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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.
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.
Averages across everyone diagnosed, often years ago. A median is the middle of a group: half the people counted lived longer than the figure shown, and some lived far longer. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
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.
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.
Same organ: Adenosquamous carcinoma of the cervix, Small cell neuroendocrine carcinoma of the cervix, Bartholin gland carcinoma, Vulvar melanoma, Vaginal melanoma, 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, HPV-associated vulvar squamous cell carcinoma, HPV-independent vulvar squamous cell carcinoma (p53-mutant), Vaginal squamous cell carcinoma (HPV-associated), Vaginal adenocarcinoma (including DES-associated clear cell adenocarcinoma), Low-risk gestational trophoblastic neoplasia (FIGO score 0 to 6), High-risk gestational trophoblastic neoplasia (FIGO score 7 or more, including ultra-high-risk), Placental-site trophoblastic tumour and epithelioid trophoblastic tumour
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Also on OnCo: Symptoms and red flags · Early detection roadmap.
Weekly cisplatin with pelvic external-beam radiotherapy followed by image-guided brachytherapy, completed within eight weeks.
Pembrolizumab with chemoradiation and for up to two years afterwards (KEYNOTE-A18).
Six weekly cycles of carboplatin-paclitaxel before chemoradiation (INTERLACE), particularly where immunotherapy is not available.
Adjuvant carboplatin-paclitaxel after chemoradiation gave no benefit in OUTBACK.
Pelvic MRI and whole-body PET-CT; surgical para-aortic staging in selected cases.
Pelvic exenteration in selected patients; re-irradiation with brachytherapy or protons in specialist centres.
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Short induction chemotherapy is a standard option before chemoradiation, particularly where pembrolizumab is unaffordable, and can be delivered in most health systems.
Women with locally advanced cervical cancer that is node-positive or stage III-IVA can be offered pembrolizumab alongside and after chemoradiotherapy to lower the chance of relapse. The result matters most in countries where cervical cancer is common but immunotherapy access is poorest, so its global impact depends on pricing and health-system capacity. It does not apply to early-stage disease treated with surgery or to lower-risk locally advanced disease without nodal involvement.
The survival gain turns the earlier progression-free survival result into a clear reason to offer pembrolizumab with and after chemoradiotherapy to women with node-positive or stage III-IVA cervical cancer. Because cervical cancer is concentrated in low- and middle-income countries, the benefit reaches most women only if pricing and access follow.
Chemotherapy after chemoradiation adds toxicity without benefit; the search for improvement has moved to induction chemotherapy (INTERLACE) and immunotherapy (KEYNOTE-A18).
Weekly cisplatin with external beam radiotherapy and brachytherapy remains the backbone of curative treatment for locally advanced cervical cancer; INTERLACE and KEYNOTE-A18 build on it.
Query for this cancer: (TITLE:"Locally advanced cervical cancer" OR ABSTRACT:"Locally advanced cervical cancer" OR TITLE:"Stage IB3 to IVA cervical cancer" OR ABSTRACT:"Stage IB3 to IVA cervical cancer" OR TITLE:"LACC disease state, not the surgical trial" OR ABSTRACT:"LACC disease state, not the surgical trial" OR TITLE:"Node-positive cervical cancer" OR ABSTRACT:"Node-positive cervical cancer" OR TITLE:"Bulky cervical cancer" OR ABSTRACT:"Bulky cervical cancer") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Locally advanced cervical cancer, not a curated reading list.
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Bleeding that does not stop by itself, bleeding from more than one site, or new bruising in several places or one large area.
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
Dose by Calvert formula using GFR (see the calculators).
Dose reduce or avoid for CrCl below 60 (carboplatin is the alternative).
During chemotherapy a temperature over 37.5 C or below 36 C, shivering, or feeling unwell even with a normal temperature means ringing the hospital's 24-hour line straight away; breathing very fast, confusion, mottled skin or no urine in a day means 999.
See all on the product pages:CarboplatinCisplatinPaclitaxel / nab-paclitaxelPembrolizumab·Printable cards in the navigator
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