Disease in the pregnant woman is generally managed as in the non-pregnant woman. The treatment policies must be individualized as to the stage and extent of disease, gestational age, and particularly the wishes of the patient by the multidisciplinary team.

Cervical screening and referral for colposcopy should be performed as per screening guidelines. Colposcopic guided biopsy of suspicious areas is recommended only if there is clinical suspicion of malignancy. An ECC should not be performed during pregnancy. If there is no clinical suspicion for malignancy, colposcopy should be repeated every trimester and again 2-3 months post​partum.

Should invasive carcinoma be discovered in early pregnancy and thought to be unsuitable for primary surgical therapy, termination of the pregnancy is usually carried out with the method depending on the gestational age and is followed by radiotherapy +/- chemotherapy. Patients with suspected clinical stage IA1 disease may be treated primarily with a cone biopsy. This should be performed after the first trimester to minimize complications and risks to the pregnancy.

If more advanced disease is suspected, options for management include radical hysterectomy with fetus in situ and pelvic lymphadenectomy, or delay of definitive treatment to allow for fetal maturity. In the latter situation, neoadjuvant chemotherapy during the pregnancy should be considered. For those patients diagnosed in the latter stage of pregnancy with a viable fetus, delivery by caesarean section is usually recommended although studies have not shown that vaginal delivery has produced a higher morbidity or decreased survival in patients delivered this way.

Radiotherapy

Primary radiotherapy

Pelvic +/- para-aortic radiotherapy to a dose of 45-50 Gy in 1.8-2 Gy per fraction is recommended using VMAT/IMRT techniques. Pathologic pelvic or para-aortic lymph nodes (or PET positive nodes) should receive a dose boost, using simultaneous integrated boost or sequential techniques. Pelvic radiotherapy only is recommended in cases with negative nodes. Para-aortic irradiation is recommended in cases with at least 1 pathologic node at the common iliac or above, or 3 or more pathologic pelvic nodes.

External beam radiotherapy must be accompanied by HDR image-guided brachytherapy. Combined intracavitary/interstitial brachytherapy techniques must be considered in cases of large residual disease, asymmetrical tumours, significant lateral extension and unfavourable anatomy to cover the high-risk CTV (HR-CTV) while sparing normal tissue/organs at risk (OARs). 3D image guidance is mandatory for all cervical brachytherapy cases (CT and preferably MRI at least for the first fraction). Target volumes and OARs, including bladder, rectum, sigmoid and small bowel, are contoured and volumetric dose prescription and reporting must be done following the Gynecologic​ GEC ESTRO recommendations.

Every effort should be done to deliver brachytherapy boost for cervical cancer, including referral to other BC centres for complex brachytherapy techniques. In cases of extensive residual disease following external beam radiotherapy that cannot be safely encompassed with interstitial brachytherapy, an external beam boost or salvage surgery can be considered following multidisciplinary discussion.

The overall treatment time (OTT) defi​ned as the time from beginning to the end of (chemo) radiotherapy (including external beam and brachytherapy) for definitive treatment of intact cervical cancer should be within 50 days (and not longer than 56 days), with the following conditions:

• External beam radiotherapy start date should not be delayed (meeting the OTT of 7 weeks).
• Shorter OTT needs to be balanced against proper and safe brachytherapy implantation and treatment.

 Brachytherapy dose and fractionation is typically 28 Gy in 4 fractions. Other fractionation schedules over 3 or 5 fractions can be delivered in an outpatient or inpatient setting as clinically advisable.

Adjuvant radiotherapy

Pelvic radiotherapy to a dose of 45-50 Gy in 1.8-2 Gy per fraction is recommended. A brachytherapy boost can be considered in select cases.

Chemotherapy

Primary concurrent chemoradiation

Results from five randomized phase 3 trials show an average overall survival advantage for cisplatin-based therapy given concurrently with radiation therapy15. Although the trials vary somewhat in terms of stage of disease, dose of radiation, and schedule of cisplatin and radiation, they all demonstrate signifi​cant survival benefit for this combined approach. The protocol designation for this therapy is GOCXCRT. It consists of weekly cisplatin at 40 mg/m2 weekly for five weeks during external beam radiation therapy.

Additional treatment options

KEYNOTE-A18 (ENGOT-cx11), a phase 3 randomised placebo controlled clinical trial, demonstrated that the addition of pembrolizumab 200 mg IV q3 weekly X 5 cycles to chemoradiotherapy and then as 15 cycles of 400 mg q6 weekly maintenance therapy in patients with newly diagnosed high-risk, locally advanced cervical cancer improved (regardless of PDL-1 CPS score status) both overall and progression-free survival¹⁶.

INTERLACE phase 3 randomised clinical trial demonstrated that six weeks of induction chemotherapy with weekly dose dense carboplatin and paclitaxel before standard chemoradiotherapy improved 5-year survival outcomes for patients with locally advanced cervical cancer.

Either strategy may be considered for appropriate patients in addition to standard of care CRT.  Decisions around treatment recommendations should involve multi-disciplinary discussion¹⁷. There is overlap of patient stage inclusion criteria between the two studies and based on expert consensus provincially, the following treatment algorithm has been proposed. This acknowledges that the standard of care remains chemoradiation and additional systemic therapy can be considered for selected patients based on provider-patient discussion.  

Recommendations for additional treatment option application

* the choice of therapy should be reviewed by a multidisciplinary team involving RO and MO and incorporate patient factors and preference as well as the ability to adhere to treatment timing

**CRT = chemoradiation with concurrent cisplatin

*** concurrent CRT should start no later than the 7^th week of induction chemotherapy start

^a Avoid induction chemo followed by para-aortic irradiation (i.e. > 1 pathologic lymph node at the common iliac or above or ≥3 pathologic lymph nodes) due to bone marrow toxicity

^b CDA review and recommendation: patients previously staged to have IB-IIB disease who also had with lymph node involvement (FIGO 2014) are now considered to have stage IIIC disease (FIGO 2018) and should be considered eligible for maintenance pembrolizumab.

https://www.cda-amc.ca/sites/default/files/DRR/2025/PC0411-Keytruda_FINAL_Recommendation.pdf 

Advanced or recurrent disease

The KEYNOTE-826 trial showed that in patients with persistent, recurrent, or metastatic cervical cancer, the addition of pembrolizumab to platinum-based chemotherapy with or without bevacizumab significantly improved progression-free and overall survival for patients with PD-L1 positive tumours (CPS ≥1)¹⁸.  Therefore, for patients with tumour with CPS ≥1, and no contraindications to Bevacizumab standard of care is carboplatin-paclitaxel-bevacizumab and pembrolizumab (BC Cancer protocol UGOCXCATBP).  Quadruplet therapy is given for 6 cycles, and patients with no sign of progressive disease can continue onto maintenance bevacizumab and pembrolizumab under protocol GOCXBP. Pembrolizumab can be switched to a 6 weekly dosing schedule in the maintenance setting.

BC Cancer protocol permits a maximum of 36 cycles or 18 cycles of 3 weekly and 6 weekly pembrolizumab respectively. Retreatment may be permitted (see protocol for eligibility).

For patients that are ineligible for Pembrolizumab or tumour CPS <1, standard of care treatment is carboplatin-paclitaxel +/-bevacizumab (BC Cancer protocol GOCXCATB) until disease progression or unacceptable toxicity. After 6 cycles with CAP approval patients can transition to maintenance bevacizumab alone. The addition of Bevacizumab has been shown to improve overall survival compared to chemotherapy alone¹⁹. For patients who have oligoprogression on or after completing 1^st line systemic therapy, consideration should be given to local therapy to progressive sites (i.e. SBRT, IR guided procedures) to allow continuation of maintenance therapy.  Local therapy is generally not recommended for patients with multifocal progression on bevacizumab +/- pembrolizumab maintenance and second line therapy should be considered.

In Canada, limited treatment options exist beyond first line therapy. New therapies are needed for recurrent cervical cancer and patients with progressive disease should be prioritized for clinical trial enrol​ment. Biomarker testing can be considered to identify potential druggable targets through clinical trials or patient support programs. (i.e. HER2+ disease treated with anti-HER2+ targeting agent).  Outside of clinical trials, for patients with a relatively long chemotherapy free interval (i.e. >6 months from last dose of carboplatin-paclitaxel) re-treatment with carboplatin and/or paclitaxel can be considered. Beyond this, single agent chemotherapy (i.e. gemcitabine, topotecan) can be offered but there is limited data and there is no evidence that use of these agents improves overall survival. Patients with treatment-resistant disease should be offered palliative care support alongside oncology care to optimize symptom control, psychosocial support, and quality of life.

http://www.bccancer.bc.ca/health-professionals/clinical-resources/chemotherapy-protocols/gynecology

Sexual health

Cervical cancer treatment can cause long term impacts on sexual health including premature menopause, physical and psychological impacts on sexual function. Patients undergoing treatment for cervical cancer benefit from early referrals to gynecologists and other specialists who have expertise in sexual health. Please see Section 6: Survivorship and Management of Menopausal Hormone Therapy (MHT) Following Cervical Cancer Treatment​ 

References 

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