NCG Guidelines

National Cancer Grid of India Consensus
special article
Guidelines on the Management of

Cervical Cancer
See accompanying articles doi:https://doi.org/10.1200/JGO.18.00028 and https://doi.org/10.1200/JGO.18.00074
Standard guidelines for the management of early and locally advanced cervical cancer are avail-
executive summary
able from various academic consortiums nationally and internationally. However, implementing
Copyright © 2024 American Society of Clinical Oncology. See https://ascopubs.org/go/authors/open-access for reuse terms.
standard-of-care treatment poses unique challenges within low- and middle-income countries,
Supriya J.Chopra such as India, where diverse clinical care practices may exist. The National Cancer Grid, a con-
Ashwathy Mathew sortium of 108 institutions in India, aims to homogenize care for patients with cervical cancer
by achieving consensus on not only imaging and management, but also in addressing potential
Downloaded from ascopubs.org by 172.225.137.229 on April 17, 2024 from 172.225.137.229
Amita Maheshwari
Neerja Bhatla
solutions to prevalent challenges that affect the homogenous implementation of standard-of-care
treatment. These guidelines therefore represent a consensus statement of the National Cancer
Shalini Singh Grid gynecologic cancer expert group and will assist in homogenization of the therapeutic man-
Bhawana Rai agement of patients with cervical cancer in India.
Shylasree T.Surappa
Jaya Ghosh INTRODUCTION AND METHODS clinically relevant by the core group (S.C., A.M.,
Dayanand Sharma and S.G.). Recommendations were based on
Cervical cancer is the second most common
comprehensive and objective assessment of evi-
Jaydip Bhaumik cancer in Indian women.1 A majority of patients
dence searched through the National Library of
Manash Biswas present in the locally advanced stage. In 2016,
Medicine database and the Cochrane data base
Kedar Deodhar the Ministry of Health and Family Welfare
of systematic reviews. In clinical situations in
strengthened the operational framework for the
Palak Popat which level I evidence was not available, recom-
screening and management of common can-
Sushil Giri mendations were guided by reports from large
cers and provided detailed algorithms for the
prospective studies. Where prospective data
Umesh Mahantshetty early detection and management of cervical
were not available, retrospective data reviews
Hemant Tongaonkar cancer via Indian Council of Medical Research
were used. Special emphasis was placed on
Ramesh Billimaga (ICMR) guidelines.2,3 However, the biggest chal-
published data from India and challenges that
lenge remains in its systematic execution. The
Reena Engineer were encountered during the implementation of
National Cancer Grid (NCG) of India, funded by
Surbhi Grover diagnostic and therapeutic services in low- and
the Department of Atomic Energy, Government
middle-income countries, such as India. Best
Abraham Pedicayil of India, was initiated in 2012 with a mandate
practice consensus recommendations were
Jyoti Bajpai of creating uniform standards of health care
used when there was a lack of structured clinical
Bharat Rekhi across cancer institutions to reduce disparities in
evidence. The first draft was circulated via e-mail
patient care across various geographic regions.4
Aruna Alihari to all experts in January 2017, and feedback was
Short-term steps to address this issue include the
Govind Babu requested before the NCG expert group meet-
development and implementation of evidence-
ing in February 2017. The core group meeting
Rajkumar Thangrajan based guidelines that have been adapted to
focused on summarizing the recommendations
Santosh Menon address challenges in the delivery of first-line
and discordance between experts. Consensus
Sneha Shah standard of care in India.
was achieved through voting by expert mem-
Sidhanna Palled The cervical cancer guideline development bers, and recommendations were incorporated
Yogesh Kulkarni process was initiated in November 2016. NCG in the revised draft. Recommendations were
nominated experts from all geographical regions additionally summarized at minimal, optimal,
Seema Gulia
in India to ensure adequate representation from and optional levels of execution. Revised ver-
Lavanya Naidu
both government-funded and private health care sions were circulated over two rounds of e-mails
Meenakshi Thakur providers. Initial guidelines were prepared by to the NCG expert group as well as to an exter-
Venkatesh Rangrajan lead representatives (S.C. and A.M.) under the nal international expert who has experience in
(continued) framework of questions that were identified to be working in both high- and low-resource settings
1 jgo.org JGO – Journal of Global Oncology
© 2018 by American Society of Clinical Oncology Licensed under the Creative Commons Attribution 4.0 License
Rajendra Kerkar (S.G.). Recommendations made by all experts intraoperative frozen section should be used. If
Sudeep Gupta were incorporated before submission for pub- nodes are positive on pelvic lymph node dissec-
Shyam K.Shrivastava
lication. Following are recommendations of the tion (PLND), surgery should be abandoned in
expert consensus. favor of CRT. Centers that do not have facilities
Author affiliations and for FNAC or frozen section should consider treat-
support information (if RESULTS ment with CRT.
applicable) appear at the
end of this article. What Is Optimal Radiologic Evaluation for Early
Corresponding author: and Locally Advanced Cervical Cancer? Should Patients With Equivocal Para-Aortic
Supriya Chopra, MD, Nodes Undergo PET-CT, FNAC, or Surgical
Radiation Oncology, Tata
The International Federation of Gynecology Staging?
Memorial Centre, Sector and Obstetrics recommends ultrasonography
22 Kharghar, Navi for imaging cervical cancer.5 However, it is also Integration of PET-CT in the imaging algorithm
does not affect the overall oncologic outcome.11
Mumbai, Maharashtra recommended that, whenever magnetic reso-

410210, India; e-mail: A recent study that compared PET-CT with
[email protected].
nance imaging (MRI) and contrast-enhanced
computed tomography (CECT) is available, they surgical staging reported negative and positive
be used to guide management. An American predictive values of 83% and 71%, respec-
tively.12 Therefore, confirmatory FNAC should be
College of Radiology Imaging Network study has

reported the superiority of MRI over CECT in performed.
identifying tumor size and parametrial invasion, A small, randomized study reported increased
with equivalent performance in identifying nodal morbidity after surgical staging.13 Other studies
disease6,7; therefore, CECT should be considered have demonstrated improved survival after sur-
as minimal investigation, if available, and MRI gical staging14 as the addition of surgical staging
as optimal investigation for imaging early cervi- over negative PET-CT detects para-aortic (PA)
cal cancer. In select patients with ectocervical nodes in an additional 22% of patients15; how-
tumors < 2 cm, only ultrasonography may be ever, a review of the Cochrane database noted
performed before surgery, with MRI reserved for a lack of robust data by which to recommend
patients who desire fertility-sparing surgery. surgical staging.16 An ongoing phase III random-
In locally advanced cervical cancer (LACC), MRI ized study is investigating the effect of surgical
at baseline and at the time of brachytherapy staging.17 Hence, surgical staging is not recom-
facilitates image-based brachytherapy8-10 and mended outside of clinical trials. A summary of
has equivalent performance to CECT for iden- imaging recommendations is listed in Table 1.
tifying nodal disease; therefore, MRI should be
considered as optimal investigation and CECT as MANAGEMENT
minimal investigation, if available. For those with
suspected bladder or rectal infiltration, addi- Early Cervical Cancer (Stages IA1 to IB1 and
IIA1)
tional confirmatory cystoscopy and/or proctosig-
moidoscopy should be performed. What is the adequate management for stage IA1
disease? Type I/class A (extrafascial hysterec-
A template for synoptic reporting for MRI in cer-
tomy) is recommended for stage IA1 disease.
vical cancer is included in the Data Supplement.
Ovarian preservation should be offered to young
patients with squamous histology. Conization
Should Patients With Early Cervical Cancer may be considered for fertility preservation. If
With Equivocal Pelvic Nodes Undergo Positron
Emission Tomography-CT or Fine-Needle margins are involved, then trachelectomy may
Aspiration Cytology to Facilitate Therapeutic be considered. PLND with ovarian transposition
Decision? should be considered if the specimen demon-
strates lymphovascular space invasion (LVSI).
Positron emission tomography (PET) -CT scan
Radical brachytherapy (BT) alone to a dose of
does not have incremental specificity over
up to 65 Gy equivalent dose in 2 Gy to point A
CECT to predict pathologic nodal involvement.6
(that anatomically represents crossing of ureter
Patients with nodes ≥ 10 mm in size should
and uterine artery on either side) should be con-
undergo upfront chemoradiation (CRT). In the
sidered for medically inoperable patients.
case of equivocal nodes, fine-needle aspiration
cytology (FNAC) should be performed. If the What is the adequate management for stage IA2
decision is made for upfront surgery, then an disease? Type II/class B radical hysterectomy

Table 1. Summary of Imaging and Management Recommendations for Optimal and Minimal Resources Setting
Disease Optimal Minimal Optional Remarks
Imaging
Stage
Early cervical MRI abdomen and pelvis CECT abdomen and pelvis, EUA is preferred if there
cancer (stage Chest X-ray if available, otherwise USG is a discrepancy in clinical
IA1, IA2, IB1, abdomen and pelvis staging and MRI findings
and IIA1) Chest X-ray of parametrial involvement
For ectocervical tumors < 2 cm, MRI should be considered
USG may be sufficient in patients who desire
fertility preservation
Locally advanced MRI abdomen and pelvis CECT abdomen and pelvis, PET-CT As incidence of lymph
cervical if available, otherwise USG node metastasis is high,
cancer (IB2, abdomen and pelvis CECT is preferred over

IIA2-IVA) Chest X-ray USG
Para-aortic Nodes identified on CECT and/ Radiologic size criteria is used to PET-CT Adding whole-body PET-
nodes or MRI should be confirmed with diagnose nodal involvement CT after CECT of abdomen
fine-needle aspiration cytology, and pelvis has additional
especially with negative pelvic cost implications and is

lymph nodes not encouraged
CT of the thorax should be done for
patients with positive PA nodes
Management
FIGO stage
IA1 Type 1/class A extrafascial Conization Radical BT 60 Gy Patients with positive
hysterectomy to point A. LVSI should be referred
or Consider ovarian for PLND or assessment
Conization transposition in for the need for adjuvant
or premenopausal pelvic RT
Radical trachelectomy if fertility patients
desired
IA2 Type 2/class B radical hysterectomy Type 2/class B radical Radical BT alone Patients with LVSI
and pelvic lymphadenectomy hysterectomy and pelvic 65-70 Gy point A. should be assessed
or lymphadenectomy Consider ovarian for the presence of
Radical trachelectomy and PLND if transposition in other risk factor(s) for
fertility is desired premenopausal recommending adjuvant
patients radiation
IB1-IIA1 Type 3/class C radical hysterectomy Type III/Class C radical Para-aortic lymph Preoperative thorough
with PLND hysterectomy with PLVD. node assessment. assessment of size,
Adjuvant radiation in those Adjuvant radiation in those Radical parametrial involvement,
with postoperative two or three with postoperative two or three trachelectomy and and nodal status is
intermediate risk factors (size > 4 intermediate risk factors (size PLND in suitable recommended to avoid
cm, LVSI, deep stromal infiltration). > 4 cm, LVSI, deep stromal cases of stage adjuvant treatment.
Concurrent chemotherapy to be infiltration). Concurrent IB1, if fertility is Patients with nodes >
added in the case of any high-risk chemotherapy to be added in desired 1 cm in size should be
features (vaginal cut margins, the case of any high-risk features offered upfront CTRT. If
nodes, or parametria positive). (vaginal cut margins, nodes, the decision is made to
3DCRT represents the current or parametria positive). 3DCRT operate in the presence
standard of care for postoperative represents the current standard of equivocal nodes on
RT. of care for postoperative RT. imaging, then frozen
Additional BT to be used only in Additional BT to be used only in section should be used to
patients with insufficient vaginal patients with insufficient vaginal assess nodes.
cuff or vaginal cut margin positive. cuff or positive vaginal cut margin. Surgery should be
Patients with adenocarcinoma and Patients with adenocarcinoma abandoned if nodes are
> 2 cm in size and an additional and > 2 cm in size and an positive on frozen section
risk factor may be considered for additional risk factor may be
adjuvant radiation considered for adjuvant radiation
or or
Upfront 3DCRT and BT with or Upfront 3DCRT and BT with or
without chemotherapy without chemotherapy
CT/MR-based planning is 2D BT transition toward CT-based
recommended for BT BT is recommended
(Continued on following page)

Table 1. Summary of Imaging and Management Recommendations for Optimal and Minimal Resources Setting (Continued)
IB2 Concurrent pelvic chemoradiation Concurrent pelvic chemoradiation Radical RT alone Surgery is not the
(3DCRT) and 3D CT/MR BT (3DCRT) and 2D BT (in patients who preferred treatment;
Patients with positive para- Patients with positive para-aortic are unable to however, it may be used
aortic nodes should receive nodes should receive extended- tolerate concurrent only in select patients.
extended-field radiation with field radiation with concurrent chemoradiation Such patients should
concurrent chemotherapy, and chemotherapy, and 3DCRT is as a result of undergo surgery in select
intensity-modulated radiation is recommended for these patients. low creatinine centers with access to
recommended for these patients. Sequential nodal boost may clearance or frozen section facilities for
Nodal boost may be considered. be considered. This should advanced age) nodal assessment at the
This should be followed by CT/MR- preferably be followed by CT/MR- Patients who time of surgery. Surgery
based BT based BT are reluctant to should be abandoned if
undergo RT and nodes are positive; in such
with small IB2 select patients, ovarian

tumors with no transposition should be
nodes or deep performed if patients
invasion of the are premenopausal.
cervix on MRI may Use of Neoadjuvant
be considered chemotherapy prior

for type 3/class C to surgery is not
hysterectomy with recommended
PLND
Ovarian
preservation in
young patients
with squamous
histology
IIA2-IIIB Concurrent pelvic chemoradiation Concurrent pelvic chemoradiation Radical RT alone Use of neoadjuvant or
(3DCRT) and CT/MR-based BT (3DCRT) and 2D BT (in patients adjuvant chemotherapy
Patients with positive para- Patients with positive para-aortic who are unable is not recommended.
aortic nodes should receive nodes should receive extended- to tolerate No prophylactic stenting
extended-field radiation with field radiation with concurrent concurrent is recommended in
concurrent chemotherapy, and chemotherapy, and 3DCRT is chemoradiation patients with IIIB and
intensity-modulated radiation is recommended for these patients. as a result of hydroureteronephrosis.
recommended for these patients; Sequential nodal boost may low creatinine Percutaneous nephrostomy
nodal boost may be considered; this be considered. This should clearance or and DJ stenting should be
should be followed by CT/MR-based preferably be followed by CT/MR- advanced age) avoided in patients with
BT based BT deranged creatinine
> 3 g/dL; such patients
should be considered for
palliative RT
IVA If focal bladder/rectal infiltration, If focal infiltration, then pelvic Select patients
then pelvic chemoradiation chemoradiation (3DCRT); this with IVA
(3DCRT). This should be followed should be followed by cystoscopy, disease may
by cystoscopy/rectosigmoidoscopy, then BT be considered
then CT/MR-based BT or for exentration
Patients with focal bladder/ Radical RT alone (in patients who after pelvic
rectal infiltration and large para- are unable to tolerate concurrent RT, depending
aortic nodes may be considered chemoradiation as a result of low on treatment
for 2-3 cycles of neoadjuvant creatinine clearance or advanced response, patient
chemotherapy followed by re- age) wishes, and the
evaluation with cystoscopy and or availability of
nodal response, then decide Palliative RT alone in the case infrastructure and
on extended-field radiation and of extrapelvic disease or frank expert
concurrent chemotherapy followed bladder infiltration
by BT v palliative RT or
Patients with frank bladder Palliative care reference should be
infiltration may be considered done early on in patients who are
for upfront palliative RT and/or planning for palliative treatment
palliative chemotherapy
Palliative care reference should be
done early on in patients who are
planning for palliative treatment
(Continued on following page)

Table 1. Summary of Imaging and Management Recommendations for Optimal and Minimal Resources Setting (Continued)
IVB Palliative RT with or without Palliative RT with or without Bevacuzimab use
palliative chemotherapy palliative chemotherapy is optional and
Palliative care consult or is not advised as
Best supportive care a result of the
Palliative care consult limited benefit
and high costs
Abbreviations: 2D, two-dimensional; 3DCRT, three-dimensional conformal radiation therapy; BT, brachytherapy; CT, computed tomography; CECT, contrast-enhanced
computed tomography; DJ, double J stent; EUA, examination under anesthesia; MRI, magnetic resonance imaging; LVSI, lymphovascular space invasion; PET-CT,
positron emission tomography-computed tomography; PLND, pelvic lymph node dissection; RT, radiation therapy; USG, ultrasonography.
and PLND with or without bilateral salpingo- Supplement) with synoptic pathology reporting,
ophrectomy is recommended for stage IA2 dis- including International Federation of Gynecology
ease. Conization with extraperitoneal or laparo- and Obstetrics stage, is strongly recommended
scopic lymphadenectomy or radical trachelectomy to harmonize surgical pathology reports within
should be considered in those patients who desire the National Cancer Grid. The gross pathology
fertility preservation. BT alone or external beam report should include the description of tumor
radiation therapy (EBRT) and BT to a dose of up
size, vaginal cuff and parametrial length, and the
to 70 Gy to point A should be considered for med-
number of dissected nodes. The microscopic
ically inoperable patients.
report should include the description of patho-
What Is the optimal management of stage IB1 and logic subtype, grade, vaginal and parametrial
IIA1 disease? Type III/class C radical hysterectomy margins, the extent of stromal infiltration (< 50%
with or without bilateral salpingo-ophrectomy v ≥ 50%), and the presence or absence of LVSI.
with PLND or EBRT and BT has similar outcomes Pathologists should also report nodal yield and
for stage IB1 and IIA1 cervical cancer; however, nodal involvement.
surgery may be associated with lower long-term What are additional measures by which to improve
vaginal morbidity. Therefore, the choice of treat- the quality of surgery? Regular surgicopathologic
ment depends mainly on the patient and the audits should be conducted in all institutions.
availability of expertise. Patients with stage IB1 The NCG expert committee noted an increase in
disease who desire fertility preservation can be suboptimal surgeries within the community and
offered radical trachelectomy, provided that the thus recommends that only gynecologic oncol-
tumor is small and lymph nodes are negative on ogists or gynecologists with adequate oncology
PLND. A consultation with a fertility expert can training perform cervical cancer surgery. Subop-
be considered if feasible. Patients who favor rad- timal surgery represents a serious deviation from
ical radiation should be offered a combination of clinical practice that compromises oncologic
EBRT and BT (75 to 80 Gy to point A). In such outcomes and is strongly discouraged.
patients, ovarian transposition may be considered.
Which patients can be observed after surgery
Should minimal access surgery be the standard and how should such patients be evaluated on
of care? There is a lack of level I evidence follow-up? Patients with tumor size < 4 cm with
for minimal access surgery in the management no adverse risk factors (eg, deep stromal inva-
of cervical cancer, and, hence, the treat sion, LVSI, nodal or parametrial positivity, cut
ment remains investigational.18 However, single- margin positivity, or inadequate vaginal cuff
institution studies have demonstrated oncologic removal) should be offered observation. Patients
safety and a reduction in patient morbidity.19 should thereafter be scheduled for follow-up
Minimal access surgery should be performed every 4 months for up to 2 years, every 6 months
after adequate training and within a clinical for another 3 years, and yearly thereafter. Cyto-
protocol. Institutional audit committees should logic evaluation should be considered optional.
monitor and report on the rates of conversions Follow-up imaging should be directed by symp-
and complications. toms and is not recommended for all patients.
What should a standard histopathology report Which patients need postoperative adjuvant treat-
contain? Use of standardized templates (Data ment? Patients with two intermediate risk factors

(tumor size > 4 cm, deep stromal invasion, or is associated with high use of adjuvant treatment
LVSI) should be offered radiation therapy.20 and is not recommended.24 The expert commit-
Patients with any high-risk features (positive tee acknowledges that ICMR recommends the
vaginal or parametrial margins or positive pelvic use of surgery in patients with stage IB2 disease,
lymph nodes) should be offered CRT.21 The EBRT and there is unacceptably high use of surgery
dose should be 45 to 46 Gy in 23 to 25 fractions with or without neoadjuvant chemotherapy (NACT)
delivered over 5 weeks. Additional BT should be in India for stage IB2 disease; however, this prac-
recommended in patients with involved vaginal tice should be replaced with concurrent CRT as
margins or with suboptimal removal of vaginal new results from phase III Indian trials are now
cuff (< 2 cm vaginal cuff or tumor-free margin available.3,25
of < 1 cm). The target volume for BT should be
the upper one third of residual vagina and in no In 2017, a phase III randomized trial from India
case > 4 cm in length. High-dose rate BT should investigated the role of NACT followed by surgery
be delivered in two fractions of 6 Gy each, pre- versus concurrent CRT in stage IB2 to IIB dis-
scribed at 5 mm from the vaginal cylinder sur- ease.25 The study reported high rates of crossover
face and delivered 1 week apart, keeping the to CRT (23%) and the need for adjuvant radiation
overall treatment time (OTT) within 8 weeks. (20%) within the NACT arm. Overall, NACT and
These recommendations apply to patients who surgery arm were associated with reduced 5-year
have undergone recommended surgical pro- disease-free survival (DFS; 67.5% v 72.2%; P =
cedures for their disease stage. Patients who .07); therefore, CRT should represent the stan-
undergo suboptimal surgery, either in terms of dard of care in all patients with stage IB2 disease.
lymph node or parametrium dissection or vagi- For young patients with small IB2 tumors and
nal cuff removal, should be considered to be at no adverse factors on imaging, such as nodes or
high risk for relapse and should be offered adju- deep stromal invasion on MRI, the surgical option
vant CRT and vaginal BT. may be discussed; however, patients should be
apprised of the potential need for adjuvant radia-
In all patients, attempts should be made to initi- tion as well as the cumulative adverse effects as a
ate EBRT within 6 weeks of treatment initiation. result of combination treatment.
The expert panel acknowledges that there may be
delays in referring patients from the community What is the optimal treatment for stage IIA2 to
surgeon and that recommendations for treatment IIIB disease? Pelvic CRT and BT constitute the
initiation may often be violated. The expert panel standard of care in LACC.25-27 The radiation field
therefore encourages conducting educational should encompass the uterus, cervix, vaginal
forums to improve the referral practice. disease extension, ovary, parametrium, and
pelvic lymph nodes with adequate margins.
Should intensity-modulated radiation therapy be Mesorectum should be included in patients with
offered for postoperative radiation therapy? An mesorectal nodal involvement or gross uterosa-
interim analysis of a phase III trial from India of cral infiltration. 3DCRT with CT-based planning
intensity-modulated radiation therapy (IMRT) or should be used as two-dimensional planning
three-dimensional conformal radiation (3DCRT) can underdose the target.28,29 In radiologically
demonstrated reduced incidence of late bowel node-negative patients, the upper extent of the
toxicity with IMRT; however, the difference was field should be the L4 and L5 junction; however,
not statistically significant.22 Another phase III in patients with enlarged nodes, the field should
trial demonstrated improved patient-reported extend to the aortic bifurcation.28 If nodes are
outcomes at week 5 with IMRT, with no differ- identified at the aortic bifurcation, extending the
ence reported at 6 weeks after treatment com- treatment fields 2 to 3 cm above the gross nodes
pletion.23 Until additional data become available, or up to the renal vein should be considered.30
3DCRT should remain the standard of care. Medial inguinal nodal irradiation should be con-
sidered in patients with disease that extends to the
lower one third of the vagina. Nodal boost should
LACC (Stages IB2 and IIA2 to IVA)
be considered in those patients with enlarged
What is the optimal treatment for stage IB2 dis- nodes, and doses should be individualized on the
ease? Concurrent CRT is the standard of care basis of the contribution received during BT if CT-/
for the treatment of stage IB2 disease. Surgery MRI-based BT planning is performed.

Equal efficacy of cisplatin that is administered administered with the aim of delivering 80 to
every week or every 3 weeks has been reported, 84 Gy to point A within 8 weeks while minimiz-
with lower toxicity with the weekly schedule.31,32 ing the dose to the rectum and bladder to 65
Prospective studies have demonstrated improved to 68 Gy and 80 to 85 Gy, respectively.39,40 The
outcomes in patients who received five or more expert group acknowledges that many centers
cycles,33 and careful scheduling of CRT is recom- may be currently practicing two-dimensional or
mended to improve clinical outcomes. In patients X-ray–based planning; however, the transition to
with reduced creatinine clearance (CC), a dose CT-based planning is recommended as it allows
reduction of up to 20% may be used, or carbo- for better assessment of the applicator position
platin may be considered.34,35 If CC is < 40 mL/min, in relationship to the target and facilitates accu-
chemotherapy should be omitted. rate dose reporting to organs that are at risk.
Combined intracavitory and interstitial BT with
There is no proven role for NACT25 or adjuvant magnetic resonance–based treatment planning
chemotherapy in the standard management of and delivery should be performed for patients
LACC. A single randomized study demonstrated with residual parametrial disease beyond point
a benefit for adjuvant chemotherapy after CRT; A. Dose escalation > 84 Gy is recommended in
however, this approach has not been widely this patient cohort. IMRT or stereotactic radiation
adopted. Patients with LACC (IIB to IVA) who are not alternatives for BT and are associated
were treated with cisplatin/gemcitabine, both with reduced local control.41
during and after radiation therapy, demonstrated
improvement in progression-free survival and Should IMRT be recommended for pelvic radia-
overall survival (OS).36 However, the OUTBACK tion in patients undergoing radical CRT? Clinical
trial (ClinicalTrials.gov identifier: NCT01414608) implementation of pelvic IMRT is challenging
is awaited to define clinical use of adjuvant che- and extreme care must be taken with regard
motherapy; however, in patients with large pelvic to organ motion. The need for large margins
nodes (> 3 to 4 cm) or those with focal bladder may reduce the anticipated benefit of IMRT. A
infiltration (infiltration > 1 × 1 cm), NACT may small, randomized trial of 44 patients demon-
be considered with the consensus of a multidis- strated that the use of whole-pelvic IMRT had
ciplinary team. In such cases, patients should fewer grade II and III GI toxicities.42 The recently
receive two to three cycles of paclitaxel 175 mg/m2 published results of the INTERTECC trial demon-
and carboplatin (area under curve, 5), followed strate reduced GI and hematologic toxicity; how-
by clinical and radiologic nodal reassessment ever, the trial did not have a comparator arm.43
before the initiation of CRT.37 Patients with blad- Considering that pelvic IMRT may be associated
der infiltration at baseline should undergo cys- with significant uncertainties and unconfirmed
toscopy after NACT to evaluate their response. benefit in large studies, the use of pelvic IMRT
Patients who achieve a good response (ie, dis- should be restricted to clinical trials until addi-
appearance of infiltration or minimal residual tional information becomes available.
infiltration) should proceed to CRT. Patients with Can recommended guidelines for cervical cancer
small-cell cancer of the cervix should receive radiation be adequately implemented? A multi-
four cycles of systemic chemotherapy (cisplatin institutional registry from India (n = 7,336),
and etoposide) before the initiation of CRT. published in 2015, reported that only 55.5% of
There is no role for prophylactic ureteric stent- patients receive optimal radiation, with only 44.4%
ing in patients with hydronephrosis and normal receiving CRT. A cumulative cisplatin dose of
CC. Palliative radiation therapy should be con- > 150 mg was associated with improved out-
sidered in patients who present with obstructive comes but also with increased toxicity.33 Another
uropathy with serum keratinize > 3 mg/dL, as study from rural India reported poor compliance,
percutaneous nephrostomy followed by radical higher grade III toxicity, and treatment breaks.44
radiation or CRT is associated with survival of Up to 16% to 20% of patients had treatment gaps
< 8 months.38 as a result of toxicity and received three or fewer
cycles, which reduced the cumulative dose to
BT should be initiated in the last week of EBRT 152 mg/m2 (80 to 200 mg/m2) rather than the
for patients with LACC, and three to four frac- desired cisplatin dose of 225 to 250 mg/m2.33,45
tions of 7 to 8 Gy (high-dose rate) should be In patients with coexisting HIV infection, potential

interactions between antiretroviral drugs and improvement in DFS49; however, no difference
cancer therapy should be considered, and higher in OS was reported in an European Organisation
toxicity and poor outcomes46 may be anticipated. for Research and Treatment of Cancer trial.50 In
CRT should be cautiously used in patients with RTOG 90-01 (Pelvic Irradiation With Concurrent
CD4 counts of > 200 cells/μL.47 Chemotherapy Versus Pelvic and Para-Aortic
Irradiation for High-Risk Cervical Cancer: An
The NCG expert panel also noted that academic
Update of Radiation Therapy Oncology Group
centers treat significantly higher numbers of
Trial 90-01) pelvic CRT improved OS compared
patients than their existing infrastructure can
with extended-field radiotherapy (EFRT) alone51;
support and also accept patient referrals only
therefore, there is no role for prophylactic EFRT.
for BT. An unpublished audit from the lead
institute indicated that treatment breaks were What should be the optimal management in
often a direct result of toxicity that was incurred patients with involved PA nodes? Patients with
during treatment (most often diarrhea) or tech- involved PA nodes should receive EFRT with
nical infrastructure-related problems, such as concurrent weekly cisplatin 40 mg/m2, followed
machine breakdown or an imbalance between by BT. High acute (33% to 87%) and late (10%
available infrastructure and the number of to 40%) toxicity have been reported with con-
patients who required treatment, often increas- ventional techniques.52-54 IMRT studies report
ing OTT to > 8 weeks. An unpublished audit of reduced acute (24% to 76%) and late (5%)
chemotherapy compliance reported that up to toxicity30,55-57; therefore, wherever feasible, IMRT
86% of patients receive more than four cycles should be considered for EFRT. Select patients
of concurrent chemotherapy; however, only 48% with bulky PA nodes (> 3 to 4 cm in size) may
proceed to receive five or more cycles of concur- be considered for NACT followed by EFRT and
rent chemotherapy. chemotherapy.38,58
The expert panel therefore recommends that, What is the optimal management of stage IVA
to improve compliance with the proposed CRT cervical cancer? Patients with focal infiltration
guidelines, all patients should undergo detailed of the bladder (< 1 × 1 cm) should be consid-
evaluation of performance and nutritional sta- ered for upfront CRT. Patients who have a larger
tus and renal function at the first consultation area of infiltration should receive palliative radi-
and that remedial actions be taken whenever ation therapy. Use of palliative radiation ther-
applicable. Patients should also be provided an apy leads to a reduction in symptoms in 40%
institutional social worker referral before treat- to 100% of patients, with a median survival of
ment initiation. For treatment planning, 3DCRT 7 to 8 months.59-62 Select patients who present
should be considered as a standard treatment to with a urinary or rectal fistula without parame-
minimize toxicity. To ensure compliance to five trial involvement may be considered for pelvic
or more cycles of concurrent chemotherapy, it exentration.63
is mandatory that patients receive the first che-
What should be the treatment of choice for meta-
motherapy cycle by day 2 of radiation initiation.
static cervical cancer? Platinum-containing com-
Coordination between medical and radiation
bination regimens have demonstrated improved
oncology is recommended to ensure the delivery
progression-free survival.64-66 Patients with an
of five or more cycles of chemotherapy. Adopt-
isolated visceral metastasis may also be consid-
ing abbreviated equieffective BT fractionation
ered for stereotactic radiation and palliative pel-
schedules can strengthen compliance to OTT. A
vic radiation therapy.
final analysis of the International Atomic Energy
Agency trial that compared 4x7 Gy with 2x9 Gy What should be an optimal follow-up strategy for
demonstrated the superiority of the four-fraction patients with LACC? Follow-up should include
schedule.48 Therefore, instead of two fractions of per-speculum and bimanual pelvic examination
9 Gy, twice weekly BT schedules using 7 Gy per every 4 months for 2 years, then every 6 months
fraction may be considered. thereafter with symptom-directed imaging as
indicated.67 Routine cytologic evaluation is not
Should prophylactic PA radiation be used in
recommended.
patients with LACC? Prophylactic PA radiation
therapy within the RTOG 7920 trial demon- What should be the optimal treatment of postradiation
strated an 11% improvement in OS without any residual disease? In patients who have persistent

residual disease after treatment, options for addi- the minimal recommendations are deviations
tional treatment should be considered. The deci- from evidence-based guidelines and are likely
sion to administer salvage surgery should be to result in suboptimal oncologic outcomes and
made no sooner than 5 to 6 months after the are not recommended for the treatment of cer-
completion of treatment to minimize unneces- vical cancer in India. ICMR guidelines provide
sary surgical intervention. an evidence-based framework; however, dis-
Patients with isolated central recurrences should crepancies in delivery have been reported as a
be evaluated for salvage hysterectomy. If this is result of the unique challenges within low- and
not feasible, re-irradiation (preferably with intra- middle-income countries. NCG guidelines there-
cavitary or interstitial BT) should be considered. fore make an attempt to address the common
Outcomes after re-irradiation for local recur- challenges encountered in the delivery of stan-
rence have been published from the Tata Memo- dard practice and provide either evidence-based
rial Centre. Re-irradiation is associated with 44% or best practice–based solutions that can lead
2-year local control and 52% OS in carefully to the optimal adaptation of standard guidelines,
selected patients.68 Patients who are not can- thereby ensuring that cost-effective optimal care
didates for surgical or radiation salvage should is offered to women with cervical cancer.
be considered for systemic chemotherapy and As with any guideline, the biggest challenge
be reassessed for BT or surgery. If local salvage remains in uniform and widespread adaptation,
is not feasible, then additional chemotherapy and the NCG provides the framework to ensure
should be considered on the basis of response this adaptation, as participating institutions and
and the general condition of the patient69 local experts were extensively consulted for the
What should be the optimal salvage therapy for development of recommendations. In addition to
recurrent disease after surgery? Postsurgical agreement on the contents of the recommenda-
recurrences should be treated with CRT and tions, the expert committee and our coauthors
vaginal intracavitary or interstitial BT.70,71 A pro- have agreed to audit and report compliance with
spective phase II study from India reported local NCG guidelines within their institutions.
control of 89% and 5-year DFS of 75% at a A multi-institutional, two-phased clinical audit
median follow-up of 42 months.72 would be initiated to report compliance with
guidelines and quality indices for the treatment
DISCUSSION of cervical cancer by NCG member institutions
that will further guide cervical cancer care imple-
In addition to already available national2,3 and mentation policies in India.
international cervical cancer management guide-
lines,73 resource-stratified guidelines have been
published for the management of cervical can-
cer by ASCO.74 Although ASCO guidelines intend DOI: https://doi.org/10.1200/JGO.17.00152
to provide resource-stratified recommendations, Published online on jgo.org on June 21, 2018.
AUTHOR CONTRIBUTIONS Data analysis and interpretation: Ashwathy Mathew, Neerja

Conception and design: Supriya Chopra, Amita Maheshwari, Bhatla, Shalini Singh, Shylasree T. Surappa, Dayanand
Manash Biswas, Palak Popat, Sushil Giri, Umesh Sharma, Jaydip Bhaumik, Manash Biswas, Kedar Deodhar,
Mahantshetty, Hemant Tongaonkar, Ramesh Billimaga, Palak Popat, Sushil Giri, Hemant Tongaonkar, Ramesh
Aruna Alihari, Govind Babu, Rajkumar Thangrajan, Billimaga, Reena Engineer, Surbhi Grover, Jyoti Bajpai,
Sneha Shah, Sidhanna Palled, Meenakshi Thakur, Govind Babu, Sneha Shah, Sidhanna Palled, Yogesh
Rajendra Kerkar, Sudeep Gupta, Shyam K. Shrivastava Kulkarni, Seema Gulia, Lavanya Naidu, Meenakshi Thakur,
Provision of study materials or patients: Manash Biswas, Sudeep Gupta, Shyam K. Shrivastava
Venkatesh Rangrajan, Rajendra Kerkar, Shyam K. Manuscript writing: All authors
Shrivastava Final approval of manuscript: All authors
Collection and assembly of data: Supriya Chopra, Ashwathy Accountable for all aspects of the work: All authors
Mathew, Neerja Bhatla, Shalini Singh, Bhawana Rai, Jaya
Ghosh, Manash Biswas, Palak Popat, Sushil Giri, Hemant AUTHORS' DISCLOSURES OF
Tongaonkar, Ramesh Billimaga, Abraham Pedicayil, Jyoti POTENTIAL CONFLICTS OF INTEREST
Bajpai, Bharat Rekhi, Govind Babu, Santosh Menon,
The following represents disclosure information provided
Sidhanna Palled, Seema Gulia, Meenakshi Thakur,
by authors of this manuscript. All relationships are
Venkatesh Rangrajan, Sudeep Gupta

considered compensated. Relationships are self-held Reena Engineer
unless noted. I = Immediate Family Member, Inst = My No relationship to disclose
Institution. Relationships may not relate to the subject
matter of this manuscript. For more information about Surbhi Grover
ASCO's conflict of interest policy, please refer to www. No relationship to disclose
asco.org/rwc or ascopubs.org/jco/site/ifc.
Abraham Pedicayil
Supriya Chopra No relationship to disclose
Research Funding: Varian Medical Systems
Jyoti Bajpai
Ashwathy Mathew No relationship to disclose
Employment: Sanofi (I)
Bharat Rekhi
Amita Maheshwari No relationship to disclose
No relationship to disclose
Aruna Alihari
Neerja Bhatla No relationship to disclose
Govind Babu
Shalini Singh No relationship to disclose
Rajkumar Thangrajan
Bhawana Rai Patents, Royalties, Other Intellectual Property: Memorandum

No relationship to disclose of understanding with HLL Life Care, India, for transfer of
technology for a cervical cancer screening kit for which we
Shylasree T. Surappa have applied for a patent (Inst)
Santosh Menon
Jaya Ghosh No relationship to disclose
Sneha Shah
Dayanand Sharma No relationship to disclose
Yogesh Kulkarni
Jaydip Bhaumik
Sidhanna Palled
Manash Biswas
Seema Gulia
Kedar Deodhar
Lavanya Naidu
Palak Popat
Meenakshi Thakur
Sushil Giri
Venkatesh Rangrajan
Umesh Mahantshetty
Rajendra Kerkar
Hemant Tongaonkar No relationship to disclose
Sudeep Gupta
Ramesh Billimaga Research Funding: Roche (Inst), Sanofi (Inst), Johnson &
Employment: Health Care Global Enterprises Johnson (Inst), Amgen (Inst), Celltrion (Inst), Oncostem
Leadership: Health Care Global Enterprises Diagnostics (Inst), Novartis (Inst)
Stock and Other Ownership Interests: Health Care Global
Enterprises Shyam K. Shrivastava
Honoraria: Health Care Global Enterprises
Consulting or Advisory Role: Health Care Global Enterprises
Affiliations
Supriya Chopra, Ashwathy Mathew, Amita Maheshwari, Shylasree T. Surappa, Jaya Ghosh, Kedar Deodhar, Palak Popat, Umesh
Mahantshetty, Reena Engineer, Jyoti Bajpai, Bharat Rekhi, Aruna Alihari, Santosh Menon, Sneha Shah, Seema Gulia, Lavanya
Naidu, Meenakshi Thakur, Venkatesh Rangrajan, Rajendra Kerkar, Sudeep Gupta, and Shyam K. Shrivastava, Tata Memorial
Centre; Hemant Tongaonkar, PD Hinduja Hospital and Research Centre; Yogesh Kulkarni, Kokilaben Dhirubhai Ambani
Hospital, Mumbai; Neerja Bhatla and Dayanand Sharma, All India Institute of Medical Oncology, New Delhi; Shalini
Singh, Sanjay Gandhi Postgraduate Institute, Lucknow; Bhawana Rai, Postgraduate Institute of Medical Education and

Research, Chandigarh; Jaydip Bhaumik, Tata Medical Centre, Kolkata; Manash Biswas, Roorkee Army Hospital, Roorkee;
Sushil Giri, Acharya Hariharan Regional Cancer Centre, Cuttack; Ramesh Billimaga, HCG Hospital; Govind Babu, Kidwai
Institute of Oncology, Bangalore; Abraham Pedicayil and Sidhanna Palled, Christian Medical College, Vellore; Rajkumar
Thangrajan, Cancer Institute Adyar, Chennai, India; Surbhi Grover, University of Pennsylvania, Philadelphia, PA; and
Surbhi Grover, Princess Marina Hospital, Gaborone, Botswana.
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National Cancer Grid of India Consensus

Guidelines on the Management of

1 jgo.org JGO – Journal of Global Oncology

Mumbai, Maharashtra recommended that, whenever magnetic reso-

College of Radiology Imaging Network study has

2 jgo.org JGO – Journal of Global Oncology

cancer (IB2, abdomen and pelvis CECT is preferred over

especially with negative pelvic cost implications and is

3 jgo.org JGO – Journal of Global Oncology

with small IB2 select patients, ovarian

be considered chemotherapy prior

4 jgo.org JGO – Journal of Global Oncology

5 jgo.org JGO – Journal of Global Oncology

6 jgo.org JGO – Journal of Global Oncology

7 jgo.org JGO – Journal of Global Oncology

8 jgo.org JGO – Journal of Global Oncology

AUTHOR CONTRIBUTIONS Data analysis and interpretation: Ashwathy Mathew, Neerja

9 jgo.org JGO – Journal of Global Oncology

Bhawana Rai Patents, Royalties, Other Intellectual Property: Memorandum

10  jgo.org JGO – Journal of Global Oncology

Oncol 35:226-227, 2014

11  jgo.org JGO – Journal of Global Oncology

12  jgo.org JGO – Journal of Global Oncology

the cervix. J Clin Oncol 29:1678-1685, 2011

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