# Locally advanced cervical cancer

Source: https://onco.cc/cancers/locally-advanced-cervical-cancer/  
OnCo record `locally-advanced-cervical-cancer` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Cancer
- Last checked: 2026-09-17
- Also known as: Stage IB3 to IVA cervical cancer; LACC (disease state, not the surgical trial); Node-positive cervical cancer; Bulky cervical cancer
- Tags: subtype-page
- Group: gynaecologic
- Burden: 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.
- 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: 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)

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/locally-advanced-cervical-cancer/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/locally-advanced-cervical-cancer/#overview [3 state-of-the-art points]
- Types and stages (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/locally-advanced-cervical-cancer/#what-it-is [7 subtypes]
- Symptoms and diagnosis (on the hub): How this cancer shows itself, how the diagnosis is confirmed, and the biomarkers clinicians test for. https://onco.cc/cancers/locally-advanced-cervical-cancer/#finding-it [7 biomarkers]
- Treatment (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/locally-advanced-cervical-cancer/#treating-it [6 settings, 6 decisions with options]
- Trials and papers (on the hub): Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/locally-advanced-cervical-cancer/#evidence [8 trials, 5 key papers, 6 milestones]
- Biology and targets (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/locally-advanced-cervical-cancer/#science [1 target]
- Countries and centres (own page): Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes. https://onco.cc/cancers/locally-advanced-cervical-cancer/where-you-are/
- Decisions and support (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/locally-advanced-cervical-cancer/#living-with-it [22 questions, 6 red cards]
- Pipeline and open problems (own page): Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/locally-advanced-cervical-cancer/coming/ [4 medicines, 8 trials, 1 idea, 3 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/locally-advanced-cervical-cancer/data/ [37 connected records]

## Standard of care

- Standard chemoradiation: Weekly cisplatin with pelvic external-beam radiotherapy followed by image-guided brachytherapy, completed within eight weeks. ([Cisplatin](https://onco.cc/drugs/cisplatin/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Brachytherapy](https://onco.cc/technologies/brachytherapy/), [Chemoradiation (chemoradiotherapy, CRT)](https://onco.cc/terms/chemoradiation/), [Radiotherapy](https://onco.cc/terms/radiotherapy/))
- High-risk disease (node-positive IB2 to IIB, III to IVA): Pembrolizumab with chemoradiation and for up to two years afterwards (KEYNOTE-A18). ([Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [KEYNOTE-A18 / ENGOT-cx11 / GOG-3047](https://onco.cc/trials/keynote-a18/), [PD-1 blockade + chemoradiation (locally advanced cervical cancer)](https://onco.cc/pairings/io-plus-crt-cervical/), [Cisplatin](https://onco.cc/drugs/cisplatin/), [Brachytherapy](https://onco.cc/technologies/brachytherapy/))
- Induction option: Six weekly cycles of carboplatin-paclitaxel before chemoradiation (INTERLACE), particularly where immunotherapy is not available. ([Carboplatin](https://onco.cc/drugs/carboplatin/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/), [INTERLACE](https://onco.cc/trials/interlace/), [Induction chemotherapy → chemoradiation (locally advanced cervical cancer)](https://onco.cc/pairings/induction-chemo-then-crt/))
- Not recommended: Adjuvant carboplatin-paclitaxel after chemoradiation gave no benefit in OUTBACK. ([OUTBACK / ANZGOG 0902 / GOG-0274](https://onco.cc/trials/outback/), [Carboplatin](https://onco.cc/drugs/carboplatin/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/))
- Staging: Pelvic MRI and whole-body PET-CT; surgical para-aortic staging in selected cases. ([MRI](https://onco.cc/technologies/mri/), [PET/CT](https://onco.cc/technologies/pet-ct/), [Laparoscopy (keyhole surgery)](https://onco.cc/terms/staging-laparoscopy/))
- Central pelvic recurrence after radiotherapy: Pelvic exenteration in selected patients; re-irradiation with brachytherapy or protons in specialist centres. ([Brachytherapy](https://onco.cc/technologies/brachytherapy/), [Proton therapy](https://onco.cc/technologies/proton-therapy/), [Robotic & minimally invasive surgery](https://onco.cc/technologies/robotic-surgery/))

## State of the art

- KEYNOTE-A18 made pembrolizumab part of chemoradiation for high-risk disease, the first systemic advance in this setting since 1999.
- INTERLACE showed that a short induction course of cheap chemotherapy adds eight percentage points of five-year survival.
- MRI-guided adaptive brachytherapy (EMBRACE) achieves local control above ninety percent.

## Open problems

- 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.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Cervical_cancer
- Wikipedia: https://en.wikipedia.org/wiki/Cervical_cancer

## Connected records

- cancers: [Cervical cancer](https://onco.cc/cancers/cervical/), [Early cervical cancer and fertility-sparing surgery](https://onco.cc/cancers/early-cervical-cancer/), [Localised anal squamous cell carcinoma (stage I to III)](https://onco.cc/cancers/localised-anal-cancer/), [Recurrent or metastatic cervical cancer](https://onco.cc/cancers/recurrent-metastatic-cervical-cancer/), [Vaginal squamous cell carcinoma (HPV-associated)](https://onco.cc/cancers/vaginal-squamous-cell-carcinoma/)
- trials: [A Phase III Clinical Study of Adebrelimab Combined With Concurrent Chemoradiotherapy Versus Placebo Combined With Concurrent Chemoradiotherapy for the](https://onco.cc/trials/nct07168200/), [A Study of AK104/Placebo Combined With Chemoradiotherapy For The Treatment of Locally Advanced Cervical Cancer](https://onco.cc/trials/nct05235516/), [A Study of Volrustomig in Women With High Risk Locally Advanced Cervical Cancer (IVOLGA)](https://onco.cc/trials/nct06943833/), [CALLA](https://onco.cc/trials/calla/), [INTERLACE](https://onco.cc/trials/interlace/), [KEYNOTE-A18 / ENGOT-cx11 / GOG-3047](https://onco.cc/trials/keynote-a18/), [OUTBACK / ANZGOG 0902 / GOG-0274](https://onco.cc/trials/outback/), [Study of Volrustomig in Women With High Risk Locally Advanced Cervical Cancer (eVOLVE-Cervical)](https://onco.cc/trials/nct06079671/)
- key papers: [GOG 120: concurrent cisplatin-based chemotherapy with radiotherapy for locally advanced cervical cancer](https://onco.cc/key-papers/paper-rose-cisplatin-chemoradiation-cervical-nejm-1999/), [INTERLACE: induction chemotherapy before chemoradiotherapy for locally advanced cervical cancer](https://onco.cc/key-papers/paper-interlace-lancet-2024/), [KEYNOTE-A18: pembrolizumab with chemoradiotherapy for locally advanced cervical cancer (overall survival)](https://onco.cc/key-papers/paper-keynote-a18-os-lancet-2024/), [KEYNOTE-A18: pembrolizumab with chemoradiotherapy for locally advanced cervical cancer (progression-free survival)](https://onco.cc/key-papers/paper-keynote-a18-pfs-lancet-2024/), [OUTBACK: adjuvant carboplatin-paclitaxel after chemoradiotherapy for locally advanced cervical cancer](https://onco.cc/key-papers/paper-outback-lancet-oncol-2023/)
- drugs: [Carboplatin](https://onco.cc/drugs/carboplatin/), [Cisplatin](https://onco.cc/drugs/cisplatin/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- terms: [Chemoradiation (chemoradiotherapy, CRT)](https://onco.cc/terms/chemoradiation/), [Laparoscopy (keyhole surgery)](https://onco.cc/terms/staging-laparoscopy/), [Radiotherapy](https://onco.cc/terms/radiotherapy/)
- technologies: [Brachytherapy](https://onco.cc/technologies/brachytherapy/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [MRD / molecular residual disease testing](https://onco.cc/technologies/mrd-testing/), [MRI](https://onco.cc/technologies/mri/), [PET/CT](https://onco.cc/technologies/pet-ct/), [Proton therapy](https://onco.cc/technologies/proton-therapy/), [Robotic & minimally invasive surgery](https://onco.cc/technologies/robotic-surgery/)
- ideas: [HPV circulating tumour DNA to guide cervical cancer therapy](https://onco.cc/ideas/idea-hpv-ctdna-cervical/)
- pairings: [Induction chemotherapy → chemoradiation (locally advanced cervical cancer)](https://onco.cc/pairings/induction-chemo-then-crt/), [PD-1 blockade + chemoradiation (locally advanced cervical cancer)](https://onco.cc/pairings/io-plus-crt-cervical/)

---
JSON: https://onco.cc/api/v1/entities/locally-advanced-cervical-cancer.json