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Prostate Cancer – Treatment Options According to International Guidelines 2026
What Is Prostate Cancer and Why Do International Guidelines Matter?
Prostate cancer is the most common cancer in men in the United States, with an estimated 313,780 new cases diagnosed in 2025 , representing 30% of all male cancers. In Romania, the situation is similar to global trends: incidence is increasing, but diagnosis in advanced stages remains a challenge.
Why do NCCN or ESMO guidelines matter? Because they reflect the latest expert consensus from the most prestigious oncology centers in the world and are updated several times a year, rapidly integrating the results of new clinical trials. The NCCN Guidelines version 5.2026, published in January 2026, contains significant updates over previous versions, including the approval of new precision therapies that are not yet routinely available in public hospitals.
How Is Prostate Cancer Classified? Understanding Risk Groups
The first step after diagnosis is risk stratification – that is, determining how aggressive the cancer is and how far it has spread. This classification guides all subsequent treatment decisions.
NCCN 2026 Risk Groups
| Risk Group | Main Features |
| Low Risk | cT1-cT2a, Grade Group 1, PSA < 10 ng/mL |
| Favourable Intermediate Risk | 1 intermediate risk factor, Grade Group 1-2, < 50% positive biopsies |
| Unfavorable Intermediate Risk | 2-3 risk factors, Grade Group 3, ≥ 50% positive biopsies |
| High Risk | cT3-cT4 OR Grade Group 4-5 OR PSA > 20 ng/mL |
| Very High Risk | At least two high-risk criteria |
| Regional (N1) | Metastases in regional pelvic nodes |
| Metastatic (M1) | Distant metastases (bone, visceral organs) |
Important: Version 1.2026 of the NCCN guidelines eliminated the “very low risk” group , simplifying the decision algorithm.
Modern Diagnostic Tools: Beyond PSA
PSA – The Starting Point, Not the End
The PSA (Prostate Specific Antigen) test remains the basic screening tool, but its value in isolation is not sufficient for therapeutic decisions. Numerous studies have shown that PSA alone can lead to unnecessary biopsies or, conversely, can miss aggressive cancers.
New Biomarkers Approved in 2025
According to data from recent clinical updates:
1. IsoPSA Test (FDA approved – December 2025)
- Analyzes PSA protein isoforms at the structural level
- Sensitivity: 88.7%; can avoid ~46% of unnecessary biopsies
- Recommended for men ≥ 50 years old with elevated PSA
- New: Included in the 2025 NCCN Guidelines
2. MyProstateScore 2.0 (MPS2) – NCI Validated
- 18-gene panel based on urine analysis
- Sensitivity and negative predictive value: 95% for Grade Group 2 and 99% for Grade Group 3+
- Can avoid ~40% of unnecessary biopsies
3. Johns Hopkins 3-Biomarker Panel (September 2025)
- Markers: TTC3, H4C5 and EPCAM in urine
- AUC: 0.92; detects cancer even when PSA is normal
- Sensitivity 91%, specificity 84%
Multiparametric MRI (mpMRI) – The Gold Standard
Prostate mpMRI is now recommended as standard before biopsy for:
- Detection of clinically significant cancers (Grad Group ≥ 2)
- Evaluation of extracapsular extension
- Targeted biopsy guidance
PET Imaging with PSMA – The Diagnostic Revolution
PSMA-PET/CT or PSMA-PET/MRI is the most sensitive and specific imaging tool available in 2026 for prostate cancer. It is recommended in:
- Initial staging of disease with intermediate, poor, high, or very high risk
- Detection of biochemical relapse
- Evaluation before Lutetium-177 therapy
NCCN Guideline 5.2026 lists three FDA-approved PSMA-PET agents :
- Ga-68 PSMA-11 (sensitivity 40%, specificity 95% for lymph nodes)
- F-18 piflufolastat (DCFPyL)
- F-18 flotufolast PSMA
- New 2025: Gallium-68 Gozetotide (Gozellix) – FDA approved in March 2025
Treatment Options by Stage – Complete Guide 2026
1. LOCALIZED DISEASE – LOW RISK
Active Surveillance (Preferred – Recommended by First Intention)
What it means: You don’t treat the cancer right away, but you monitor it closely, intervening curatively only if it progresses.
Who is the ideal candidate?
- Low-risk patients with life expectancy > 10 years
- Selected patients with favorable intermediate risk
NCCN 2026 Monitoring Protocol:
- PSA at most 6 months
- Rectal exam at least 12 months
- Repeat biopsy every 1-3 years (no more often than 12 months)
- mpMRI considered at most 12 months
How safe is it? Approximately 50% of eligible patients can avoid active treatment for 10 years without negative oncological consequences.
Note: Factors that may suggest a higher risk of progression include: high PSA density (≥ 0.15), increased number of positive biopsies, BRCA2 germline mutation, or increased genomic risk. In these cases, upfront treatment may be preferable.
2. LOCALIZED DISEASE – INTERMEDIATE, HIGH OR REGIONAL RISK
Radical Prostatectomy (Surgery)
Indicated in patients with life expectancy ≥ 10 years, without major surgical contraindications.
Available techniques:
- Robotic-assisted prostatectomy (most commonly used)
- Laparoscopic or open prostatectomy
- Pelvic lymph node dissection (PLND) – recommended for intermediate, high, very high and regional risk
Possible adverse effects: urinary incontinence (20-50%), erectile dysfunction (40-60%), urethral strictures.
External Beam Radiotherapy (EBRT) + Brachytherapy
Modern image-guided radiotherapy (IGRT) and IMRT planning represent an oncologically equivalent alternative to surgery.
Recommended irradiation schemes in 2026:
- Ultra-hypofractionated (SBRT): 7.25-8 Gy × 5 fractions – preferred for convenience and equivalent results
- Moderate hypofractionation: 3 Gy × 20 fractions (60 Gy) – recommended by the HYDRA meta-analysis as the standard regimen
- Conventional fractionation – no longer preferred
Brachytherapy (LDR or HDR) – a valid option especially as a boost combined with EBRT for intermediate- and high-risk disease.
ADT combined with Radiotherapy – Duration Matters:
- Intermediate adverse risk: short ADT 4-6 months (concurrent and adjuvant)
- High risk: long ADT 12-36 months
- Very high risk + regional disease: ADT 18-36 months ± abiraterone
3. METASTATIC CASTRATIVE SENSITIVE DISEASE (mCSPC)
Fundamental principle: ADT alone is no longer the standard of care for metastatic disease. The NCCN 2026 guidelines strongly recommend intensification of treatment .
Double Therapies (Doublet) – ADT + ARPI
All of the options below have demonstrated overall survival benefit over ADT alone:
| Agent | Pivotal Study | Status |
| Abiraterone | LATITUDE, STOMPEDE | Category 1, Preferred |
| Apalutamide | TITANIUM | Category 1, Preferred |
| Enzalutamide | ENZAMET, ARCHES | Category 1, Preferred |
| Darolutamide | ARANOTE | Another recommended option (2B) |
New 2025: Darolutamide approved by the FDA in June 2025 as monotherapy with ADT for mCSPC, without the need to add docetaxel . Important advantage: lower brain penetration → fewer cognitive effects and falls.
Triple Therapies (Triplet) – ADT + Docetaxel + ARPI
Recommended for high-volume disease in patients eligible for chemotherapy:
- ADT + Docetaxel + Abiraterone (PEACE-1) – Category 1, Preferred
- ADT + Docetaxel + Darolutamide (ARASENS) – Category 1, Preferred
What does “high volume” mean? According to CHAARTED criteria: visceral metastases OR ≥ 4 bone lesions with at least one outside the vertebrae and pelvis.
🆕 NEW 2025-2026: Precision Therapy for BRCA2 Mutation
**Akeega (Niraparib + Abiraterone) – FDA Approval December 2025 **
This represents the first precision therapy approved for mCSPC – a revolution in the treatment of metastatic prostate cancer.
Who benefits? Patients with mCSPC who carry the BRCA2 mutation (germline or somatic).
Mechanism: Unique combination of PARP inhibitor (niraparib) + CYP17 inhibitor (abiraterone) in a single daily tablet.
Clinical results (AMPLITUDE trial):
- 54% reduction in risk of progression vs. standard of care
- Significantly improved rPFS in the BRCA2-mutated population
Important: Requires confirmed diagnostic companion testing. NCCN Guideline 5.2026 includes this combination as an option for high-volume disease and, controversially, also for low-volume disease (Category 2B).
Common adverse effects (≥ 20%): anemia, lymphocytopenia, musculoskeletal pain, fatigue, thrombocytopenia, constipation, hypertension, nausea.
4. CASTRATIVE-RESISTANT DISEASE WITHOUT METASTASE (M0 CRPC)
In patients with PSADT ≤ 10 months, three preferred category 1 options are available:
- Apalutamide (SPARTAN – MFS 40.5 vs. 16.2 months)
- Darolutamide (ARAMIS – MFS 40.4 vs. 18.4 months)
- Enzalutamide (PROSPER – MFS 36.6 vs. 14.7 months)
In patients with PSADT > 10 months: active monitoring is preferred.
5. METASTATIC CASTRATION-RESISTANT DISEASE (mCRPC)
This is the most complex therapeutic stage. The NCCN 2026 guidelines organize treatments according to prior exposure to ARPI and docetaxel.
Before ARPI (Pre-ARPI)
Favorites (Category 1):
- Abiraterone
- Enzalutamide
- Docetaxel
Useful in certain circumstances (biomarkers):
- BRCA mutation: Niraparib/Abiraterone, Olaparib/Abiraterone, Talazoparib/Enzalutamide
- HRR mutation (other than BRCA1/2): Talazoparib/Enzalutamide
- Bone metastases: Radium-223 + Enzalutamide
After ARPI, Before Docetaxel (Post-ARPI/Pre-Docetaxel)
Preferred (Category 1): Docetaxel
Useful in certain circumstances:
- BRCA mutation: Olaparib (preferred), Rucaparib (preferred)
- PSMA-positive: Lutetium Lu-177 PSMA-617 (Pluvicto)
🆕 NEW: Lutetium-177 PSMA-617 – Now Earlier in the Therapeutic Sequence
Expanded indication 2025: Lutetium-177 PSMA-617 is now also approved before taxane chemotherapy in patients with PSMA-positive mCRPC who have progressed on ARPI.
PSMAfore trial: rPFS of 9.3 vs. 5.6 months versus ARPI change (HR 0.41).
Advantages over chemotherapy:
- Superior tolerability, especially in elderly/frail patients
- Main adverse effects: fatigue, dry mouth, nausea, bone marrow suppression
- Early monitoring through PSA
Mandatory condition: PSMA-PET imaging confirming predominantly PSMA-positive disease without dominant PSMA-negative lesions.
🆕 Rucaparib – FDA Regular Approval (December 2025)
Conversion from accelerated approval (2020) to regular approval based on the TRITON3 trial:
- Indicated: BRCA1/2 mutated mCRPC previously treated with ARPI and chemotherapy
- Dose: 600 mg orally twice a day
- Important: ATM mutation does not benefit from rucaparib (rPFS HR 0.95, no benefit)
- Median rPFS: 11.2 vs. 6.4 months (HR 0.50; p < 0.0001)
Talazoparib + Enzalutamide – Clarifications 2025
The FDA updated the labeling in June 2025:
- Approved: mCRPC with HRR mutations → median OS 45.1 vs. 31.1 months (HR 0.68)
- Rejected for unselected population (without HRR mutations) – committee vote: 0-8 against due to toxicity
PARP Inhibitors – Summary Table 2026
| Agent | Indication | Biomarker Required | Trial |
| Olaparib | mCRPC post-enzalutamide/abiraterone | BRCA1/2, ATM and other HRR genes | PROfound |
| Rucaparib | mCRPC post-ARPI + taxane | BRCA1/2 exclusive | TRITON2/3 |
| Olaparib + Abiraterone | mCRPC | BRCA1/2 | PROPEL |
| Talazoparib + Enzalutamide | mCRPC | BRCA1/2, ATM, ATR, CDK12, CHEK2, and others | TALAPRO-2 |
| Niraparib + Abiraterone | mCRPC and mCSPC (BRCA2) | BRCA1/2 | MAGNITUDE, AMPLITUDE |
Genetic Testing – Why It’s Crucial Now More Than Ever
Germinal Testing
The NCCN 2026 guideline recommends mandatory germline testing for:
- All patients with metastatic disease
- Regional (N1) or localized high/very high risk disease
- Significant family history of cancer
- Ashkenazi descendants (BRCA risk of 5.2%)
Genes tested: BRCA1, BRCA2, ATM, PALB2, CHEK2, MLH1, MSH2, MSH6, PMS2, HOXB13
Why does it matter? The presence of the BRCA2 mutation opens access to specific treatments (Akeega in mCSPC, PARP inhibitors in mCRPC) and has implications for family members.
Somatic (Tumor) Testing
Recommended for:
- All patients with mCRPC – mandatory HRR testing
- MSI-H/dMMR → Eligible Pembrolizumab (Category 2B)
- TMB > 10 mut/mB → Pembrolizumab may be beneficial
Management of Biochemical Relapse (PSA Rise Post-Treatment)
After Radical Prostatectomy
Biochemical relapse is defined as PSA that does not decline to undetectable levels or detectable PSA that increases on ≥ 2 determinations.
NCCN Strategy 2026:
- Imaging: PSMA-PET/CT – at PSA ≥ 0.2 ng/mL (detects disease in 30-40% of cases)
- No metastases detected: Early secondary radiotherapy (PSA 0.1-0.2 ng/mL) ± ADT 6-24 months
- Oligometastatic: Metastasis-directed therapy (MDT) ± ADT
- Polymetastatic: Treatment according to mCSPC
Second Biochemical Relapse (BCR2) – New Guide 2026
Important change in version 3.2026: New algorithm for second biochemical relapse (BCR2) after maximal pelvic therapy:
- Low Risk: Monitoring Preferred
- High risk (PSADT ≤ 9 months):
- Enzalutamide with or without leuprolide (EMBARK study: MFS improved by 58%)
- Apalutamide + ADT (PRESTO study – Category 2B)
Managing Treatment Side Effects
Bone Health Under ADT
ADT increases the risk of osteoporosis and fractures by 21-54%. Practical recommendations:
- FRAX assessment at initiation of any ADT
- DEXA scan for high-risk patients; repeated every 1-2 years
- Supplementation: Calcium 1000-1200 mg/day + Vitamin D3 (target: 30-50 ng/mL)
- Drug therapy when indicated:
- Denosumab 60 mg sc every 6 months (preferred for fracture prevention)
- Zoledronic acid 5 mg iv annually
- Alendronate 70 mg po weekly
For mCRPC with bone metastases: Denosumab 120 mg every 4 weeks or zoledronic acid 4 mg every 12 weeks.
Cardiovascular Health
ADT and ARPI increase cardiovascular risk – one of the leading causes of death in prostate cancer survivors.
Recommended systematic assessment (ABCDE):
- Awareness + Aspirin (secondary prevention)
- Blood pressure – monitoring and management
- Cholesterol + Cigarette cessation
- Diet + Diabetes prevention
- Exercise + ECG/Echo at high risk
Technological Innovations and Artificial Intelligence in Prostate Oncology
ArteraAI Prostate – FDA Approval 2025
The first AI risk assessment tool in prostate cancer, using digital analysis of pathology slides for risk stratification and potential prediction of ADT benefit.
Validated post-hoc in 8 randomized phase III trials (NRG/RTOG). Now included in the 2026 NCCN Guidelines as an advanced risk stratification tool.
Remote Robot-Assisted HIFU (March 2025)
Cleveland Clinic has performed the world’s first remote (>7,000 miles) robot-assisted HIFU procedure. This technology has the potential to expand access to focal therapy globally.
Physical Exercise – Proven Therapy
A study published in JAMA Network Open 2025 demonstrates that 6 months of supervised exercise (resistance + aerobic) significantly improves erectile function post-cancer treatment, compared to standard care.
What Does Precision Medicine Mean in Prostate Cancer?
In 2026, we no longer live in an era of one-size-fits-all. The modern therapeutic algorithm involves:
- Molecular biopsy – germline and somatic testing for HRR, MSI, TMB
- Functional imaging – PSMA-PET for precise staging
- Genomic Scores – Decipher, ArteraAI for Advanced Stratification
- Targeted therapy – agent selection based on the molecular profile of the tumor
Concrete example: Two patients with the same clinical stage and Gleason score may receive completely different treatments. The patient with a BRCA2 mutation and metastatic disease will benefit from Akeega (niraparib + abiraterone), while the patient without the mutation will be directed to triplet therapy or another standard combination.
What You Can Do Concretely: Practical Guide for the Patient
If You Are Recently Diagnosed
✅ Request full risk stratification (PSA, Grad Group, clinical stage) ✅ Ask about germline testing (especially if you have a family history of cancer or aggressive disease) ✅ Request mpMRI if it has not been performed ✅ Discuss therapeutic options according to international guidelines , not just what the local standard protocol offers ✅ Consider a second oncology opinion if you have high-risk or metastatic disease
If You Have Metastatic or Recurrent Disease
✅ Requires complete somatic testing (HRR, MSI, TMB) – mandatory for access to targeted therapies ✅ Ask about PSMA-PET for precise staging ✅ Find out about PARP inhibitors if you have a BRCA or HRR mutation ✅ Discuss optimal sequencing of therapies with an oncologist updated with 2026 guidelines ✅ Actively monitors bone and cardiovascular health
Note: Due to model limitations, the response may not account for all data in the uploaded file(s). For better results, consider using fewer or smaller file(s) with essential excerpts. Learn more
📊 Charts and Tables – Prostate Cancer 2026
Patient-friendly visual guide
📋 TABLE 1: Risk Groups – Where Do You Fit?
| Risk Group | What does it mean in practice? | PSA | Gleason grade | Clinical stage |
| 🟢 Low Risk | Slow, localized cancer | Below 10 ng/mL | Group 1 (Gleason ≤6) | cT1–cT2a |
| 🟡 Favourable Intermediate Risk | 1 single intermediate risk factor | 10–20 ng/mL | Group 1–2 | cT2b–cT2c |
| 🟠 Unfavorable Intermediate Risk | 2–3 risk factors or more extensive biopsy | 10–20 ng/mL | Group 3 | ≥50% positive biopsies |
| 🔴 High Risk | At least one aggressive factor | Above 20 ng/mL | Group 4–5 | cT3–cT4 |
| 🔴🔴 Very High Risk | At least 2 high risk factors | Above 40 ng/mL | Group 4–5 | cT3–cT4 |
| 🔵 Regional (N1) | Cancer has spread to the pelvic lymph nodes | Any | Any | Any T, N1, M0 |
| ⚫ Metastatic (M1) | Cancer spread distantly (bones, organs) | Any | Any | Any T, Any N, M1 |
ℹ️ Important note: The “Very Low Risk” group has been removed from the NCCN guidelines version 1.2026
📋 TABLE 2: Diagnostic Tools – What New Analyses Are There?
| Instrument | What is it? | Why is it useful? | Who should ask for it? |
| 🧪 IsoPSA (FDA approved 2025) | Analyze PSA at a structural level | Avoids ~46% of unnecessary biopsies | Men ≥50 years with elevated PSA |
| 🧪 MyProstateScore 2.0 (MPS2) | 18-gene urine panel | Sensitivity 95–99%; avoids 40% of biopsies | Before biopsy, with uncertain PSA |
| 🧪 Johns Hopkins Panel | 3 urine biomarkers (TTC3, H4C5, EPCAM) | Detects cancer even with normal PSA | Patients with clinical suspicion |
| 🔬 Multiparametric MRI (mpMRI) | Advanced prostate imaging | Detects clinically significant cancers | Before any biopsy |
| ☢️ PSMA-PET/CT or PET/MRI | Scintigraphy with PSMA marker | Accurate staging; detects small metastases | High-risk/intermediate-unfavorable disease; biochemical relapse |
| 🤖 ArteraAI Prostate (FDA 2025) | AI on biopsy slides | Advanced risk stratification | Intermediate/high risk patients at RT |
📋 TABLE 3: Treatment Options – Localized Disease
| Risk Group | First Recommended Option | Other Options | What is NOT recommended |
| 🟢 Low Risk | ✅ Active Surveillance (preferred) | Surgery (RP), Radiotherapy | ADT, Lymph node irradiation, Brachytherapy + RT |
| 🟡 Favorable Intermediary | ✅ Active Surveillance or RT/Surgery | Mono brachytherapy | Routine ADT, Lymph node irradiation |
| 🟠 Intermediate Unfavorable | ✅ RT + short ADT (4–6 months) or Surgery | Mono brachytherapy; Brachytherapy + RT | RT without ADT (if high risk) |
| 🔴 High Risk | ✅ RT + long ADT (12–36 months) | Surgery ± PLND | ADT alone (if life expectancy >5 years) |
| 🔴🔴 Very High Risk | ✅ RT + ADT (18–36 months) ± Abiraterone | Surgery in selected patients | Brachytherapy alone |
| 🔵 Regional (N1) | ✅ RT + ADT (24 months) + Abiraterone | Surgery in selected patients | ADT alone (if RT can be done) |
Legend: RP = Radical Prostatectomy | RT = Radiotherapy | ADT = Androgen Deprivation Therapy | PLND = Pelvic Lymph Node Dissection
📋 TABLE 4: Active Surveillance – How Does It Work?
| What is being monitored? | How often? | Why is it important? |
| 🩸 PSA | At most 6 months | Detects early growth |
| 👨 ⚕️ Digital Rectal Exam (DRE) | At most 12 months | Evaluate local changes |
| 🔬 Confirmatory biopsy | At 1–3 years (no more often than 12 months) | Confirms the aggressiveness of the cancer |
| 🏥 Prostate MRI (mpMRI) | At most 12 months | Detects suspicious lesions |
✅ Benefit: ~50% of eligible patients can avoid treatment for 10 years without negative consequences
📋 TABLE 5: Treatment – Metastatic Castration-Sensitive Disease (mCSPC)
| Situation | Preferred Treatment | Other Option | Special Note |
| Small Volume + BRCA2 Mutation | ✅ ADT + Abiraterone / Apalutamide / Enzalutamide ( Cat. 1) | ADT + Niraparib/Abiraterone (Cat. 2B) | Niraparib/Abi benefit controversial at low volume |
| High Volume + Chemo Ready | ✅ TRIPLE: ADT + Docetaxel + Abiraterone OR + Darolutamide (Cat. 1) | ADT + any ARPI alone | The most effective regimen available |
| Large Volume + BRCA2 Mutation | ✅ TRIPLET + consideration of Niraparib/Abi after docetaxel | ADT + Abiraterone (Cat. 1) | First precision therapy for mCSPC |
| Small Volume without BRCA2 | ✅ ADT + Abiraterone OR Apalutamide OR Enzalutamide (Cat. 1) | ADT + Darolutamide (Cat. 2B) | Darolutamide – less cognitive effects |
| Oligometastatic Disease (few metastases) | ✅ MDT (Metastatic Radiotherapy) ± ADT | ADT + ARPI | SBRT on each metastasis |
Abbreviations: ADT = Castration Therapy | ARPI = Androgen Pathway Inhibitor | Cat. = NCCN Evidence Category
📋 TABLE 6: Treatment – Castration-resistant Cancer without Metastasis (M0 CRPC)
| Situation | What’s going on? | Recommended Treatment |
| PSADT ≤ 10 months (PSA doubles rapidly) | High risk of metastases | ✅ Apalutamide OR Darolutamide OR Enzalutamide (all Cat. 1) |
| PSADT > 10 months (PSA rises slowly) | Low risk of rapid progression | ✅ Active monitoring (preferred) |
What does PSADT mean? The time it takes for PSA to double. The shorter it is, the more aggressive the disease is
📋 TABLE 7: Treatment – Metastatic Castration-Resistant Cancer (mCRPC)
| Treatment Stage | Preferred Treatment | Useful in Certain Situations |
| Before ARPI (Pre-ARPI) | ✅ Abiraterone ( Cat . 1) OR Enzalutamide (Cat. 1) | Docetaxel (Cat. 1); PARP inhibitors (if BRCA+) |
| After ARPI, Before Chemo (Post-ARPI/Pre-Chemo) | ✅ Docetaxel (Cat. 1) | Lu-177 PSMA-617 (if PSMA+); Olaparib/Rucaparib (if BRCA+) |
| After ARPI and Chemo (Post-ARPI/Post-Chemo) | ✅ Cabazitaxel (Cat. 1); Docetaxel (re-treatment) | Lu-177 PSMA-617 (Cat. 1 if PSMA+); Olaparib (if BRCA+) |
| Regardless of previous treatments | — | Radium-223 (symptomatic bone metastases); Pembrolizumab (MSI-H/dMMR); Sipuleucel-T (asymptomatic) |
📋 TABLE 8: PARP Inhibitors – Precision Treatments
| Drug | Disease Treated | What Mutation Is Necessary? | Clinical Study |
| Olaparib | mCRPC after ARPI | BRCA1/2, ATM, CDK12 and others | PROfound |
| Rucaparib (full FDA approval Dec. 2025) | mCRPC after ARPI + chemo | BRCA1/2 EXCLUSIVE (ATM does not benefit!) | TRITON2/3 |
| Olaparib + Abiraterone | mCRPC | BRCA1/2 | PROPEL |
| Talazoparib + Enzalutamide | mCRPC with HRR mutations | BRCA1/2, ATM, CDK12, CHEK2 and others | TALAPRO-2 |
| Niraparib + Abiraterone (Akeega) | mCRPC AND mCSPC (new 2025!) | BRCA2 exclusive to mCSPC | AMPLITUDE / MAGNITUDE |
⚠️ Important: Rucaparib does NOT help patients with ATM mutation. Requires confirmed molecular testing
📋 TABLE 9: Lutetium-177 PSMA-617 (Pluvicto) – Quick Guide
| appearance | Details |
| What is it? | Radiopharmaceutical that “finds” and destroys cells with PSMA |
| Mandatory condition | PSMA-PET positive (without dominant PSMA-negative lesions) |
| Old Indication (2022) | After ARPI + Taxane chemotherapy |
| New indication (2025) | ✅ Before chemotherapy (after ARPI, if chemo can be postponed) |
| Administration | IV, 7.4 GBq every 6 weeks, maximum 6 doses |
| Advantage over chemo | Better tolerated, especially in the elderly/frail |
| Main side effects | Fatigue, dry mouth, nausea, bone marrow suppression |
| Study that confirmed the indication | PSMAfore: rPFS 9.3 vs 5.6 months (HR 0.41) |
📋 TABLE 10: Genetic Testing – Who Should Be Tested and What?
| Type Testing | Who Needs It? | What Genes Are Tested? | Why Does It Matter? |
| 🧬 Germline (from blood) | All with metastatic disease; high/very high risk; family history | BRCA1, BRCA2, ATM, PALB2, CHEK2, MLH1, MSH2, MSH6, HOXB13 | Accessibility to Akeega, PARP inhibitors; testing family members |
| 🔬 Somatic (from tumor) | All with mCRPC; also recommended for mCSPC | HRR (BRCA1/2, ATM, CDK12…), MSI-H/dMMR, TMB | Eligibility for targeted treatments + immunotherapy |
| 🩺 When to request testing? | At the time of diagnosis of metastatic or aggressive disease | — | Don’t wait for progression to request testing |
📋 TABLE 11: Bone Health Under ADT
| Situation | What are you doing? | Drug | Dose |
| At the start of ADT | DEXA scan (if increased FRAX risk) + FRAX assessment | Calcium + Vitamin D3 | Calcium 1000–1200 mg/day; Vit D3 – target 30–50 ng/mL |
| ADT in progress | DEXA at 1–2 years | — | — |
| Fracture prevention (ADT) | Antiresorptive treatment | Denosumab 60 mg sc every 6 months (preferred) OR Zoledronic Acid 5 mg IV annually OR Alendronate 70 mg orally/week | According to medical indication |
| Bone metastases (mCRPC) | Prevention of skeletal complications | Denosumab 120 mg every 4 weeks OR Zoledronic Acid 4 mg IV every 12 weeks | According to medical indication |
📋 TABLE 12: Cardiovascular Monitoring (ABCDE)
| Letter | What does this mean? | Practical Action |
| 🅰 ️ A | Awareness + Aspirin | Know the signs of heart disease; aspirin for secondary prevention |
| 🅱️ B | Blood Pressure | Monitoring and treatment of hypertension |
| 🅲 C | Cholesterol + Cigarettes (Cholesterol + Smoking) | Statins for prevention; smoking cessation |
| 🅳 D | Diet + Diabetes | Weight control; diabetes prevention/treatment |
| 🅴 It is | Exercise + ECG/Echocardiogram | Daily physical exercise; cardiac monitoring at high risk |
⚠️ Warning: ADT and ARPI increase cardiovascular risk. Cardiological evaluation recommended at high risk
📋 TABLE 13: Biochemical Relapse (PSA increases after treatment)
| Situation | Definition | First Step | Treatment Options |
| Post-Surgery (PS) | PSA does not decrease to undetectable OR increases on 2 determinations | PSMA-PET/CT (if PSA ≥ 0.2 ng/mL) | Early secondary RT (PSA 0.1–0.2 ng/mL) ± ADT 6–24 months |
| Post-Radiotherapy | PSA increases by ≥ 2 ng/mL from nadir | PSADT calculation; imaging | PSADT-based ADT; secondary local therapy |
| 2nd Relapse (BCR2) – Low Risk | PSADT > 9 months, no metastases | imagery | ✅ Monitoring ( preferred ) |
| 2nd Relapse (BCR2) – High Risk | PSADT ≤ 9 months, no metastases | imagery | ✅ Enzalutamide ± Leuprolide OR Apalutamide + ADT |
| Oligometases (few metastases) | 1–5 lesions detected | PSMA-PET | MDT (Metastatic Radiotherapy) ± ADT |
📋 TABLE 14: What to Ask the Doctor – Patient Checklist
| Situation | The Key Question |
| 🆕 New diagnosis | “Do I need germline genetic testing (BRCA, ATM)?” |
| 🔬 Before the biopsy | “Is the MPS2 or Johns Hopkins test available to avoid an unnecessary biopsy?” |
| 📊 STAGING | “Can I do PSMA-PET instead of CT+Scintigraphy for a more accurate image?” |
| 💊 Metastatic treatment | “Do I have a BRCA2 mutation? If so, am I eligible for Akeega or Olaparib?” |
| ⚛️ Chemotherapy vs. something else | “Am I eligible for Lutetium-177 PSMA-617 before chemotherapy?” |
| 🦴 ADT | “Do I need a DEXA scan and bone treatment?” |
| ❤️ Side effects | “What cardiovascular monitoring do you recommend during ADT?” |
| 🏃 Recovery | “What exercise program do you recommend for me?” |
How Can OncoExpert AI Help?
Navigating this complex therapeutic landscape is difficult even for specialist physicians. The OncoExpert AI platform can:
- Analysis of your oncology profile in relation to the latest NCCN 2026 guidelines
- Identify the therapeutic options for which you are potentially eligible
- Interpret molecular testing reports in the context of available therapeutic options
- Generate intelligent questions for the consultation with the specialist doctor
- Monitor guide updates and alert you to new options relevant to your case
Conclusion
Prostate cancer in 2026 is no longer a single disease with a single treatment. It is a spectrum of molecular entities that require an individualized approach, based on data from the international NCCN and ESMO guidelines, and the specific molecular profile of each patient.
The main messages to remember:
🔬 Genetic testing (germinal and somatic) is now mandatory for optimal therapeutic decisions in metastatic disease
🎯 Precision medicine has reached the front line of treatment (Akeega for BRCA2-mCSPC)
⚛️ Lu-177 PSMA-617 can be used earlier in the therapeutic sequence, before chemotherapy
📊 Advanced risk stratification with AI (ArteraAI) and genomic biomarkers can personalize treatment of localized disease
🏃 Physical exercise is part of the therapeutic management of side effects
Most importantly: accurate and up-to-date information can make the difference between receiving last year’s standard treatment and the most effective protocol available today.
Disclaimer: The information in this article is for informational and educational purposes only and does not constitute medical advice, diagnosis or therapeutic recommendation and does not replace the consultation of an oncologist. For diagnosis, treatment or interpretation of tests, always contact your medical team. . In case of a medical emergency, contact emergency services immediately ( call an ambulance immediately or go to the nearest emergency room) or the medical team that is following your treatment… Before making any medical decision, always consult an oncologist or your family doctor
Sources: NCCN Clinical Practice Guidelines in Oncology – Prostate Cancer Version 5.2026 (published January 23, 2026) and Comprehensive Prostate Cancer Document Update 2025.
Dr. Onisim Florin Senior Medical Oncologist Founder of OncoExpertAI