Cervical Cancer


  • 1.6% of all cancers in women
  • ~ 4070 deaths / year
  • 1.5% of all cancer deaths in women
  • Average age → mid- to late 40s
  • 25% of cases : > 65
  • 50% of deaths : > 65
  • At the time of presentation :
    • 45%: localized
    • 34%: regional spread
    • 10%: disseminated disease.
  • During the last five decades, the incidence has dropped
  • Development of effective screening techniques for the identification of preinvasive lesions
  • Highest rates: Latin America
  • Lowest: Jewish women in Israel


All about HPV

  • HPV: small, double-stranded non-enveloped DNA virus
  • Induce squamous epithelial and fibroepithelial tumors in their natural hosts
  • Have a specific tropism for keratinocytes
  • Express their full productive cycle only in squamous epithelial cells.
  • Belongs to the papovavirus group
  • Two strains of HPV (16 and 18) → high malignant potential
  • Mechanism of HPV infection:
    • HPV infection occurs in the basal cell layer of the epithelium
      • Basal cell become a continuous reservoir of HPV DNA
        • The viral genome replicates itself in the dividing cells
    • However, even in absence of basal cell division —> viral DNA replication continues (as the epithelial cells mature)
    • ==> Increase the HPV DNA copy number per cell
    • Microscopically: koilocytosis1: Pathognomonic of HPV infection
  • HPV DNA sequences are identified in 80%-100% of cases by PCR
  • HPV Types:
    • 18 and 16
      • There is a reason why these two types are more carcinogenic
      • E6 proteins of oncogenes from these strains bind TP53 more efficiently than oncogenes from other non-carcinogenic HPV strains.
    • HPV 18 more aggressive
      • More LN+ and DM
    • Also HPV 31, 33, 35 are associated
    • HPV 16 more common —> ~50% of cervical ca
    • HPV 18 the second —> 16% of cervical ca
  • HPV-6 and HPV-11 —> benign viral condyloma or mild dysplastic epithelial(CIN1)
  • HPV carcinogenesis:
    • Capable of inducing chromosome abnormalities in normal keratinocytes
    • Interfere with cell cycle regulatory proteins and checkpoints
    • Mediated through oncogenes E6 & E7
    • E6
      • E6 protein of HPV oncogenes binds with the E6-associated protein (E6-AP) to the TP53 protein
      • ==> degradation of TP53
      • By itself, E6 is not capable of inducing transformation
        • Induces immortalization of keratinocytes in conjunction with E7
    • E7
      • E7 binds to Rb tumour suppressor gene and inactivates Rb
        • Remember when Rb is phosphorylated becomes inactivated? :)
      • ==> upregulates p16
        • p16 staining is a surrogate marker for detection of HPV
      • ==> Inactivates the gene product
      • ==> Uncontrolled release of active transcription factors (E2F)
        • ==> Unregulated progression through the cell cycle
  • Evidence implicating HPV in pathogenesis of Cervical Ca
    1. Multiple epidemiologic studies demonstrating HPV infection as an important risk factor for the development of squamous cell intraepithelial lesions and cervical ca
    2. Detection of HPV DNA in more than 90% of cervical cancers and their precursor lesions
    3. Evidence of HPV transcriptional activity in neoplastic tissues
    4. Evidence that HPV oncogenes can mediate malignant transformation in transgenic mice

Some Epidemiologic points about HPV and Cervical Ca:

  • Incidence of HPV infections among cytologically normal sexually active young women is high
  • Most women infected with oncogenic HPV eliminate the infection and are at low or no risk for developing cervical neoplasia.
  • The median duration of most new HPV infections: < 1yr
    • Transient infection of HPV infection ~ CIN low grade frequently regress to normal
  • > 30% remain consistently or intermittently (+) for HPV DNA
  • Possible factors which may promote HPV carcinogenesis:
    • Smoking
      • Carcinogens found in cigarette smoke are concentrated in cervical mucus
      • Decreased numbers of antigen-presenting cells in cervical epithelium
      • Changes in local immunity
    • OCP
    • HIV
      • Cervical Ca is a AIDS defining neoplasm
        • Like Kaposi Sarcoma and NHL

HPV Vaccine

  • Quadrivalent HPV (types 6, 11, 16, and 18)
  • Bivalent (16 and 18)
  • Incidence of HPV infection or genital tract disease fell by 90% after vaccination
  • Highly Safe
  • The quadrivalent and bivalent vaccines are both FDA approved
  • Female 9 to 26 years of age

More about Risk Factors:

  • Cervical Ca is the most common HPV-induced cancer
    • more common than anal ca and H&N
  • Herpes simplex virus type 2 (HSV2) as a potential cofactor with HPV
  • Early age at initiation of sexual activity
  • Multiple sexual partners
  • Cigarette smoking
    • Twofold increase in incidence
  • Diethylstilbestrol (DES), a nonsteroidal estrogen
    • 1940s → prevention of recurrent or threatened miscarriages
    • Intrauterine exposure to DES → clear cell adenocarcinoma of the cervix and vagina
    • 91% → diagnosed between the ages of 15 and 27
    • > 90% presenting with early (stage I or II) disease


The cervix is sandwiched between the trigone of the bladder, the ureters, the anterior wall of the rectum, and the sigmoid colon

  • Uterus
  • Fundus
  • Body=corpus uteri
  • Covered by the reflection of the peritoneum
    • Anteriorly becomes the peritoneal reflection over the bladder
    • Posteriorly extends down over the cervix and posterior fornix of the vagina before covering the anterior portion of the rectum and sigmoid colon.

SEPARATED by a constriction known as the isthmus
Broad ligament

  • A double layer of peritoneum
  • Through which the blood supply, lymphatics, and nerves of the uterus course.
  • Connect the lateral aspects of the uterus with the pelvic side walls

Three ligaments

  • Round ligament anteriorly, which courses out through the abdominal inguinal ring
  • Ovarian ligament posteriorly connecting the uterine pole of the ovary and the lateral uterus
    • Ovaries lie posteriorly to the ligament
  • Suspensory ligament of the ovary between the two layers of the broad ligament connecting the lateral pole of the ovary and the pelvic side wall

Uterus is sited above the pelvic diaphragm (mainly the levator ani muscle) by two ligaments
Cardinal ligament→ at the lateral margins of cervix and vagina → extends to lateral pelvic wall
Combined with the paravesical fascias that surround the cervix, upper vagina, bladder base
Cardinal ligament forms the bottom of the broad ligament
Posteriorly ⇒ form the uterosacral ligaments, the lateral boundaries of the cul-de-sac of Douglas and insert into the periosteum of the fourth sacral vertebrae. These ligaments serve to pull the cervix and lower uterine segment backward, maintaining an anteflexed position for the uterus.
Resting on the urogenital diaphragm anterior to the cervix, the trigone of the bladder is continuous with the upper third of the vagina and the anterior fornix. The remainder of the base presses against the anterior cervix and lower uterine segment. The ureters, leaving the renal pelvis, run caudally along the psoas muscle and along the anterior border of the greater sciatic notch. They enter the pelvis by crossing the iliac vessels at the bifurcation of the common iliacs into the external and internal branches, and pass along the posterolateral pelvic walls. They then enter the cardinal ligament (base of the broad ligament), pass beneath the uterine arteries, and travel immediately around the cervix and vaginal fornices, inserting into the trigone of the bladder. Their location on the lateral aspect of the cervix and cardinal ligaments and along the uterine artery make them prone to injury from expanding tumor in the cervix, as well as from both surgical and radiotherapeutic interventions.
Posterior to the uterus, the sigmoid colon dives below the peritoneal reflection to become the rectum and is closely related to the uterus and posterior fornix of the vagina. The rectum is separated from the posterior vagina by only a thin wall of loose areolar tissue. The thickness of the rectovaginal septum is approximately 5 mm.


Lymphatics of the cervix

  • Laterally → along the uterine artery to the external iliac LN
  • Posterolaterally → behind the ureters → internal LN
  • Posteriorly → common iliac & lateral sacral LN
  • Fundus of the uterus → Broad Ligament → internal iliac LN
  • Some drainage → Ovarian vessels → Para-aortic chain → to the external iliac chain → inguinal nodes via the round ligament

Lymphatic Drainage of Vagina:

  • The upper vagina → laterally → internal and external iliac LN
  • Middle third → internal iliac group ALONE
  • Lower third → merge with those of the vulva → Superficial inguinal region


Superior hypogastric plexus
L1 – L4 → Superior hypogastric plexus ( the presacral nerve ) → Sympathetic nervous supply of the bladder, rectum, and female genitalia (with the exception of the ovary)

  • A plexus of nerves situated on the vertebral bodies below the bifurcation of the aorta
  • Between two common iliac arteries
  • These nerves spreads out in the retroperitoneum over the fourth and fifth lumbar vertebrae, and forms the bilateral hypogastric nerves

Inferior hypogastric plexus
S2 – S4 → Sympathetic & Parasympathetic fibers ( SACRAL PLEXUS )→ Join Hypogastric Plexus & Pelvic Plexus

  • FROM Pelvic plexus → Uterine vaginal and vesical plexuses IS ARISED
  • Uterine vaginal and vesical plexus supply the uterus, vagina, and bladder
  • Uterine plexus enters the uterus via the base of the broad ligament along with the uterine artery

Major sensory nerves to the uterus traverse along with the autonomic sympathetic fibers
L1 - L4 → corpus
S2 - S4 → cervix

  • Cervical pain is often experienced as referred low back pain.

Which nerves may be affected by cervical Ca LN progression?

  • Lumbosacral nerve trunks
  • Rests on the Pyriform muscle in the posterolateral pelvis where it joins the sacral nerves → SACRAL PLEXUS
  • Sacral plexus
  • Sciatic nerve

sacral nerves to form the sacral plexus, which in turn gives rise to the sciatic nerve. The sciatic nerve passes through the greater sciatic foramen on its way to innovate the muscles of the lower extremity.


  • The cervix is covered by a nonkeratinized squamous epithelium that merges into the surrounding vaginal wall
  • The squamous cells may be full of glycogen and have a plump cleared-out cytoplasm (see Figure 4.8B)
  • The transition zone
    • Abrupt transition to mucous-secreting columnar and glandular epithelium
    • Location
      • At the os or within the endocervical canal
  • Squamous metaplasia
    • By definition, can only occur at or above the transition zone, and so mentioning it confirms that the transition zone was sampled.

Squamous Cell Carcinoma

  • ~80% of cervical ca
  • Although squamous neoplasms are often subclassified as large cell keratinizing, large cell nonkeratinizing, or small cell carcinomas, these designations do not correlate well with prognosis.
  • Deep keratinization
  • Large nucleoli
  • Blurred or sawtooth interface between epithelium and stroma
  • Loss of palisading basal layer
  • Desmoplastic response within stroma

Verrucous Carcinoma

  • Very well-differentiated
  • Lacking cellular atypia
  • Can be massive exophytic
  • Differentiated from condylomata
    • Presence of invasion
    • Lack of fibrovascular cores in the papillae
    • Exophytic expansion of surrounding normal tissue
  • Spread to lymph nodes —> rare

Papillary squamous cell

  • High degree of nuclear atypia
  • Warty, exophytic appearance
  • Papillae with atypical immature basaloid cells
    • reminiscent of transitional cell carcinoma of the bladder
  • Large exophytic component may be associated with a minimal amount of invasion

Lymphoepithelioma-like carcinoma

  • Solid cords of cells
  • Minimal squamous differentiation
  • Resting like islands in a diffuse stromal chronic inflammatory reaction
  • With
    • Lymphocytes
    • Plasma cells
    • Eosinophils
  • Nests of poorly differentiated cells with vesivulated nuclei with well circumscribed margins
  • Like their counterparts in the nasopharynx, thymus, larynx, stomach, and salivary glands

Low-grade squamous intraepithelial lesion (LSIL)

Cervical Intraepithelial Neoplasia grade 1 (CIN1)

  • Viral cytopathic effect
  • Affects primarily the upper cell layers of the epithelium

High-grade squamous intraepithelial lesion (HSIL; CIN2–3)

  • Persistence of immaturity along with dysplastic changes
  • Basal cells are becoming “immortalized,” like a cancerous cell, and are not maturing and differentiating as they should.
  • Denser and darker epithelium due to the high nuclear/ cytoplasmic (N/C) ratios.


  • 10% to 20% of cervical neoplasms
  • Increase recently because of decrease in SCC <== screening

Endocervical adenocarcinoma

  • Mucin-producing glands of varying differentiation
  • Fibrous stroma
  • Might be difficult to differentiate from adenocarcinoma of uterine corpus origin

Minimal deviation adenocarcinoma

  • Extremely well-differentiated lesion
  • Endocervical glands
  • Basal nuclei
  • Low nuclear/cytoplasmic ratios
  • However aggressive clinical nature
  • Poor prognosis
  • High rate associated mucinous tumors of the ovary

Villoglandular papillary adenocarcinoma

  • Younger women (average age 33)
  • Surface papillary component with fibrous stroma
  • Unless there is clear evidence of vascular involvement or deep invasion, conservative management may be warranted owing to the excellent prognosis.

Endometrioid adenocarcinoma

  • Hard to distinguish from uterine adenoca
  • Clinical course like endocervival

Clear cell adenocarcinomas

  • Most commonly seen in young women exposed to DES in utero
  • Identical to the lesions that show up in the vagina, endometrium, and ovary
  • Can be seen in women of any age in the absence of DES exposure history
  • Three patterns
    • Tubulocystic
    • Solid
    • Papillary
  • Vacuolated cells filled with glycogen
  • Cells bearing a “hobnailâ€ configuration

Serous papillary adenocarcinoma

  • Rare
  • Similar to its namesake in the uterus and ovar
  • Shall make sure that it is not a metastatic deposit from another site in the pelvis
  • Intraperitoneal dissemination(?)

Mesonephric, signet ring cell, and intestinal-type adenocarcinomas are additional extremely rare subtypes

Adenosquamous and Glassy Cell Carcinoma

  • Mucin or glands in an admixture with clearly recognizable squamous elements
  • Poorly differentiated adenocarcinoma
  • A particularly aggressive form of poorly differentiated adenosquamous carcinoma is the glassy cell carcinoma
    • Ground-glass appearance
    • Finely granulated cytoplasm
    • Clearly defined cell walls
    • Large nuclei with prominent nucleoli
    • 1% to 2% of all cervical neoplasms
    • High mitotic rate
    • Aggressive course

Small Cell (Neuroendocrine) Carcinoma

  • Arise from amine precursor uptake and decarboxylation cells
  • <2%
  • Small monomorphous cells with a high nuclear/cytoplasmic ratio
  • Up to one half may stain for markers:
    • Serotonin
    • Adrenocorticotrophic hormone (ACTH)
    • Somatostatin
    • Gastrin
    • Early systemic mets

Other rare cervical tumors:

  • Carcinoid
  • Adenoid basal
  • Adenoid cystic
  • Sarcomas (mixed millerian, endocervical stromal)
  • Embryonal rhabdomyosarcoma
  • Melanoma

Microinvasion = Invasion to a depth of less than 3 mm is considered

Natural History and Patterns of Spread

  • Squamous columnar junction (transformation zone) of the endo-cervical canal and the portion of the cervix is the origin of SCC of Cervix
  • Frequently associated with severe cervical dysplasia & carcinoma in situ,
    • Then —> progressing to invasive carcinoma over 10 to 20 years
  • Invasive process —> breaks through the basement membrane of the epithelium & invades the cervical stroma.
  • Incidence of metastatic pelvic lymph nodes is related to the depth of invasion

Manifestation of lesions:

  • Superficial ulceration
  • Exophytic tumour in the ecto-cervix
  • Extensive infiltration of the endocervix
  • if untreated—> spread to the adjacent vaginal fornices or to the paracervical and parametrial tissues
  • Eventually direct invasion of the bladder, the rectum, or both

Risk Factors for recurrence:

  • Major Risk Factors:
    • Involvement of parametrium
    • Positive margins
    • Positive LN

Presence of these factors increase the chance of recurrence up to 50-70%

  • Minor Risk Factors:
    • Large Tumour Diameter ( >4cm )
    • Deep Stromal Invasion
    • Capillary Lymphatic Space Invasion

These factors are present in 25% of all stage IB

Presence of these factors increase the chance of recurrence from 3% —> 30%(in stage IB)

Famous Landoni serie:

  • Stage IB and IIA
  • ~ 25% parametrical involvement
  • Ant parametric > rectovaginal & post.

Factors related to paracervical extension

  • Depth of stromal invasion
  • Tumor size
  • Lymphatic invasion
  • Presence of lymph node metastasis

Sometimes Cervix Ca extends into uterine segment and endometrial cavity ( 10% ) —> decreased survival & higher distant metastases

Spread of tumour:

  • Regional
  • Hematogenous

Chance of Parametrial Node Involvement:

  • Obturator is the sentinal node in cervical ca.
    • On the lateral wall of pelvis, where the internal obturator a. and v. penetrate levator ani m.
  • then to hypogastric or internal iliac nodes
    • Obturator LN follow the uterine vein, which drains into the internal and not the external iliac
  • With increase of depth of invasion ==> chance of LN+ increases
  • Invasion to the parametrium & fixed to sidewall of the pelvis ==> External iliac nodes +
  • Vaginal invasions up to its lower third ==> inguinal nodes +
  • Rectal invasions ==> inferior mesenteric nodes being at risk.
Stage Chance of Pelvic LN+
IA 1-5%
IB 15%
II 30%
III 50%
IV 60%
Stage Chance of Para-AO LN+
IA 0%
IB 5%
IIA 10%
IIB 20%
III 30%
IV 40%
Stage 5yr LC
IA 95%
IB1(<4cm) 90%
1B2(>4cm) 75%
IIA 80%
IIB(parametrium+) 70%
IIIA(lower vagina) 60%
IIIB(pelvic wall+) 50%
IV 30%
Stage 5yr OS
IA 95%
IB1(<4cm) 85%
IB2(>4cm) 65%
IIA(upper vagina) 75%
IIB(parametrium+) 65%
IIIA 40%
IIIB 30%
IV 15%
Stage 10yr Risk of development of metastasis
I 15%
II 30%
III 40%

Surgery in Cervix Ca Treatment

Radical and Modified Radical Hysterectomy

  • Stage IB and IIA cervical carcinomas is radical (type III) hysterectomy and bilateral pelvic lymphadenectomy
    • En bloc removal of:
      • Uterus
      • Cervix
      • Proximal third of vagina
      • Paracolpium
      • Paracervical, parametrial, and paravaginal tissues to the pelvic sidewalls bilaterally
      • As much of the uterosacral ligaments as possible
      • Uterine vessels are ligated at their origin
  • Modified radical (type II) hysterectomy
    • Stage IA2 & selected small (<2 cm in diameter) stage IB lesions
    • Parametrial and paracervical tissue is removed medial to the ureter
    • the uterosacral ligaments are partially resected
    • Only the proximal 1-2 cm of the vagina
    • decision to remove the ovaries should be individualized and based on the patient’s age, menopausal status, and other factors
      • Ovarian mets: rare in LN -
Radical Hysterectomy(type III) Modified Radical hysterectomy(type II) Total Abdominal hysterrectomy(type I)extrafascial
Uterus removed removed removed
Cervix removed removed removed
Vagina Proximal 1/3 1-2cm small rim
Ovaries Usually but not necessariliy Maybe no
Parametrium to pelvic side wall medial to ureters no, just outside pubocervical fascia
Uterosacral lig. resected at postpelvic insertion partially no

Extended Radical Hysterectomy:

  • Same as class III
  • Full mobilization of ureters pass the bladder
  • removes more para cervical tissue

Acute Complications:

  • Blood loss
  • Ureterovaginal fistula (~2%)
  • Vesicovaginal fistula (<1%)
  • PE (~2%)
  • Small bowel obstruction (~2%)
  • DVT
  • Pulmunary infection
  • Pelvic cellulitis
  • UTI
  • Wound infection(30-50%)

Subacute complications:

  • Lymphocyst formation
    • May cause ureter obstruction and hydronephrosis
  • Lower extremity edema
    • Risk is related to the extent of the node dissection
  • BSO
    • will increase with RT
  • Transient decreased bladder sensation(mostly)
    • Severe and long term —> rare
  • Chronic bladder hypotonia(3-5%)

Radical Trachelectomy

  • to preserve fertility in selected small IB1(≤2 cm)
  • Keep the residual uterine segment intact, a nonabsorbable cervical cerclage is placed around the uterine isthmus at the time of the trachelectomy
  • Less blood loss
  • Less op time
  • less hospital stay
  • less bladder hypotpny
  • More dysmenorrhea
  • Irregular mensturation
  • Vaginal discharge
  • More preterm labour; complicated pregnancy
  • should have NOT extensive endocervical extension
  • Preoperative MRI

Benefits of Surgery over Radiation as Radical Treatment

  • Shorter treatment time
  • Preservation of ovarian function(gonadal function)
  • Possibly better sexual function
  • No risk of second malignancy
  • Assessment of LN status
  • Possible preservation of fertility if Trachelectomy

Adjuvant Radiotherapy for Cervical Cancer

We have two randomized trial that support our decision in the clinics :

Absolute indication for adjuvant CRT:

High risk features:

  • Microscopic involvement of the parametrium (upstaged to IIB)
  • Positive pelvic lymph nodes (upstaged to IIIB)
  • Positive margins
  • PETERS STUDY GOG 109 / Intergroup 0107 / SWOG 8797 / RTOG 9112 (1991-96)
    • 268 patients
    • Clinical stage IA2, IB, and IIA
    • Radical hysterectomy & pelvic lymphadenectomy
    • With high risk features
      • Positive pelvic lymph nodes
      • Positive margins
      • Microscopic involvement of the parametrium
    • Randomized to RT vs RT+Chemo
      • Chemotherapy : cisplatin 70 mg/m^2 + 96-hour infusion of fluorouracil 1,000 mg/m^2/d q3 weeks x 4 cycles (1st and 2nd cycles concurrent with RT)
      • RT 49.3 Gy in 29 fractions (1.7 Gy/fx) AND 45 Gy (1.5 Gy/fx) given to paraaortic area if positive common iliac LN

@4-years; 2000

  • OS 71% (RT) vs 81% (RT+CT)
    • HR=2.01
  • 4-year PFS 63% (RT) vs 80% (RT+CT)
    • HR=1.96


  • Smaller benefit for chemo+RT when only 1 LN is positive.

What we do in Ottawa:

  • 45Gy/25fr
  • 1.8Gy/fr
  • 5days/wk
  • Concurrent with chemo
    • Cisplatin

Relative Indications for adjuvant RT

  • Rotman/Sedlis Study :
    • 277 pts.
    • Stage IB, node negative, but with high estimated risk of recurrence (from GOG 49)
      1. LVI involved, Deep 1/3 stromal invasion, any size
      2. LVI involved, middle 1/3 invasion, size >= 2cm
      3. LVI involved, superficial 1/3 invasion, >= 5 cm
      4. LVI not involved, deep or middle 1/3 invasion, >= 4 cm
      5. These pts were estimated to have a 31% recurrence at 3 yrs.
    • Radical hysterectomy and lymphadenectomy
    • Randomized to +/- adjuvant pelvic XRT 50.4 Gy
  • @1999
    • Recurrences in 15% (RT) vs 28% (no RT)
    • 2-year recurrence free rate 88% (RT) vs 79%(no RT)
      • Hazard ratio=0.53
    • Grade 3/4 adverse effects were 6% (RT) vs 2.1% (no RT)
    • Distant mets 2% (RT) vs 7% (no RT)
  • @2006
    • Decreased rate of recurrence by 46%
    • Local recurrence 13.9% (RT) vs 20.7% (no RT)
    • Distant metastasis 2.9% (RT) vs 8.6% no RT)
    • Improved PFS by 42%
    • Decreased death rate by 30% (28.6% (RT) vs 19.7%(no RT))
      • Not S.S. (p=0.07)
      • RT has improved benefit for adenocarcinoma or adenosquamous histologies (8.8% vs 44% recurrence).

Side effects of Adjuvant RT

  • GU
  • Hematologic
  • GI ( most common )
  • Neurologic ( less frequent )

Landmark studies in cervical Ca

Rotman/Sedlis Study ( GOG 92 )

  • Stage IB
  • Surgical Resection
  • Node Negative and Margin Negative
  • Out of these adverse features >1 (+):
    • >1/3 stromal invasion
    • LVI +
    • >4cm

Mean duration of F/U —> 10yr

Adj RT No RT SS?
Local Recurrence 14% 20% Y
Distal Recurrence 3% 9% Y
OS 80% 70% N
Grade III Toxicity 6% 2% N

local recurrence means: vagina and/or pelvis

  • Results showed RT may be even more valuable for adenocarcinoma


  • Role of adding chemo to adj RT
  • Showed indication of adding chemo
    • Positive pelvic lymph nodes
    • Positive margins
    • Microscopic involvement of the parametrium
Adj RT Adj CRT
4yr Progression Free Survival 60% 80%
4yr OS 70% 80%
Local Failure 17% 6%
Grade IV toxicity 4% 17%

No difference in outcome based on histology (squamous vs adeno) for patients who underwent chemo-RT

Landoli Study

  • RT vs Surgery
    • Same OS
    • Toxicity
      • Surgery —> 28%
        • Bowel obstruction <== combination of Sx+RT is toxic
      • RT —> 12%
  • Stage IB1 —> 50% required post-op RT
  • Stage IB2 —> 80% required post-op RT

GOG 123

  • Arms
    • RT
    • RT+Chemo+Hysterectomy

CRT+Sx did better

Eifel/Morris; RTOG Trial

  • Pelvic RT + Chemo
  • Pelvic and para-aortic RT
  • CRt did better OS, PFS

Tips on outcome and treatment