◉ Carcinoma Cervix — Complete Clinical Reference
Evidence-based guide for gynaecologic oncologists & clinicians • FIGO 2018 • NCCN v1.2024 • ESGO/ESTRO/ESP 2023 • GEC-ESTRO EMBRACE • WHO 2023 • MoHFW India
FIGO 2018
NCCN 2024
ESGO/ESTRO/ESP 2023
GEC-ESTRO EMBRACE
WHO 2023
MoHFW India
KEYNOTE-A18 2024
innovaTV 301 2023
Epidemiology & global burden
4th
Most common cancer in women worldwide
604k
New cases globally/year (WHO 2022)
342k
Deaths annually worldwide
2nd
Commonest gynaecological cancer India
~123k
New cases annually in India
>90%
Cases attributable to high-risk HPV
Risk factors
- !Persistent high-risk HPV infection (types 16,18,31,33,45,52,58)
- !Early age at first sexual intercourse (<16 years)
- !Multiple sexual partners (patient or partner)
- !High parity (≥3 full-term pregnancies)
- !Long-term combined oral contraceptive use (>5 years)
- !Immunosuppression: HIV infection (15–22× increased risk)
- !Cigarette smoking — doubles risk for squamous cell carcinoma
- !History of other lower genital tract neoplasia (VIN, VAIN)
- !Low socioeconomic status; limited access to cervical screening
HPV types & cancer association
- HHPV 16: ~55–60% of cervical cancers (predominantly SCC)
- HHPV 18: ~10–15% (predominantly adenocarcinoma)
- HHPV 31,33,45,52,58: additional 15–20%
- HHPV-independent: gastric-type ADC (~10%) — worse prognosis
Prevention & vaccination
- V9-valent Gardasil-9 (HPV 6,11,16,18,31,33,45,52,58) — preferred
- V2 doses (9–14 yrs); 3 doses (≥15 yrs or immunocompromised)
- VIndia: CERVAVAC (quadrivalent) — National Immunisation Programme 2023
- VVaccination does NOT replace cervical screening
Carcinogenesis pathway
1
HPV infects squamocolumnar junction (transformation zone)
E6 degrades p53 → apoptosis failure; E7 degrades Rb → uncontrolled cell proliferation
↓
2
Persistent HR-HPV infection → CIN 1 (LSIL)
Most cleared by immune system within 12–24 months
↓
3
CIN 2 / CIN 3 (HSIL) — precancerous lesion
10–20 year window for intervention; CIN 3 → invasive cancer in ~30–50% if untreated
↓
4
Microinvasive carcinoma (Stage IA) → Invasive carcinoma
Local extension → parametrial spread → lymphatic → haematogenous metastasis
Screening — WHO 90-70-90 strategy by 2030
Primary HPV screening (preferred)
WHO recommends HPV DNA testing from age 30 (age 25 in HIV+). Screen-positive → colposcopy/biopsy or ablative treatment. India NCP: HPV test or VIA at 30 & 45 years.
Pap smear / Liquid-based cytology
Conventional Pap: 3-yearly from age 25–65. Co-testing (HPV + LBC) every 5 years is preferred (NCCN, age 30–65). LBC has equivalent sensitivity.
VIA / VILI (resource-limited settings)
Visual inspection with acetic acid or Lugol’s iodine. See-and-treat approach with cryotherapy or LLETZ for VIA-positive lesions. Frontline in India’s LMIC context.
WHO targets
90% girls vaccinated by age 15; 70% screened by age 35 and 45; 90% with CIN or cancer receiving adequate treatment.
Symptoms by disease phase
- !Often completely asymptomatic — detected on routine cervical screening (Pap / HPV test)
- !Post-coital bleeding (PCB) — earliest and most specific symptom; must never be dismissed
- !Inter-menstrual spotting or irregular vaginal bleeding
- !Thin, watery or slightly blood-tinged vaginal discharge
- !Dyspareunia (pain during intercourse)
- !Abnormal cervical smear result (ASCUS, LSIL, HSIL, AGC on Pap / positive high-risk HPV)
- !Persistent, heavy or spontaneous vaginal bleeding (contact or intermenstrual)
- !Post-menopausal vaginal bleeding — always investigate urgently
- !Offensive, purulent or blood-stained vaginal discharge
- !Pelvic or low back pain radiating to thighs (parametrial or nerve involvement)
- !Urinary frequency, dysuria, haematuria (early bladder involvement)
- !Constipation, rectal tenesmus, blood per rectum (early rectal involvement)
- !Deep dyspareunia; pelvic pressure or fullness
- !Unilateral or bilateral leg oedema (lymphatic / venous obstruction by parametrial mass)
- !Vesico-vaginal fistula — continuous uncontrollable urinary incontinence
- !Recto-vaginal fistula — passage of flatus or faeces per vagina
- !Ureteric obstruction → hydronephrosis → uraemia / prerenal AKI
- !Sciatic nerve involvement → shooting pain down posterior thigh and leg
- !Gross haematuria or frank rectal bleeding (fistula / direct invasion)
- !Pyometra — uterus distended with pus if cervical os obstructed by tumour
- !Bone pain, pathological fracture (ilium, lumbar spine — skeletal metastasis)
- !Cough, haemoptysis, dyspnoea (pulmonary metastasis — cannon-ball shadows)
- !Jaundice, right upper quadrant pain (hepatic metastasis)
- !Supraclavicular or inguinal lymphadenopathy (distant nodal spread)
- !Anorexia, profound weight loss, cachexia, profound fatigue
- !Severe anaemia: pallor, breathlessness on exertion (chronic blood loss / BM involvement)
Clinical signs
General appearance
Pallor (anaemia from chronic blood loss); cachexia; muscle wasting; jaundice (hepatic mets)
Lymphadenopathy
Inguinal nodes (palpable); supraclavicular (Virchow’s node — advanced disease / Stage IVB); para-aortic (IIIC2 — detected by imaging)
Abdominal examination
Pelvic mass (large tumour or pyometra); renal angle tenderness (hydronephrosis); hepatomegaly (mets); ascites (rare, advanced)
Lower limbs
Unilateral or bilateral pitting oedema; lymphoedema; DVT risk significantly increased with advanced disease
Vital signs
Tachycardia / hypotension in acute haemorrhage; fever + rigors (sepsis, pyometra); signs of uraemia in advanced bilateral obstruction
Performance status
ECOG / WHO performance status essential for treatment planning. Cachexia, poor PS indicates advanced or palliative disease.
Lesion morphology
Exophytic (cauliflower-like — most common); endophytic (barrel-shaped cervix); ulcerative/necrotic; or normal-looking cervix (endocervical tumour)
Surface characteristics
Friable tissue; bleeds on light touch with speculum or swab; contact bleeding; necrotic slough; abnormal surface vascularity visible
Cervical os
Distorted or replaced by tumour; stenotic (endocervical spread with os obstruction); dilated with bulging tumour mass protruding
Vaginal discharge
Serosanguineous, purulent, watery, or foul-smelling necrotic discharge; haematocolpos or pyometra if os obstructed
Vaginal wall extension
Upper two-thirds vaginal involvement = Stage IIA. Lower one-third = Stage IIIA. Inspect all four fornices carefully.
Fornices
Obliteration of fornices indicates parametrial or vaginal wall infiltration; loss of distinct cervical contour on bimanual
Parametrial assessment
Medial parametrium involved = Stage IIB. Tumour reaching pelvic sidewall (frozen pelvis) = Stage IIIB. Assessed by combined bimanual + recto-vaginal examination.
Uterosacral ligaments
Nodular, thickened, indurated or fixed uterosacral ligaments indicate deep parametrial tumour infiltration
Rectal mucosa
Intact mucosa (Stages IIB/IIIB) vs. bullous oedema vs. frank mucosal invasion (Stage IVA). Biopsy must confirm invasion — bullous oedema alone does NOT = IVA.
EUA indications
Pain limiting outpatient examination; obesity; uncooperative patient; equivocal staging. Allows simultaneous cystoscopy + proctoscopy.
Frozen pelvis
Tumour palpable at lateral pelvic sidewall bilaterally = Stage IIIB. Unilateral fixity + hydronephrosis = Stage IIIB. Gold standard: EUA for formal clinical staging.
Acetowhite epithelium
Dense, thick acetowhitening with sharp margins after 3–5% acetic acid = high-grade lesion (CIN 2/3 or microinvasion). Appears rapidly and persists.
Atypical vessels
Corkscrew, comma, spaghetti, or looped-shaped abnormal vessels = invasive cancer until proven otherwise. Immediate directed biopsy mandatory.
Coarse vascular patterns
Coarse punctation and coarse mosaic pattern — associated with high-grade CIN or early invasion. Require directed biopsy.
Schiller’s iodine test (VILI)
Normal glycogen-rich squamous epithelium: mahogany brown. HSIL/cancer: iodine-non-staining (Schiller-positive). Useful when colposcopy equivocal.
Transformation zone (TZ) types
Type 1: fully ectocervical (fully visible). Type 2: partially endocervical. Type 3: fully endocervical — worst visibility; ECC mandatory; diagnostic cone if needed.
Colposcopic adequacy
Adequate: entire SCJ and lesion visible. Inadequate: lesion extends into canal → ECC or diagnostic cone biopsy required. Document at each colposcopy.
FIGO 2018 staging system
FIGO 2018 permits imaging (MRI, CT, PET-CT) and pathological findings to assign or modify stage — a major change from the purely clinical 2009 system. Suffix “r” = radiologically confirmed; “p” = pathologically confirmed (used for Stage IIIC).
| Stage | Description | Key criteria | Approx 5-yr OS |
|---|---|---|---|
| IA1 | Microinvasive — stromal invasion ≤3mm | Microscopy only; width not used in 2018 | 98–99% |
| IA2 | Microinvasive — >3mm, ≤5mm | Microscopy; LVSI recorded separately | 95–97% |
| IB1 | Confined to cervix, <2cm | MRI / clinical <2cm; invasion >5mm | 88–93% |
| IB2 | Confined to cervix, ≥2cm <4cm | MRI / clinical ≥2–<4cm | 75–85% |
| IB3 | Confined to cervix, ≥4cm | New 2018 subgroup; bulky tumour | 65–75% |
| IIA1 | Upper ⅔ vaginal involvement, <4cm | No parametrial involvement | 70–78% |
| IIA2 | Upper ⅔ vaginal involvement, ≥4cm | No parametrial involvement | 60–70% |
| IIB | Parametrial involvement | Medial parametrium; not reaching pelvic sidewall | 55–65% |
| IIIA | Lower ⅓ vaginal involvement | No pelvic sidewall fixity | 40–50% |
| IIIB | Pelvic sidewall fixity or hydronephrosis | Tumour to pelvic wall; OR hydronephrosis / non-functioning kidney | 30–40% |
| IIIC1r/p | Pelvic lymph node metastasis | New 2018; r=radiological, p=pathological | 28–38% |
| IIIC2r/p | Para-aortic lymph node metastasis | New 2018; requires extended-field RT | 20–30% |
| IVA | Bladder or rectal mucosa invasion | Biopsy must confirm — bullous oedema alone does NOT qualify | 14–22% |
| IVB | Distant metastasis | Lung, liver, bone, distant nodes, peritoneum | <10% |
Key rules: (1) Bullous oedema of bladder ≠ Stage IVA — mucosal biopsy required. (2) Hydronephrosis / non-functioning kidney = minimum Stage IIIB regardless of tumour size. (3) Nodal status now formally incorporated (Stage IIIC). (4) Staging can be revised upward but NOT downward.
Histological classification (WHO 5th edition 2020)
Squamous cell carcinoma (~65–70%)
Keratinising, non-keratinising, basaloid, warty, verrucous, papillary. Arise at squamocolumnar junction. HPV-associated in majority. Best prognosis among main types.
Adenocarcinoma (~20–25%)
HPV-associated: endocervical mucinous (usual type), villoglandular. HPV-independent: gastric-type (worse prognosis, CDX2+, p53 mut), clear cell, mesonephric, endometrioid.
Adenosquamous carcinoma (~3–5%)
Mixed glandular + squamous elements. HPV-associated. Glassy cell carcinoma — poorly differentiated variant; aggressive. Generally worse prognosis than pure SCC.
Small cell neuroendocrine (SCNEC)
Rare (<3%), highly aggressive. HPV 18-associated predominantly. Treat as SCLC regimen. Early haematogenous spread. Systemic staging mandatory at diagnosis.
Key prognostic IHC markers
p16 (block diffuse = HPV-associated); Ki-67 (proliferation); p53 (mutant = HPV-independent); PD-L1 CPS (immunotherapy eligibility); synaptophysin / chromogranin / CD56 (SCNEC).
LVSI — lymphovascular space invasion
Critical prognostic factor especially in microinvasive disease. Determines need for lymph node dissection in Stage IA1. Must be specified: absent / present / substantial.
Diagnostic & staging investigations
Full blood count (CBC)
Anaemia (chronic blood loss); leucocytosis (infection / tumour necrosis); thrombocytopenia (BM involvement, rare)
Renal function (U&E, creatinine, eGFR)
Baseline essential; detect uraemia (ureteric obstruction); eGFR >50 mL/min required for full-dose cisplatin; reassess post-stenting before chemotherapy
Liver function tests
Pre-chemotherapy baseline; hepatic metastasis (elevated ALP, bilirubin, ALT); serum albumin (nutritional status and prognostic)
Coagulation profile (PT, APTT, fibrinogen)
Pre-operatively essential; DIC possible with advanced necrotic tumour; bleeding risk assessment before biopsy / EUA
Blood group & cross-match
Pre-operative; acute haemorrhage management; anaemia requiring transfusion before radiotherapy
Urine analysis & MC&S
Haematuria (bladder involvement); pyuria / UTI (common with advanced disease); mandatory pre-treatment infection screen
HIV serology (with consent)
22× higher risk in HIV+. Assess CD4 count; viral load; optimise ART before treatment; review ARV-chemotherapy drug interactions
Tumour markers
SCC antigen (normal <1.5 ng/mL) — squamous cell ca. CEA, CA-125 — adenocarcinoma. Baseline value for response monitoring — NOT diagnostic alone.
Thyroid function (TFTs)
If extended-field RT to para-aortic / neck nodes planned; hypothyroidism risk post-irradiation; baseline mandatory
Bone profile & serum Ca
If bone metastasis suspected; pre-bisphosphonate therapy in Stage IVB; elevated ALP signals bone / liver disease
Colposcopy-directed punch biopsy
Gold standard for diagnosis. 3–4 biopsies from most abnormal areas. Directed by acetowhite + vascular changes. Mandatory before any definitive treatment.
Cone biopsy (CKC / LLETZ / LEEP)
Diagnostic + therapeutic for microinvasive disease (Stage IA). Must assess: depth of stromal invasion (mm), margin status, LVSI presence, horizontal extent. Minimum 3mm clear margin required.
Endocervical curettage (ECC)
TZ type 3 (fully endocervical); negative colposcopy with abnormal Pap; adenocarcinoma screening; suspected glandular pathology extending into canal
Histopathology report must include
Tumour type; grade; depth of stromal invasion (mm); width (mm); LVSI (absent / present / substantial); margin status (distance); parametrial involvement; nodal status
Immunohistochemistry panel
p16 (block diffuse = HPV-associated, mandatory); Ki-67; p53 (aberrant pattern = HPV-independent); PD-L1 CPS (immunotherapy selection); synaptophysin / chromogranin / CD56 (SCNEC)
HPV genotyping
ISH or PCR-based. Identifies HPV type (16/18 vs. other HR-HPV). Gastric-type adenocarcinoma is HPV-DNA negative — important diagnostic and prognostic distinction.
MRI pelvis (standard of care)
Best soft-tissue contrast for local staging. Tumour size, parametrial involvement, vaginal extension, bladder/rectal integrity. 1.5T minimum; 3T preferred. Use DWI + T2 sagittal + axial + DCE sequences.
CT chest / abdomen / pelvis + contrast
Lymph node assessment (short axis >1cm = suspicious); hydronephrosis; pulmonary, hepatic, skeletal metastasis. Preferred when MRI contraindicated. Minimum for staging IB3 and above.
18F-FDG PET-CT
Most accurate for nodal staging and occult distant metastasis. Detects unsuspected M1 disease in 10–15%. Mandatory for IB3+ for RT field planning. SUVmax as independent prognostic marker. Guides extended-field RT decisions.
MRI with DWI (diffusion-weighted)
ADC maps improve tumour delineation and treatment response assessment. ADC increase = early response. Used for adaptive brachytherapy contouring (IGABT) per GEC-ESTRO guidelines.
Ultrasound (pelvis + renal)
First-line in resource-limited settings. Assess hydronephrosis, adnexal pathology, pelvic mass dimensions. Not adequate alone for formal staging of invasive disease. Complements MRI.
Chest X-ray
Baseline pre-treatment; pulmonary metastasis detection (cannon-ball pattern); mediastinal lymphadenopathy; pleural effusion; aspiration screening pre-operatively
Cystoscopy + biopsy
Mandatory if bladder involvement suspected on imaging or EUA. Bullous oedema ≠ Stage IVA — biopsy of bladder mucosa must confirm invasion.
Proctoscopy / sigmoidoscopy
If rectal involvement suspected clinically or on imaging. Biopsy of rectal mucosa to confirm Stage IVA. Excludes synchronous rectal pathology pre-treatment.
Examination under anaesthesia (EUA)
When outpatient examination is inadequate (pain, obesity, uncooperative). Combined bimanual + recto-vaginal + speculum under anaesthesia. Simultaneous cystoscopy + proctoscopy + ECC.
Sentinel LN biopsy (SLNB)
Standard for Stage IB1 undergoing radical surgery. Tc-99m periservical injection ± patent blue dye ± ICG near-infrared fluorescence. Bilateral mapping required. Pathological ultrastaging: serial 2mm sections + IHC (CK AE1/AE3).
Image-guided LN biopsy (FNA / core)
For suspicious nodes not accessible surgically. Confirms IIIC staging. Guides decision for pelvic vs. extended-field RT.
Laparoscopic para-aortic lymphadenectomy
Pathological PA staging before RT at specialist centres. More sensitive than PET-CT for nodes <1cm. Confirms IIIC2; tailors RT field. Experienced centres only.
PD-L1 combined positive score (CPS)
IHC using 22C3 antibody (Dako PharmDx). CPS = PD-L1+ cells (tumour + immune) / total viable tumour cells × 100. CPS ≥1: pembrolizumab eligibility (KEYNOTE-826 / A18). Most cervical cancers qualify.
MMR / MSI testing
dMMR / MSI-H: pembrolizumab (pan-tumour tissue-agnostic indication). Rare in cervical cancer (<5%) but actionable. IHC for MLH1, MSH2, MSH6, PMS2 loss.
NTRK fusion testing
Pan-tumour NTRK1/2/3 gene fusion: larotrectinib or entrectinib (NCCN Cat.2B). Rare but highly responsive. Tested by NGS or FISH in advanced/metastatic setting.
TMB (tumour mutational burden)
High TMB (>10 mut/Mb) may predict immunotherapy response. NCCN: consider in metastatic setting when PD-L1 and MSI negative. Tested by NGS panel.
Bone scan / PET-CT skeletal
If bone pain or elevated ALP suggests skeletal metastasis (Stage IVB). CT/PET-CT usually sufficient; technetium bone scan more sensitive for multifocal disease.
Liquid biopsy (circulating HPV DNA)
Emerging biomarker for treatment response and MRD detection after treatment. Investigational; not yet standard of care. Research / specialist centres only.
Treatment by FIGO 2018 stage
Select a stage below to view evidence-based treatment protocols aligned with FIGO 2018, NCCN v1.2024, ESGO/ESTRO 2023, and MoHFW India guidelines. All locally advanced cases (≥IB3) must be discussed at a dedicated gynaecological oncology MDT. Brachytherapy MUST NOT be omitted from curative-intent treatment.
Surgical cure rate >99%. Fertility-sparing strongly preferred in appropriate candidates.
LVSI negative + fertility desired
Cold-knife cone biopsy (CKC) or LLETZ/LEEP with clear margins ≥3mm. Colposcopic surveillance at 6 months then annually ×5 years. HPV test at 6 months (test of cure). Observation acceptable if margins clear and reliable follow-up guaranteed.
LVSI negative + family complete
Simple extrafascial hysterectomy (Querleu-Morrow Type A / Piver-Rutledge Type I). Ovarian conservation acceptable in premenopausal patients with SCC histology. Laparoscopic or open — both acceptable for simple hysterectomy (NOT affected by LACC trial).
LVSI positive
Modified radical hysterectomy (Q-M Type B1 / Piver Type II) + sentinel lymph node biopsy (SLNB) or bilateral pelvic lymph node dissection (PLND). Lymph node positivity rate <1% at Stage IA1 even with LVSI.
Medically inoperable
Intracavitary brachytherapy (ICBT) alone: HDR 3 × 7Gy or 4 × 5.5Gy to Point A (EQD2 ~50–55Gy). Excellent local control in microinvasive disease. Refer to specialist brachytherapy centre.
Lymph node risk ~5% (especially with LVSI). Sentinel LN biopsy preferred over full PLND to minimise morbidity.
Standard surgical treatment
Modified radical hysterectomy (Q-M Type B / Piver Type II) + bilateral PLND or SLNB with ultrastaging. Open or minimally invasive approach acceptable for tumours <2cm without LVSI at experienced centres.
Fertility-sparing
Radical vaginal trachelectomy (Dargent procedure) or radical abdominal trachelectomy + PLND / SLNB. Isthmic cerclage (Mersilene tape) placed at surgery. Conception attempts from 12 months post-surgery. Elective caesarean section mandatory at term.
Adjuvant therapy — Peters criteria (any ONE feature)
Positive pelvic nodes; positive surgical margin; parametrial involvement → Concurrent chemoradiotherapy: cisplatin 40mg/m² weekly ×5–6 + EBRT 45–50.4Gy/25–28fr + brachytherapy boost (Peters criteria, GOG 109).
Adjuvant therapy — Sedlis criteria (2 of 3 features)
LVSI + tumour size >4cm + deep ⅓ stromal invasion; or LVSI + any size + middle/deep ⅓ invasion → EBRT 45–50.4Gy/25–28fr ± vaginal vault brachytherapy boost (Sedlis GOG 92).
Medically inoperable
EBRT 45Gy/25fr + concurrent cisplatin 40mg/m² weekly + HDR ICBT boost: total EQD2 ≥75Gy to HRCTV. Discuss at MDT; refer to specialist centre.
Radical surgery and radical radiotherapy are equivalent in overall survival (Landoni RCT 1997). Do NOT combine both modalities — doubles morbidity without survival benefit.
Preferred surgical approach (IB1)
Radical hysterectomy (Q-M Type C1 nerve-sparing or C2 / Piver Type III) + bilateral PLND ± SLNB. OPEN SURGERY PREFERRED for tumours ≥2cm based on LACC trial 2018. Minimally invasive acceptable for tumours <2cm, no LVSI, at experienced centres with informed consent and closed-vault technique.
Fertility-sparing (IB1, tumour ≤2cm)
Radical vaginal trachelectomy (RVT) or radical abdominal trachelectomy (RAT) + PLND/SLNB. Prerequisites: SCC or usual-type ADC; no LVSI (relative CI); negative nodes confirmed; tumour ≤2cm; no endocervical extension above isthmus; residual endocervix ≥5mm.
Definitive radiotherapy (alternative)
EBRT 45–50.4Gy/25–28fr (IMRT/VMAT) + concurrent cisplatin 40mg/m² weekly ×5–6 + IGABT: HDR 5.5–6Gy ×4–5fr; total EQD2 ≥80Gy to HRCTV D90. Equivalent survival to surgery for IB1.
Adjuvant therapy after surgery
Peters criteria → CCRT (cisplatin + EBRT + BT boost). Sedlis criteria → EBRT ± ICBT. Ovarian transposition before adjuvant RT if premenopausal with SCC histology. Avoid dual-modality treatment unless high-risk features mandate.
CCRT is preferred for IB2. Primary surgery is an acceptable alternative. Do NOT plan surgery + full-dose RT routinely — combined morbidity unacceptable.
Preferred: definitive CCRT
EBRT 45–50.4Gy/25–28fr (IMRT) + cisplatin 40mg/m² weekly ×5–6 + HDR IGABT: total EQD2 ≥85Gy to HRCTV D90. GEC-ESTRO contouring (HRCTV, IRCTV, GTV-T BT).
Surgical option (IB2, experienced centre)
Radical hysterectomy (Type III, open approach) + PLND in selected patients. Adjuvant CCRT if Peters or Sedlis criteria met post-operatively. Avoid planned dual-modality treatment.
Neoadjuvant chemotherapy (NACT) → surgery (select centres)
INTERLACE trial (2023): weekly NACT (paclitaxel + carboplatin) ×6wks → CCRT improved 5-yr OS (72% vs 65%). Paclitaxel 175mg/m² + cisplatin 75mg/m² or carboplatin AUC5 q3w ×3 cycles then radical hysterectomy. Not universal standard — MDT decision.
Definitive CCRT ± pembrolizumab is the standard of care for IB3 and IIA2. Pembrolizumab now NCCN Category 1 for high-risk locally advanced disease (KEYNOTE-A18, 2024).
Standard CCRT ± pembrolizumab (NCCN Cat.1 2024)
Pembrolizumab 200mg q3w ×5 cycles concurrent with EBRT + cisplatin → maintenance 400mg q6w ×15 cycles (KEYNOTE-A18: improved PFS and OS, HR 0.70, p=0.0021). OR CCRT alone: cisplatin + EBRT 45–50.4Gy + IGABT (EQD2 ≥85Gy HRCTV).
EBRT technique
IMRT/VMAT preferred. PTV includes: cervix + uterus + upper vagina (3cm) + parametria + presacral + bilateral common, external, internal iliac, obturator nodes (to L4/L5). SIB to involved nodes: 55–60Gy. Image guidance: daily CBCT.
Brachytherapy (MANDATORY — never omit)
HDR IGABT per GEC-ESTRO/ABS. MRI-based planning preferred at each insertion. HRCTV D90 ≥85Gy (EQD2, α/β=10). OAR constraints: bladder D2cc <90Gy; rectum D2cc <75Gy; sigmoid D2cc <75Gy. Ring-and-tandem or tandem-and-ovoids. 4–5 × 5.5–6Gy HDR fractions.
Cisplatin-ineligible patients
5-FU 1000mg/m²/d ×4d + mitomycin C 10mg/m² (GOG 120 regimen). Or carboplatin AUC2 weekly (limited data). RT alone if no chemotherapy tolerated — discuss risk/benefit at MDT; worse locoregional control.
Stage IIB: definitive CCRT + IGABT. Parametrial involvement precludes upfront curative surgery. CCRT + IGABT achieves locoregional control in ~80% at 3 years (EMBRACE I data).
Definitive CCRT + IGABT
Parametrial boost if residual parametrial disease after 45Gy: additional 5–10Gy via EBRT parametrial field. Ureteric stent mandatory if hydronephrosis present before starting RT. Confirm eGFR post-stenting before cisplatin.
Pembrolizumab + CCRT (KEYNOTE-A18, 2024)
Pembrolizumab 200mg q3w ×5 concurrent → maintenance 400mg q6w ×15 cycles. NCCN Cat.1 for IIB high-risk (node-positive or large tumour ≥4cm). Significantly improved PFS and OS vs CCRT alone.
Cisplatin dose management
Cisplatin 40mg/m² weekly (max 70mg/dose). Aim: ≥5 of 6 cycles completed. Monitor eGFR weekly. If eGFR 30–50: reduce to 25–30mg/m² or switch to carboplatin AUC2. If eGFR <30: omit platinum; discuss RT alone or alternative sensitiser.
Stage III: CCRT + IGABT ± extended-field RT (for IIIC2). Ureteric stenting MANDATORY for IIIB with hydronephrosis before treatment. Correct anaemia to Hb ≥10g/dL during RT.
Stage IIIA / IIIB
Pelvic CCRT + IGABT. Parametrial EBRT boost for lateral wall disease. Bilateral ureteric obstruction: bilateral percutaneous nephrostomies or stents before RT. Target Hb ≥10g/dL during RT (improves tumour oxygenation and locoregional control).
Stage IIIC1 (pelvic lymph node metastasis)
Standard pelvic CCRT + IGABT + SIB to involved nodes (55–60Gy). Pembrolizumab concurrent + maintenance (KEYNOTE-A18, NCCN Cat.1). PET-CT mandatory for accurate field planning.
Stage IIIC2 (para-aortic lymph node metastasis)
Extended-field RT (EFRT): EBRT field extended to include para-aortic nodes (L1–L2 level; to diaphragm if high para-aortic involvement). Dose: 45Gy/25fr to both pelvic + PA fields simultaneously (IMRT-EFRT) + cisplatin + IGABT. SIB to involved PA nodes: 55–60Gy. Pembrolizumab concurrent + maintenance.
EMBRACE data (brachytherapy dose escalation)
HRCTV D90 ≥87Gy (EQD2) associated with 3-year local control 92% for tumours ≤5cm (EMBRACE I). Dose-volume adaptation at each fraction is critical to meet OAR constraints while maximising tumour dose.
Curative intent is possible in selected Stage IVA (no distant disease). Fistula and organ dysfunction must be managed before or concurrent with treatment. PET-CT essential to exclude occult distant disease.
Curative CCRT (IVA, PS 0–2, no distant metastasis)
Pelvic EBRT 50.4Gy/28fr + cisplatin + IGABT (EQD2 ≥85Gy). Defunctioning colostomy or urinary diversion first if fistula present. PET-CT to exclude distant metastasis before committing to curative treatment intent.
Pelvic exenteration (highly selected IVA)
Anterior (bladder removal), posterior (rectal), or total pelvic exenteration for central disease without pelvic sidewall fixity or distant spread. Prerequisites: no lateral wall fixity, no distant mets, adequate PS (0–1), complete pre-operative counselling. 5-yr OS ~25–50% at specialist centres.
Palliative intent (IVA, poor PS or patient choice)
Palliative EBRT (30Gy/10fr or 20Gy/5fr) for haemostasis and pain relief. Platinum-based chemotherapy if PS adequate. Urinary diversion (ileal conduit) or colostomy for fistula palliation. Early palliative care team referral.
Systemic therapy is the primary modality. Pembrolizumab-based regimens are first-line standard (NCCN 2024 Category 1). Tisotumab vedotin is preferred second-line (innovaTV 301, 2023).
1st-line preferred: pembrolizumab + chemo ± bevacizumab (KEYNOTE-826)
Pembrolizumab 200mg q3w + cisplatin 50mg/m² or carboplatin AUC5 + paclitaxel 175mg/m² q3w ×6 cycles ± bevacizumab 15mg/kg → pembrolizumab maintenance 400mg q6w up to 2 years. mOS ~28 months (CPS≥1). NCCN Category 1 preferred regimen 2024.
1st-line: bevacizumab + chemotherapy (if pembrolizumab unavailable)
Cisplatin + paclitaxel + bevacizumab 15mg/kg q3w OR topotecan + paclitaxel + bevacizumab. mOS 17 vs 13 months (GOG-240, NEJM 2014). Bevacizumab contraindicated: active fistula, uncontrolled hypertension, poor wound healing, prior pelvic RT with bowel involvement.
2nd-line preferred: tisotumab vedotin (innovaTV 301, NCCN Cat.1)
ADC targeting tissue factor. Dose: 2mg/kg IV q3w. mOS 11.5 vs 9.5 months vs investigator’s choice (innovaTV 301, NEJM 2023). MANDATORY eye prophylaxis: artificial tears q2h + topical steroid eye drops + sunglasses. Monitor: peripheral neuropathy, bleeding, alopecia.
2nd-line alternatives
Pembrolizumab monotherapy (CPS≥1, not used 1st line; RR ~14.3%, KEYNOTE-158); topotecan + paclitaxel; gemcitabine ± cisplatin; ifosfamide + paclitaxel; vinorelbine; pemetrexed; best supportive care (BSC) if PS ≥3.
Central pelvic recurrence — surgical option
Pelvic exenteration for central recurrence >6 months after primary RT; no lateral sidewall fixity; no distant metastasis; adequate PS (0–1). 5-yr OS 30–60% in carefully selected series at specialist centres.
SCNEC (small cell neuroendocrine carcinoma)
Treat as SCLC protocol. Etoposide 100mg/m² d1–3 + cisplatin 75mg/m² d1 q3w ×4–6 cycles ± concurrent RT (early stages). No prophylactic cranial irradiation (PCI) as standard. Median OS in advanced disease <12 months.
Chemotherapy regimens & drug reference
Cisplatin concurrent with radiotherapy is the standard sensitiser. Minimum 5 of 6 planned weekly doses should be completed for optimal locoregional control. Meta-analysis (Cochrane 2022): CCRT provides ~6% absolute OS benefit over RT alone.
| Regimen | Drug / dose | Schedule | Evidence / indication |
|---|---|---|---|
| Cisplatin (preferred) | Cisplatin 40mg/m² IV (max 70mg/dose) | Weekly ×5–6 cycles during EBRT | NCCN Cat.1; 5 GOG/RTOG landmark RCTs; Cochrane meta-analysis |
| Cisplatin + 5-FU | Cisplatin 75mg/m² d1 + 5-FU 1000mg/m²/d ×4d | q4w ×3 during EBRT | GOG 85, RTOG 9001; alternative if weekly schedule not feasible |
| Carboplatin (cisplatin-ineligible) | Carboplatin AUC2 IV weekly | Weekly ×5–6 during EBRT | Used when eGFR <50 or cisplatin allergy; limited prospective data |
| 5-FU + mitomycin C | 5-FU 1000mg/m²/d ×4d + MMC 10mg/m² d1 | Cycles 1 & 4 of EBRT | GOG 120; when platinum contraindicated |
Pre-cisplatin checklist: eGFR >50 mL/min · Hb >8 g/dL · Platelets >100×10⁹/L · Audiogram (if prior hearing issues) · Anti-emetics: ondansetron + aprepitant (NK1) + dexamethasone · IV hydration: 1–2L NS before + 1L after · Mg supplementation 2g IV per cycle · Avoid NSAIDs and aminoglycosides
| Regimen | Drugs / doses | Schedule | mOS / evidence |
|---|---|---|---|
| Pembro + carbo + pacli ± bev (PREFERRED) | Pembro 200mg + carbo AUC5 + pacli 175mg/m² ± bev 15mg/kg | q3w ×6 → pembro 400mg q6w maint | ~28mo (CPS≥1); KEYNOTE-826 (NEJM 2021) |
| Pembro + cisplatin + pacli ± bev | Pembro 200mg + cis 50mg/m² + pacli 175mg/m² ± bev | q3w ×6 → pembro maint | As above — cisplatin arm of KEYNOTE-826 |
| Carboplatin + paclitaxel + bevacizumab | Carbo AUC5 + pacli 175mg/m² + bev 15mg/kg | q3w ×6 | ~17mo; GOG-240 (NEJM 2014) |
| Cisplatin + paclitaxel | Cisplatin 50mg/m² d1 + pacli 135–175mg/m² d1 | q3w | RR ~36%; standard doublet backbone |
| Topotecan + paclitaxel ± bev | Topotecan 0.75mg/m² d1–3 + pacli 175mg/m² d1 | q3w | Equivalent to cis+pacli; GOG-204. Add bev: GOG-240 |
| Tisotumab vedotin (2nd-line preferred) | 2mg/kg IV | q3w | mOS 11.5 vs 9.5mo; innovaTV 301 (NEJM 2023) |
| Pembrolizumab monotherapy (2nd-line) | 200mg IV | q3w | RR ~14.3%; KEYNOTE-158; CPS≥1 required |
| Gemcitabine + cisplatin | Gem 1000mg/m² d1,8 + cis 50mg/m² d1 | q3w | RR ~22%; 2nd/3rd-line option |
Pembrolizumab (anti-PD-1)
KEYNOTE-826: 1st-line metastatic/recurrent (CPS≥1). KEYNOTE-A18: locally advanced + CCRT + maintenance. KEYNOTE-158: 2nd-line monotherapy. Dose: 200mg q3w; maintenance 400mg q6w. irAEs: pneumonitis, colitis, hepatitis, endocrinopathies, rash — manage per ESMO guidelines.
Bevacizumab (anti-VEGF)
GOG-240: added to doublet chemo in recurrent/metastatic. Dose: 15mg/kg q3w. Contraindications: active fistula, uncontrolled hypertension, recent GI perforation, poor wound healing. Fistula formation risk 6–9% in cervical cancer patients.
Tisotumab vedotin (ADC — tissue factor)
innovaTV 301 (2023): 2nd-line preferred. Dose: 2mg/kg q3w. Mandatory eye prophylaxis: artificial tears q2h during infusion week; topical corticosteroid eye drops; sunglasses (photophobia). Monitor: peripheral neuropathy (cumulative), bleeding, alopecia. Hold for Grade 3+ ocular toxicity.
PD-L1 CPS interpretation
CPS = PD-L1+ cells (tumour + stromal immune) / total viable tumour cells × 100. CPS ≥1: pembrolizumab eligibility (most cervical cancers qualify). CPS ≥10: greater OS benefit magnitude. Standard companion diagnostic: 22C3 PharmDx (Dako) assay.
irAE management protocol
Grade 1: continue with close monitoring. Grade 2: hold pembrolizumab; oral prednisolone 0.5–1mg/kg/d; resume when ≤Grade 1. Grade 3–4: permanently discontinue; IV methylprednisolone 1–2mg/kg/d → oral taper; specialist involvement.
Larotrectinib / Entrectinib (NTRK fusion)
NTRK1/2/3 gene fusion (pan-tumour agnostic). Larotrectinib 100mg BD or entrectinib 600mg OD. NCCN Cat.2B for cervical cancer with confirmed NTRK fusion by NGS. Rare (<1%) but highly responsive targeted therapy.
Cisplatin nephrotoxicity
Prevention: IV hydration 1–2L NS before + 1L after; mannitol diuresis; avoid concomitant NSAIDs / aminoglycosides. Monitor creatinine + eGFR weekly. Hold if creatinine rises >25% from baseline. Supplement Mg 2g IV per cycle.
Cisplatin ototoxicity
Irreversible sensorineural hearing loss (high-frequency, bilateral, cumulative). Audiogram baseline if risk factors. Cumulative dose >400mg/m² increases risk significantly.
Myelosuppression
CBC weekly during CCRT. Cisplatin: mainly anaemia + thrombocytopenia. Carboplatin: mainly thrombocytopenia. G-CSF if ANC <1.0×10⁹/L. Blood transfusion if Hb <8g/dL. Target Hb ≥10g/dL during RT for optimal tumour oxygenation.
Nausea / vomiting
Cisplatin = highly emetogenic (HEC). Triple antiemetic: ondansetron 8mg IV + aprepitant 125mg oral (day 1) + dexamethasone 12mg IV. Olanzapine 10mg nocte (MASCC 2023 guideline). Breakthrough: metoclopramide or haloperidol.
Paclitaxel toxicities
Peripheral sensory neuropathy (cumulative, dose-limiting — hold if Grade 3). Alopecia (100%). Hypersensitivity reactions (premedicate: dexamethasone 20mg + chlorphenamine + ranitidine 30–60min before). Myalgia/arthralgia (d3–5): NSAIDs or tramadol.
Bevacizumab toxicities
Hypertension: monitor BP at each cycle. Proteinuria: dipstick at each cycle; 24h urine if 2+; hold if >2g/24h. VTE risk increased: anticoagulate DVT/PE with LMWH. GI perforation: rare but life-threatening. Fistula risk 6–9%. Wound: hold 4–6wks peri-op.
Radiotherapy — comprehensive guide
IMRT / VMAT (preferred technique)
Intensity-modulated RT reduces dose to bowel, bladder, and bone marrow vs. conventional 4-field box technique. VMAT: faster delivery, equivalent dosimetry. Bone marrow sparing reduces myelosuppression and improves CCRT completion rates.
Standard curative pelvic field
Dose: 45–50.4Gy in 25–28 fractions (1.8Gy/fr). CTV includes: cervix + uterus + upper vagina (3cm margin) + bilateral parametria + presacral space + bilateral common iliac, external iliac, internal iliac, and obturator nodes (to L4/L5 bifurcation).
Extended-field RT (EFRT)
Indicated for para-aortic node involvement (IIIC2). Upper border: diaphragm (high PA disease) or L1/L2 (low PA nodes). Dose: 45Gy/25fr to PA + pelvic fields simultaneously using IMRT-EFRT technique. Increased bowel and renal toxicity risk — IMRT essential.
Simultaneous integrated boost (SIB)
Involved nodal gross disease: 55–60Gy SIB to GTV-N while pelvis receives 45Gy, within the same treatment schedule. Improves nodal locoregional control without increasing overall treatment time.
Simulation, positioning & image guidance
CT simulation with bladder filling protocol. Prone (belly board) or supine. MRI-CT fusion for target delineation. Daily CBCT or kV planar image guidance. Contour targets per RTOG/EMBRACE consensus atlas.
Palliative EBRT
Haemostasis: 30Gy/10fr, 20Gy/5fr, or 8Gy ×1. Bone metastasis pain: 8Gy ×1 (equivalent to 20Gy/5fr — ASTRO guideline). Brain metastasis: WBRT 30Gy/10fr or SRS for ≤3 lesions ≤3cm.
Brachytherapy is an essential and non-negotiable component of curative-intent treatment. Omission significantly reduces local control and overall survival. Image-guided adaptive brachytherapy (IGABT) per GEC-ESTRO is the international standard of care.
HDR brachytherapy (standard)
Iridium-192 source. Remote afterloading (microSelectron, Flexitron). Fractionation: 5.5–6Gy ×4–5 fractions (EQD2 ~85–95Gy to HRCTV). Typically 1–2 fractions per week, commencing during or after EBRT completion.
Applicators
Tandem-and-ring (Vienna ring — preferred); tandem-and-ovoids (Fletcher-Suit-Delclos). Interstitial needles via Vienna template, Venezia combined applicator, or Utrecht interstitial applicator for irregular tumour geometry.
GEC-ESTRO target volume definitions
GTV-T BT: gross tumour visible at time of each BT insertion. HRCTV: GTV-T BT + whole cervix + areas of presumed tumour extension. IRCTV: HRCTV + initial tumour extent at diagnosis (microscopic spread). Recontoured at each fraction (truly adaptive).
MRI-based planning (IGABT)
MRI at each insertion preferred: axial + sagittal T2-weighted. Applicator reconstruction on MRI. DVH optimisation per fraction. CT-based acceptable when MRI per insertion not feasible: use MRI for 1st fraction, CT for subsequent fractions.
Interstitial BT indications
Residual parametrial disease after EBRT; distal vaginal involvement; irregular tumour geometry; tumour bulk >5cm; poor intracavitary dose distribution. Interstitial needles significantly improve HRCTV D90 coverage.
EQD2 calculation principle
EQD2 = D × (d + α/β) / (2 + α/β). α/β = 10 for tumour; α/β = 3 for late-reacting tissues. Accumulate EQD2 from all EBRT + all BT fractions. Total HRCTV D90 target: ≥85Gy (EQD2).
EQD2 values are cumulative (EBRT + brachytherapy combined). α/β = 10 for tumour targets; α/β = 3 for late-responding OARs. Per GEC-ESTRO/EMBRACE recommendations and NCCN 2024.
| Target / OAR | Parameter | Constraint / target (EQD2) | Clinical relevance |
|---|---|---|---|
| HRCTV (tumour) | D90 | ≥85Gy (target ≥87Gy bulky disease) | Primary determinant of local control |
| IRCTV | D98 | ≥60Gy | Microscopic disease coverage |
| Bladder | D2cc | <90Gy | Bladder fistula, severe late cystitis |
| Rectum | D2cc | <75Gy | Rectal fistula, proctitis, stenosis |
| Sigmoid colon | D2cc | <75Gy | Sigmoid fistula, obstruction |
| Small bowel | D2cc | <75Gy | Bowel obstruction, enteritis |
| Pelvic bone marrow | V10Gy | <90% of pelvic marrow volume | Myelosuppression during CCRT |
| Kidneys (EFRT) | Mean dose per kidney | <18Gy each | Radiation nephropathy (EFRT) |
| Spinal cord (EFRT) | D-max | <45Gy | Radiation myelopathy |
Acute toxicity (during / within 90 days)
- ARadiation proctitis: diarrhoea, tenesmus, rectal bleeding — loperamide, sucralfate enemas, mesalazine suppositories
- ARadiation cystitis: dysuria, frequency, haematuria — hydration, alkalisation, urine MC&S, antispasmodics
- ASkin reaction (perineum / groins): moist desquamation — aqueous cream, silver sulphadiazine, gentle washing
- AMyelosuppression (concurrent cisplatin): weekly CBC mandatory — G-CSF if ANC <1.0; hold RT if ANC <0.5
- AFatigue: commonest acute effect; light exercise encouraged; treat reversible causes (anaemia, dehydration)
- ANausea / vomiting: manage as per cisplatin antiemetic protocol if receiving concurrent chemotherapy
Late toxicity (after 90 days)
- LVaginal stenosis: near-universal — vaginal dilators from 4–6 wks post-RT, 3× weekly; topical oestrogen
- LChronic radiation proctitis: sucralfate enemas; mesalazine; hyperbaric oxygen (Grade 3+); argon plasma coagulation
- LRadiation cystitis (chronic): cystoscopy; haematuria — hydration, alum bladder irrigation, hyperbaric oxygen
- LFistula (VVF / RVF): incidence 1–5%. Surgical repair after 3–6 months minimum; diversion first
- LBowel obstruction / adhesions: surgical review; conservative management first; resection if indicated
- LLymphoedema: compression stockings (Class II); manual lymphatic drainage (MLD); skin care
- LPremature menopause: HRT safe in SCC; DEXA scan; Ca + Vit D; vaginal oestrogen for GSM
Surgical procedures & classification
Querleu-Morrow (Q-M) classification 2017 is the current international standard. The Piver-Rutledge system (Types I–V) is cross-referenced for familiarity.
| Q-M Type | Piver type | Paracervical resection | Uterine artery | Indication |
|---|---|---|---|---|
| Type A | Type I (simple) | Minimal — medial to ureter | At uterine wall | Stage IA1 (LVSI−); benign / preinvasive disease |
| Type B1 | Type II (modified radical) | At ureter level (~50%) | At crossing with ureter | Stage IA1 (LVSI+), IA2; selected IB1 low-risk |
| Type B2 | Type II + node dissection | As B1 + bilateral PLND | As B1 | IA2 with formal lymph node assessment |
| Type C1 | Type III (nerve-sparing radical) | Complete paracervical; pelvic autonomic nerves preserved | At origin from internal iliac | IB1 (≥2cm), IB2 — standard radical hysterectomy |
| Type C2 | Type III (full radical) | Complete without nerve-sparing | At origin | IB1 with posterior parametrial involvement |
| Type D1 | Type IV/V | Paravascular (hypogastric resection) | Ligated at origin + internal iliac | Laterally extended resection; selected pelvic sidewall disease |
Eligibility criteria (all must be met)
Stage IA1 (LVSI+) to IB1 (selected IB2 ≤4cm at specialist centres); SCC or usual-type ADC histology; no LVSI (relative CI); negative nodes confirmed; tumour ≤2cm; no endocervical extension above isthmus; desire to preserve fertility; residual endocervix ≥5mm feasible.
Radical vaginal trachelectomy (RVT — Dargent)
Vaginal approach. Wide excision of cervix + parametria + upper vagina. Isthmic cerclage (Mersilene tape). PLND laparoscopic. Most extensively studied approach. 5-yr DFS ~95% for IB1 ≤2cm. Pregnancy rate 50–70% of those attempting.
Radical abdominal trachelectomy (RAT)
Open abdominal approach. Allows larger tumour clearance (up to 4cm). Broader parametrial clearance. Isthmic cerclage placed abdominally. Suitable for tumours 2–4cm at specialist centres.
Oncologic & obstetric outcomes
Recurrence rate ~4–5% (comparable to radical hysterectomy for ≤2cm SCC). Pregnancy rate post-RVT: 50–70%. Preterm delivery <37wks: 10–25%. Miscarriage rate ~20%. Conception attempts deferred 12 months minimum post-surgery.
Post-trachelectomy surveillance
MRI pelvis 3-monthly ×2yr, then 6-monthly ×3yr. Vault cytology + HPV 6-monthly. Elective caesarean section at term (37–38wks) mandatory — vaginal delivery contraindicated. Obstetric care at specialist centre.
Sentinel LN biopsy (SLNB)
Standard for IB1–IB2 undergoing radical surgery. Tc-99m periservical injection (± patent blue dye ± ICG near-infrared fluorescence). Bilateral mapping required. If unilateral mapping only: full PLND on unmapped side per ESGO guidelines.
Ultrastaging of sentinel nodes
Serial sections (2mm) + IHC (CK AE1/AE3 or CAM5.2). Detects micrometastases (<2mm) and isolated tumour cells (ITC). Micrometastases: most centres treat as node-positive (adjuvant CCRT). ITCs: close surveillance without adjuvant treatment in many protocols.
Pelvic lymph node dissection (PLND)
Bilateral removal of external iliac, internal iliac, obturator, common iliac, presacral nodes. Minimum 10–12 nodes per side for adequate staging. Laparoscopic or open. Complications: lymphocyst (10–25%), lymphoedema.
Para-aortic lymphadenectomy (LAPLA)
Laparoscopic PA LN dissection for pathological PA staging before RT (specialist centres). More sensitive than PET-CT for nodes <1cm. Confirms IIIC2; tailors RT field.
Lymphocyst management
Most asymptomatic — conservative management. Symptomatic (pain, leg oedema, ureteric obstruction): US-guided aspiration ± sclerotherapy (doxycycline or ethanol). Laparoscopic fenestration for large persistent symptomatic cysts.
Indications
Central pelvic recurrence after primary radiotherapy (>6 months from completion); selected Stage IVA (bladder/rectal invasion) without pelvic sidewall fixity or distant metastasis; disease-free interval is key prognostic factor.
Absolute contraindications
Bilateral ureteric obstruction; pelvic sidewall fixity; distant metastasis (any site); peritoneal spread; unresectable lymph nodes; poor performance status (PS ≥2).
Types of exenteration
Anterior: bladder + uterus + vagina (VVF / bladder invasion). Posterior: uterus + vagina + rectum (RVF / rectal invasion). Total (most common for recurrence): bladder + uterus + vagina + rectum. Supra-levator vs. infra-levator.
Reconstruction
Urinary: ileal conduit (Bricker) or continent neobladder (Indiana pouch). Colorectal: colorectal anastomosis or end colostomy. Vaginal: myocutaneous flaps (gracilis, VRAM, Singapore flap). Multi-specialist procedure at tertiary centre.
Outcomes
5-yr OS: 25–60% (highly selected patients). Operative mortality: 1–5% at high-volume specialist centres. Major morbidity: 30–50%. Extensive pre-operative counselling mandatory.
Quality of life & psychology
Significant body image disruption; stoma management; sexual function impairment. Long-term QoL data shows adaptation and acceptable wellbeing in motivated survivors with adequate support. Specialist stoma nurse and clinical psychologist integral from pre-op phase.
LACC Trial (Ramirez PT et al. NEJM 2018;379:1895–1904)
RCT of 631 patients Stage IA1 LVSI+ to IB1 (<4cm). Open vs. minimally invasive (laparoscopic / robotic) radical hysterectomy.
· Disease-free survival at 4.5 years: 91.2% (open) vs. 74.0% (MIS) — HR 3.74 for disease recurrence (MIS arm).
· Overall survival: 93.8% (open) vs. 85.9% (MIS) — HR 6.00 for cancer-related death (MIS arm).
· Trial terminated early due to significant inferiority of MIS approach.
Proposed mechanisms of inferiority: Tumour dissemination from CO₂ pneumoperitoneum; uterine manipulator disruption of cervical tumour; colpotomy-related tumour spillage vs. closed-vault approach in open surgery.
Current recommendation (NCCN 2024 / ESGO 2023):
· OPEN ABDOMINAL radical hysterectomy is the standard for ALL tumours ≥2cm or when radical hysterectomy is the primary treatment intent.
· Minimally invasive approach may be considered for tumours <2cm, no LVSI, at experienced very high-volume centres — with full informed consent, no uterine manipulator, and closed-vault colpotomy technique.
· Simple hysterectomy (Type A/I) is NOT affected by LACC trial findings — MIS simple hysterectomy remains acceptable for Stage IA1 (LVSI−) and benign indications.
RCT of 631 patients Stage IA1 LVSI+ to IB1 (<4cm). Open vs. minimally invasive (laparoscopic / robotic) radical hysterectomy.
· Disease-free survival at 4.5 years: 91.2% (open) vs. 74.0% (MIS) — HR 3.74 for disease recurrence (MIS arm).
· Overall survival: 93.8% (open) vs. 85.9% (MIS) — HR 6.00 for cancer-related death (MIS arm).
· Trial terminated early due to significant inferiority of MIS approach.
Proposed mechanisms of inferiority: Tumour dissemination from CO₂ pneumoperitoneum; uterine manipulator disruption of cervical tumour; colpotomy-related tumour spillage vs. closed-vault approach in open surgery.
Current recommendation (NCCN 2024 / ESGO 2023):
· OPEN ABDOMINAL radical hysterectomy is the standard for ALL tumours ≥2cm or when radical hysterectomy is the primary treatment intent.
· Minimally invasive approach may be considered for tumours <2cm, no LVSI, at experienced very high-volume centres — with full informed consent, no uterine manipulator, and closed-vault colpotomy technique.
· Simple hysterectomy (Type A/I) is NOT affected by LACC trial findings — MIS simple hysterectomy remains acceptable for Stage IA1 (LVSI−) and benign indications.
Special clinical situations
Every case of cervical cancer diagnosed in pregnancy must be managed by a specialist MDT: gynaecological oncologist + maternal-fetal medicine specialist + neonatologist + radiation oncologist. Full informed consent and shared decision-making essential.
Stage IA1 (any trimester)
CKC for diagnosis + staging. Conservative management until fetal maturity (≥34wks). Colposcopy q6–8 weeks. Definitive treatment postpartum. No adverse oncological outcome with delay demonstrated.
Stage IA2–IB1 ≤2cm (2nd trimester)
Options: (1) Delay to ≥34wks, expedite delivery by CS, then definitive treatment within 4–6wks postpartum. (2) Radical trachelectomy during pregnancy (experimental, specialist centres only). MRI q6–8 wks (no gadolinium in 1st trimester).
Stage IA2–IB1 (1st trimester)
Treatment should not be delayed. Termination of pregnancy recommended followed by definitive treatment. NACT (cisplatin-based, 2nd trimester only) to bridge to fetal maturity — experimental; detailed informed consent essential.
Stage IB2 and above (any trimester)
Before 20 weeks: do NOT delay — termination recommended, then definitive CCRT. After 22–24 weeks: NACT (cisplatin ± paclitaxel) to gain fetal maturity → expedited delivery by CS → definitive CCRT.
Mode of delivery
Caesarean section is MANDATORY for all invasive cervical cancer in pregnancy. Vaginal delivery risks: tumour haemorrhage, tumour dissemination, implantation metastasis at episiotomy site.
NACT in pregnancy (2nd trimester)
Cisplatin ± paclitaxel (avoid 1st trimester — organogenesis risk). Monitor fetal growth, amniotic fluid. Do not deliver within 3 weeks of last chemotherapy dose (risk of neonatal myelosuppression).
Epidemiology & risk
22-fold increased cervical cancer risk in HIV+ vs. HIV−. Cervical cancer is an AIDS-defining illness. HPV persistence and CIN progression significantly accelerated with immunosuppression (CD4 <200 = highest risk).
Pre-treatment assessment
CD4 count + HIV viral load mandatory. Optimise ART before and throughout treatment. Target viral suppression (VL <50 copies/mL). CD4 <200: prophylactic co-trimoxazole. Hepatitis B/C co-infection screen.
ART – chemotherapy interactions
Efavirenz / ritonavir (CYP3A4): interactions with paclitaxel — pharmacist review essential. Tenofovir (TDF): additive nephrotoxicity with cisplatin — intensive renal monitoring required. Dolutegravir / bictegravir (integrase inhibitors): fewest interactions; preferred ART backbone during chemotherapy.
Treatment approach
Same staging and treatment principles as HIV-negative patients. CCRT is standard for locally advanced disease. Surgery: CD4 >200 generally safe for radical hysterectomy. Outcomes improving with modern ART.
Screening in HIV+
Annual HPV test or Pap smear from HIV diagnosis (from age 25). Two consecutive normal annual screens → every 3 years. Colposcopy for any high-risk HPV or abnormal cytology. BHIVA / WHO 2023 screening guidelines.
HPV vaccination (HIV+)
9-valent HPV vaccine (Gardasil-9) recommended up to age 45 for HIV+ patients (BHIVA 2023). 3-dose schedule regardless of age (0, 2, 6 months). Administer when CD4 >200 if possible.
Ovarian transposition (oophoropexy)
Recommended before pelvic RT in premenopausal patients <40–45 years with SCC histology. Ovaries mobilised on vascular pedicle to lateral aspect of iliac crest and fixed to lateral abdominal wall. Metal clip placed for RT planning identification.
NOT recommended for adenocarcinoma
Cervical adenocarcinoma has 5–10% risk of ovarian metastasis — conservation not routinely recommended. HPV-independent gastric-type ADC: higher ovarian involvement risk. Case-by-case MDT decision.
HRT after cervical cancer treatment
Systemic HRT (oestrogen ± progestogen) is SAFE in cervical cancer survivors — no evidence of increased recurrence risk (unlike breast / endometrial cancer). Strongly recommended for premenopausal women after bilateral oophorectomy or RT-induced premature ovarian insufficiency.
Bone health management
DEXA scan at baseline and 2 years post-treatment. Pelvic RT accelerates bone loss. Calcium 1000–1200mg/day + Vitamin D 800–1000 IU/day. Bisphosphonate if T-score <−2.5 or fragility fracture.
Vaginal oestrogen (topical)
Safe for urogenital atrophy / GSM after cervical cancer. Minimal systemic absorption. Estriol cream or oestradiol vaginal ring or pessary. Use in conjunction with vaginal dilators post-RT. No contraindication in SCC survivors.
CIN 1 (LSIL) management
Conservative management preferred — most regress spontaneously within 12–24 months. Repeat HPV/Pap at 12 months (BSCCP guideline). If persistent ≥2 years or progressing: colposcopy-directed biopsy → consider ablation or excision. Do NOT treat without histological confirmation.
CIN 2 management
LLETZ/LEEP preferred in most. Conservative management acceptable in young patients (<25) or pregnancy (regression rate ~60% in 2 years). Colposcopy q6 months ×2 years if conservative. Treat if persistent or progressing.
CIN 3 / HSIL management
Treatment mandatory — do NOT observe. LLETZ preferred (simultaneous diagnosis + treatment in see-and-treat setting). Cold-knife cone (CKC) if glandular involvement suspected, TZ type 3, or LLETZ margin likely inadequate. Post-treatment: HPV test at 6 months.
LLETZ / LEEP technique
Local anaesthesia: lidocaine 1% + 1:200,000 adrenaline (paracervical + subepithelial). Loop wire excision of entire transformation zone. Aim: 2–3mm clear ectocervical margin + endocervical margin. Ball electrode for haemostasis. Single-pass excision preferred.
Post-treatment surveillance
HPV test at 6 months post-LLETZ (test of cure — NHSCSP). Negative HPV: return to 3–5 year national screening interval. HPV positive: repeat colposcopy. Inform patients: LLETZ does NOT eliminate HPV.
Geriatric assessment
Comprehensive geriatric assessment (CGA) before treatment planning in patients ≥70 years. G8 screening tool (≤14 = abnormal; full CGA needed). Charlson Comorbidity Index. ECOG/WHO PS. Nutritional assessment (MNA-SF). Cognitive function (MMSE).
Radical radiotherapy for elderly
CCRT and IGABT can be safely administered to elderly fit patients (PS 0–2) with acceptable toxicity. Age alone is NOT a contraindication. Comorbidities, renal function (for cisplatin), and performance status guide chemotherapy eligibility, not age per se.
Cisplatin eligibility in elderly
eGFR ≥50 mL/min required. Audiogram baseline (ototoxicity risk greater with cumulative prior hearing loss). Carboplatin AUC2 weekly if cisplatin-ineligible. RT alone if no chemotherapy tolerated — discuss risk/benefit clearly.
Modified treatment approaches
Hypofractionated EBRT (if standard 28fr not tolerated): 40Gy/16fr or 45Gy/20fr. Reduced-fraction brachytherapy: 3 × 7Gy HDR to HRCTV (acceptable for early-stage). Palliative-intent for Stage III–IVB with poor PS: 20Gy/5fr EBRT + BSC.
Palliative care threshold
Early palliative care referral for Stage III–IVB elderly patients with PS ≥2. Symptom management priority: pain, bleeding (palliative EBRT), fistula, nutritional support, social care coordination. Advance care planning discussed early and documented.
Incidental invasive cancer at simple hysterectomy
Unsuspected invasive carcinoma found in uterus removed for presumed benign indication. MDT review mandatory before any further surgery or RT. Urgent MRI pelvis + PET-CT for re-staging. Assess: stage, margin status, LVSI, depth of invasion, histological type.
Stage IA1 — LVSI negative
Observation if surgical margins clear. No further treatment required. Surveillance as per Stage IA1 follow-up schedule. Annual vault cytology + HPV.
Stage IA1 (LVSI+) / IA2 — margins clear
Options: (1) Re-operation: radical parametrectomy + upper vaginectomy + PLND/SLNB. (2) EBRT ± ICBT boost. Both options have equivalent outcomes. MDT decision based on surgical fitness and patient preference.
Stage IB1+ or positive surgical margins
Positive margin: CCRT (cisplatin + EBRT 45–50.4Gy + vaginal vault brachytherapy boost). Parametrium positive: treat as IIB — full CCRT + IGABT. Re-operation (radical parametrectomy): technically feasible if no RT planned — discuss at MDT.
Imaging post-incidental finding
MRI pelvis urgently: assess residual tumour in parametria, vaginal cuff, bladder/rectum. PET-CT for Stage ≥IB to exclude nodal / distant disease. Staging may change on imaging — re-discuss at MDT before finalising treatment intent.
Follow-up schedule & surveillance
Year 1–2 (every 3–4 months)
Full clinical history (new symptoms); speculum examination of vaginal vault / cervix; bimanual pelvic examination; recto-vaginal assessment (CCRT-treated). SCC-Ag / CEA if elevated at baseline.
Year 3–5 (every 6 months)
Same clinical examination. Review of late treatment-related toxicities. Psychosexual assessment at each visit. Bone health review if post-RT or surgical menopause. Vaginal dilator compliance check.
Year 5+ (annually)
Annual clinical review. Vault cytology / HPV only if clinically indicated. Return to national cervical screening programme if cervix present (post-trachelectomy). Not routine per NCCN 2024.
Imaging in follow-up
NOT routinely recommended at each visit (NCCN 2024 / ESGO 2023). CT / MRI / PET-CT: only if symptomatic or clinical suspicion for recurrence. Rising SCC-Ag (>25% above nadir) warrants imaging.
Tumour markers in follow-up
SCC-Ag measured at completion of RT, then at each visit if initially elevated. Rising marker (especially >1.5 ng/mL + symptoms): proceed to CT/PET-CT. Correlate with clinical examination — not used as sole decision criterion.
Red flags — suspect recurrence
New pelvic / back pain; vaginal bleeding; unilateral or bilateral leg oedema; haematuria; rectal bleeding; new palpable pelvic / vault mass; constitutional symptoms (weight loss, fatigue); rising SCC-Ag
Survivorship & toxicity management
Vaginal stenosis prevention
Vaginal dilators: commence 4–6 weeks post-RT. Use 3× per week minimum. Gradual progressive dilatation. Topical oestrogen lubricant (estriol cream). Continue ≥2–3 years post-RT. Refer specialist vaginal health clinic if severe. Silicone dilators preferred.
Chronic radiation proctitis
Sucralfate enemas 2g BD. Mesalazine suppositories / enemas. Hyperbaric oxygen: 40 sessions at 2.4 ATA for Grade 3+ or refractory haemorrhage (evidence-based). Argon plasma coagulation for bleeding vessels. Avoid NSAIDs.
Lymphoedema management
Early referral to specialist lymphoedema physiotherapist. Complete decongestive therapy (CDT): MLD + multilayer bandaging + exercise + skin care. Maintenance: compression garments Class II minimum. Cellulitis: prompt antibiotic treatment. Lifelong compression recommended.
Psychosexual support
Sexual dysfunction affects up to 70% of survivors (dyspareunia, dryness, loss of libido, body image disruption). Screen at each visit using FSFI or brief validated tool. Refer: clinical psychologist / sex therapist. Partner involvement encouraged.
Psychological wellbeing
Screen PHQ-9 (depression) and GAD-7 (anxiety) at each visit. Cancer-specific Distress Thermometer. Refer: clinical psychologist; cancer support group; social worker. Fertility grief counselling if reproductive loss.
Nutritional support
Dietitian referral if weight loss >5% or severe GI toxicity. High-protein, high-calorie diet. Enteral nutrition (NGT/PEG) if oral intake <60% of requirements. MUST nutritional screening tool at each visit.
Prognosis by FIGO stage
| FIGO Stage | Approx 5-yr OS | Key prognostic factors |
|---|---|---|
| IA1–IA2 | 95–99% | LVSI, margin status, depth of invasion |
| IB1 | 88–93% | Tumour size, LVSI, nodal status, histological type |
| IB2 | 75–85% | Tumour bulk, parametrial proximity, IGABT dose adequacy |
| IB3 / IIA | 65–75% | Bulk, nodal involvement, BT adequacy, pembrolizumab use |
| IIB | 55–65% | Parametrial extent, nodal burden, response to CCRT |
| IIIA / IIIB | 35–50% | Bilateral hydronephrosis, PS, anaemia correction during RT |
| IIIC1 (pelvic nodes) | 28–40% | Number of positive nodes, nodal bulk, BT dose achieved |
| IIIC2 (PA nodes) | 20–30% | Para-aortic nodal bulk, EFRT adequacy, PS |
| IVA | 14–22% | Fistula presence, organ invasion extent, PS, response |
| IVB / Recurrent | <10% | PS, number of metastatic sites, PD-L1 CPS, bevacizumab eligibility |
Palliative & supportive care
WHO analgesic ladder (3-step)
Step 1: Paracetamol 1g QDS ± NSAIDs (if renal function adequate). Step 2: Weak opioid (codeine 30–60mg QDS or tramadol 50–100mg QDS) + Step 1 agents. Step 3: Strong opioid (morphine, oxycodone, fentanyl) ± Step 1. Adjuvant agents at all steps.
Strong opioid prescribing
Morphine sulphate immediate release (MSIR): 2.5–5mg q4h (opioid-naïve). Titrate to comfort (increase by 30–50% if ≥3 breakthrough doses/day). Breakthrough dose: 1/6 of 24h total morphine dose. Mandatory laxatives from Day 1 (senna + macrogol).
Neuropathic pain adjuvants
Pelvic nerve / sciatic pain. Add: gabapentin 300mg TDS (titrate to 1800–3600mg/day) or pregabalin 75mg BD (titrate to 300mg BD). Amitriptyline 10–75mg nocte or duloxetine 60mg OD.
Interventional pain management
Superior hypogastric plexus block: pelvic visceral pain (60–70% response rate; CT or fluoroscopy-guided). Ganglion impar block: perineal and sacrococcygeal pain. Epidural / spinal analgesia: bilateral pelvic / lower limb neuropathic pain.
Bone metastasis pain
Denosumab 120mg SC monthly (preferred over bisphosphonate; no renal dose adjustment). OR Zoledronic acid 4mg IV q4wks (check eGFR; contraindicated eGFR <30). Palliative EBRT: 8Gy ×1 (equivalent to 20Gy/5fr for pain — ASTRO/CARO guideline). Dexamethasone 4–8mg OD for cord compression.
Corticosteroids in palliative care
Dexamethasone 4–16mg/day: anorexia, nausea, bowel obstruction, raised ICP, bone pain, fatigue. Oral or SC route. Reduce to minimum effective dose after 1 week. Gastric protection with PPI mandatory. Review every 1–2 weeks; taper if no benefit.
Acute massive haemorrhage
Resuscitation: 2 large-bore IV lines; crossmatch 4–6 units; IV crystalloid (1–2L) → colloid if haemodynamically compromised. Transfuse to Hb ≥8g/dL. Vaginal packing: gauze soaked in tranexamic acid solution (1g in 20mL NS). ICU/HDU care if haemodynamically unstable.
Haemostatic pharmacotherapy
Tranexamic acid 1g IV over 10 min → then 1g over 8h (CRASH-2 protocol). Topical: alginate dressings (Kaltostat), oxidised cellulose (Surgicel), haemostatic gauze (QuikClot). Antifibrinolytic therapy reduces blood transfusion requirements and mortality in acute haemorrhage.
Palliative radiotherapy for haemostasis
Highly effective in 80–90% of cases within 24–72 hours. Not previously irradiated: 30Gy/10fr or 20Gy/5fr. Previously irradiated (re-irradiation): single 8Gy or 3×4Gy with careful OAR re-planning. Refer urgently to radiation oncology on-call if acute haemorrhage.
Interventional radiology
Bilateral internal iliac artery embolisation (IIAE): 70–90% success rate for pelvic haemorrhage. Selective uterine artery embolisation (UAE). Emergency IR if active contrast extravasation on CT angiography.
Catastrophic haemorrhage — end-of-life planning
In terminal patients: anticipatory prescribing — midazolam 5–10mg SC + morphine SC for acute symptom management. Dark-coloured towels at bedside (psychological impact of visible haemorrhage). Family education and advance warning.
Vesico-vaginal fistula (VVF)
Continuous uncontrollable urinary incontinence. Confirm with methylene blue dye test / cystoscopy + biopsy (exclude malignant involvement of fistula tract). Urinary diversion (ileal conduit or suprapubic catheter) for palliation. Surgical VVF repair: only after ≥3 months, no active malignancy.
Recto-vaginal fistula (RVF)
Faecal / flatal passage per vagina. Confirm with water-soluble contrast enema or proctoscopy. Defunctioning loop colostomy for palliation — significantly improves QoL and dignity. Surgical repair deferred until tumour controlled + radiation healing complete (6–12 months minimum).
Medical management of fistulae
Skin protection: barrier cream (Cavilon, zinc oxide paste) for perineal / perianal excoriation. Urinary: clean intermittent self-catheterisation or suprapubic catheter. Odour management: metronidazole 400mg BD orally (10–14 days) + topical metronidazole gel.
Specialist nursing care
Specialist stoma / continence nurse essential from fistula diagnosis. Odour-absorbing dressings (activated charcoal dressings). Continent urinary / faecal collection pouches. Skin integrity management. Psychological support for body image and dignity concerns.
Fistula prevention
Strict OAR dose constraints (bladder D2cc <90Gy; rectum D2cc <75Gy). Bevacizumab: 6–9% VVF risk — counsel patients before prescribing; do not use in patients with prior fistula. Early treatment completion reduces tumour necrosis-related fistula formation.
Diagnosis of ureteric obstruction
Obstructive uropathy → hydronephrosis → AKI or CKD. Bilateral obstruction = prerenal uraemia (rapidly fatal without intervention). Assess: serum creatinine, eGFR, U&E, US kidneys. Clinical features: loin pain, anuria / oliguria, nausea, uraemic encephalopathy.
Emergency management — bilateral obstruction
Urgent urology referral. Bilateral percutaneous nephrostomies (PCN) within 24–48h if uraemic. OR bilateral retrograde ureteric stents (double-J) if cystoscopic access feasible. Monitor electrolytes closely (post-obstructive diuresis: hypokalaemia risk). IV fluid replacement per urine output.
Ureteric stent management
Retrograde double-J stent: preferred if ureteric orifices accessible. Requires cystoscopy under GA / sedation. Exchange 3–6 monthly (metallic stents every 12 months). Tumour ingrowth into plastic stents: metallic covered stents more durable in malignant obstruction.
Pre-treatment obstruction management
Mandatory: ureteric stent or PCN before initiating RT/CCRT for bilateral obstruction. Recommended for unilateral if symptomatic or eGFR declining. Post-decompression: reassess eGFR before cisplatin initiation (allow 48–72h for renal function recovery).
Chronic obstruction — palliative setting
In terminal disease: open, honest discussion of goals of care with patient ± family. PCN may prolong life but also prolongs dying process — patient-centred decision. Refer renal palliative care team. Document advance care planning wishes regarding dialysis and interventional procedures.
Long-term stent monitoring
Serum creatinine at each follow-up visit. US kidneys annually if prior obstruction. Stent exchange at 3–6 months (or earlier if symptomatic UTI / blockage). Antibiotic prophylaxis (trimethoprim 100mg nocte) reduces UTI risk in long-term stent patients.
Early integration of palliative care
ASCO guideline: palliative care referral at diagnosis of Stage III–IVB disease (not just at end of life). Improves QoL, reduces aggressive EOL interventions, may improve survival (Temel et al. NEJM 2010). Oncology–palliative medicine joint clinic model is gold standard.
Advance care planning (ACP)
DNACPR / DNAR discussion and documentation. Preferred place of death (home, hospice, hospital). ReSPECT or equivalent advance care plan completed. Lasting power of attorney (health and welfare). Reviewed at each deterioration. Communicated to GP, community nursing, out-of-hours services.
Anticipatory prescribing
SC medications prescribed in advance for crisis symptoms at home: morphine / diamorphine (pain, dyspnoea); midazolam (agitation, seizure); haloperidol (nausea, delirium); glycopyrronium (respiratory secretions). Syringe driver if unable to swallow. Community palliative nursing access 24/7.
Symptom management (terminal phase)
Pain: SC opioid titrated to comfort. Agitation / delirium: midazolam ± haloperidol SC. Respiratory secretions: glycopyrronium 200mcg SC PRN or via syringe driver. Nausea: haloperidol 1.5–3mg SC. Fever: paracetamol PR / SC. Mouth care: regular moistening.
Family & carer support
Carer needs assessment. Psychological support for anticipatory grief. Practical support: community nurse, social worker, Macmillan / cancer support nurse. Bereavement support post-death (follow-up call/letter, referral to bereavement counselling).
Spiritual & cultural care
Chaplaincy / spiritual care referral as requested by patient and family. Cultural and religious needs documented and respected. Preferred rites and practices at time of death accommodated where possible. Interpreter services for those for whom the primary language is not English/Hindi.
Key guidelines & landmark references
FIGO 2018 staging
Bhatla N et al. Int J Gynaecol Obstet. 2019;145(1):129–135. Revised FIGO staging for carcinoma of the cervix uteri.
NCCN Guidelines v1.2024
Cervical Cancer. National Comprehensive Cancer Network. Available at: www.nccn.org (requires free registration).
ESGO/ESTRO/ESP Guidelines 2023
Cibula D et al. Int J Gynecol Cancer. 2023. Cervical cancer management — ESGO/ESTRO/ESP joint guidelines update.
EMBRACE I — IGABT brachytherapy
Pötter R et al (EMBRACE investigators). Radiother Oncol. 2021. Image-guided adaptive brachytherapy: 5-year outcomes from the EMBRACE I study.
KEYNOTE-826 (1st-line pembrolizumab)
Colombo N et al. NEJM. 2021;385(20):1856–1867. Pembrolizumab + chemotherapy ± bevacizumab for recurrent/metastatic cervical cancer.
KEYNOTE-A18 (CCRT + pembrolizumab)
Lorusso D et al. NEJM. 2024. Pembrolizumab + CCRT for locally advanced cervical cancer (ENGOT-cx11/KEYNOTE-A18).
innovaTV 301 (tisotumab vedotin)
Coleman RL et al. NEJM. 2023;389(26):2444–2455. Tisotumab vedotin vs. chemotherapy in recurrent/metastatic cervical cancer.
LACC Trial (surgical approach)
Ramirez PT et al. NEJM. 2018;379(20):1895–1904. Minimally invasive vs. open radical hysterectomy for cervical cancer — landmark RCT.
GOG-240 (bevacizumab)
Tewari KS et al. NEJM. 2014;370(8):734–743. Bevacizumab + chemotherapy for persistent/recurrent/metastatic cervical cancer.
INTERLACE trial (NACT + CCRT)
McCormack M et al. Lancet. 2023. Weekly neoadjuvant chemotherapy before CCRT improves overall survival in locally advanced cervical cancer.
GEC-ESTRO contouring guidelines
Härkonen K et al. Radiother Oncol. 2020. GEC-ESTRO guidelines for target volume delineation in image-guided adaptive brachytherapy for cervical cancer.
Fertility-sparing — systematic review
Bentivegna E et al. Lancet Oncol. 2015;16(13):1388–1398. Fertility-sparing treatments for cervical cancer: a systematic review and meta-analysis.
WHO Cervical Cancer Elimination Strategy
WHO. Global strategy to accelerate the elimination of cervical cancer as a public health problem. Geneva: World Health Organization; 2020.
MoHFW India — Standard Treatment Workflow
Standard Treatment Workflow (STW) for Cervical Cancer. Ministry of Health & Family Welfare, Government of India. 2022. Available via National Cancer Grid India.
Clinical disclaimer
This tool is intended as a clinical decision-support reference for qualified medical professionals only. It does not replace individualised clinical judgement, multidisciplinary tumour board review, or institution-specific protocols. All treatment decisions must be made in the context of the individual patient’s overall performance status, comorbidities, patient preferences, and available institutional resources. Guidelines evolve — always verify with the most current published guidance. Last updated: 2024.
All cases of locally advanced cervical cancer (≥IB3) should be discussed at a dedicated gynaecological oncology MDT meeting. Brachytherapy is an essential component of curative-intent treatment — omission is associated with significantly inferior local control and overall survival and should not be accepted as a standard practice at any centre offering curative treatment.