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Specialized Gynecological Markers — Complete Patient Guide: From CA-125 and HE4 to L1CAM, BRCA and Liquid Biopsy
Have you recently received a result with values for CA-125, HE4 or maybe your doctor recommended BRCA1/2 testing and you don’t know what it means? Or the histopathology report mentions L1CAM, Ki-67 or MSI and you don’t understand why these terms are important for your treatment? This guide explains, in an understandable way, the most important specialized gynecological tumor markers — what they detect, how they are interpreted and especially what therapeutic decision they can directly influence.
Why does gynecological cancer need specialized markers?
Gynecological cancers — ovarian, endometrial, cervical, fallopian tube, and ovarian germ cell tumors — are among the most complex female malignancies. Each has a different biological profile, progresses differently, and requires specific treatments. An elevated marker does not automatically mean cancer, and a normal marker does not rule out the disease.
That is why specialized gynecological markers are not used to make a diagnosis, but to:
- stratify risk in patients with pelvic masses discovered by ultrasound
- guide the surgical decision — which specialist to see and how urgently
- choose the right treatment, including immunotherapy or biological therapy
- monitor response to chemotherapy or immunotherapy
- detect recurrence months before it is visible on imaging
1. CA-125 + HE4 + ROMA score — Standard triad for ovarian cancer
What are they and why are they used together?
CA-125 (normal value: < 35 U/mL) is the best-known ovarian marker. It is elevated in 80–90% of advanced ovarian cancers, but also in endometriosis, fibroids, or peritonitis — making it less specific when used alone.
HE4 (Human Epididymis Protein 4) is the revolutionary marker that has changed the practice of gynecologic oncology. Unlike CA-125, HE4 does not increase in endometriosis — one of the most common causes of false-positive CA-125 results.
- Normal values: < 70 pmol/L (premenopausal women) / < 140 pmol/L (postmenopausal)
- Specificity for ovarian cancer: 94%
- Combined with CA-125, it achieves a diagnostic performance with AUC (overall accuracy) of 0.96
The ROMA (Risk of Ovarian Malignancy Algorithm) score combines HE4 + CA-125 + menopausal status into a risk algorithm:
- Low risk: ROMA < 11.4% (premenopausal) or < 29.8% (postmenopausal)
- Increased risk: requires imaging evaluation and consultation with a gynecological oncologist
What therapeutic decision does it influence?
HE4 increases 126 days before clinical confirmation of recurrence — nearly 4 months earlier than any other monitoring method. This allows resumption of treatment with PARP inhibitors (olaparib, niraparib) or bevacizumab before the disease becomes extensive.
Also, BRCA1/2 and HRD (homologous recombination deficiency) status determined from tumor tissue or blood establish eligibility for maintenance therapy with PARP inhibitors, which significantly prolong progression-free survival.
2. Inhibin B + AMH — The “forgotten” markers of ovarian granulosa tumors
What are they?
Inhibin B and AMH (Anti-Müllerian Hormone) are produced by the granulosa cells of the ovary — the same cells from which granulosa ovarian tumors, a rare type of non-epithelial ovarian cancer, develop.
Unlike CA-125, which is rarely elevated in these tumors, the combination of Inhibin B + AMH achieves a sensitivity of 76–93% for the detection and recurrence of granulosa tumors.
AMH has recently become commercially available on standardized immunoassay platforms, which has made this combination the preferred post-operative surveillance strategy for granulosa tumors.
Important: AMH is usually undetectable in postmenopausal women. An elevated AMH in a postmenopausal woman is highly specific for an ovarian granulosa tumor.
What therapeutic decision does it influence?
An increase in Inhibin B or AMH during post-surgical surveillance requires:
- Urgent pelvic CT/MRI for confirmation
- Discussion within a multidisciplinary oncology committee
- Eligibility assessment for leuprolide acetate (GnRH analogue), anastrozole or BEP chemotherapy (bleomycin, etoposide, cisplatin) in case of advanced recurrence
3. β-hCG + AFP — The “perfect” markers for germ cell tumors and trophoblastic disease
Beta-hCG (human chorionic gonadotropin) and AFP (alpha-fetoprotein) represent the most powerful duo of markers in gynecological oncology for germ cell tumors and gestational trophoblastic disease (GTD).
- β-hCG : normal value < 5 mIU/mL (non-pregnant adults)
- AFP : normal value ≤ 10 ng/mL
Why is β-hCG the “perfect” marker for BTG? Because it can be used both for the decision to initiate treatment and to monitor cure. A complete normalization after chemotherapy is, in practice, equivalent to a complete cure — even in metastatic disease.
The cure rate in appropriately treated gestational choriocarcinoma exceeds 95% , including in advanced stages.
What therapeutic decision does it influence?
- Stagnation or increase in β-hCG during post-evacuation surveillance of hydatidiform mole = diagnostic criterion for gestational trophoblastic neoplasia (GTN) → requires immediate chemotherapy (methotrexate or dactinomycin for low risk; EMA/CO for high risk)
- AFP halving every 5–7 days under BEP chemotherapy = sign of therapeutic response in germ cell tumors; absence of decline requires change of regimen
- Pembrolizumab immunotherapy is being evaluated in clinical trials for chemotherapy-resistant NTG
4. L1CAM — The new molecular classifier of endometrial cancer
What is it and why is it revolutionary?
L1CAM (L1 Cell Adhesion Molecule) is a cell surface protein detected by immunohistochemistry on biopsied tumor tissue. It is not measured in the blood, but directly on the histopathological specimen.
Its clinical value: L1CAM expression ≥ 10% of tumor cells identifies a high-risk subgroup of endometrial cancer, with significantly lower survival and increased risk of lymph node metastases.
This led to the inclusion of L1CAM in the new ESGO/ESMO/ESP molecular stratification system for endometrial cancer — the most important European guideline for this condition.
What therapeutic decision does it influence?
| L1CAM status | Therapeutic implication |
| L1CAM < 10% | Standard risk → conservative treatment (hysterectomy ± vaginal brachytherapy) |
| L1CAM ≥ 10% | High risk → external pelvic radiotherapy + mandatory adjuvant chemotherapy |
L1CAM is integrated into the ProMisE molecular classification (alongside POLE, MSI/dMMR, and TP53), which now guides therapeutic decisions according to the 2023–2026 guidelines.
5. Ki-67/MIB1 — Your Tumor’s Proliferation Clock
Ki-67 (detected by the MIB1 antibody) shows exactly how many cells in the tumor are actively dividing at the time of biopsy. The result is expressed as a percentage:
- Ki-67 < 15–20%: slow-growing, less aggressive tumor
- Ki-67 > 30–40%: rapidly dividing, aggressive tumor — but often with better response to chemotherapy
In endometrial cancer , Ki-67 combined with ER/PR status, POLE mutation and MMR/MSI status make up the ProMisE molecular classification, which determines:
- Who needs adjuvant chemotherapy?
- Who can be exempt from radiotherapy?
- Who is a candidate for pembrolizumab immunotherapy?
6. MSI/dMMR + PD-L1 — The key to accessing immunotherapy
MSI (Microsatellite Instability) and dMMR (deficient Mismatch Repair) are two sides of the same coin.
An MSI-H/dMMR positive tumor means that the DNA repair system is defective — which generates a large number of mutations and makes the tumor highly visible to the immune system.
PD-L1 (detected by IHC on biopsy) shows whether the tumor is “hiding” from immunity.
Why are they critical?
- MSI-H/dMMR endometrial cancer : pembrolizumab + levantinib as first-line for advanced/recurrent disease — objective response rates 30–40%
- Cervical cancer with PD-L1 CPS ≥ 1 : pembrolizumab + chemotherapy ± bevacizumab (KEYNOTE-826) as standard of care in advanced disease
- MSI-H ovarian cancer : pembrolizumab as a therapeutic option regardless of histotype
7. ctDNA (Liquid Biopsy) — Detecting recurrence months before imaging
ctDNA (Circulating Tumor DNA) is DNA fragments released by cancer cells into the blood. It is detected through a simple blood sample — without a tissue biopsy.
The most important result in 2026 for ovarian cancer HGSOC (High-Grade Serous Ovarian Cancer):
- ctDNA detected recurrence 10 months before imaging — with 100% sensitivity and specificity in cohort studies
- ctDNA methylation analysis can identify ovarian cancer 2 years before clinical diagnosis
- Somatic BRCA1/2 mutations in ctDNA determine eligibility for PARP inhibitors
Summary table — Specialized gynecological markers and therapeutic implications
| Marker | Type of cancer | Direct therapeutic implication |
| CA-125 + HE4 + ROME | Ovarian | Surgical decision; chemotherapy monitoring |
| BRCA1/2 + HRD | Ovarian, breast | Eligibility PARP inhibitors (olaparib, niraparib) |
| Inhibin B + AMH | Granular tumor | Surveillance for recurrence; GnRH or chemotherapy |
| β-hCG + AFP | Germ cell, BTG | Treatment decision; healing monitoring |
| SCC antigen | Cervical squamous | Chemoradiotherapy monitoring; recurrence detection |
| L1CAM ≥ 10% | Endometrial | Adjuvant chemotherapy + radiotherapy mandatory |
| Ki-67/MIB1 | Endometrial, ovarian | ProMisE classification; adjuvant decision |
| MSI-H / dMMR | Endometrial, cervical | Pembrolizumab (immunotherapy) eligibility |
| PD-L1 | Cervical, endometrial | Pembrolizumab ± levantinib eligibility |
| ctDNA (somatic BRCA) | Ovarian HGSOC | Recurrence detection 10 months before imaging |
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🎗 ️ Specialized Gynecological Markers — Explanatory Tables for Patients
📊 TABLE 1 — What each marker measures and what the values mean (by definition)
| Marker | What is it, in simple terms | Normal value | INCREASED value — what can it mean? | LOW or NORMAL value — what can it mean? |
| CA-125 | A protein produced by ovarian cells and other tissues. The classic “alarm” for the ovaries. | < 35 U/mL | ⚠️ Suspicion of ovarian cancer (if > 200 U/mL); but also endometriosis, fibroids, peritonitis, pregnancy | ✅ Low risk — but beware : 20% of early ovarian cancers have normal CA-125 ! |
| HE4 | A more specific protein than CA-125. It does NOT increase in endometriosis — a major advantage. | < 70 pmol/L (pre-menopause) / < 140 pmol/L (post-menopause) | ⚠️ High risk of ovarian or endometrial cancer (serous/clear cell) | ✅ Ovarian cancer unlikely; endometriosis possible if CA-125 is elevated |
| ROME score | An algorithm that combines CA-125 + HE4 + menopausal status into a risk score | < 11.4% (pre-menopause) / < 29.8% (post-menopause) = LOW RISK | ⚠️ High risk → requires ultrasound/MRI and consultation with a gynecologist-oncologist | ✅ Low risk of malignant ovarian cancer |
| Inhibin B | Hormone produced by ovarian granulosa cells. Specific to a rare type of ovarian tumor. | Variable with cycle; undetectable post-menopausal | ⚠️ Suspicion of ovarian granulosa tumor ( especially in post-menopausal women ! ) | ✅ Normal ; granulosa tumor unlikely |
| AMH (anti-Müllerian hormone) | Hormone produced by the ovaries; in young women reflects ovarian reserve. In post-menopausal women — MUST be undetectable. | Undetectable in post-menopause | ⚠️ AMH detectable in post-menopause = specific sign for granulosa tumor | ✅ Normal in premenopausal women ( reflects ovarian reserve ) |
| β-hCG (chorionic gonadotropin) | Pregnancy hormone — but also produced by trophoblastic tumors and some germ cell tumors | < 5 mIU/mL (non-pregnant adults) | ⚠️ Gestational trophoblastic tumor ( hydatidiform mole , choriocarcinoma ) , germ cell tumors | ✅ Normal value excludes trophoblastic activity ; exclude pregnancy first ! |
| AFP (alpha-fetoprotein) | Fetal protein; in adults, elevated values = tumor signal | ≤ 10 ng/mL | ⚠️ Ovarian germ cell tumor ( yolk sac ) , immature teratoma | ✅ Normal value — Does NOT exclude all germ cell tumors |
| SCC antigen | Marker for squamous cell carcinomas (cell type) | < 2 ng/mL | ⚠️ Squamous cervical cancer ( in 28 – 85% of cases, depending on stage ) | ✅ Normal — less specific for cervical adenocarcinomas |
| L1CAM | Protein detected on tumor biopsy (NOT in blood). Risk classifier in endometrial cancer. | < 10% positive tumor cells = STANDARD RISK | ⚠️ ≥ 10% positive cells = HIGH RISK → chemotherapy + radiotherapy mandatory | ✅ < 10% = more conservative treatment possible |
| Ki-67/MIB1 | It shows how many cells in the tumor are actively dividing (expressed in %). | Variable; interpreted in clinical context | ⚠️ Ki-67 > 30–40% = aggressive tumor, fast growth | ✅ Ki-67 < 15% = slow-growing tumor |
| MSI/dMMR | DNA repair system test (on biopsy). Opens the door to immunotherapy. | Intact MMR (MLH1, MSH2, MSH6, PMS2 present) | ⚠️ dMMR / MSI-H = defective repair system → ELIGIBLE for immunotherapy (pembrolizumab) | ✅ MSS (stable) = chemotherapy remains the standard treatment |
| PD-L1 | The protein by which the tumor “hides” from the immune system. Detected on biopsy. | CPS < 1 = negative | ⚠️ CPS ≥ 1 or ≥ 10 ( depending on cancer ) = candidate for immunotherapy with pembrolizumab | ✅ PD-L1 negative = immunotherapy may be less effective ( but does not completely exclude benefit) |
| ctDNA (liquid biopsy) | Circulating tumor DNA detected from a simple blood sample. | Undetectable | ⚠️ Detectable = signal of recurrence or residual disease ; precedes imaging by up to 10 months | ✅ Undetectable post-treatment = favorable prognosis |
📊 TABLE 2 — Sample type, when to collect and preparation required
| Marker | Sample type | When is it harvested? | Special preparation | Important conditions |
| CA-125 | Venous blood (serum) | Any time | No special restrictions | ⚠️ Avoid harvesting during menstruation ( may be physiologically increased) |
| HE4 | Venous blood (serum) | Any time | No restrictions | Not influenced by endometriosis or fibroids |
| ROME score | Calculated from CA-125 + HE4 | Simultaneously with the 2 analyses | No restrictions | Requires specification of menopausal status on ID card |
| Inhibin B | Venous blood (serum) | Morning (recommended) | No restrictions | ⚠️ In premenopausal women, values vary with the phase of the menstrual cycle — specify the day of the cycle |
| AMH | Venous blood (serum) | Any time of the cycle | No restrictions | ✅ Does not vary significantly with the menstrual cycle — advantage over Inhibin B |
| β-hCG | Venous blood (serum) | Any time | No restrictions | ⚠️ Always rule out pregnancy before interpretation |
| AFP | Venous blood (serum) | Any time | No restrictions | ⚠️ Physiological growth in pregnancy and in the first postpartum months |
| SCC antigen | Venous blood (serum) | Morning (recommended) | No restrictions | ⚠️ Can be falsely attributed to skin diseases (psoriasis, eczema) |
| L1CAM | Tumor tissue (biopsy) | At the time of biopsy or surgery | Not applicable (not from blood) | Detected by immunohistochemistry (IHC) on pathology slide |
| Ki-67/MIB1 | Tumor tissue (biopsy) | At the time of biopsy | Not applicable | Reported as a percentage of tumor cells examined under a microscope |
| MSI/dMMR | Tumor tissue (biopsy) | At the time of biopsy or surgery | Not applicable | It is tested by IHC (4 proteins: MLH1, MSH2, MSH6, PMS2) |
| PD-L1 | Tumor tissue (biopsy) | At the time of biopsy | Not applicable | Reported as TPS (% tumor cells) or CPS (includes immune cells) |
| ctDNA | Venous blood (EDTA plasma) | Any time | No dietary restrictions | ⚠️ Plasma must be separated within 2 hours of harvest ; transported on ice |
📊 TABLE 3 — Which gynecological cancer is associated with each marker
| Marker | Ovarian cancer | Endometrial cancer | Cervical cancer | Ovarian germ cell tumors | Granular tumors | Trophoblastic disease |
| CA-125 | ✅ Main | ⚠️ Partial | ⚠️ Limited | ❌ No | ❌ No | ❌ No |
| HE4 | ✅ Main | ✅ Useful (serous/clear) | ❌ No | ❌ No | ❌ No | ❌ No |
| ROME score | ✅ Pelvic adnexal triage | ❌ No | ❌ No | ❌ No | ❌ No | ❌ No |
| Inhibin B + AMH | ❌ No | ❌ No | ❌ No | ❌ No | ✅ Specific | ❌ No |
| β-hCG | ❌ No | ❌ No | ❌ No | ✅ Dysgerminon, choriocarcinoma. | ❌ No | ✅ Main |
| AFP | ❌ No | ❌ No | ❌ No | ✅ Yolk sac, immature teratoma | ❌ No | ❌ No |
| SCC antigen | ❌ No | ❌ No | ✅ Squamous (neck) | ❌ No | ❌ No | ❌ No |
| L1CAM | ⚠️ Prognosis (stage) | ✅ Risk classifier | ❌ No | ❌ No | ❌ No | ❌ No |
| Ki-67/MIB1 | ✅ Grading | ✅ ProMisE (ranking) | ⚠️ Partial | ✅ Grading | ✅ Useful | ❌ No |
| MSI/dMMR | ⚠️ Rare (endometrioid) | ✅ 20 – 40% of cases | ❌ No | ❌ No | ❌ No | ❌ No |
| PD-L1 | ⚠️ Partial | ✅ Recurrent/advanced | ✅ Advanced/metastatic | ❌ No | ❌ No | ⚠️ In studies |
| ctDNA | ✅ Monitoring / recurrence | ✅ Post-op MRD | ⚠️ In evaluation | ⚠️ In evaluation | ❌ No | ❌ No |
Legend: ✅ = primary use / ⚠️ = secondary use / ❌ = not applicable
📊 TABLE 4 — Direct therapeutic implications (what medical decision does each marker influence)
| Marker | The result that matters | What medical decisions does it influence? | Concretely — what is happening? |
| CA-125 + HE4 + ROMA elevated | ROMA ≥ 11.4% (pre) or ≥ 29.8% (post) | Surgical decision + mandatory referral to gynecologist oncologist | The operation must be performed by a surgeon specialized in gynecological oncology. |
| CA-125 decreasing under chemotherapy | ≥ 50% reduction from baseline | Confirms therapeutic response → chemotherapy works | Continue current regimen (carboplatin + paclitaxel ± bevacizumab) |
| HE4 increased in post-treatment follow-up | Increase from minimum value | Recurrence signal 126 days before imaging confirmation | Urgent CT/MRI scan + evaluation for resumption of treatment |
| BRCA1/BRCA2 mutated | Any confirmed pathogenic mutation | Eligibility for PARP inhibitors | Olaparib or niraparib as maintenance therapy after chemotherapy |
| HRD positive (no BRCA mutation) | High genomic instability score | Eligibility for niraparib (monotherapy) as maintenance | NCCN 2026: niraparib recommended even without BRCA mutation if HRD positive |
| Elevated inhibin B or AMH at follow-up | Any increase from the post-operative level | Granulosa tumor recurrence signal | Urgent pelvic CT/MRI + multidisciplinary oncology committee discussion |
| Stagnant or rising β-hCG after molar evacuation | Plateau or increase on ≥ 3 weekly determinations | Diagnosis of gestational trophoblastic neoplasia (GTN) | Immediate chemotherapy (methotrexate or dactinomycin for low risk; EMA/CO for high risk) |
| AFP slowly decreasing under chemotherapy | Decrease < 50% every 5–7 days | Signals resistance to treatment | The chemotherapy regimen is changed (from BEP to another salvage regimen) |
| L1CAM ≥ 10% on endometrial biopsy | Expression ≥ 10% tumor cells | Reclassifies the tumor into the HIGH RISK category | Adjuvant chemotherapy + external pelvic radiotherapy is mandatory |
| MSI-H/dMMR positive on biopsy | Any lesion of the MMR system (MLH1, MSH2, MSH6, PMS2) | Eligibility for pembrolizumab immunotherapy | Recurrent/advanced endometrial cancer: pembrolizumab + lenvatinib (first line) |
| PD-L1 CPS ≥ 1 (cervix) | CPS ≥ 1 in advanced cervical cancer | Eligibility for pembrolizumab + chemotherapy ± bevacizumab | Standard of Care in Advanced Illness (KEYNOTE-826) |
| Ki-67 > 30% in endometrial cancer | High proliferation index | Part of the ProMisE classification → guides the decision for adjuvant chemotherapy | Combined with POLE, MMR, TP53, L1CAM → determines the intensity of treatment |
| Detectable ctDNA post-surgery | Any detectable level 4–12 weeks post-op | Indicates microscopic residual disease (MRD) | Negative prognosis → may justify intensification of adjuvant treatment |
📊 TABLE 5 — Treatments associated with each molecular profile (simplified guide 2026)
| Molecular profile of the tumor | What does it mean for the patient? | Recommended treatment (2026) |
| BRCA1/2 mutated + HRD positive | Tumor has DNA repair defect — vulnerable to a special class of drugs | Olaparib or niraparib (PARP inhibitors) as maintenance after chemotherapy |
| MSI-H / dMMR | The DNA repair system is defective → the tumor is ” visible ” to the immune system | Pembrolizumab (immunotherapy) ± lenvatinib |
| PD-L1 CPS ≥ 1 (cervical cancer) | The tumor “hides” from immunity through PD-L1 | Pembrolizumab + carboplatin/paclitaxel ± bevacizumab |
| L1CAM ≥ 10% (endometrial cancer) | Tumor cells are more invasive and aggressive | Adjuvant chemotherapy (carboplatin + paclitaxel) + external pelvic radiotherapy |
| Mutant POLE (endometrial cancer) | The tumor has many mutations, but paradoxically has a good prognosis | Possible de-escalation of adjuvant treatment; eligible for immunotherapy |
| Mutant TP53 (serous endometrial cancer) | Aggressive form of endometrial cancer | Mandatory intensive chemotherapy ± bevacizumab; strict supervision |
| Mutant KRAS (low-grade serous ovarian carcinoma) | Mutation in the MAPK signaling pathway | Avutometinib + defactinib (NCCN 2026 approved for recurrent LGSOC) |
| HER2-low (IHC 1+ or 2+/FISH neg) | HER2 intermediate expression—a new niche | Trastuzumab deruxtecan (T-DXd) for HER2-low cancers |
| Granulosa tumors (Inhibin B+ / AMH+) | Rare, slow-growing tumor; late recurrence possible | GnRH analogues (leuprolide), anastrozole, or BEP chemotherapy for advanced recurrence |
| Low-risk trophoblastic disease (β-hCG+) | Excellent response to mild chemotherapy | Methotrexate or dactinomycin alone; >95% cure |
| High-risk trophoblastic disease (β-hCG++ / metastases) | More aggressive form, but still curable in most cases | EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine); pembrolizumab in clinical trials |
📊 TABLE 6 — Recommended monitoring rate depending on the clinical situation
| Clinical situation | CA-125 + HE4 | Inhibin B + AMH | β-hCG | ctDNA | Imaging (CT/MRI) |
| Initial pelvic mass assessment | ✅ Mandatory | If granulosa tumor is suspected | ✅ Mandatory | Not standard | Ultrasound + ± pelvic MRI |
| Under chemotherapy (ovarian cancer) | Every 2–3 cycles | Not | Not | Emerging (clinical studies) | Every 2–3 cycles (CT) |
| Post-surgery ovarian cancer | Every 3 months for the first 2 years | No (unless it’s a granulosa tumor) | Not | 4–12 weeks post-op | At 6 months (or if markers increase) |
| Granular tumor follow-up | ⚠️ Less useful | ✅ Every 3 – 6 months mandatory | Not | Not standard | Annually or on growth markers |
| Post-hydatidiform mole follow-up | Not | Not | ✅ Weekly until normalization , then monthly for 6 – 12 months | Not | When clinically indicated |
| Endometrial cancer in follow-up | ⚠️ If it was originally grown | Not | Not | ⚠️ Clinical studies ( promising ) | CT every 3–6 months in the first 3 years |
| Cervical cancer under treatment | Not | Not | Not | Not standard | CT + MRI 3 months after completion of treatment |
💡 TABLE 7 — Traffic light of values — Quick visual guide
| 🟢 GREEN — Everything as expected | 🟡 YELLOW — Attention, requires evaluation | 🔴 RED — Urgent medical action |
| CA-125 < 35 U/mL + HE4 normal | CA-125 35–200 U/mL with borderline HE4 | HE4 detectable in post-menopause + increased CA-125 |
| ROMA < 11.4% (pre) or < 29.8% (post) | ROME on the verge of collapse | ROMA enlarged with ovarian mass on ultrasound |
| β-hCG < 5 mIU/mL (non-pregnant) | β-hCG 5–50 mIU/mL (exclude pregnancy) | β-hCG rising/plateau after molar evacuation |
| Inhibin B/AMH undetectable (post-menopause) | AMH detectable at low levels in post-menopause | Significantly elevated AMH in post-menopause (granulosa tumor!) |
| L1CAM < 10% on biopsy | L1CAM 5–10% (gray area) | L1CAM ≥ 10% = confirmed high risk |
| MSI stable (MSS) = standard chemotherapy | Equivocal MMR result — requires additional testing | dMMR/MSI-H confirmed = immunotherapy available |
| Undetectable ctDNA post-surgery | Very low ctDNA (careful follow-up) | Rising ctDNA on follow-up = likely recurrence months before imaging |
📋 TABLE 8 — What to ask the doctor at the consultation (checklist for patients)
| If you have this diagnosis/result | Essential questions to ask the doctor |
| Ovarian mass discovered on ultrasound | “Has the ROMA score (CA-125 + HE4) been calculated? Is pelvic MRI indicated before surgery? Should the surgery be performed by a gynecologic oncologist?” |
| CA-125 increased in isolation | “Is HE4 elevated too? What does the ultrasound/MRI show? Could it be endometriosis or another benign cause?” |
| Confirmed ovarian cancer | “Has the tumor been tested for BRCA1/2 and HRD? Am I eligible for PARP inhibitors after chemotherapy? Is ctDNA testing indicated?” |
| Endometrial cancer confirmed | “Has L1CAM been tested? Has the tumor been classified in the ProMisE system (POLE/MMR/TP53/L1CAM)? Do I need adjuvant chemotherapy in addition to radiotherapy?” |
| Recurrent endometrial cancer | “Have you been tested for MSI/dMMR? Am I eligible for pembrolizumab + lenvatinib?” |
| Granulosa ovarian tumor | “Will Inhibin B and AMH be monitored in follow-up? At what interval? What signs of recurrence should I watch for?” |
| Evacuated hydatidiform mole | “When is β-hCG considered to have completely normalized? How long should I avoid a new pregnancy? What are the criteria for chemotherapy treatment?” |
| Advanced cervical cancer | “Has PD-L1 (CPS) been tested? Am I eligible for pembrolizumab? Is tisotumab vedotin indicated?” |
| Any gynecological cancer | “Has BRCA1/2 genetic testing been recommended for me and my family? Is a genetic counselor consultation indicated?” |
Disclaimer: The information in these tables is for informational and educational purposes only. It does not constitute a medical diagnosis, does not replace a specialist consultation, and does not represent a personalized therapeutic recommendation. Reference values may vary depending on the laboratory and method used — always consult the ranges indicated on your analysis report and discuss the results with your gynecological oncologist.
How can Oncoexpertai.com help you?
If you have received positive results for any of these markers and do not know what the next step is or if your treatment regimen is aligned with the international ESGO, ESMO, NCCN 2026 guidelines, the Oncoexpertai.com platform offers you a preliminary assessment assisted by Artificial Intelligence.
Our algorithms correlate your results — tumor markers, biopsy, molecular status — with the latest international protocols and generate a structured analysis that you can use as a starting point for your discussion with your gynecological oncologist.
Don’t show up for your consultation with an incomplete file or unformulated questions. Arrive prepared.
Disclaimer: The information in this article is for informational and educational purposes only. It does not constitute a medical diagnosis, does not replace the consultation of a specialist doctor, and does not represent a personalized therapeutic recommendation. Any medical decision should be made exclusively after consultation with a qualified doctor, based on a complete assessment of your health condition. Reference values may vary slightly depending on the laboratory and method used — always refer to the ranges indicated on the analysis report.
Bibliography
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- Moore K, Colombo N, Scambia G, et al. Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. New England Journal of Medicine. 2018;379:2495–2505. doi: 10.1056/NEJMoa1810858
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- Ngan HYS, Seckl MJ, Berkowitz RS, et al. Diagnosis and management of gestational trophoblastic disease: 2021 update. International Journal of Gynecology & Obstetrics. 2021;155(Suppl 1):86–93. doi: 10.1002/ijgo.13877
- Concin N, Matias-Guiu X, Vergote I, et al. ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma. International Journal of Gynecological Cancer. 2021;31(1):12–39. doi: 10.1136/ijgc-2020-002230
- Colombo N, Dubot C, Lorusso D, et al. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. New England Journal of Medicine. 2021;385:1856–1867. doi: 10.1056/NEJMoa2112435
- Pereira E, Camacho-Vanegas O, Anand S, et al. Personalized Circulating Tumor DNA Biomarkers Dynamically Predict Treatment Response and Survival in Gynecologic Cancers. PLOS ONE. 2015;10(12):e0145754. doi: 10.1371/journal.pone.0145754
Dr. Onisim Florin Senior Medical Oncologist | Founder of OncoExpertAI
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