cancersCancer

Locally advanced cervical cancer

aka Stage IB3 to IVA cervical cancer, LACC (disease state, not the surgical trial), Node-positive cervical cancer, Bulky cervical cancer

Locally advanced cervical cancer has grown beyond the cervix or into the pelvic lymph nodes but not to distant organs. It is treated with cisplatin chemotherapy given alongside external radiotherapy and brachytherapy, and two recent trials have improved on that: adding pembrolizumab, and giving six weeks of chemotherapy before the radiotherapy starts.

Part ofCervical cancer

The group spans FIGO 2018 stage IB3 (tumour over four centimetres), IIA2 and IIB (vaginal or parametrial extension), III (lower vagina, pelvic sidewall, hydronephrosis or pelvic and para-aortic nodes, which FIGO 2018 now stages as IIIC) and IVA (bladder or rectal invasion). Squamous carcinoma predominates; adenocarcinoma responds slightly less well. MRI defines the primary tumour and PET-CT the nodes, and nodal status has become the strongest prognostic factor. In 1999 five trials reported together and the National Cancer Institute issued a clinical alert that cisplatin given weekly during radiotherapy improved survival; concurrent chemoradiation, delivered as external-beam radiotherapy to the pelvis followed by image-guided brachytherapy to a high dose in the cervix within eight weeks, has been the standard since. Intensity-modulated radiotherapy reduces bowel toxicity and the EMBRACE studies showed that MRI-guided adaptive brachytherapy gives local control above ninety percent.

Attempts to add more chemotherapy after chemoradiation failed: OUTBACK's four cycles of adjuvant carboplatin-paclitaxel gave five-year survival of 72 percent against 71 percent with chemoradiation alone, while adding toxicity. INTERLACE instead gave six weeks of induction carboplatin-paclitaxel before chemoradiation and improved five-year overall survival from 72 to 80 percent, with a hazard ratio of 0.60; the short, dose-dense induction schedule is now a guideline option, especially where immunotherapy is unavailable. KEYNOTE-A18 added pembrolizumab to chemoradiation for high-risk disease, defined as node-positive stage IB2 to IIB or stage III to IVA, and improved progression-free survival with a hazard ratio of 0.70 and overall survival at thirty-six months from 74.8 to 82.6 percent, leading to approval in January 2024. CALLA, which tested durvalumab in the same setting, was negative, a reminder that the antibody and the trial population both matter.

How to combine induction chemotherapy and immunotherapy, whether to add para-aortic radiotherapy for high pelvic nodes, and how to bring MRI-guided brachytherapy to low-income countries where most patients live are the current questions. Circulating HPV DNA after chemoradiation predicts relapse and may allow response-adapted follow-up or consolidation. Surgery has a small role: completion hysterectomy after chemoradiation does not improve survival, but exenteration can salvage central pelvic recurrence.

State of the art

KEYNOTE-A18 made pembrolizumab part of chemoradiation for high-risk disease, the first systemic advance in this setting since 1999.
MRI-guided adaptive brachytherapy (EMBRACE) achieves local control above ninety percent.

Show survival figures (1)

Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.

INTERLACE showed that a short induction course of cheap chemotherapy adds eight percentage points of five-year survival.

Red cards

From the labels and guidelines behind the standard of care. Your team's thresholds win.

Emergency services now
Bleeding or bruising
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
Carboplatin Cisplatin Paclitaxel / nab-paclitaxel source
Emergency services now
Hypophysitis or adrenal crisis
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
Pembrolizumab source
Check before combining
Food and drink: Pembrolizumab
No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
Pembrolizumab source
Check before combining
Kidneys: Carboplatin
Dose by Calvert formula using GFR (see the calculators).
Carboplatin source
Check before combining
Kidneys: Cisplatin
Dose reduce or avoid for CrCl below 60 (carboplatin is the alternative).
Cisplatin source
Good to know
Immune-related endocrinopathies (thyroiditis, hypophysitis)
Immunotherapy can attack hormone-producing glands: most often the thyroid (usually ending in an under-active thyroid needing lifelong tablets), and less often the pituitary (hypophysitis) or adrenal glands, which can be life-threatening if missed.
Pembrolizumab source

See all on the product pages:Carboplatin Cisplatin Paclitaxel / nab-paclitaxel Pembrolizumab·Printable cards in the navigator

Anatomy and lymph node drainage

Uterus, cervix, ovaries, tubes and vulva: subsites and node stations · wireframe schematic, not to scale

Organ atlas →

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.

Subsites

Fallopian tube fimbria (origin of high-grade serous)
Ovary (other histologies, germ cell)
Endometrium
Myometrium (uterine sarcoma)
Placental site (gestational trophoblastic)High-risk locally advanced (KEYNOTE-A18 population: node-positive IB2 to IIB, or III to IVA)
Cervix, transformation zoneFIGO 2018 stage IB3 and IIA2 (bulky, confined to cervix and upper vagina) · High-risk locally advanced (KEYNOTE-A18 population: node-positive IB2 to IIB, or III to IVA) · Squamous cell carcinoma and adenocarcinoma of the cervix
Vulva

Regional lymph nodes

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, Clear cell 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, POLE-ultramutated endometrial cancer, Mismatch-repair-deficient endometrial cancer, p53-abnormal endometrial cancer, including uterine serous carcinoma, Endometrial cancer with no specific molecular profile, Advanced or recurrent endometrial cancer, Uterine carcinosarcoma, Early cervical cancer and fertility-sparing surgery, Recurrent or metastatic cervical cancer, Platinum-sensitive ovarian cancer, Platinum-resistant ovarian cancer

Who gets it and what has changed

Most cervical cancers worldwide present at this stage because screening is absent; even with chemoradiation about a third of women relapse, so it is the stage where the disease kills most of its victims and where the newest trials have made the largest gains.

Group

gynaecologic

What is being done about this

Finding cancer earlier

and how the field plans to fix it →

Available now

MRIStandard of care

In trials

Nothing recorded yet.

Ideas and roadmaps

Nothing recorded yet.

Also on OnCo: Symptoms and red flags · Early detection roadmap.

Cases by country

Cases by country · GLOBOCAN 2022

All countries →

No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.

Standard of care

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Lines of therapy by subgroup →Staging and risk scores →

Decisions you may face

6 with more than one option · full decision page →

One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.

Standard chemoradiation3 High-risk disease (node-positive IB2 to IIB, III to IVA)3 Induction option2 Not recommended2 Staging2 Central pelvic recurrence after radiotherapy3

Standard chemoradiation

Weekly cisplatin with pelvic external-beam radiotherapy followed by image-guided brachytherapy, completed within eight weeks.

CisplatinIMRT / IGRT (modern external beam)Brachytherapy Chemoradiation (chemoradiotherapy, CRT)Radiotherapy

High-risk disease (node-positive IB2 to IIB, III to IVA)

Pembrolizumab with chemoradiation and for up to two years afterwards (KEYNOTE-A18).

PembrolizumabKEYNOTE-A18 / ENGOT-cx11 / GOG-3047 PD-1 blockade + chemoradiation (locally advanced cervical cancer)CisplatinBrachytherapy

Induction option

Six weekly cycles of carboplatin-paclitaxel before chemoradiation (INTERLACE), particularly where immunotherapy is not available.

CarboplatinPaclitaxel / nab-paclitaxelINTERLACE Induction chemotherapy → chemoradiation (locally advanced cervical cancer)

Not recommended

Adjuvant carboplatin-paclitaxel after chemoradiation gave no benefit in OUTBACK.

OUTBACK / ANZGOG 0902 / GOG-0274CarboplatinPaclitaxel / nab-paclitaxel

Staging

Pelvic MRI and whole-body PET-CT; surgical para-aortic staging in selected cases.

MRI PET/CT Laparoscopy (keyhole surgery)

Central pelvic recurrence after radiotherapy

Pelvic exenteration in selected patients; re-irradiation with brachytherapy or protons in specialist centres.

Brachytherapy Proton therapy Robotic & minimally invasive surgery

Subtypes & biomarkers

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Subtypes

FIGO 2018 stage IB3 and IIA2 (bulky, confined to cervix and upper vagina)
Stage IIB (parametrial invasion)
Stage IIIA to IIIB (lower vagina, pelvic wall, hydronephrosis)
Stage IIIC1 and IIIC2 (pelvic and para-aortic node-positive)
Stage IVA (bladder or rectal invasion)
High-risk locally advanced (KEYNOTE-A18 population: node-positive IB2 to IIB, or III to IVA)
Squamous cell carcinoma and adenocarcinoma of the cervix

Biomarkers clinicians test

FIGO 2018 stage including nodal status on PET-CT
Tumour volume on MRI
Para-aortic node involvement
Haemoglobin before and during radiotherapy
HPV type and p16
PD-L1 (not required for pembrolizumab in this setting)
Circulating HPV DNA after treatment (investigational)

How often this target appears

History

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1999NCI clinical alert: cisplatin chemoradiation improves survival in five trials
CisplatinChemoradiation (chemoradiotherapy, CRT)
2021OUTBACK: adjuvant chemotherapy after chemoradiation gives no benefit
OUTBACK / ANZGOG 0902 / GOG-0274
2021EMBRACE-I: MRI-guided adaptive brachytherapy gives local control above ninety percent
Brachytherapy
2023INTERLACE: induction carboplatin-paclitaxel improves five-year survival from 72 to 80 percent
INTERLACE
2023KEYNOTE-A18: pembrolizumab with chemoradiation improves progression-free and overall survival
KEYNOTE-A18 / ENGOT-cx11 / GOG-3047
2024Pembrolizumab approved with chemoradiation for high-risk locally advanced disease
Pembrolizumab

What changed

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Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.

All 10 changes by month →

FollowWatch this cancer and Saved shows what changed since you last looked.Follow by feed

In development

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What is in development for Locally advanced cervical cancer, drawn from the whole corpus: 6 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.

Trials reported · 3

INTERLACE · phase 3 · 2023 · positive
KEYNOTE-A18 / ENGOT-cx11 / GOG-3047 · phase 3 · 2023 · positive
OUTBACK / ANZGOG 0902 / GOG-0274 · phase 3 · 2021 · negative

Combinations being explored · 2

Induction chemotherapy → chemoradiation (locally advanced cervical cancer)PD-1 blockade + chemoradiation (locally advanced cervical cancer)

Ideas not yet in a trial · 1

HPV circulating tumour DNA to guide cervical cancer therapy

Open problems and what is being done

Whether induction chemotherapy and pembrolizumab should be combined.
Access to brachytherapy and PET-CT where most patients live.
Why durvalumab (CALLA) failed where pembrolizumab succeeded.

Trials

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Trials recruiting now

Recruiting trials near you · live from ClinicalTrials.gov

Locally advanced cervical cancer

condition: Locally advanced cervical cancer

Open on ClinicalTrials.gov →

within

Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.

Landmark trials

INTERLACE KEYNOTE-A18 / ENGOT-cx11 / GOG-3047 OUTBACK / ANZGOG 0902 / GOG-0274

Expert centres

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Where the expertise is

Expert centres

185 centres in 53 countries · 4 with a trial for this cancer on record · second-opinion finder →

Choose a region from the globe in the header to mark centres near you.

185 centres


MD Anderson Cancer Center Houston · cancer center	United States	NCI comprehensive	0	6,724	95,007	CAR-NK & CAR-macrophage Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems Gamma Knife +2	#2
Samsung Medical Center Seoul · hospital	South Korea	none recorded	0	1,312	17,172	Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems Gamma Knife Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)	#3
Mayo Clinic Rochester, MN · hospital	United States	NCI comprehensive	0	4,511	44,748	Carbon-ion therapy Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems Gamma Knife +1	#5
Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center Baltimore · cancer center	United States	NCI comprehensive	0	2,955	41,449	Multi-cancer early detection (MCED)Liquid biopsy (ctDNA)Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems +2	#10
Charité Universitätsmedizin Berlin Berlin · university	Germany	none recorded	0	1,563	17,749	Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems CyberKnife robotic radiosurgery Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)	#12
Massachusetts General Hospital Cancer Center Boston · hospital	United States	NCI comprehensive	0	3,582	54,857	Proton therapy Small-molecule kinase inhibitors Proton therapy machines: cyclotrons, synchrotrons and single-room systems Gamma Knife +1	#16
Heidelberg University Hospital / NCT / DKFZ Heidelberg · cancer center	Germany	none recorded	0	3,456	45,745	FAPI PET Targeted alpha therapy Carbon-ion therapy DNA methylation profiling +5	#18
Cleveland Clinic Taussig Cancer Institute Cleveland · hospital	United States	NCI comprehensive	0	2,264	29,412	Off-the-shelf cancer vaccines Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems Gamma Knife +1	#20
Institut Curie Paris · cancer center	France	none recorded	0	1,065	15,111	Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems	#21
Severance Hospital, Yonsei University Seoul · hospital	South Korea	none recorded	0	464	3,248	Carbon-ion therapy Robotic & minimally invasive surgery Carbon-ion synchrotrons and facilities Gamma Knife +1	#22
The Christie NHS Foundation Trust Manchester · cancer center	United Kingdom	none recorded	0	104	2,145	Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems MR-guided adaptive radiotherapy TomoTherapy and Radixact (helical radiotherapy)	#23
Fudan University Shanghai Cancer Center Shanghai · cancer center	China	none recorded	0	1,678	18,354	TROP2 PET Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems Carbon-ion therapy +1	#55
GOG Foundation Philadelphia, PA · consortium	United States	none recorded	2	165	1,237	Immune checkpoint inhibitors Antibody-drug conjugate (ADC)Anti-angiogenic therapy	-
NRG Oncology Philadelphia, PA · consortium	United States	none recorded	1	87	2,130	none recorded	-
Cancer Research UK London · consortium	United Kingdom	none recorded	1	not matched	-	none recorded	-

(showing the first 15)

These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with Locally advanced cervical cancer but is thinly recorded here will look small.

Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.

Seeking a second opinion: ask your oncologist for a referral to a high-volume centre; most accept records and pathology by mail or telehealth. In the US, use the NCI's Find a Cancer Center tool or the nonprofit Cancer Commons, which navigates options for advanced cancers at no cost. The second-opinion finder explains how referral works in your country.

Questions to ask

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Bring to your appointment

Questions to ask your oncologist about Locally advanced cervical cancer

Generated from this cancer's standard of care, biomarkers, and pipeline · 22 questions

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 FIGO 2018 stage including nodal status on PET-CT, Tumour volume on MRI, Para-aortic node involvement, Haemoglobin before and during radiotherapy, HPV type and p16), 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 FIGO 2018 stage IB3 and IIA2, Stage IIB, Stage IIIA to IIIB.
Is germline (inherited) genetic testing recommended for me or my family?
Why: Inherited variants can change treatment and matter for relatives.