How do you determine platinum resistance in ovarian cancer?

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Last updated: November 6, 2025 • View editorial policy

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How to Determine Platinum Resistance in Ovarian Cancer

Platinum resistance in ovarian cancer is determined by clinical response patterns, not molecular biomarkers—specifically by progression during platinum therapy (proven resistance) or recurrence within 6 months of completing platinum-based chemotherapy (assumed resistance). 1

Clinical Definitions of Platinum Resistance

The ESMO-ESGO consensus provides clear, therapy-oriented definitions 1:

Proven Platinum Resistance

  • Progression during active platinum therapy 1
  • This represents the most definitive form of resistance
  • These patients should receive sequential non-platinum therapy with bevacizumab if indicated 1

Assumed/Expected Platinum Resistance

  • Early symptomatic relapse with low probability of response to platinum 1
  • Historically defined as recurrence <6 months after last platinum dose 1
  • These patients should be treated with non-platinum therapy 1

Additional Criteria for Platinum Ineligibility

The 2023 ESMO guidelines expand the definition to include 1:

  • Platinum intolerance (severe toxicity precluding further use)
  • Patient choice to decline platinum
  • Quality of life issues making platinum inappropriate

Critical Limitations of Current Assessment Methods

No Molecular Biomarkers Available

  • There are currently no validated molecular biomarkers to predict platinum response 1
  • Testing for BRCA status does not predict platinum resistance, though BRCA-mutated patients may respond to rechallenge even with short treatment-free intervals 1
  • Genetic modifications associated with resistance (RB1, NF1, RAD51B, PTEN inactivation, BRCA reversions, MDR1 overexpression, CCNE1 amplification) are not clinically validated for decision-making 1

The 6-Month Cut-off Has Significant Shortcomings 1

  • Not all patients with treatment-free interval >6 months respond to platinum (response rates 47-66%) 1
  • Some patients with intervals <6 months do respond, particularly BRCA-mutated patients 1
  • The interval depends on follow-up frequency and diagnostic sensitivity 1
  • Patients with complete primary cytoreduction may have no evaluable disease to assess response 1

Practical Clinical Algorithm

When evaluating a patient with recurrent ovarian cancer, assess:

  1. Timing and pattern of progression 1

    • Did progression occur during platinum therapy? → Proven resistance
    • Did symptomatic relapse occur early after platinum? → Assumed resistance
    • Was there a previous response to platinum without early relapse? → Consider platinum rechallenge

  2. Prior treatment response 1

    • Document whether patient responded to previous platinum
    • Consider that response to non-platinum therapy followed by platinum rechallenge is possible if no progression occurred during prior platinum 1

  3. Clinical factors indicating poor platinum candidacy 1

    • Poor performance status (ECOG ≥2)
    • Low baseline global health status
    • Poor physical function
    • Presence of abdominal/gastrointestinal symptoms
    • These predict early discontinuation and poor response 1

  4. Histological subtype 1

    • Low-grade serous, clear cell, and mucinous carcinomas have inherently poor platinum response regardless of timing 1

Treatment Implications Based on Resistance Status

For proven or assumed platinum-resistant disease 1, 2:

  • Single-agent non-platinum chemotherapy (weekly paclitaxel, pegylated liposomal doxorubicin, topotecan, or gemcitabine) 1
  • Add bevacizumab if no contraindications (improves PFS, response rate, and quality of life) 1, 3
  • Early integration of palliative care is strongly recommended 1, 2
  • Focus on quality of life and symptom control rather than cure 2

Common Pitfalls to Avoid

  • Do not rely solely on the 6-month platinum-free interval as the sole determinant—consider the entire clinical picture including prior response, symptoms, and performance status 1
  • Do not order molecular testing to predict platinum resistance—no validated biomarkers exist for this purpose 1
  • Do not withhold palliative care until later lines—early integration improves quality of life and possibly survival 1, 2
  • Do not assume all patients with short intervals are resistant—BRCA-mutated patients in particular may benefit from platinum rechallenge 1

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

2
Guideline

Tratamento para Carcinoma Seroso de Alto Grau de Ovário Resistente à Platina

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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