Clear cell ovarian cancer
Clear cell ovarian cancer grows out of endometriosis, is usually caught early and cured by surgery, but when advanced it resists platinum chemotherapy. Its distinct genetics, with ARID1A and PIK3CA mutations, are the focus of targeted and immune approaches.
Overview
Clear cell carcinoma is strongly associated with endometriosis and is commoner in East Asian women. About half carry ARID1A mutations and a third PIK3CA mutations; TP53 is usually wild-type. It presents as a large unilateral mass, often at stage I, with a raised risk of venous thromboembolism and hypercalcaemia. Surgery is curative for most early disease, with adjuvant carboplatin-paclitaxel for stage IC and above; advanced and recurrent disease respond poorly to chemotherapy and do not benefit from PARP inhibitors. Immune checkpoint inhibitors have produced responses in a minority, and trials target ARID1A loss (ATR and EZH2 inhibitors), PI3K and the hypoxia pathway.
State of the art
- Recognition of clear cell cancer as a separate disease has ended its lumping into serous trials.
- ARID1A loss creates dependencies (ATR, EZH2, immune) now being exploited in dedicated trials.
- Early detection through endometriosis follow-up is under study in Japan.
Anatomy and lymph node drainage
Most high-grade ovarian cancers begin at the tip of the fallopian tube; endometrial cancer lines the uterus, cervical cancer starts at the transformation zone; each drains to a different node group.
- Fallopian tube fimbria (origin of high-grade serous)
- Ovary (other histologies, germ cell)Clear cell carcinoma arising in endometriosis · Stage I clear cell carcinoma (most cases) · Advanced and recurrent clear cell carcinoma (chemoresistant)
- Endometrium
- Myometrium (uterine sarcoma)
- Placental site (gestational trophoblastic)
- Cervix, transformation zone
- Vulva
- obturator and external iliac
- internal iliac
- para-aortic (ovary, high uterus)
- inguinal (vulva)
Same organ: High-grade serous ovarian cancer, Low-grade serous ovarian cancer, Mucinous ovarian cancer, Adult granulosa cell tumour of the ovary, Ovarian cancer, Endometrial cancer, Cervical cancer, Vulvar cancer, Gestational trophoblastic neoplasia, Uterine sarcoma, Vaginal cancer
About one in ten ovarian cancers in Western countries and a quarter in Japan; most present at an early stage and are cured, but advanced disease responds poorly to chemotherapy and carries a worse outlook than high-grade serous cancer.
- AI in radiologyEstablished
- cfDNA fragmentomicsEstablished
- Colorectal cancer screening (colonoscopy, FIT, stool DNA, blood)Standard of care
- DNA methylation profilingEstablished
- HCC surveillance in cirrhosis (ultrasound + AFP)Standard of care
- High-risk pancreatic surveillance (CAPS / PRECEDE)Established
- A 28-day national pathway for people with a positive multi-cancer blood test
- A breath test to rule out cancer in people with vague symptoms
- A cancer blood test for older people arriving at A&E with unexplained symptoms
- A legislated, publicly reported 28-day standard from urgent referral to diagnosis
- A live national dashboard of stage at diagnosis as the scorecard for early detection
- A single 'cancer check at 60' appointment bundling all screening tests
Background: Alpha-fetoprotein (AFP), Barrett's oesophagus, CA 19-9, Early detection, Faecal immunochemical test (FIT). Also on OnCo: Symptoms and red flags · Early detection roadmap.
Cases by country
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
Complete staging surgery; adjuvant carboplatin-paclitaxel for stage IC and above; observation may be considered for stage IA.
Cytoreduction and platinum-based chemotherapy despite modest responses; clinical trials of immunotherapy and ARID1A-directed drugs are preferred where available.
Subtypes & biomarkers
top- Clear cell carcinoma arising in endometriosis
- Stage I clear cell carcinoma (most cases)
- Advanced and recurrent clear cell carcinoma (chemoresistant)
- ARID1A mutation (about 50 percent)
- PIK3CA mutation
- HNF1B expression (diagnostic)
- Mismatch repair deficiency (a minority)
- Wild-type TP53
How often this target appears
- 1973WHO recognises clear cell carcinoma as an ovarian type
- 2010ARID1A mutations discovered in clear cell carcinoma
What is in development for Clear cell ovarian cancer, drawn from the whole corpus: 1 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.
Technologies being tested · 1
Open problems and what is being done
No effective treatment for platinum-resistant disease.
and how the field plans to fix it →What is being done about thisResistance to treatmentAvailable now- AmivantamabApproved
- CamizestrantApproved
- Comprehensive genomic profilingStandard of care
- Liquid biopsy (ctDNA)Standard of care
- LorlatinibApproved
- MRD / molecular residual disease testingEstablished
In trials- ADC payload neutralisersPhase 1
- BGB-16673Phase 3
- Bispecific ADCPhase 3
- BRUIN CLL-321Positive
- CaDAnCe-304Recruiting
- CIRCULATE-Japan (GALAXY / VEGA / ALTAIR)Active
Ideas and roadmaps- A clone report from blood at every treatment cycle
- A fast route to the matched drug when it is licensed for another cancer
- A multi-cancer platform trial of adaptive (dose-holiday) therapy
- A national rapid research autopsy network for end-stage cancer
- A standard evolvability score for every tumour
- A standing platform trial that assigns treatment by how the tumour escaped
Background: ADC sequencing, Antigen escape (antigen loss, lineage switch), BCG-unresponsive, Castration-resistant prostate cancer (CRPC), Circulating tumour DNA (ctDNA). Also on OnCo: Resistance atlas · Lines of therapy.
Which early-stage patients can skip chemotherapy.
Whether treating endometriosis reduces risk.
Trials
topTrials recruiting now
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Expert centres
topExpert centres
- Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer CenterBaltimore, USNewsweek oncology #10NCI comprehensivevia Pembrolizumab
- via Ovarian cancer
- Alliance for Clinical Trials in OncologyChicago, IL, USvia Carboplatin, Pembrolizumab
- GOG FoundationPhiladelphia, PA, USvia Pembrolizumab, Ovarian cancer
- via Pembrolizumab, Ovarian cancer
- ARCAGY-GINECOParis, FRvia Ovarian cancer
- BC CancerVancouver, BC, CAvia Ovarian cancer
- via Ovarian cancer
- Centre hospitalier de l'Université de Montréal (CHUM)Montréal, QC, CAvia Ovarian cancer
- Centre Oscar LambretLille, FRvia Ovarian cancer
- Chris O'Brien LifehouseSydney, AUvia Ovarian cancer
- Edinburgh Cancer Centre / CRUK Scotland CentreEdinburgh, GBvia Ovarian cancer
- via Ovarian cancer
- German Breast Group (GBG)Neu-Isenburg, DEvia Carboplatin
- Institut BergoniéBordeaux, FRvia Ovarian cancer
- Institut Jules BordetBrussels, BEvia Pembrolizumab
- Institute of Oncology LjubljanaLjubljana, SIvia Carboplatin
- via Ovarian cancer
- via Ovarian cancer
- Newcastle Cancer Centre / Northern Centre for Cancer CareNewcastle upon Tyne, GBvia Ovarian cancer
- Northwell Health Cancer InstituteNew Hyde Park, NY, USvia Ovarian cancer
- via Ovarian cancer
- Ontario Institute for Cancer ResearchToronto, ON, CAvia Ovarian cancer
- via Ovarian cancer
- Peking Union Medical College HospitalBeijing, CNvia Ovarian cancer
- QIMR Berghofer Medical Research InstituteBrisbane, AUvia Ovarian cancer
- Shaare Zedek Medical CenterJerusalem, ILvia Ovarian cancer
- Society of Gynecologic OncologyChicago, IL, USvia Ovarian cancer
- via Ovarian cancer
- via Ovarian cancer
- via Ovarian cancer
- via Ovarian cancer
- UZ Leuven / Leuven Cancer InstituteLeuven, BEvia Ovarian cancer
Questions to ask
topQuestions to ask your oncologist about Clear cell ovarian cancer
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example ARID1A mutation, PIK3CA mutation, HNF1B expression, Mismatch repair deficiency, Wild-type TP53), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include Clear cell carcinoma arising in endometriosis, Stage I clear cell carcinoma, Advanced and recurrent clear cell carcinoma.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Early stage
- For my situation (early stage), which of the standard options do you recommend and why?Why: Guideline options include: Complete staging surgery; adjuvant carboplatin-paclitaxel for stage IC and above; observation may be considered for stage IA.
- Am I a candidate for Carboplatin, Paclitaxel / nab-paclitaxel, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Advanced or recurrent
- For my situation (advanced or recurrent), which of the standard options do you recommend and why?Why: Guideline options include: Cytoreduction and platinum-based chemotherapy despite modest responses; clinical trials of immunotherapy and ARID1A-directed drugs are preferred where available.
- Am I a candidate for Pembrolizumab, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Supportive
- For my situation (supportive), which of the standard options do you recommend and why?Why: Guideline options include: Thromboprophylaxis awareness because of the high clot risk.
Any stage
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “No effective treatment for platinum-resistant disease”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Which early-stage patients can skip chemotherapy”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
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Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
4targets
1drugs
3companies
2Latest papers
topQuery for this cancer: (TITLE:"Clear cell ovarian cancer" OR ABSTRACT:"Clear cell ovarian cancer" OR TITLE:"Ovarian clear cell carcinoma" OR ABSTRACT:"Ovarian clear cell carcinoma" OR TITLE:"OCCC" OR ABSTRACT:"OCCC") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Clear cell ovarian cancer, not a curated reading list.
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