Cervical Cancer Treatment by Stage

Cervical cancer uses the FIGO system. NCI says it is the one most commonly used.

Stage I means the cancer is strictly confined to the cervix. Within that, the divisions are measured in millimeters and centimeters:

• IA can only be diagnosed by microscopy. The depth of invasion is 5 mm at most.
• IA1 is invasion of 3 mm or less. IA2 is more than 3 mm and up to 5 mm.
• IB is deeper than 5 mm. It is still limited to the cervix. Size is measured across the widest part.
• IB1 is up to 2 cm. IB2 is over 2 cm and up to 4 cm. IB3 is over 4 cm.

Two footnotes in NCI's table matter. Imaging and pathology can add to clinical findings on size and extent, at every stage. Where they disagree, pathology wins. And involvement of blood or lymph vessel spaces does not change the stage, even though it changes the plan.

At the smallest end, treatment can be very limited.

For stage IA1, NCI lists two options. Conization, and total hysterectomy. Conization alone may suit someone who wants to preserve fertility. Three conditions apply. Invasion under 3 mm. No vascular or lymphatic channel invasion. And clear cone margins.

If those hold, lymph node dissection is not required at hysterectomy. Removing the ovaries is optional. NCI says it should be deferred in younger women.

For stage IA2 the list widens. Modified radical hysterectomy with lymphadenectomy. Radical trachelectomy. Or intracavitary radiation. Trachelectomy takes the cervix and leaves the uterus, so pregnancy stays possible.

This is where a real choice appears.

NCI reports cure rates of 85 to 90 percent for small-volume stage IA2 and IB1 disease. That figure holds for radiation therapy, and for radical hysterectomy with node dissection on both sides. A randomized trial found identical 5-year overall and disease-free survival between them.

So the decision turns on other things. NCI names patient factors and local expertise. It also notes that younger patients may prefer surgery. That keeps the ovaries and avoids the vaginal narrowing and thinning that radiation can cause. Tumor size is the factor NCI says to weigh carefully.

The full list for these stages is longer. Radiation with chemotherapy at the same time. Radical hysterectomy with lymphadenectomy, with or without radiation and chemotherapy afterward. Radical trachelectomy. Radiation alone. Immunotherapy. Two more are listed as still under study: chemotherapy before surgery, and intensity-modulated radiation.

From here the backbone is fixed. The evidence behind it is unusually solid.

Five randomized phase III trials showed a survival advantage for cisplatin-based chemotherapy given at the same time as radiation. One trial found no benefit. NCI states the size of the effect plainly. The risk of death from cervical cancer fell by 30 to 50 percent.

Brachytherapy is part of that treatment, not an optional finish. NCI describes two kinds. Low-dose-rate treatment, traditionally with cesium-137. And high-dose-rate treatment, usually with iridium-192, which is rapidly increasing. High-dose-rate spares staff from radiation, takes less time, and can be done as an outpatient. Three randomized trials found the two comparable, both for local control and for complications.

Some tumors are too bulky for a standard applicator to sit properly. For those, NCI describes interstitial brachytherapy as a way to still deliver an adequate dose.

One trial pushed further. Gemcitabine was added to cisplatin during radiation, then two cycles were given afterward. In 515 patients, 3-year progression-free survival rose from 65.0 percent to 74.4 percent. Overall survival improved too. The cost was more grade 3 and 4 toxicity. Two deaths in that arm were possibly related to treatment.

KEYNOTE-A18 tested this in 1,060 women with newly diagnosed disease. They had stage IB2 or IIB with positive nodes, or stage III to IVA. Everyone received brachytherapy. Ninety-four percent had PD-L1-positive tumors.

Progression-free survival improved significantly. The 24-month rate was 68 percent against 57 percent. The 24-month overall survival rate was 87 percent against 81 percent, with a confidence interval that still crossed 1. The gain was larger in stage III and IV disease.

NCI's framing here is worth quoting rather than softening. Apart from immunotherapy, which has given prolonged disease-free survival, the other options are unlikely to cure. They are mostly used for comfort.

The listed options are immunotherapy, radiation with chemotherapy, palliative chemotherapy and other systemic therapy, and pelvic exenteration.

Three trials define the immunotherapy picture. KEYNOTE-158 led the FDA to approve pembrolizumab for recurrent or metastatic disease with a PD-L1 combined positive score of 1 or higher. The response rate in that marker-positive group was 16 percent. KEYNOTE-826 added pembrolizumab to platinum and paclitaxel in 617 women. Median overall survival was 26.4 months against 16.8. NCI notes the benefit was not maintained below a score of 1. BEATcc added atezolizumab to bevacizumab and chemotherapy in 410 women, without selecting for PD-L1. Median overall survival was 32.1 months against 22.8.

If a drug such as fluorouracil is planned, NCI flags a genetic issue.

DPYD is the gene for the enzyme that clears these drugs. NCI estimates 1 to 2 percent of people carry a harmful variant, and those who do can have severe, life-threatening, sometimes fatal toxicity. What a positive result means in practice is not a single rule: it depends on which variant was found, whether one or both copies carry it, and which regimen is planned, and it is worked out by your oncologist with a pharmacist against current pharmacogenomic guidance. The options range from a reduced starting dose with close monitoring to a different drug altogether. Do not apply a dose change of your own to anything you have been prescribed. Ask whether testing is available to you, what it would cost, and whether waiting for the result would delay the start of treatment.

For the wider picture see cervical cancer and what a PD-L1 CPS means. For the surgical decisions above, see cervical cancer stages.

• Call 911 or go to an emergency department if vaginal bleeding is heavy enough to soak through pads quickly, or comes with dizziness, faintness or a racing heart.
• Call your cancer team straight away, at any hour, if you have a temperature of 100.4°F (38°C) or higher, or chills, during chemoradiation. The chemotherapy given with the radiation drops your white cells, and CDC counts that fever as a medical emergency. Do not wait for a routine callback: if no one answers soon, go to an emergency department and tell them you are having chemoradiation.
• Call your care team the same day for diarrhea that will not stop or has blood in it, or for severe mouth sores, especially in the first weeks of fluorouracil, since that is how a DPYD-related toxicity announces itself. Call the same day if you pass little or no urine, if you have pain in one side of your back near the ribs, or if urine or stool leaks from the vagina.
• Call your care team within a day or two if passing urine burns, you bleed from the back passage, or the skin in the radiation field breaks down. Do the same for new swelling of one or both legs.

• https://www.cancer.gov/types/cervical/hp/cervical-treatment-pdq
• https://www.cancer.gov/about-cancer/treatment/side-effects/infection
• https://www.cdc.gov/cancer-preventing-infections/patients/fever.html
• https://www.ncbi.nlm.nih.gov/books/NBK431093/