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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
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.
| Setting | Approach | Guideline |
|---|---|---|
| Standard chemoradiation | Weekly cisplatin with pelvic external-beam radiotherapy followed by image-guided brachytherapy, completed within eight weeks. | not mapped |
| High-risk disease (node-positive IB2 to IIB, III to IVA) | Pembrolizumab with chemoradiation and for up to two years afterwards (KEYNOTE-A18). | not mapped |
| Induction option | Six weekly cycles of carboplatin-paclitaxel before chemoradiation (INTERLACE), particularly where immunotherapy is not available. | not mapped |
| Not recommended | Adjuvant carboplatin-paclitaxel after chemoradiation gave no benefit in OUTBACK. | not mapped |
| Staging | Pelvic MRI and whole-body PET-CT; surgical para-aortic staging in selected cases. | not mapped |
| Central pelvic recurrence after radiotherapy | Pelvic exenteration in selected patients; re-irradiation with brachytherapy or protons in specialist centres. | not mapped |