DOI: 10.1002/ijgo.

12611

FIGO CANCER REPORT 2018

Cancer of the cervix uteri

Neerja Bhatla1,* | Daisuke Aoki2 | Daya Nand Sharma3 | Rengaswamy Sankaranarayanan4

1
Department of Obstetrics and
Gynecology, All India Institute of Medical Abstract
Sciences, New Delhi, India Since the publication of the last FIGO Cancer Report there have been giant strides in
2
Department of Obstetrics and
the global effort to reduce the burden of cervical cancer, with WHO announcing a call
Gynecology, Keio University School of
Medicine, Tokyo, Japan for elimination. In over 80 countries, including LMICs, HPV vaccination is now included
3
Department of Radiation Oncology, All India in the national program. Screening has also seen major advances with implementation
Institute of Medical Sciences, New Delhi, India
of HPV testing on a larger scale. However, these interventions will take a few years to
4
Early Detection and Prevention
Group, International Agency for Research on show their impact. Meanwhile, over half a million new cases are added each year.
Cancer, Lyon, France Recent developments in imaging and increased use of minimally invasive surgery have

*Correspondence changed the paradigm for management of these cases. The FIGO Gynecologic
Neerja Bhatla, Department of Obstetrics and Oncology Committee has revised the staging system based on these advances. This
Gynecology, All India Institute of Medical
Sciences, New Delhi, India. chapter discusses the management of cervical cancer based on the stage of disease,
Email: nbhatla@aiims.ac.in including attention to palliation and quality of life issues.

KEYWORDS
Cervix; FIGO Cancer Report; Gynecologic cancer; HPV vaccination; Radiation; Screening;
Staging; Surgery

1 | INTRODUCTION the junction with the uterus to the external os which opens into the
vagina and is lined by columnar epithelium. Almost all cases of cervi-
Globally, cervical cancer continues to be one of the most common cal carcinoma originate in the transformation zone from the ecto-­ or
cancers among females, being the fourth most common after breast, endocervical mucosa. The transformation zone is the area of the cer-
colorectal, and lung cancer. In 2012, it was estimated that there were vix between the old and new squamocolumnar junction.
approximately 527 600 new cases of cervical cancer with 265 700 The fact that the cervix can be easily visualized and sampled, and
1
deaths annually. In low-­ and middle-­income countries (LMICs), it is can be treated by freezing and burning with little or no anesthesia, has
more common, being the second most common cancer in incidence contributed to the understanding of the natural history of this can-
among women and the third most common in terms of mortality. cer along with the development of simple outpatient techniques of
The majority of new cases and deaths (approximately 85% and 90%, screening and prevention.
respectively) occur in low-­resource regions or among people from
socioeconomically weaker sections of society.
3 | EARLY DETECTION AND
PREVENTION OF CERVICAL CANCER
2 | ANATOMICAL CONSIDERATIONS
It is now recognized that cervical cancer is a rare long-­term out-
The cervix, which is the lowermost part of the uterus, is a cylindrical-­ come of persistent infection of the lower genital tract by one of
shaped structure composed of stroma and epithelium. The intravaginal about 15 high-­risk HPV types, which is termed the “necessary”
part, the ectocervix, projects into the vagina and is lined by squamous cause of cervical cancer. Of the estimated 530 000 new cervi-
epithelium. The endocervical canal extends from the internal os at cal cancer cases annually, HPV 16 and HPV 18 account for 71%

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium,
provided the original work is properly cited.
© 2018 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and
Obstetrics

22  |  wileyonlinelibrary.com/journal/ijgo Int J Gynecol Obstet 2018; 143 (Suppl. 2): 22–36
Bhatla ET AL. |
      23

of cases; while HPV types 31, 33, 45, 52, and 58 account for for immunocompromised patients irrespective of age, the recom-
2,3
another 19% of cervical cancer cases It is well documented that mendation is for three doses (0.5 mL at 0, 1, 6 months).5 WHO has
nearly 90% of incident HPV infections are not detectable within reviewed the latest data and concluded that there is no safety con-
a period of 2 years from the acquisition of infection and persist cern regarding HPV vaccines.5
only in a small proportion. It is debatable whether the virus is There is evidence for the effectiveness of vaccination at the
completely cleared or whether it remains latent in basal cells with population level in terms of reduced prevalence of high-­risk HPV
the potential for reactivation in some cases. Persistent HPV infec- types, and reduction in anogenital warts and high-­grade cervical
tion denotes the presence of the same type-­specific HPV DNA on abnormalities caused by the vaccine types among young women;
repeated sampling after 6–12 months. Only one-­tenth of all infec- there is some evidence of cross-­protection from nonvaccine types
tions become persistent, and these women could develop cervical also. There is no evidence of type replacement6–8 Recent observa-
precancerous lesions. tional studies have reported evidence for effectiveness in prevent-
This knowledge has resulted in the development of new initia- ing high-­risk HPV infections following a single dose and further
tives for prevention and early detection. The two major approaches long-­term follow-­up will clarify the role of one dose in preventing
for control of cervical cancer involve: (1) prevention of invasive can- cervical neoplasia.9,10
cer by HPV vaccination; and (2) screening for precancerous lesions.
Prevention and elimination are potential possibilities but the tragedy is
3.2 | Secondary prevention of cervical cancer by
that it is not yet prevented on a large scale in many LMICs due to lack
early detection and treatment of precancerous lesions
of efficient and effective intervention programs. WHO has recently
given a call to action for elimination of cervical cancer. This is foresee- Even with the advent of effective vaccines, screening will remain a
able if implemented in earnest in successful public health programs priority for cervical cancer prevention for several decades. Cervical
achieving high coverage. cancer screening has been successful in preventing cancer by
detection and treatment of precursor lesions, namely, high-­grade
cervical intraepithelial neoplasia (CIN 2 and 3) and adenocarcinoma
3.1 | Primary prevention of cervical cancer with HPV
in-­situ (AIS).
vaccination
Several cervical screening strategies have been found to be
The fact that more than 80% of women followed over time will effective in varied settings. The tests used widely include conven-
acquire at least one high-­risk HPV infection suggests the ubiquitous tional cytology (Pap smear), in recent years liquid-­based cytology
nature of the HPV infection and reflects the ease of transmission. The and HPV testing, and, in LMICs, visual inspection with acetic acid
estimated cross-­sectional HPV prevalence worldwide among healthy (VIA).11 While the Pap smear is still the major workhorse of screen-
women is around 11.7%, with the highest in Sub-­Saharan Africa at ing and is associated with substantial declines in cervical cancer risk
around 24%, and country-­specific prevalence ranging between 2% in high-­income countries, it is a challenging and resource intensive
and 42% globally4 Age-­specific cross-­sectional HPV prevalence peaks technology that is not feasible in low-­resource settings11 where poor
at 25% in women aged less than 25 years, which suggests that the organization, coverage, and lack of quality assurance result in sub-
infection is predominantly transmitted through the sexual route fol- optimal outcomes. In the context of declining HPV infections after
lowing sexual debut. Thus, prophylactic HPV vaccination as a preven- the introduction of HPV vaccines a decade ago, many healthcare sys-
tive strategy should target women before initiation of sexual activity, tems are considering switching to primary HPV screening, which has
focusing on girls aged 10–14 years. higher sensitivity and negative predictive value, and allows extended
Three prophylactic HPV vaccines are currently available in many screening intervals or even a single lifetime screening in low-­
countries for use in females and males from the age of 9 years for resource settings.12,13 VIA involves detection of acetowhite lesions
the prevention of premalignant lesions and cancers affecting the on the cervix 1 minute after application of 3%–5% freshly prepared
cervix, vulva, vagina, and anus caused by high-­risk HPV types: a acetic acid. In view of its feasibility, VIA screening has been widely
bivalent vaccine targeting HPV16 and HPV18; a quadrivalent vac- implemented in opportunistic settings in many low-­income countries
cine targeting HPV6 and HPV11 in addition to HPV16 and HPV18; in Sub-­Saharan Africa. A single-­visit approach (SVA) for screening
and a nonavalent vaccine targeting HPV types 31, 33, 45, 52, and with rapid diagnosis and treatment improves coverage, eliminates
58 in addition to HPV 6, 11, 16, and 18. The last two vaccines tar- follow-­up visits, and makes screening more time and cost-­efficient in
get anogenital warts caused by HPV 6 and 11 in addition to the low-­resource settings.14–16 VIA screening is particularly suitable for
above-­mentioned malignant and premalignant lesions. All the vac- SVA and WHO has issued guidelines for implementing SVA in public
cines are recombinant vaccines composed of virus-­like particles health settings.
(VLPs) and are not infectious since they do not contain viral DNA. A single screening modality will never be universally applicable,
For girls and boys aged 9–14 years, a two-­dose schedule (0.5 mL at but it is possible to adapt cost-­effective means of cervical cancer
0 and 5–13 months) is recommended. If the second vaccine dose screening to each country. The screening strategy chosen must be
is administered earlier than 5 months after the first dose, a third feasible, simple, safe, accurate, acceptable, and easily accessible to
dose is recommended. For those aged 15 years and above, and highest-­risk women. A judicious combination of HPV vaccination and
24       | Bhatla ET AL.

screening has enormous potential to eliminate cervical cancer in the is shown in Table 1 (presented at the FIGO XXII World Congress of
foreseeable future. Gynecology and Obstetrics17).

4.1 | Diagnosis and evaluation of cervical cancer

4 |  FIGO STAGING
4.1.1 | Microinvasive disease
Cervical cancer spreads by direct extension into the parametrium,
vagina, uterus and adjacent organs, i.e., bladder and rectum. It also Diagnosis of Stage IA1 and IA2 is made on microscopic examination
spreads along the lymphatic channels to the regional lymph nodes, of a LEEP (loop electrosurgical excision procedure) or cone biopsy
namely, obturator, external iliac and internal iliac, and thence to the specimen, which includes the entire lesion. It can also be made on
common iliac and para-­aortic nodes. Distant metastasis to lungs, a trachelectomy or hysterectomy specimen. The depth of invasion
liver, and skeleton by the hematogenous route is a late phenomenon. should not be greater than 3 mm or 5 mm, respectively, from the base
Until now, the FIGO staging was based mainly on clinical exam- of the epithelium, either squamous or glandular, from which it origi-
ination with the addition of certain procedures that were allowed by nates. The horizontal dimension is no longer considered in the 2018
FIGO to change the staging. In 2018, this has been revised by the FIGO revision as it is subject to many artefactual errors. Note must be made
Gynecologic Oncology Committee to allow imaging and pathologi- of lymphovascular space involvement, which does not alter the stage,
cal findings, where available, to assign the stage. The revised staging but may affect the treatment plan. Extension to the uterine corpus is

T A B L E   1   FIGO staging of cancer of the cervix uteri (2018).

Stage Description

I The carcinoma is strictly confined to the cervix (extension to the uterine corpus should be disregarded)
IA Invasive carcinoma that can be diagnosed only by microscopy, with maximum depth of invasion <5 mma
IA1 Measured stromal invasion <3 mm in depth
IA2 Measured stromal invasion ≥3 mm and <5 mm in depth
IB Invasive carcinoma with measured deepest invasion ≥5 mm (greater than Stage IA), lesion limited to the cervix uterib
IB1 Invasive carcinoma ≥5 mm depth of stromal invasion, and <2 cm in greatest dimension
IB2 Invasive carcinoma ≥2 cm and <4 cm in greatest dimension
IB3 Invasive carcinoma ≥4 cm in greatest dimension
II The carcinoma invades beyond the uterus, but has not extended onto the lower third of the vagina or to the pelvic wall
IIA Involvement limited to the upper two-­thirds of the vagina without parametrial involvement
IIA1 Invasive carcinoma <4 cm in greatest dimension
IIA2 Invasive carcinoma ≥4 cm in greatest dimension
IIB With parametrial involvement but not up to the pelvic wall
III The carcinoma involves the lower third of the vagina and/or extends to the pelvic wall and/or causes hydronephrosis or nonfunction-
ing kidney and/or involves pelvic and/or para-­aortic lymph nodesc
IIIA The carcinoma involves the lower third of the vagina, with no extension to the pelvic wall
IIIB Extension to the pelvic wall and/or hydronephrosis or nonfunctioning kidney (unless known to be due to another cause)
IIIC Involvement of pelvic and/or para-­aortic lymph nodes, irrespective of tumor size and extent (with r and p notations)c
IIIC1 Pelvic lymph node metastasis only
IIIC2 Para-­aortic lymph node metastasis
IV The carcinoma has extended beyond the true pelvis or has involved (biopsy proven) the mucosa of the bladder or rectum. (A bullous
edema, as such, does not permit a case to be allotted to Stage IV)
IVA Spread to adjacent pelvic organs
IVB Spread to distant organs

When in doubt, the lower staging should be assigned.

a
Imaging and pathology can be used, where available, to supplement clinical findings with respect to tumor size and extent, in all stages.
b
The involvement of vascular/lymphatic spaces does not change the staging. The lateral extent of the lesion is no longer considered.
c
Adding notation of r (imaging) and p (pathology) to indicate the findings that are used to allocate the case to Stage IIIC. Example: If imaging indicates pelvic
lymph node metastasis, the stage allocation would be Stage IIIC1r, and if confirmed by pathologic findings, it would be Stage IIIC1p. The type of imaging
modality or pathology technique used should always be documented.
Source: Bhatla et al.17
Bhatla ET AL. |
      25

also disregarded for staging purposes as it does not in itself alter either FIGO no longer mandates any biochemical investigations or inves-
the prognosis or management. The margins should be reported to be tigative procedures; however, in patients with frank invasive carci-
negative for disease. If the margins of the cone biopsy are positive for noma, a chest X-­ray, and assessment of hydronephrosis (with renal
invasive cancer, the patient is allocated to Stage IB1.18 ultrasound, intravenous pyelography, CT, or MRI) should be done. The
Clinically visible lesions, and those with larger dimensions, are allo- bladder and rectum are evaluated by cystoscopy and sigmoidoscopy
cated to Stage IB, subdivided in the latest staging as IB1, IB2, and IB3 only if the patient is clinically symptomatic. Cystoscopy is also recom-
based on the maximum diameter of the lesion. mended in cases of a barrel-­shaped endocervical growth and in cases
where the growth has extended to the anterior vaginal wall. Suspected
bladder or rectal involvement should be confirmed by biopsy and his-
4.1.2 | Invasive disease
tologic evidence. Bullous edema alone does not warrant a case to be
In the case of visible lesions, a punch biopsy may generally suffice, but allocated to Stage IV.
if not satisfactory a small loop biopsy or cone may be required. Clinical
assessment is the first step in allocation of staging.
4.2 | Pathologic staging
Imaging evaluation may now be used in addition to clinical exam-
ination where resources permit. The revised staging permits the use In case a surgical specimen is available or where image-­guided fine-­
of any of the imaging modalities according to available resources, i.e. needle aspiration cytology has been done, the pathologic report is an
ultrasound, CT, MRI, positron emission tomography (PET), to provide important source for accurate assessment of the extent of disease. As
information on tumor size, nodal status, and local or systemic spread. in the case of imaging, the pathologic methods should also be recorded
The accuracy of various methods depends on the skill of the operator. for future evaluation. The stage is to be allocated after all imaging and
MRI is the best method of radiologic assessment of primary tumors pathology reports are available. It cannot be altered later, for example
greater than 10 mm.19–23 However, ultrasound has also been shown to at recurrence. The 2018 FIGO staging includes involvement of nodes
24
have good diagnostic accuracy in expert hands. The modality used in and thus enables both the selection and evaluation of therapy, as well
assigning staging should be noted for future evaluation. Imaging has the as estimation of the prognosis and calculation of end results.
advantage of the ability to identify additional prognostic factors, which The FIGO and TNM classifications have been virtually identical
can guide the choice of treatment modality. The goal is to identify the in describing the anatomical extent of disease. The TNM nomencla-
most appropriate method and to avoid dual therapy with surgery and ture has hitherto been used for the purpose of documenting nodal
radiation as this has the potential to greatly augment morbidity. and metastatic disease status.38 The revised FIGO classification is now
For detection of nodal metastasis greater than 10 mm, PET-­CT is more closely aligned with the TNM classification in this respect as well.
more accurate than CT and MRI, with false-­negative results in 4%–15% In some cases, hysterectomy is performed in the presence of
20,25–28
of cases. In areas with a high prevalence of tuberculosis and unsuspected invasive cervical carcinoma that is diagnosed later on
inflammation, especially HIV-­endemic areas, large lymph nodes are not histopathology. Such cases cannot be clinically staged or included in
necessarily metastatic. The clinician may make the decision on imaging therapeutic statistics for obvious reasons, but reporting them sepa-
or, when possible, can use fine needle aspiration or biopsy to establish rately is desirable.
27,29,30
or exclude metastases. This is especially true in advanced stages,
where surgical assessment of para-­aortic lymph nodes may be used
4.3 | Histopathology
to tailor treatment according to extent of disease.31–33 They can be
accessed by minimally invasive surgery or laparotomy. Surgical exclu- It is essential that all cancers must be confirmed by microscopic exam-
sion of para-­aortic lymph node involvement has been reported to have ination. Cases are classified as carcinomas of the cervix if the primary
a better prognosis than radiographic exclusion alone.34 growth is in the cervix. All histologic types must be included. The his-
A review of 22 articles that assessed the safety and impact of pre- topathologic types, as described in the World Health Organization’s
treatment para-­aortic lymph node surgical staging (PALNS) found that 2014 Tumours of the Female Reproductive Organs39 are:
18% (range, 8%–42%) of patients with Stage IB–IVA cervical cancer
had para-­aortic lymph node metastases.35 The mean complication rate 1. Squamous cell carcinoma (keratinizing; non-keratinizing; papillary, bas­
of PALNS was 9% (range 4%–24%), with lymphocyst formation being aloid, warty, verrucous, squamotransitional, lymphoepithelioma-like)
the most common. In another study, up to 35% of clinically assessed 2. Adenocarcinoma (endocervical; mucinous, villoglandular, endometrioid)
Stage IIB and 20% of Stage III tumors were reported to have posi- 3. Clear cell adenocarcinoma
tive para-­aortic nodes.36 In the revised staging, all these cases will be 4. Serous carcinoma
assigned to Stage IIIC as lymph node involvement confers a worse 5. Adenosquamous carcinoma
prognosis.37 If only pelvic nodes are positive, it is Stage IIIC1; if para-­ 6. Glassy cell carcinoma
aortic nodes are also involved it is Stage IIIC2. A further notation must 7. Adenoid cystic carcinoma
be added to indicate whether this allocation is based on only imaging 8. Adenoid basal carcinoma
assessment (r) or whether pathological confirmation is available (p). In 9. Small cell carcinoma
due course, the data can be analyzed and reported accordingly. 10. Undifferentiated carcinoma
 |
26       Bhatla ET AL.

Grading by any of several methods is encouraged, but it is not a basis be recommended.40 Any route can be chosen, i.e. abdominal,
for modifying the stage groupings in cervical carcinoma. Histopathologic vaginal, or laparoscopic. When LVSI is evident, pelvic lymphad-
grades are as follows: enectomy should be considered, along with modified radical hys-
terectomy.41,42 If fertility is desired, cervical conization with close
1. GX: Grade cannot be assessed follow-­up will be adequate.
2. G1: Well differentiated
3. G2: Moderately differentiated 5.1.1.2 | Stage IA2
4. G3: Poorly or undifferentiated Since there is a small risk of lymph node metastases in these cases,42–45
pelvic lymphadenectomy is performed in addition to type B radical
hysterectomy or more radical surgery.46,47 In low risk cases, simple
5 |  MANAGEMENT OF CERVICAL CANCER hysterectomy or trachelectomy, with either pelvic lymphadenec-
tomy or sentinel lymph node assessment, may be adequate surgi-
Management of cervical cancer is primarily by surgery or radiation cal treatment.48,49 When the patient desires fertility, she may be
therapy, with chemotherapy a valuable adjunct. offered a choice of the following: (1) cervical conization with lapa-
roscopic (or extraperitoneal) pelvic lymphadenectomy; or (2) radi-
cal abdominal, vaginal, or laparoscopic trachelectomy with pelvic
5.1 | Surgical management
lymphadenectomy.50,51
Surgery is suitable for early stages, where cervical conization, total
simple hysterectomy, or radical hysterectomy may be selected accord- 5.1.1.3 | Post-­treatment follow-­up
ing to the stage of disease and extent of spread of cervical cancer. Follow-­up with 3-­monthly Pap smears for 2 years, then 6-­monthly
Table 2 shows the types of radical hysterectomy. In Stage IVA, there for the next 3 years is recommended after treatment of microinvasive
is a place for pelvic exenteration in selected cases. carcinoma. With normal follow-­up at 5 years, the patient can return to
the routine screening schedule according to the national guidelines.40

5.1.1 | Microinvasive cervical carcinoma: FIGO

Stage IA 5.1.2 | Invasive cervical carcinoma: FIGO Stage IB1,
IB2, IIA1
5.1.1.1 | Stage IA1
The treatment is completed with cervical conization unless there Surgical treatment is the preferred modality for the treatment of
is lymphovascular space invasion (LVSI) or tumor cells are present Stage IB1, IB2, and IIA1 lesions. It would usually consist of type C radi-
at the surgical margin. In women who have completed childbear- cal hysterectomy with pelvic lymphadenectomy.52–54 The routes of
ing or elderly women, total extrafascial hysterectomy may also surgery may be open or minimally invasive, i.e. laparoscopic or robotic.

T A B L E   2   Types of radical hysterectomy.

Simple extrafascial hysterectomy Modified radical hysterectomy Radical hysterectomy

Piver and Rutledge Type I Type II Type III

Classification
Querleu and Morrow Type A Type B Type C
classification
Indication Stage IA1 Type IA1 with LVSI. IA2 Stage IB1 and IB2, selected
Stage IIA
Uterus and cervix Removed Removed Removed
Ovaries Optional removal Optional removal Optional removal
Vaginal margin None 1–2 cm Upper one-­quarter to one-­third
Ureters Not mobilized Tunnel through broad ligament Tunnel through broad ligament
Cardinal ligaments Divided at uterine and cervical border Divided where ureter transits broad Divided at pelvic side wall
ligaments
Uterosacral ligaments Divided at cervical border Partially removed Divided near sacral origin
Urinary bladder Mobilized to base of bladder Mobilized to upper vagina Mobilized to middle vagina
Rectum Not mobilized Mobilized below cervix Mobilized below cervix
Surgical approach Laparotomy or laparoscopy or Laparotomy or laparoscopy or Laparotomy or laparoscopy
robotic surgery robotic surgery or robotic surgery
Bhatla ET AL. |
      27

practice. It may have some role in early stage cervical cancer, i.e. FIGO
5.1.2.1 | FIGO Stage IB1
Stage IA, IB1, and IB2.58–60 Dual labeling using blue dye and radiocol-
FIGO Stage IB1 is considered as low risk with the following criteria:
loid increases the accuracy of sentinel lymph nodes can be performed
largest tumor diameter less than 2 cm, cervical stromal invasion less
with.61,62 Indocyanine green dye with near infrared technique has
than 50%, and no suspicious lymph nodes on imaging. The standard
been used in robotic surgery and laparoscopy. Pelvic lymphadenec-
management is a type C radical hysterectomy, but modified radical
tomy needs to be considered if LVSI is present.
hysterectomy may be considered in these cases. Pelvic lymphadenec-
The route of surgery may be laparotomy or minimally invasive
tomy should always be included on account of the high frequency of
surgery, either laparoscopic or robotic. The LACC trial (Laparoscopic
lymph node involvement.46,47
Approach to Cervical Cancer) compared the overall survival with open
A pelvic nerve-­sparing surgical procedure is recommended in
surgery versus laparoscopy or robotic surgery in early stage cervical
patients undergoing radical hysterectomy, in so far as radical curabil-
cancer and showed a decreased overall survival (3 of 312 vs 19 of 319,
ity is maintained, as intrapelvic injuries to the autonomic nerves (i.e.
HR 6.00, 95% CI, 1.48–20.3, P=0.004). Disease-­free survival events
hypogastric nerve, splanchnic nerve, and pelvic plexus) often lead to
showed a three-­fold increase in the minimally invasive surgery group
impairment of urination, defecation, and sexual function, and conse-
(7 of 312 vs 27 of 319, HR 3.74, 95% CI, 1.63–8.58; P=0.002). Rates of
quent deterioration of the postoperative quality of life (QOL).55,56
intraoperative complications did not differ by treatment received (11%
In young women desiring fertility sparing, a radical trachelectomy
in both). They concluded that hysterectomy by a minimally invasive
may be performed, indicated for Stage IA2–IB1 tumors measuring
route was associated with higher rates of recurrence than the open
less than or equal to 2 cm in largest diameter.57 The cervix along with
approach in early-­stage cervical cancer patients.63 Further studies may
the parametrium is removed followed by anastomosis of the uterus
be required to further confirm these findings.
with the vaginal end. Trachelectomy can be done by open abdominal,
vaginal, or by minimally invasive routes. When a vaginal approach is
planned, the pelvic nodes are first removed laparoscopically and sent 5.1.3 | FIGO Stage IB3 and IIA2
for frozen section to confirm node negativity and then proceed with
In Stage IB3 and IIA2, the tumors are larger and the likelihood of
the radical trachelectomy vaginally. Alternatively, the nodes may be
high risk factors such as positive lymph nodes, positive parametria,
first be assessed by conventional pathologic methods and the radical
or positive surgical margins that increase the risk of recurrence and
trachelectomy done as a second surgery after 1 week.
require adjuvant radiation after surgery are high. Other risk factors
that increase the risk of pelvic recurrence even when nodes are not
5.1.2.2 | FIGO Stage IB2 and IIA1 involved include: largest tumor diameter greater than 4 cm, LVSI, and
In FIGO Stage IB2 and IIA1 cervical cancer, surgery or radiotherapy invasion of outer one-­third of the cervical stroma.64,65 In such cases,
can be chosen as the primary treatment depending on other patient adjuvant whole pelvic irradiation reduces the local failure rate and
factors and local resources, as both have similar outcomes. The advan- improves progression-­free survival compared with patients treated
tages of surgical treatment are: (1) that it is feasible to determine the with surgery alone.65 However, the dual modality treatment increases
postoperative stage precisely on the basis of histopathologic findings, the risk of major morbidity to the patient.
thereby enabling individualization of postoperative treatment for The treatment modality must, therefore, be determined based on
each patient; (2) that it is possible to treat cancers that are likely to the availability of resources and tumor-­ and patient-­related factors.
be resistant to radiotherapy; and (3) that it is possible to conserve Concurrent platinum-­based chemoradiation (CCRT) is the preferred
ovarian function. Intraoperative transpositioning of the ovaries high treatment option for Stage IB3 to IIA2 lesions. It has been demon-
in the paracolic gutters away from the radiation field, in case it should strated that the prognosis is more favorable with CCRT, rather than
be required subsequently, is also feasible. The preservation of ovar- radiotherapy alone, as postoperative adjuvant therapy as well in terms
ian and sexual function makes surgery the preferred mode in younger of overall survival, progression-­free survival, and local and distant
women. Type C radical hysterectomy represents a basic procedure for recurrences.52,66,67
the treatment of cervical cancer, consisting of removal of the uterus, In areas where radiotherapy facilities are scarce, neoadjuvant che-
parametrium, upper vagina, and a part of the paracolpium, along with motherapy (NACT) has been used with the goal of: (1) down-­staging of
pelvic lymphadenectomy. As for the adjacent connective tissues, the the tumor to improve the radical curability and safety of surgery; and
anterior vesicouterine ligament (anterior and posterior leaf), lateral (2) inhibition of micrometastasis and distant metastasis. There is no
cardinal ligaments, and posterior sacrouterine and rectovaginal liga- unanimity of view as to whether it improves prognosis compared with
ments are cut from the uterus at sufficient distances from their attach- the standard treatment.68,69
ments to the uterus. Lymphadenectomy constitutes one of the bases The extent of surgery after NACT remains the same, i.e. radical
of this surgical procedure, and the extent of regional lymph node exci- hysterectomy and pelvic lymphadenectomy. The greater difficulty is
sion includes the parametrial nodes, obturator nodes, external, inter- in determining the indications for adjuvant therapy which are often
nal, and common iliac nodes. kept the same as those after primary surgery.66,67 However, it must be
The role of sentinel lymph node (SLN) mapping in cervical cancer remembered that NACT may give a false sense of security by masking
is still experimental and needs more evidence to include into routine the pathologic findings and thus affecting evaluation of indications
 |
28       Bhatla ET AL.

for adjuvant radiotherapy/CCRT. NACT surgery is best reserved for arm (28% vs 12%), likely due to contributions from both treatment
research settings or those areas where radiotherapy is unavailable. modalities. An update of the same trial with 20-­year follow-­up data
This is especially true in patients with very large tumors or adenocarci- has shown marginally better results with radiotherapy compared with
noma, which have lower response rates.70 surgery (77% vs 72%, P=0.280).80 Multivariate analysis confirmed
that risk factors for survival are histopathologic type (P=0.020), tumor
diameter (P=0.008), and lymph node status (P<0.001).80
5.1.4 | FIGO Stage IVA or recurrence
Rarely, patients with Stage IVA disease may have only central disease
5.2.2 | Adjuvant radiotherapy
without involvement to the pelvic sidewall or distant spread. Such
cases, or in case of such a recurrence, pelvic exenteration can be con- Following radical hysterectomy, PORT with or without chemotherapy
sidered but usually has a poor prognosis.71–75 is indicated for patients with adverse pathologic factors such as posi-
tive pelvic nodes, parametrial infiltration, positive margins, deep stro-
mal invasion, etc. According to various prognostic factors, patients
5.2 | Radiation management
may be categorized into high-­risk, intermediate-­risk, or low-­risk dis-
In LMICs, the majority of patients present with locally advanced dis- ease. High-­risk disease includes patients with either positive surgical
ease,76 where surgery plays a limited role, and radiotherapy has an margins or lymph node metastases or parametrial spread, and such
important role. Over the last two decades, development of sophisti- patients should be offered PORT with chemotherapy since the GOG
cated planning and delivery techniques, and introduction of computer 109 trial has shown overall survival advantage.67 Intermediate-­risk
technology and imaging have galvanized the practice of radiotherapy, patients with any two of three factors (tumor size more than 4 cm,
resulting in improved clinical outcome and reduced toxicity.77,78 lymphovascular invasion, deep stromal invasion) require PORT64,81
Apart from its curative role, radiotherapy can also be used as adju- and no chemotherapy should be offered to these patients. All other
vant therapy for operated patients to prevent locoregional recurrence, patients following radical hysterectomy are termed as low-­risk disease
although the role of “dual modality” is discouraged, and as palliative patients and do not need any adjuvant therapy.
therapy for alleviating distressing symptoms in patients with advanced Tumor size of more than 4 cm is a well-­known risk factor. Since
incurable disease. 2009 it was incorporated in the FIGO staging system as Stage IB2
and now in the 2018 staging revision as Stage IB3. Recent literature,
especially with the advent of more and more fertility sparing surgery
5.2.1 | Radiation therapy for early stage disease
suggests tumor size more than 2 cm is a risk factor.82–91. In a recent
(FIGO Stage IA, IB1, IB2, and IIA1)
study, Gemer et al.91 evaluated various clinical and pathologic risk fac-
Although surgery is preferred for early stage disease, in cases with tors that may reduce the rate of multimodality treatment of early cer-
contraindications for surgery or anesthesia, radiotherapy provides vical cancer. The authors observed that 89% of patients with tumors
equally good results in terms of local control and survival. Treatment 2 cm or greater and LVSI received radiotherapy and 76% of patients
decision should be made on the basis of clinical, anatomic, and social with tumors 2 cm or greater and depth of invasion greater than 10 mm
factors. Patients with microinvasive disease have been treated by received radiotherapy. They suggest that in patients with early cervical
intracavitary radiation therapy (ICRT) alone with good results if sur- cancer, evaluation of tumor size and LVSI should be undertaken before
gery is contraindicated owing to medical problems. Selected patients performing radical hysterectomy to tailor treatment and to reduce the
with very small Stage IB1 disease (less than 1 cm) may also be treated rate of employing both radical hysterectomy and chemoradiation. In
with ICRT alone, particularly if there are relative contraindications to view of the above-­mentioned emerging literature, tumor size of more
external beam radiation therapy (EBRT).79 A dose of 60–65 Gy equiv- than 2 cm has been taken as the first cut-­off in the 2018 revision of
alent is usually prescribed to Point A. Combination of EBRT and ICRT the FIGO staging system.
is also an option for such patients. PORT consists of whole pelvic EBRT to cover the tumor bed and
Both surgery and radiotherapy remain viable options for early draining lymph node areas. A dose of 45–50 Gy is usually prescribed.
stage disease. Definitive radiotherapy or concurrent chemoradiation Intensity modulated radiation therapy (IMRT), an advanced and refined
(CCRT) is preferred in patients likely to require postoperative radio- technique of irradiation, has been explored in the postoperative set-
therapy to avoid compounding treatment-­related morbidity. There is ting to reduce the toxicity.92,93 A recent Phase III trial93 revealed
a single randomized trial comparing surgery and radiotherapy52 but improved patient reported outcomes at week five with IMRT, with no
none comparing surgery to CCRT, which is the current standard in difference after treatment completion. Therefore, postoperative pelvic
patients treated by definitive radiotherapy. Landoni et al.52 random- IMRT remains investigational until further data are published.
ized patients with IB or IIA cervical cancer to surgery with or with- The role of vaginal brachytherapy boost following EBRT is not
out postoperative radiotherapy (PORT) versus definitive radiotherapy clear; however, it may be considered for patients with close or pos-
alone. PORT was administered to 64% of patients in the surgery arm. itive margins, large or deeply invasive tumors, parametrial or vaginal
The two treatment arms resulted in similar overall survival (83%) and involvement, or extensive LVSI.94 Vaginal cuff brachytherapy is usually
disease-­free survival (74%); severe morbidity was higher in the surgery delivered by ovoids or cylinders to the upper one-­third of the residual
Bhatla ET AL. |
      29

vagina and should include two weekly fractions of high dose rate T A B L E   3   Field design for the pelvic radiotherapy.
(HDR) brachytherapy of 6 Gy each prescribed to 5 mm from the vagi-
Field Border Landmark
nal cylinder/ovoid surface.
AP-­PA Superior L4–5 vertebral interspace
fields Inferior 2 cm below the obturator foramen or 3 cm
5.2.3 | Radiation therapy for FIGO Stage inferior to distal disease, whichever is lower
IB3 and IIA2 Lateral 1.5–2 cm lateral to the pelvic brim

Although feasible, surgery as initial treatment is not encouraged for Lateral Superior Same as AP-­PA field
fields Inferior Same as AP-­PA field
patients with Stage IB3 and IIA2 disease since 80% of them require
52 Anterior Anterior to the pubic symphysis
PORT or CCRT. It is well known that the addition of adjuvant radi-
otherapy to surgery increases morbidity and thus compromises the Posterior 0.5 cm posterior to the anterior border of the
quality of life.95,96 Additionally, combined modality treatment will S2/3 vertebral junction. May include the
entire sacrum to cover the disease extent
unnecessarily overburden the surgical and radiation facilities, which
are already inadequate in low-­resource countries. Therefore, CCRT
is the standard of care for Stage IB3 and IIA2 disease. CCRT includes
higher energy beams resulting in more homogeneous dose delivery to
external radiation and intracavitary brachytherapy.65,66
deep tissues with relative sparing of superficial tissues. Recently, con-
formal radiotherapy techniques like 3D-­CRT and IMRT are increasingly
5.2.4 | Radiation therapy for FIGO Stage IIB–IVA being used with encouraging results in terms of reduced toxicity owing
to relative sparing of normal tissues (Fig. 1).
Concurrent chemoradiation is considered the standard treatment for
Although EBRT plays an important role in the treatment of cervical
patients with locally advanced cervical cancer (LACC). The chemo-
cancer, ICRT is also an extremely important component of curative
therapy regimen is intravenous administration of weekly cisplatin dur-
treatment of cervical cancer since it delivers a high central dose to the
ing the course of EBRT.
Based on the results of five large randomized trials67,97–100 that
tested addition of chemotherapy to pelvic radiation, the National (A)
Cancer Centre issued an alert in 1999 that all patients with locally
advanced cervical cancer should receive CCRT.67 These stud-
ies67,97–100 demonstrated that CCRT had a significant survival
advantage of 10%–15% at 5 years after treatment compared with
radiotherapy alone. A subsequent meta-­analysis showed maximum
benefit of chemoradiation of 6% in Stage IB2 (now termed IB3) to
Stage IIB and only 3% benefit in Stage IIIB patients.101 Concurrent
chemoradiotherapy also reduced local and distant recurrence, and
improved disease-­free survival.
A once-­weekly infusion of cisplatin (40 mg/m2 weekly with appro-
priate hydration) for 5–6 cycles during external beam therapy is a
commonly used concurrent chemotherapy regimen.99,102 For patients
(B)
who are unable to receive platinum chemotherapy, 5–fluorouracil-­
based regimens are an acceptable alternative.102–104 Data on the
toxicity associated with concurrent chemotherapy and extended field
irradiation are limited.105,106
Additional adjuvant chemotherapy after concurrent chemoradio-
therapy is being explored in an international randomized controlled
trial (OUTBACK Trial).107
The combination of EBRT and ICRT maximizes the likelihood of
locoregional control while minimizing the risk of treatment compli-
cations. The primary goal of EBRT is to sterilize local disease and to
shrink the tumor to facilitate subsequent ICRT. Standard EBRT should
deliver a dose of 45–50 Gy to the whole pelvis by 2 or 4 field box
technique (Table 3) encompassing uterus, cervix, adnexal structures,
F I G U R E   1   CT scan images showing radiotherapy planning
parametria, and pelvic lymph nodes. Although EBRT is commonly
using: (A) conventional four-­field box technique; and (B) intensity
delivered by a Cobalt-­60 teletherapy machine in several low-­resource modulated radiation therapy (IMRT) planning. Normal tissues such as
countries, linear accelerators are preferred nowadays as they provide bladder and bowel are relatively spared in IMRT planning.
 |
30       Bhatla ET AL.

primary tumor and reduced doses to adjacent normal organs owing to (A)
sharp dose fall-­off.
Standard ICRT is usually performed using a tandem and two
ovoids, or a tandem and ring. Any of the dose rate systems, namely
low-­dose-­rate (LDR), high-­dose-­rate (HDR), or pulsed-­dose-­rate (PDR)
may be practiced as all three yield comparable survival rates.108 The
dose is usually prescribed to Point A or to high-­risk clinical target vol-
ume (HRCTV) if image-­based planning is used.
With an LDR system, a dose of 30–40 Gy is prescribed in one or
two sessions. With HDR, various dose fraction schedules are used,
employing a dose of 5.5–8 Gy by 3–5 weekly fractions. Owing to
resource constraints and long travelling distances in low-­resource
countries, delivering three instead of five fractions is often more
realistic and allows for treatment of a higher number of patients. The
total combined dose with EBRT and ICRT should be in the range of
80–90 Gy. Though PDR is rarely used, the overall treatment time and (B)
dose in PDR remains almost the same as in LDR except that the treat-
ment is given in multiple hourly pulses each lasting for a few minutes.
If ICRT is not feasible either due to distorted anatomy or inade-
quate dosimetry, then interstitial brachytherapy should be considered.
Interstitial brachytherapy consists of insertion of multiple needles/
catheters into the primary tumor and parametria (Fig. 2) through the
perineum with the help of a template. Due to the risk of trauma to
normal structures like bowel and bladder, use of ultrasound imaging
(especially transrectal) is suggested during the implant procedure.109
Completion of the radiotherapy protocol within the stipulated time
is an important goal as it has a direct correlation on the outcome. In
retrospective analyses, patients whose radiotherapy treatment times
exceeded 9–10 weeks had significantly higher rates of pelvic failure
F I G U R E   2   Interstitial brachytherapy implant: (A) clinical image
when compared with women whose treatment was completed in less of a patient showing the perineal template and the steel needles;
than 6–7 weeks.110,111 Currently the recommendation is to complete (B) CT scan image showing the brachytherapy needles inserted into
the entire protocol of EBRT and brachytherapy within 8 weeks. the pelvis.

Patients with an ECOG (Eastern Cooperative Oncology Group)

5.2.5 | FIGO Stage IVB/distant metastases
performance status of 0–2 may be considered for palliative systemic
Presentation with distant metastatic disease is rare, reported in about 2% chemotherapy. Where feasible, these patients could be offered partic-
of cases. A management plan should consider that the median duration ipation in clinical trials, especially when the interval to relapse is less
of survival with distant metastatic disease is approximately 7 months. than 12 months.
Concurrent chemoradiation may have better response than systemic GOG 240 studied the efficacy of antiangiogenic therapy with bev-
chemotherapy with overall and disease-­free survivals of 69% and 57%, acizumab, a humanized anti-­VEGF monoclonal antibody. When incor-
respectively, reported in patients with positive para-­aortic and supraclavic- porated in the treatment of recurrent and metastatic cervical cancer,
112
ular lymph nodes. Currently there is no role for prophylactic extended it showed increased overall survival (17.0 months vs 13.3 months, HR
field radiotherapy (EFRT) in locally advanced cervical cancer. When para-­ for death 0.71, 98% CI 0.54–0.95, P=0.004 in a one-­sided test).115
aortic nodes are involved, EFRT with concurrent chemotherapy should be The treatment is presently expensive and patients and their families
used. IMRT may be used in such patients to reduce the toxicity. need to be counseled. Adverse effects include increased incidence of
Despite limited response rates, cisplatin has been the standard hypertension, thromboembolic events, and gastrointestinal fistulae.
chemotherapy used in the setting of distant metastatic disease.113
Given low response rates to cisplatin alone after concurrent chemo-
5.2.6 | Radiation therapy after inadvertent
radiation, recent evidence supports the use of platinum doublets over
incomplete surgery
cisplatin alone, although with very modest benefits in response rates.
Cisplatin may be combined with taxanes, topotecan, 5-­fluorouracil, Invasive cervical cancer may be found during pathologic evaluation
gemcitabine, or vinorelbine.114 Carboplatin-­paclitaxel combination has of the specimen of a simple hysterectomy for an apparent benign
also been successful in these cases. condition. Inadvertent simple hysterectomy is considered inadequate
Bhatla ET AL. |
      31

surgery for invasive cervical carcinoma and subsequent therapy is thereof. The risk of both pelvic and distant failure increases in propor-
required for all such cases. In such a situation, the extent of the dis- tion to tumor volume.120,121 Most recurrences are seen within 3 years
ease should be assessed by a PET/CT scan if available, or a pelvic and and the prognosis is poor, as most patients die from progressive disease
abdominal CT or MRI scan, and chest imaging. The subsequent treat- with uremia being the most common terminal event.119,122 The treat-
ment plan is formulated based on the histologic and radiologic findings. ment plan depends on the patient’s performance status, site and extent
Although PORT for patients following inadvertent simple hyster- of recurrence and/or metastases, and prior treatment received.123
116,117
ectomy has been shown to be beneficial, the outcome for such If there is extensive local disease or distant metastatic disease,
patients even after PORT remains very poor with 5-­year recurrence-­ the patient is assigned to palliative therapy, with best supportive care
free survival of 49%,33 and therefore CCRT is generally added. In a and symptom control the recommended management. However, if the
116
study from India, Sharma et al. reported the results of 83 patients performance status is good and there is only limited metastatic dis-
treated with PORT following either inadvertent simple hysterec- ease, a trial of platinum doublet chemotherapy is justified, counseling
tomy (33 patients) or radical hysterectomy (50 patients). The 5-­year the patient and her family with respect to the limited benefits with
recurrence-­free survival was found to be significantly inferior in respect to response rate and progression-­free survival.113 Local recur-
patients who underwent PORT after inadvertent simple hysterectomy rence that cannot be salvaged with surgery or radiotherapy is likely to
(49% vs 72%, respectively; P=0.04). PORT, therefore, does not com- have a very poor response to systemic chemotherapy.
pensate for lack of adequate surgery.
In centres where the expertise is available, some of these patients
5.4.1 | Local recurrence
may be found suitable for repeat laparotomy with parametrectomy
and pelvic lymphadenectomy. The procedure is challenging due to The pelvis is the most common site of recurrence and patients who
previous scarring, adhesions, and distortion of anatomy, but does have have only locally recurrent disease after definitive therapy, whether
the potential for curative surgery as well as allow assessment of the surgery or radiotherapy, are in a more favorable situation as the dis-
118
need for adjuvant CCRT. ease is potentially curable. Good prognostic factors are the presence
of an isolated central pelvic recurrence with no involvement of the
pelvic sidewall, a long disease-­free interval from previous therapy, and
5.3 | Post-­treatment follow-­up
the largest diameter of the recurrent tumor is less than 3 cm.74,124
In a systematic review of 17 retrospective studies that followed up When the pelvic relapse follows primary surgery, it may be treated
women treated for cervical cancer, the median time to recurrence by either radical chemoradiation or pelvic exenteration. Confirmation
ranged from 7 to 36 months after primary treatment.119 Therefore, of recurrence with a pathologic specimen obtained by biopsy is essen-
closer clinical follow-­up in the 2–3 years after treatment may be impor- tial prior to proceeding with either therapy. Radical irradiation with or
tant. Routine follow-­up visits are recommended every 3–4 months for without concurrent chemotherapy) may result in 5-­year disease-­free
the first 2–3 years, then 6-­monthly until 5 years, and then annually for survival rates of 45%–74% with isolated pelvic failure after primary
life. At each visit, history taking and clinical examination are carried surgery.125,126 The extent of recurrent disease and involvement of pel-
out to detect treatment complications and psychosexual morbidity, as vic lymph nodes are prognostic factors for survival.127
well as assess for recurrent disease. Concurrent chemotherapy with either cisplatin and/or
Routine imaging is not indicated. Special circumstances, such as 5-­fluorouracil may improve outcome.128 IMRT is reported to be supe-
involved high pelvic lymph nodes, may justify interval imaging of the rior to conventional concurrent chemoradiation yielding better dose
abdomen to assess for potentially curable progression of disease. In sparing of small bowel, rectum, and bladder than chemoradiation with
the systematic review, asymptomatic recurrent disease was detected significantly higher 5-­year overall survival and progression-­free sur-
using physical exam (29%–71%), chest X-­ray (20%–47%), CT (0%– vival rates (35.4% vs 21.4%; 26.1% and 15.1%, respectively).
34%), and vaginal vault cytology (0%–17%). Frequent vaginal vault Pelvic exenteration may be feasible in some patients in whom
cytology does not significantly improve the detection of early disease there is no evidence of intraperitoneal or extrapelvic spread, and there
recurrence. Patients should return to annual population-­based screen- is a clear tumor-­free space between the recurrent disease and the pel-
ing after 5 years of disease-­free survival.119 vic sidewall.71–75 Owing to its high morbidity, it is reserved for those
Women under the age of 50 years who have lost ovarian function with expected curative potential and requires careful patient selec-
should be considered for menopausal hormone therapy. As women tion regarding the associated physical and psychological demands. A
age, the routine exam should include other age-­indicated well-­woman PET/CT scan is the most sensitive noninvasive test to determine any
checks also to ensure quality of life, including assessment of thyroid sites of distant disease, and should be performed prior to exentera-
and renal status. tion, if possible.129–136 Patient assessment and counseling regarding
the implications and ability to manage stoma and ostomy sites must
also be addressed prior to surgery.137 The overall survival is 10% but
5.4 | Recurrent disease
careful selection of patients has been reported to yield a 5-­year sur-
Recurrences may occur locally in the pelvic or para-­aortic, the patient vival with pelvic exenteration in the order of 30%–60%,71,72,74 and an
may develop distant metastases, or there may be a combination operative mortality of less than 10%.138
 |
32       Bhatla ET AL.

Broadly, the management of cervical cancer in pregnancy fol-

5.4.2 | Para-­aortic nodal recurrence
lows the same principles as in the nonpregnant state. Before
The second most common site of recurrence is in the para-­aortic 16–20 weeks of pregnancy, patients are treated without delay. The
lymph nodes. Where there is isolated para-­aortic nodal recurrence, mode of therapy can be either surgery or chemoradiation depend-
curative-­intent radiation therapy or chemoradiation, can achieve long-­ ing on the stage of the disease. Radiation often results in sponta-
139
term survival in approximately 30% of cases. Better outcomes are neous abortion of the conceptus. From the late second trimester
seen in asymptomatic patients with low-­volume recurrences occur- onward, surgery and chemotherapy can be used in selected cases
ring more than 24 months from initial treatment. while preserving the pregnancy.143 When the diagnosis is made
after 20 weeks, delaying definitive treatment is a valid option for
Stages IA2 and IB1 and 1B2, which has not been shown to have any
5.5 | Comprehensive palliative care
negative impact on the prognosis compared with nonpregnant con-
Symptom control is the essence of palliative care and plays a major role trols.144–146 Timing of delivery requires a balance between mater-
in maintaining dignity and quality of life. As the disease progresses, nal and fetal health interests. When delivered at a tertiary center
patients may present with a wide range of symptoms that need to be with appropriate neonatal care, delivery by classical cesarean and
managed with individual attention. Common symptoms of advanced radical hysterectomy at the same time is undertaken not later than
cervical cancer include: pain, ureteric obstruction causing renal failure, 34 weeks of pregnancy.
hemorrhage, malodorous vaginal discharge, lymphedema, and fistulae. For more advanced disease, the impact of treatment delay on sur-
Patients require support from the corresponding clinical services as vival is not known. Neoadjuvant chemotherapy may be administered
well as psychosocial care and support for their families and caregiv- to prevent disease progression in women with locally advanced cervi-
ers. Typically a tiered approach to pain is practiced. Access to oral cal cancer when a treatment delay is planned.147,148
morphine is improving within LMICs and is an important aspect of pal-
liative care. The availability of home care teams in many regions and
AU T HO R CO NT R I B U T I O NS
involvement of nongovernmental organizations in this effort can help
minimize the need to transport the patient to hospital and save costs All authors contributed to the manuscript at all stages including
too. In terminal cases, some patients may require the services of a design, planning, data abstraction, and manuscript writing.
hospice facility as well.

AC KNOW L ED G M ENTS
5.5.1 | Palliative radiotherapy
This chapter reworks and updates the information pub-
Common symptoms in patients with advanced incurable disease lished in the FIGO Cancer Report 2015 (Bermudez A, Bhatla
include vaginal bleeding, pelvic pain, malodorous discharge, and symp- N, Leung E. Cancer of the cervix uteri. Int J Gynecol Obstet.
toms related to metastatic disease, which may be distressing to the 2015;131(Suppl.2):S88–95), with approval granted by the original
patient. Short course radiotherapy is very effective in palliation of authors. Dr Jayashree Natarajan’s help in reviewing the literature
such symptoms. Although there is no standard dose fraction schedule, is gratefully acknowledged.
a dose of 20 Gy in five fractions over 1 week or 30 Gy in 10 fractions
over 2 weeks is commonly practiced.140 In patients with severe vaginal
CO NFL I C TS O F I NT ER ES T
bleeding, a short course of EBRT may be tried and, if it fails, ICRT can
be highly effective in controlling the intractable bleeding.141 Control of NB has received research funding through her Institute from MSD,
bleeding is usually achieved after 12–48 hours of radiotherapy. GlaxoSmithKline, and Digene/Qiagen Inc. DA has received hono-
In patients with pain arising from enlarged para-­aortic or supra- raria from AstraZeneca KK, Chugai Pharmaceutical Co. Ltd, Ono
clavicular nodes, skeletal metastases,142 and symptoms associated Pharmaceutical Co. Ltd, and Takeda Pharmaceutical Co. Ltd. DNS and
with cerebral metastases, palliative radiotherapy should be given via RS have no conflicts of interest to declare.
larger fractions over shorter periods of time. Commonly used sched-
ules include large single fractions, 20 Gy in five fractions, and 30 Gy
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