Introduction
This guide provides a comparative analysis of the 2025 clinical guidelines for prostate cancer from the National Institute for Health and Care Excellence (NICE) and the European Society for Medical Oncology (ESMO). While both aim to standardise and improve patient care, their perspectives differ: NICE offers a UK-specific, health-economic-focused pathway, whereas ESMO provides a broader, evidence-based European perspective. Understanding these nuances is crucial for UK clinicians to align local practice with international standards.
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Diagnosis and Initial Assessment
NICE (NG131)
NICE's approach is highly structured and integrated within the NHS pathway, emphasising risk stratification from the outset.
- Risk Stratification & MRI: A pre-biopsy multi-parametric MRI (mpMRI) is the cornerstone. The Prostate Imaging-Reporting and Data System (PI-RADS) or Likert scoring is used to determine the need for biopsy. Men with a PI-RADS/Likert score of 1-2 are unlikely to have clinically significant cancer, and a biopsy can often be avoided.
- Biopsy: For lesions with a score of 3-5, a transperineal template prostate biopsy is strongly recommended over transrectal to reduce infection risk. Targeted biopsies of suspicious lesions are mandatory.
- Staging & Biomarkers: Staging follows conventional imaging (CT, bone scan). The use of novel biomarkers (e.g., PCA3, 4Kscore) is restricted and typically only recommended in specific, equivocal situations after multidisciplinary team (MDT) discussion, reflecting cost-effectiveness considerations.
ESMO (2025)
ESMO's guidelines are similarly evidence-based but often incorporate newer technologies and biomarkers more readily.
- Risk Stratification & MRI: ESMO also strongly endorses pre-biopsy mpMRI but places equal weight on clinical parameters. It provides more detailed guidance on managing "grey zone" cases, such as those with PSA levels between 2-10 ng/mL.
- Biopsy: ESMO recommends either transperineal or transrectal biopsy, acknowledging the latter is still widely used in Europe, but highlights the superior safety profile of the transperineal approach.
- Staging & Biomarkers: ESMO is more proactive in recommending next-generation imaging (e.g., PSMA-PET/CT) for intermediate and high-risk disease at initial staging. It also has a broader acceptance of germline genetic testing for men with high-risk localised or advanced disease to guide treatment and identify hereditary risks.
Key Difference: The primary distinction lies in staging imaging and biomarker use. NICE is more conservative, relying on conventional imaging, while ESMO actively integrates PSMA-PET and genetic testing into the initial workup for higher-risk patients.
Treatment Recommendations by Disease Stage
Localised Disease (Low & Intermediate Risk)
- NICE: For low-risk disease, active surveillance is the first-line recommendation. For favourable intermediate-risk, active surveillance remains a strong option. For unfavourable intermediate-risk, treatment with radical prostatectomy or radiotherapy (with androgen deprivation therapy (ADT)) is standard. NICE provides clear, often binary, pathways.
- ESMO: Recommendations are similar but offer more nuanced options. For example, ESMO discusses focal therapies (e.g., HIFU) as an investigational but potential option within specialist centres for selected intermediate-risk patients, a topic NICE is more cautious about.
Locally Advanced & High-Risk Localised Disease
- NICE: Recommends radical radiotherapy with long-term ADT (2-3 years) or radical prostatectomy (often with pelvic lymph node dissection). The guidelines are explicit about the combination and duration of therapy.
- ESMO: Offers similar radical options but provides more detail on the intensification of therapy, such as the addition of novel hormonal agents (e.g., abiraterone, apalutamide) to ADT and radiotherapy for high-risk patients, reflecting recent trial data.
Advanced & Metastatic Disease
- Metastatic Hormone-Sensitive Prostate Cancer (mHSPC):
- NICE: Treatment escalation is based on disease volume. For high-volume disease, docetaxel chemotherapy or abiraterone are options. For low-volume disease, ADT alone or with radiotherapy (if oligometastatic) are considered. NICE options are constrained by Technology Appraisal (TA) approvals.
- ESMO: Recommends treatment intensification for most men with mHSPC, regardless of volume, using triple therapy (ADT + docetaxel + novel hormonal agent) or doublet therapy (ADT + novel agent). This is a more aggressive, data-driven approach.
- Non-Metastatic Castration-Resistant Prostate Cancer (nmCRPC): Both guidelines recommend apalutamide, enzalutamide, or darolutamide for high-risk nmCRPC.
- Metastatic Castration-Resistant Prostate Cancer (mCRPC):
- NICE: Sequence of therapy is heavily influenced by cost-effectiveness. Options include docetaxel, novel hormonal agents, radium-223 (for symptomatic bone mets), and PARP inhibitors (if HRR gene mutations are present, subject to TA approval).
- ESMO: Provides a more extensive list of options and sequences, including sipuleucel-T and cabazitaxel regimens, and gives stronger recommendations for biomarker-driven use of PARP inhibitors and pembrolizumab for MSI-High tumours.
Key Difference: In advanced disease, ESMO guidelines are generally more intensive and quicker to incorporate combination therapies from recent clinical trials. NICE guidelines are more measured, reflecting NHS funding constraints and a strict health technology assessment process.
Special Situations
Oligometastatic Disease
- NICE: Acknowledges the concept but offers cautious guidance, suggesting that metastasis-directed therapy (MDT) can be considered within a clinical trial or after MDT discussion. There is no formal recommendation for widespread adoption.
- ESMO: More strongly supports the role of MDT (e.g., stereotactic body radiotherapy - SBRT) for oligometastatic recurrence, citing growing evidence for its potential to delay disease progression and the need for systemic therapy.
Genetic Testing and Familial Risk
- NICE: Focuses on testing for homologous recombination repair (HRR) genes in mCRPC to guide PARP inhibitor use, as per TA guidance. Broader germline testing for familial risk is not routinely recommended in the primary guideline.
- ESMO: Advocates for broader germline genetic testing in men with high-risk localised, regionally advanced, or metastatic prostate cancer to inform treatment and facilitate cascade testing for relatives.
Practical Clinical Flow for UK Clinicians
Takeaway: Use the NICE pathway as your NHS operational blueprint, but refer to ESMO for deeper evidence context, especially for complex cases.
- Suspicion & Referral: Refer via the 2-week wait pathway for suspected cancer based on PSA, DRE. Perform pre-biopsy mpMRI.
- Diagnosis & Staging: If mpMRI is suspicious (score 3-5), perform transperineal template and targeted biopsy. Stage with CT and bone scan. Consider ESMO's PSMA-PET guidance for high-risk cases if available locally or via application for funding.
- MDT Discussion & Treatment: Manage according to NICE risk categories. For advanced disease, follow NICE TA-approved options. Use ESMO to understand international standards and for discussions about treatment intensification or clinical trials.
- Follow-up & Advanced Disease: Follow NICE schedules. In mCRPC, ensure HRR mutation testing is performed to enable access to NICE-approved PARP inhibitors.
Frequently Asked Questions (FAQs)
1. Which guideline should I prioritise for NHS practice?
Answer: The NICE guideline is the definitive standard for NHS care, as it determines commissioning and funding. ESMO should be used as a complementary resource for understanding the global evidence base, particularly for managing complex cases or when considering off-label treatments within a clinical trial.
2. How should I approach staging with PSMA-PET in 2025?
Answer: NICE has not yet fully incorporated PSMA-PET into its primary staging pathway for all high-risk patients due to cost-effectiveness analyses. However, its use is increasing. Check local NHS trust policies and funding arrangements. ESMO strongly recommends it for staging high-risk disease, so it is a valid topic for MDT discussion, especially where conventional imaging is equivocal.
3. A patient has high-volume mHSPC. Does NICE recommend triple therapy?
Answer: Not routinely. While trials support the efficacy of triple therapy (ADT + Docetaxel + ARSI), NICE guidance is often based on individual Technology Appraisals for specific drugs. Currently, NICE may recommend doublet therapy (e.g., ADT + docetaxel OR ADT + abiraterone). ESMO, however, gives a stronger recommendation for triple therapy where appropriate. The MDT must decide based on patient fitness, drug availability, and NICE TA status.
4. Is germline genetic testing standard for all high-risk patients?
Answer: In the UK, no. NICE primarily recommends genetic testing (for HRR genes) in the context of mCRPC to guide PARP inhibitor therapy. ESMO recommends broader testing for high-risk localised disease. In NHS practice, referral for genetic testing outside the mCRPC setting is typically based on strong personal or family history of cancer.
5. How do the guidelines differ on active surveillance?
Answer: The principles are very similar. Both strongly endorse active surveillance for low-risk disease. A minor difference is that ESMO may provide more detailed protocols for monitoring (e.g., the role of repeat mpMRI), while NICE integrates active surveillance within a clear NHS care pathway.
Source Links
- NICE Guideline NG131 (Prostate cancer: diagnosis and management): NICE NG131
- NICE Clinical Knowledge Summary (CKS) - Prostate Cancer: NICE CKS: prostate cancer
- ESMO Clinical Practice Guidelines - Prostate Cancer (2025): ESMO guidelines: genitourinary cancers
- NICE Technology Appraisals (TA): Search for individual drug appraisals (e.g., Apalutamide, Olaparib) on the NICE website: NICE (homepage)