dose reduction: from 25 to 20 and then 15 mg/m²; grade 3 or higher neuropathy: discontinue. Do not use PVC containers or infusion sets [42].
Evidence: CARD (2019)
Before prescribing, check each dose against the drug label, laboratory tests and the patient’s condition.
With DNA repair gene mutations (HRR/BRCA): PARP inhibitors in mCSPC and mCRPC
Single-agent olaparib (PROfound)
mCRPC with HRR gene mutations (greatest benefit with BRCA1, BRCA2 and ATM) after progression on enzalutamide or abirateroneCycle length: Continuous
mCRPC with HRR gene mutations (greatest benefit with BRCA1, BRCA2 and ATM) after progression on enzalutamide or abiraterone
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Olaparib | 300 mg twice daily | Oral, with or without food; swallow the tablets whole | Daily |
| ADT (GnRH agonist or antagonist, or prior orchiectomy) | Per formulation | — | Continuous |
Per the FDA label and the trial [14, 21, 43]. Moderate renal impairment (CrCl 31 to 50): 200 mg twice daily. Dose reduction: 250 mg, then 200 mg twice daily; with a strong CYP3A inhibitor, 100 mg twice daily, and with a moderate inhibitor, 150 mg twice daily. Complete blood count at baseline and monthly thereafter; warnings: MDS/AML, pneumonitis and venous thromboembolism [43].
Evidence: PROfound (2020), PROfound (2020)
Olaparib + abiraterone (PROpel)
First-line mCRPC with a BRCA mutation (FDA label indication; ESMO: abiraterone–olaparib for BRCA alterations without prior ARPI)Cycle length: Continuous
First-line mCRPC with a BRCA mutation (FDA label indication; ESMO: abiraterone–olaparib for BRCA alterations without prior ARPI) [22]
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Olaparib | 300 mg twice daily | Oral | Daily |
| Abiraterone acetate | 1000 mg once daily | Oral, on an empty stomach | Daily |
| Prednisone or prednisolone | 5 mg twice daily | Oral | Daily |
| ADT (GnRH agonist or antagonist, or prior orchiectomy) | Per formulation | — | Continuous |
Per the FDA label and the trial [29, 30, 43]. Grade 3–4 anemia occurred in 16% [30]; olaparib dose modifications and monitoring as in the PROfound regimen [43].
Evidence: PROpel (2023), PROpel (2022)
Talazoparib + enzalutamide (TALAPRO-2)
First-line mCRPC with HRR gene mutations (FDA label: ATM, ATR, BRCA1, BRCA2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, RAD51C)Cycle length: Continuous
First-line mCRPC with HRR gene mutations (FDA label: ATM, ATR, BRCA1, BRCA2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, RAD51C)
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Talazoparib | 0.5 mg once daily | Oral, with or without food; do not open the capsules | Daily |
| Enzalutamide | 160 mg once daily | Oral | Daily |
| ADT (GnRH agonist or antagonist, or prior orchiectomy) | Per formulation | — | Continuous |
Per the FDA label and the trial [15, 20, 44]. Talazoparib dose reductions: 0.35, 0.25 and 0.1 mg (more than 3 reductions: discontinue); CrCl 30 to 59: 0.35 mg, and CrCl 15 to 29: 0.25 mg. Monthly blood counts; withhold for hemoglobin below 8 (resume at ≥9), platelets below 50,000 (resume at ≥75,000) or neutrophils below 1000 (resume at ≥1500), then resume at a lower dose [44]. Grade 3–4 anemia occurred in 46% of trial patients [15].
Evidence: TALAPRO-2 (2025), TALAPRO-2 (2023)
Niraparib/abiraterone combination tablet (AMPLITUDE and FDA label)
BRCA2 mutation in mCSPC, or BRCA mutation in mCRPC (FDA label indications); with ADT
BRCA2 mutation in mCSPC, or BRCA mutation in mCRPC (FDA label indications); with ADT
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| mCSPC with a BRCA2 mutation | |||
| Niraparib/abiraterone acetate | 200/1000 mg once daily | Oral, on an empty stomach (at least 1 hour before or 2 hours after a meal) | Daily |
| Prednisone | 5 mg once daily | Oral | Daily |
| mCRPC with a BRCA mutation | |||
| Niraparib/abiraterone acetate | 200/1000 mg once daily | Oral, on an empty stomach | Daily |
| Prednisone | 10 mg once daily | Oral | Daily |
Per the FDA label [45]; AMPLITUDE trial (niraparib 200 + abiraterone 1000 mg + prednisone 5 mg daily in mCSPC with HRR alterations) [16]. Blood counts weekly during the first month, every 2 weeks for the next 2 months, monthly until the end of the first year and every other month thereafter. For hemoglobin below 8, platelets below 100,000 or neutrophils below 1000, withhold and, after recovery, resume at the reduced dose of 100/1000 mg (for a first drop in platelets to 75,000 or more, the same dose may also be resumed); for hepatotoxicity, resume at 100/500 mg. Monitor blood pressure, potassium and fluid retention [45]. Grade 3–4 anemia (29%) and hypertension (27%) were the most common adverse events in AMPLITUDE [16].
Evidence: AMPLITUDE (2025)
Before prescribing, check each dose against the drug label, laboratory tests and the patient’s condition.
PSMA-positive disease: radioligand therapy
Lutetium-177–PSMA-617 (VISION, PSMAfore, PSMAddition)
PSMA-positive disease on PSMA PET: mCRPC after an ARPI, either after a taxane (VISION) or to postpone a taxane (PSMAfore); and, per the FDA label, with an ARPI in ARPI-naive or ARPI-sensitive metastatic disease (PSMAddition)Each drug’s schedule in the table
PSMA-positive disease on PSMA PET: mCRPC after an ARPI, either after a taxane (VISION) or to postpone a taxane (PSMAfore); and, per the FDA label, with an ARPI in ARPI-naive or ARPI-sensitive metastatic disease (PSMAddition)
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| 177Lu-PSMA-617 (lutetium-177 vipivotide tetraxetan) | 7.4 GBq (200 mCi) | IV | Every 6 weeks |
| ADT (± ARPI in ARPI-sensitive disease) | Per each drug’s label | — | Continuous |
Per the FDA label and the trials [17, 18, 36, 46]. Patient selection by PSMA PET (centrally read in the trials). Only one 20% dose reduction, to 5.9 GBq (160 mCi), is allowed, and re-escalation is not permitted; if a second reduction is needed, discontinue; if a treatment delay due to an adverse reaction lasts more than 4 weeks, consider permanent discontinuation. Complete blood count and creatinine/creatinine clearance before and during treatment; withhold for creatinine clearance below 30 mL/min. The patient should drink plenty of water and urinate frequently before and after the infusion. Dry mouth is the most common adverse reaction. To be administered only by a physician licensed to use radiopharmaceuticals [46].
Evidence: PSMAddition (2026), PSMAfore (2025), VISION (2021)
Before prescribing, check each dose against the drug label, laboratory tests and the patient’s condition.
Scientific evidence
Key studies
29 itemsEuropean Study of Prostate Cancer Screening — 23-Year Follow-up
MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis
Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomised, multicentre study
Fifteen-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer
Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol
Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomised, double-blind, phase 3 trial
Improved Survival With Enzalutamide in Patients With Metastatic Hormone-Sensitive Prostate Cancer
Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer: Long-Term Survival Analysis of the Randomized Phase III E3805 CHAARTED Trial
Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design
Improved Survival with Enzalutamide in Biochemically Recurrent Prostate Cancer
Abiraterone in Metastatic Prostate Cancer without Previous Chemotherapy
Enzalutamide in Metastatic Prostate Cancer before Chemotherapy
Docetaxel plus Prednisone or Mitoxantrone plus Prednisone for Advanced Prostate Cancer
Cabazitaxel versus Abiraterone or Enzalutamide in Metastatic Prostate Cancer
Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer
Olaparib for Metastatic Castration-Resistant Prostate Cancer
Olaparib plus abiraterone versus placebo plus abiraterone in metastatic castration-resistant prostate cancer (PROpel): final prespecified overall survival results of a randomised, double-blind, phase 3 trial
Lutetium-177–PSMA-617 for Metastatic Castration-Resistant Prostate Cancer
Final overall survival and safety analyses of the phase III PSMAfore trial of [177Lu]Lu-PSMA-617 versus change of androgen receptor pathway inhibitor in taxane-naive patients with metastatic castration-resistant prostate cancer
[177Lu]Lu-PSMA-617 in patients with PSMA-positive metastatic androgen pathway modulator-naive/sensitive prostate cancer (PSMAddition): a phase 3 randomised, controlled trial
Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer
Talazoparib plus enzalutamide in men with metastatic castration-resistant prostate cancer: final overall survival results from the randomised, placebo-controlled, phase 3 TALAPRO-2 trial
Niraparib and abiraterone acetate plus prednisone for HRR-deficient metastatic castration-sensitive prostate cancer: a randomized phase 3 trial
Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer
ARCHES: A Randomized, Phase III Study of Androgen Deprivation Therapy With Enzalutamide or Placebo in Men With Metastatic Hormone-Sensitive Prostate Cancer
Improved Outcomes with Enzalutamide in Biochemically Recurrent Prostate Cancer
Abiraterone and Olaparib for Metastatic Castration-Resistant Prostate Cancer
177Lu-PSMA-617 versus a change of androgen receptor pathway inhibitor therapy for taxane-naive patients with progressive metastatic castration-resistant prostate cancer (PSMAfore): a phase 3, randomised, controlled trial
Talazoparib plus enzalutamide in men with first-line metastatic castration-resistant prostate cancer (TALAPRO-2): a randomised, placebo-controlled, phase 3 trial
Clinical guidelines
2 itemsEAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on Prostate Cancer—2026 Update. Part I: Screening, Diagnosis, and Local Treatment with Curative Intent
Advanced and metastatic prostate cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up
The cards above summarize the trials and guidelines that underpin today’s recommendations for prostate cancer screening, diagnosis and treatment. Select a card to see the details of the study and links to the original publication.
References
53 referencesShow all references, 36 with a study cardClose the reference list
Numbers in the text, such as [1], refer to these sources. Sources with a “Study card” button are summarised in the site’s evidence library.
- 1Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries
- 2
- 3European Study of Prostate Cancer Screening — 23-Year Follow-up
- 4
- 5
- 6
- 7
- 8
- 9Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer: Long-Term Survival Analysis of the Randomized Phase III E3805 CHAARTED Trial
- 10
- 11
- 12
- 13
- 14
- 15
- 16
- 17
- 18
- 19
- 20Talazoparib plus enzalutamide in men with metastatic castration-resistant prostate cancer: final overall survival results from the randomised, placebo-controlled, phase 3 TALAPRO-2 trial
- 21
- 22
- 23
- 24ARCHES: A Randomized, Phase III Study of Androgen Deprivation Therapy With Enzalutamide or Placebo in Men With Metastatic Hormone-Sensitive Prostate Cancer
- 25
- 26
- 27
- 28
- 29Abiraterone and Olaparib for Metastatic Castration-Resistant Prostate Cancer
- 30
- 31
- 32
- 33
- 34Final overall survival and safety analyses of the phase III PSMAfore trial of [177Lu]Lu-PSMA-617 versus change of androgen receptor pathway inhibitor in taxane-naive patients with metastatic castration-resistant prostate cancer
- 35
- 36
- 37
- 38
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- 40
- 41
- 42
- 43
- 44
- 45
- 46
- 47
- 48ELIGARD (leuprolide acetate) for injectable suspension, for subcutaneous use — Prescribing Information
- 49FIRMAGON (degarelix) for injection — Prescribing Information
- 50Cabazitaxel Versus the Switch to an Alternative Androgen-Receptor (AR)-Targeted Agent (Enzalutamide or Abiraterone) in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Patients Previously Treated With Docetaxel and Who Rapidly Failed a Prior AR-Targeted Agent (CARD) — NCT02485691
- 51Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer
- 52A Prospective Randomised Phase III Study of Androgen Deprivation Therapy With or Without Docetaxel With or Without Local Radiotherapy With or Without Abiraterone Acetate and Prednisone in Patients With Metastatic Hormone-naïve Prostate Cancer (PEACE-1) — NCT01957436
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This page is based on reputable scientific sources and was last updated on 21 October 2026. The content of this website is for educational and informational purposes only and does not replace consultation, diagnosis or treatment by a specialist physician. Consult your treating physician about any treatment decision.