Recurrent or metastatic cervical cancer

aka Persistent, recurrent or metastatic cervical cancer, Stage IVB cervical cancer, Advanced cervical cancer

Recurrent or metastatic cervical cancer has spread beyond the pelvis or come back where it cannot be cured by surgery or radiotherapy. Pembrolizumab added to chemotherapy and bevacizumab is the first treatment, and the antibody-drug conjugate tisotumab vedotin or the PD-1 antibody cemiplimab extend life when it progresses.

Part ofCervical cancer

Persistent disease after chemoradiation, recurrence outside a previously irradiated field and stage IVB disease at presentation are managed together. Isolated central pelvic recurrence after radiotherapy can still be cured by exenteration, and an isolated para-aortic or lung metastasis is sometimes treated with radiotherapy or resection, but most patients need systemic therapy. Cisplatin-paclitaxel was the reference doublet, with carboplatin an equivalent substitute after JCOG0505. GOG-240 added bevacizumab to chemotherapy in 2014 and extended median survival to about seventeen months, the first targeted therapy in the disease. Squamous, adenocarcinoma and adenosquamous histologies are treated alike, and PD-L1 combined positive score is measured because most trials selected or stratified by it.

KEYNOTE-826 added pembrolizumab to platinum-paclitaxel with or without bevacizumab and extended median overall survival in all comers from 16.8 to 26.4 months, with a hazard ratio of 0.63, and to 28.6 months in tumours with a combined positive score of one or more; it was approved in 2021 and is the first-line standard. BEATcc added atezolizumab to chemotherapy plus bevacizumab and reached a median survival of 32.1 months against 22.8, and COMPASSION-16 in China added the PD-1 and CTLA-4 bispecific cadonilimab with a survival hazard ratio of 0.64, confirming the class effect. Fitness for bevacizumab, prior pelvic radiotherapy and the risk of fistula shape the choice of partner drugs.

After platinum and immunotherapy, tisotumab vedotin, an antibody-drug conjugate against tissue factor, improved median survival from 9.5 to 11.5 months against chemotherapy in innovaTV 301 and gained full approval in 2024; ocular toxicity requires eye care and steroid drops. Cemiplimab improved survival from 8.5 to 12.0 months against chemotherapy in EMPOWER-Cervical 1 in immunotherapy-naive patients and remains relevant where first-line immunotherapy was not given. Trastuzumab deruxtecan produced responses in half of HER2-expressing cervical cancers in DESTINY-PanTumor02, sacituzumab tirumotecan is in phase 3, and tumour-infiltrating lymphocyte therapy has shown durable responses in small studies. How to sequence antibody-drug conjugates after first-line immunotherapy, and how to bring any of this to the low-income countries where most deaths occur, are the pressing questions.

State of the art

Tisotumab vedotin was the first antibody-drug conjugate approved in a gynaecological cancer.

Show survival figures (2)

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.

KEYNOTE-826 made chemo-immunotherapy first-line standard and lifted median survival past two years.
Three different checkpoint agents have now shown survival gains in the first line.

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 Gemcitabine Paclitaxel / nab-paclitaxel Topotecan 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.
Atezolizumab Cadonilimab Cemiplimab Pembrolizumab source
Emergency services now
Skin reaction
Blisters, peeling, or sores in the mouth or eyes with a rash. Enfortumab vedotin carries a boxed warning for Stevens-Johnson syndrome and toxic epidermal necrolysis, mostly in the first cycle.
Sacituzumab tirumotecan Tisotumab vedotin Trastuzumab deruxtecan source
Emergency services now
Bowel perforation
Sudden severe abdominal pain, a hard or very tender abdomen, or abdominal pain with vomiting and fever. Boxed warning for gastrointestinal perforation on bevacizumab.
Bevacizumab source
Call the 24-hour line now
Interstitial lung disease or pneumonitis
Any new or worsening cough, breathlessness or fever. The label says to interrupt treatment for any suspected ILD and to permanently discontinue for grade 2 or higher.
Trastuzumab deruxtecan source
Check before combining
Food and drink: Pembrolizumab
No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
Pembrolizumab source

See all on the product pages:Atezolizumab Bevacizumab Cadonilimab Carboplatin Cemiplimab Cisplatin Gemcitabine Paclitaxel / nab-paclitaxel Pembrolizumab Sacituzumab tirumotecan Tisotumab vedotin Topotecan Trastuzumab deruxtecan·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)Small cell neuroendocrine carcinoma of the cervix (platinum-etoposide, separate pathway)
Ovary (other histologies, germ cell)
EndometriumHER2-expressing cervical cancer (trastuzumab deruxtecan)
Myometrium (uterine sarcoma)
Placental site (gestational trophoblastic)
Cervix, transformation zoneSquamous cell carcinoma, adenocarcinoma and adenosquamous carcinoma (treated alike) · HER2-expressing cervical cancer (trastuzumab deruxtecan) · Small cell neuroendocrine carcinoma of the cervix (platinum-etoposide, separate pathway)
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, Locally advanced cervical cancer, Platinum-sensitive ovarian cancer, Platinum-resistant ovarian cancer

Who gets it and what has changed

Around one in ten cervical cancers present with distant spread and a third of locally advanced cases relapse; median survival was about a year before 2014, and first-line chemo-immunotherapy has now more than doubled it for many women.

Group

gynaecologic

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

4 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.

First line7 Second line after platinum3 HER2-expressing disease Later lines4 Isolated pelvic recurrence after radiotherapy2

First line

Pembrolizumab with cisplatin or carboplatin, paclitaxel and, when safe, bevacizumab (KEYNOTE-826); atezolizumab with chemotherapy and bevacizumab (BEATcc) or cadonilimab with chemotherapy (COMPASSION-16, China) as alternatives.

PembrolizumabKEYNOTE-826CisplatinCarboplatinPaclitaxel / nab-paclitaxelBevacizumabAtezolizumabBEATcc / ENGOT-Cx10 / GOG-3030CadonilimabCOMPASSION-16 / AK104-303 PD-L1

Second line after platinum

Tisotumab vedotin (innovaTV 301) with prophylactic eye care; cemiplimab (EMPOWER-Cervical 1) if no prior immunotherapy.

Tisotumab vedotininnovaTV 301 / ENGOT-cx12 / GOG-3057CemiplimabEMPOWER-Cervical 1 / GOG-3016 / ENGOT-cx9 Antibody-drug conjugate (ADC)

HER2-expressing disease

Trastuzumab deruxtecan after prior therapy (DESTINY-PanTumor02).

Trastuzumab deruxtecanDESTINY-PanTumor02 HER2

Later lines

Single-agent chemotherapy (topotecan, gemcitabine, pemetrexed, vinorelbine) with modest response; clinical trials of new antibody-drug conjugates and cell therapy preferred.

TopotecanGemcitabineSacituzumab tirumotecanLifileucel

Isolated pelvic recurrence after radiotherapy

Pelvic exenteration in fit patients without sidewall fixation.

Robotic & minimally invasive surgery IMRT / IGRT (modern external beam)

Subtypes & biomarkers

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Subtypes

Stage IVB at presentation (distant metastasis)
Persistent or recurrent disease after chemoradiation
PD-L1 combined positive score 1 or more (largest pembrolizumab benefit)
Squamous cell carcinoma, adenocarcinoma and adenosquamous carcinoma (treated alike)
HER2-expressing cervical cancer (trastuzumab deruxtecan)
Isolated central pelvic recurrence (exenteration with curative intent)
Small cell neuroendocrine carcinoma of the cervix (platinum-etoposide, separate pathway)

Biomarkers clinicians test

PD-L1 combined positive score
Tissue factor expression (not required for tisotumab vedotin)
HER2 immunohistochemistry (trastuzumab deruxtecan)
HPV type and circulating HPV DNA
Prior pelvic radiotherapy and fistula risk (bevacizumab)
MSI and tumour mutational burden (rare)

How often this target appears

History

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2009GOG-0204: cisplatin-paclitaxel confirmed as the reference doublet
CisplatinPaclitaxel / nab-paclitaxel
2014GOG-0240: bevacizumab extends survival in advanced cervical cancer
Bevacizumab
2021KEYNOTE-826: pembrolizumab with chemotherapy extends median survival to 26.4 months
KEYNOTE-826
2021Tisotumab vedotin accelerated approval; EMPOWER-Cervical 1 positive for cemiplimab
Tisotumab vedotinEMPOWER-Cervical 1 / GOG-3016 / ENGOT-cx9
2023innovaTV 301 and BEATcc positive
innovaTV 301 / ENGOT-cx12 / GOG-3057 BEATcc / ENGOT-Cx10 / GOG-3030
2024Tisotumab vedotin full approval; COMPASSION-16 positive for cadonilimab in China
Tisotumab vedotinCOMPASSION-16 / AK104-303

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 14 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 Recurrent or metastatic cervical cancer, drawn from the whole corpus: 8 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

Angiogenesis and vascular normalisation models

Trials reported · 6

BEATcc / ENGOT-Cx10 / GOG-3030 · phase 3 · 2023 · positive
COMPASSION-16 / AK104-303 · phase 3 · 2024 · positive
DESTINY-PanTumor02 · phase 2 · 2023 · positive
EMPOWER-Cervical 1 / GOG-3016 / ENGOT-cx9 · phase 3 · 2021 · positive
innovaTV 301 / ENGOT-cx12 / GOG-3057 · phase 3 · 2023 · positive
KEYNOTE-826 · phase 3 · 2021 · positive

Ideas not yet in a trial · 1

HPV circulating tumour DNA to guide cervical cancer therapy

Open problems and what is being done

Sequencing antibody-drug conjugates and immunotherapy after first-line chemo-immunotherapy.
Fistula and bleeding risk with bevacizumab after pelvic radiotherapy.
Access to any of these drugs in the countries with most deaths.

Trials

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Trials recruiting now

Recruiting trials near you · live from ClinicalTrials.gov

Recurrent or metastatic cervical cancer

condition: Recurrent or metastatic 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

BEATcc / ENGOT-Cx10 / GOG-3030 COMPASSION-16 / AK104-303 DESTINY-PanTumor02 EMPOWER-Cervical 1 / GOG-3016 / ENGOT-cx9 innovaTV 301 / ENGOT-cx12 / GOG-3057 KEYNOTE-826

Expert centres

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Where the expertise is

Expert centres

120 centres in 44 countries · 0 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.

120 centres


Gustave Roussy Villejuif · cancer center	France	none recorded	1,855	31,182	ZAP-X gyroscopic radiosurgery Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)	#6
Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center Baltimore · cancer center	United States	NCI comprehensive	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
National Cancer Center Hospital Tokyo · government	Japan	none recorded	1,599	21,937	none recorded	#13
Severance Hospital, Yonsei University Seoul · hospital	South Korea	none recorded	464	3,248	Carbon-ion therapy Robotic & minimally invasive surgery Carbon-ion synchrotrons and facilities Gamma Knife +1	#22
Cancer Hospital, Chinese Academy of Medical Sciences Beijing · cancer center	China	none recorded	371	4,070	none recorded	#50
Zhongshan Hospital, Fudan University Shanghai · hospital	China	none recorded	2,872	31,534	Liquid biopsy (ctDNA)Thermal ablation (RFA, microwave, cryo)Robotic & minimally invasive surgery	-
Moffitt Cancer Center Tampa, FL · cancer center	United States	NCI comprehensive	2,580	31,111	TIL therapy	-
Chris O'Brien Lifehouse Sydney · cancer center	Australia	none recorded	2,222	33,278	Robotic & minimally invasive surgery MR-guided adaptive radiotherapy Radioligand therapy (beta emitters)	-
UCLA Jonsson Comprehensive Cancer Center Los Angeles · cancer center	United States	NCI comprehensive	2,019	32,934	PSMA PET MR-guided adaptive radiotherapy	-
Peking Union Medical College Hospital Beijing · hospital	China	none recorded	1,784	18,230	Robotic & minimally invasive surgery Germline (hereditary) testing	-
UMC Utrecht Cancer Center Utrecht · cancer center	Netherlands	none recorded	1,422	20,323	MR-guided adaptive radiotherapy Patient-derived organoids Functional (ex vivo) drug testing IMRT / IGRT (modern external beam)+1	-
Peking University Cancer Hospital Beijing · cancer center	China	none recorded	1,344	18,195	CAR-T cell therapy Immune checkpoint inhibitors Antibody-drug conjugate (ADC)	-
First Affiliated Hospital of Sun Yat-sen University Guangzhou · hospital	China	none recorded	1,245	12,931	Robotic & minimally invasive surgery HIPEC / PIPAC (intraperitoneal chemotherapy)	-
Tianjin Medical University Cancer Institute and Hospital Tianjin · cancer center	China	none recorded	1,219	11,455	IMRT / IGRT (modern external beam)Robotic & minimally invasive surgery Mammography & tomosynthesis	-
Zhejiang Cancer Hospital Hangzhou · cancer center	China	none recorded	1,219	17,635	IMRT / IGRT (modern external beam)Proton therapy Immune checkpoint inhibitors	-

(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 Recurrent or metastatic 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 Recurrent or metastatic cervical cancer

Generated from this cancer's standard of care, biomarkers, and pipeline · 21 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 PD-L1 combined positive score, Tissue factor expression, HER2 immunohistochemistry, HPV type and circulating HPV DNA, Prior pelvic radiotherapy and fistula risk), 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 Stage IVB at presentation, Persistent or recurrent disease after chemoradiation, PD-L1 combined positive score 1 or more.
Is germline (inherited) genetic testing recommended for me or my family?
Why: Inherited variants can change treatment and matter for relatives.

First line

For my situation (first line), which of the standard options do you recommend and why?
Why: Guideline options include: Pembrolizumab with cisplatin or carboplatin, paclitaxel and, when safe, bevacizumab (KEYNOTE-826); atezolizumab with chemotherapy and bevacizumab (BEATcc) or cadonilimab with chemotherapy (COMPASSION-16, China) as alternatives.
Am I a candidate for Pembrolizumab, Cisplatin, Carboplatin or related drugs, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of KEYNOTE-826 and BEATcc / ENGOT-Cx10 / GOG-3030 apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Second line after platinum

For my situation (second line after platinum), which of the standard options do you recommend and why?
Why: Guideline options include: Tisotumab vedotin (innovaTV 301) with prophylactic eye care; cemiplimab (EMPOWER-Cervical 1) if no prior immunotherapy.
Am I a candidate for Tisotumab vedotin, Cemiplimab, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of innovaTV 301 / ENGOT-cx12 / GOG-3057 and EMPOWER-Cervical 1 / GOG-3016 / ENGOT-cx9 apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

HER2-expressing disease

For my situation (her2-expressing disease), which of the standard options do you recommend and why?
Why: Guideline options include: Trastuzumab deruxtecan after prior therapy (DESTINY-PanTumor02).
Am I a candidate for Trastuzumab deruxtecan, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of DESTINY-PanTumor02 apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Later lines

For my situation (later lines), which of the standard options do you recommend and why?
Why: Guideline options include: Single-agent chemotherapy (topotecan, gemcitabine, pemetrexed, vinorelbine) with modest response; clinical trials of new antibody-drug conjugates and cell therapy preferred.
Am I a candidate for Topotecan, Gemcitabine, Sacituzumab tirumotecan or related drugs, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Isolated pelvic recurrence after radiotherapy

For my situation (isolated pelvic recurrence after radiotherapy), which of the standard options do you recommend and why?
Why: Guideline options include: Pelvic exenteration in fit patients without sidewall fixation.

Any stage

Are there clinical trials I could join, for example of Sacituzumab tirumotecan, Trastuzumab deruxtecan, Lifileucel, Cadonilimab?
Why: Trials are how the next standard of care is set; asking early keeps options open.
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 “Sequencing antibody-drug conjugates and immunotherapy after first-line chemo-immunotherapy”. How does that affect my plan?
Why: Open problems are where trials and second opinions matter most.
I read that “Fistula and bleeding risk with bevacizumab after pelvic radiotherapy”. How does that affect my plan?
Why: Open problems are where trials and second opinions matter most.