NICE vs ESMO: Management of Ovarian Cancer (2025)
For UK clinicians managing ovarian cancer, two key guidelines inform practice: the National Institute for Health and Care Excellence (NICE) and the European Society for Medical Oncology (ESMO). While NICE provides the UK's evidence-based standard, often with a focus on cost-effectiveness within the NHS, ESMO offers a broader European perspective incorporating the latest international trial data. This comparison highlights the alignments and key differences between the NG81 (2025 update) and ESMO (2022, with 2024 updates) guidelines to aid clinical decision-making.
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Diagnosis and Initial Assessment
NICE (NG81)
- Primary Tool: Recommends using the Risk of Malignancy Index (RMI) I for women with suspected ovarian cancer. An RMI score of 250 or more warrants referral to a specialist multidisciplinary team (MDT).
- Imaging: Contrast-enhanced CT of the chest, abdomen, and pelvis is the standard for disease staging.
- Biomarkers: CA-125 is the principal serum biomarker. HE4 is not routinely recommended for diagnosis.
- MDT Focus: Strong emphasis on discussion of all cases within a specialist gynaecological cancer MDT prior to treatment initiation.
ESMO
- Primary Tool: Favours assessment by an expert gynaecological oncologist using ultrasonography (particularly the International Ovarian Tumour Analysis (IOTA) simple rules) over formal RMI calculation.
- Imaging: Also recommends CT chest/abdomen/pelvis for staging. MRI is suggested as a problem-solving tool for characterising indeterminate masses.
- Biomarkers: Acknowledges the potential utility of HE4 in combination with CA-125 (e.g., in the ROMA algorithm) but does not mandate its universal use.
Key Difference: The diagnostic pathway differs significantly. NICE provides a quantitative, protocol-driven approach (RMI) suitable for standardised NHS referral pathways. ESMO leans more heavily on the qualitative assessment of a specialised clinician, reflecting a centre-based European model.
Surgical Management
Primary Surgery (Apparent Early-Stage Disease)
Both guidelines agree on comprehensive surgical staging. However, NICE is more explicit in stating that laparoscopic management can be considered for appropriately selected cases where there is no obvious spread, provided it is performed by a trained surgeon and a full staging procedure can be completed.
Primary Surgery (Advanced Disease)
- NICE: Strongly recommends that primary surgery should be performed by a subspecialist gynaecological oncologist. The goal is maximum effort cytoreduction, aiming for complete resection (R0) where possible. It states that surgery should only be performed if optimal cytoreduction (traditionally defined as <1cm residual disease, but aiming for R0) is considered achievable.
- ESMO: Similarly advocates for complete cytoreduction (R0) as the primary goal. It provides more detailed stratification based on disease burden (e.g., using the Fagotti or AGO scores) to determine surgical resectability and the likelihood of achieving R0.
Alignment: Both guidelines are unequivocal: the quality of the initial surgery is a paramount prognostic factor, and it must be performed by a specialist surgeon.
Systemic Treatment
First-Line Chemotherapy
- Both guidelines recommend carboplatin and paclitaxel as the backbone of first-line chemotherapy.
- NICE: Recommends considering neoadjuvant chemotherapy (NACT) followed by interval debulking surgery for patients with a high tumour burden where primary cytoreduction is not deemed feasible or would lead to unacceptable morbidity.
- ESMO: Also endorses NACT for stage IV disease or when primary surgery is not feasible. It places a stronger emphasis on the requirement for confirmation of diagnosis via biopsy or cytology before starting NACT.
Maintenance Therapy
This is an area of rapid evolution and a key point of comparison.
- NICE (2025 update):
- For patients with a BRCA mutation (germline or somatic), recommends olaparib maintenance regardless of surgical outcome.
- For BRCA wild-type patients who are in response to first-line chemotherapy, NICE recommends niraparib maintenance only for those who had suboptimal cytoreduction (>1cm residual disease).
- Bevacizumab is recommended in combination with chemotherapy and as maintenance for patients with stage IV disease or those who have suboptimal debulking (>1cm residual) and are at high risk of progression.
- ESMO (2024 updates):
- Recommends PARP inhibitor maintenance for a broader group. For women with a BRCA mutation, olaparib or niraparib are options.
- Critically, for BRCA wild-type/homologous recombination proficient (HRP) tumours, ESMO suggests niraparib can be considered based on the PRIMA trial, which included a broader population than the NICE approval. This represents a significant difference.
- ESMO's use of bevacizumab is similar but is often discussed in the context of combining it with a PARP inhibitor (e.g., olaparib) in the first-line setting for eligible patients, a strategy reflected in international trial data.
Key Difference: The access to PARP inhibitors in the first-line maintenance setting for BRCA wild-type/HRP patients is the most notable divergence. ESMO's guidelines are more permissive based on clinical trial evidence, while NICE's recommendations are narrower, reflecting its health technology assessment (cost-effectiveness) mandate within the NHS.
Special Situations
Germline and Somatic Testing
- NICE: Recommends germline BRCA1/2 testing for all non-mucinous ovarian cancers. Somatic tumour testing for homologous recombination deficiency (HRD) is not routinely recommended for guiding first-line therapy due to current commissioning constraints, though this is under review.
- ESMO: Strongly recommends both germline BRCA testing and somatic HRD testing (via BRCA testing and genomic scar analysis) for all non-mucinous advanced cancers to fully inform maintenance therapy decisions.
Practical Takeaway: The absence of routine NHS funding for first-line HRD testing creates a practical gap between ESMO's ideal pathway and standard UK practice. MDTs must rely on germline BRCA status and clinical criteria (e.g., residual disease) for PARP inhibitor decisions.
Recurrent Disease
Both guidelines stratify treatment by platinum-free interval (PFI). The principles are well-aligned: platinum-based chemotherapy for platinum-sensitive recurrence, with PARP inhibitor maintenance if not used upfront. For platinum-resistant disease, non-platinum single-agent chemotherapy is standard. NICE provides specific recommendations on the cost-effectiveness of agents within the NHS.
Practical Clinical Flow for the UK Clinician
- Presentation & Referral: Calculate RMI I for women with suspected ovarian cancer. Refer to specialist gynaecological cancer MDT if RMI ≥250.
- Staging & MDT Discussion: Perform CT chest/abdomen/pelvis. Discuss all cases at MDT to formulate a personalised treatment plan, considering surgical resectability and patient fitness.
- Germline Testing: Initiate germline BRCA testing for all patients with non-mucinous ovarian cancer.
- Primary Treatment:
- If resectable to R0/low volume: Primary surgery by subspecialist surgeon, followed by adjuvant carboplatin/paclitaxel.
- If unresectable or high morbidity risk: NACT followed by interval debulking surgery.
- Maintenance Therapy Decision:
- BRCA mutant: Offer olaparib maintenance.
- BRCA wild-type, suboptimal debulking (>1cm): Offer niraparib or bevacizumab maintenance (if used with chemo).
- BRCA wild-type, optimal debulking: Discuss the evidence for niraparib (per ESMO) but note this is outside standard NICE/NHS funding. Observation is the standard funded pathway.
Frequently Asked Questions (FAQs)
1. Which guideline should I follow in the NHS?
NICE constitutes the formal standard of care for the NHS. ESMO guidelines provide invaluable context, especially for interpreting new trial data and managing complex cases. Deviations from NICE for individual patients should be discussed and justified within the MDT and may require an Individual Funding Request (IFR).
2. Why does NICE not recommend niraparib for all patients like ESMO does?
This is primarily a matter of health economic assessment. NICE evaluates whether the clinical benefit of a drug justifies its cost to the NHS. For BRCA wild-type/HRP patients with optimally debulked disease, NICE determined the benefit was not sufficient to be cost-effective at the current price.
3. Is HRD testing needed in the NHS?
Currently, routine HRD testing to guide first-line maintenance therapy is not commissioned by NHS England. Decisions are based on germline BRCA status and residual disease status. This is a key area of ongoing review and may change.
4. How should I manage a patient who is a candidate for primary surgery?
Both guidelines are clear: the patient must be referred to a centre with a subspecialist gynaecological oncologist who can attempt complete cytoreduction. The surgeon's assessment of resectability is critical.
5. What is the role of bevacizumab in 2025?
Bevacizumab remains a NICE-recommended option in combination with chemotherapy and as maintenance for high-risk patients (stage IV or suboptimally debulked). Its use may be influenced by the availability and sequencing of PARP inhibitors.
Source Links
- NICE Guideline NG81 (Ovarian cancer): NICE NG81 (Last updated April 2025)
- ESMO Clinical Practice Guidelines: Ovarian Cancer: ESMO guideline: ovarian cancer (2022, with 2024 updates)