Colorectal cancer (CRC) in India ranks amongst the lowest in comparison to most parts of the world. However, the sheer population of the country and increasing urbanization, coupled with greater awareness and scope of detection, has resulted in a gradual increase in numbers to the point that it ranks amongst the commonest cancers in India. This review discusses the relevance of specialization in CRC surgery in India and also important aspects of multidisciplinary care such as advances in chemotherapy and radiotherapy. This article also deals specifically with the problem of rectal cancer in young Indians. Furthermore, the impact of minimal access CRC surgery and cutting edge issues in CRC surgery such as approach to complete responders after neo-adjuvant treatment in rectal cancer, concepts in sphincter preservation, and dealing with metastatic CRC are also addressed. Lastly, modern molecular biology with a clinical relevance and modern surgical approaches such as TEMS and TAMIS are also discussed.

1. Problem of colorectal cancer in India and
issues related to management

2. Review Article
Problem of colorectal cancer in India and issues
related to management
Shailesh V. Shrikhande *, Ashwin deSouza
Gastrointestinal and Hepato-Pancreato-Biliary Surgery, Department of Surgical Oncology, Tata Memorial Hospital,
Mumbai, India
1. Magnitude of colorectal cancer in India
The National Cancer Registry Program (NCRP) of the Indian
Council of Medical Research (ICMR) has 28 population-based
cancer registries. Furthermore, there are a number of
regional cancer centers all over the country with a potential
for 55 centers to be linked by a web-based Hospital Based
Cancer Registry (HBCR). The NCRP and ICMR form the
backbone for information about colorectal cancer (CRC) in
India. As per GLOBOCAN 2012 (IARC), the age-standardized
incidence of CRC in India is 7.7/100,000 population for
males and 5.1/100,000 for females.1
These figures are
considerably lower compared to western data and even data
from far eastern countries. One of the primary reasons for
this low incidence could be the Indian lifestyle and a
predominantly vegetarian diet. However, the incidence of
CRC is gradually increasing in urban India, perhaps indicat-
ing environmental and lifestyle influences as major co-
factors. However, the sheer population of India makes CRC
one of the leading causes of cancer (approx 36,000 cases
annually) and cancer-related mortality in this country. In the
absence of screening protocols, this number could easily be
an underestimate.
a p o l l o m e d i c i n e x x x ( 2 0 1 5 ) x x x – x x x
a r t i c l e i n f o
Article history:
Received 28 July 2015
Accepted 29 July 2015
Available online xxx
Keywords:
Colorectal cancer
Incidence
India
Surgery
Challenges
a b s t r a c t
Colorectal cancer (CRC) in India ranks amongst the lowest in comparison to most parts of the
world. However, the sheer population of the country and increasing urbanization, coupled
with greater awareness and scope of detection, has resulted in a gradual increase in
numbers to the point that it ranks amongst the commonest cancers in India. This review
discusses the relevance of specialization in CRC surgery in India and also important aspects
of multidisciplinary care such as advances in chemotherapy and radiotherapy. This article
also deals specifically with the problem of rectal cancer in young Indians. Furthermore, the
impact of minimal access CRC surgery and cutting edge issues in CRC surgery such as
approach to complete responders after neo-adjuvant treatment in rectal cancer, concepts in
sphincter preservation, and dealing with metastatic CRC are also addressed. Lastly, modern
molecular biology with a clinical relevance and modern surgical approaches such as TEMS
and TAMIS are also discussed.
# 2015 Published by Elsevier B.V. on behalf of Indraprastha Medical Corporation Ltd.
* Corresponding author at: Chief, GI and HPB Surgery, Professor, Department of Surgical Oncology, Tata Memorial Hospital, Ernest Borges
Marg, Parel, Mumbai 400 012, India. Tel.: +91 22 24177173; fax: +91 22 24148114.
E-mail addresses: shailushrikhande@hotmail.com, shrikhandesv@tmc.gov.in (S.V. Shrikhande).
APME-313; No. of Pages 4
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Available online at www.sciencedirect.com
ScienceDirect
journal homepage: www.elsevier.com/locate/apme
http://dx.doi.org/10.1016/j.apme.2015.07.017
0976-0016/# 2015 Published by Elsevier B.V. on behalf of Indraprastha Medical Corporation Ltd.

3. 2. Rectal cancer in young Indians
Rectal cancer in the young is a major problem in India. The
etiology remains unclear but patients less than 40 years of age
present with locally advanced disease (predominantly stage III
and above) and both disease-free survival and overall survival
is significantly lower compared to those over 40 years of age.2
In a recent publication from Tata Memorial Hospital, it was
observed that approximately 40% patients undergoing CRC
surgery were 40 years of age or lower. Furthermore, the vast
majority received neo-adjuvant chemo-radiation with very
few patients presenting in earlier stages. Thus, rectal cancer in
young Indians is clearly one of the major research questions
facing colorectal specialists and warrants further investigation
into genetics and tumor biology.
3. Lymph node yield in CRC
Both colorectal surgeons and dedicated pathologists need to be
aware that a minimum of 12 lymph nodes should be resected/
grossed/reported in the treatment of CRC. This not only ensures
surgicalquality but alsoaidsinoptimal pathology reporting that
enables accurate disease staging and further planning of
adjuvant treatment. Radical R0 resection by specialized CRC
surgeons isthekeytoimprove lymph nodeyield.Ina recentCRC
study from Department of Pathology and Surgery at Tata
Memorial Hospital, the median lymph node yield was 12.7 with
more nodes being reported in the younger ages and more
numbers observed in colon resections compared to rectal
resections. Furthermore, the yield was more in treatment naïve
resections compared to resections after neo-adjuvant treat-
ment. It was concluded that surgical expertise and diligence of
pathologist remain the two most crucial factors influencing
lymph node yield in CRC resections.3
4. Specialization in CRC surgery
It has been convincingly demonstrated 2 decades ago in
Sweden that there is no substitute for specialized CRC surgery,
especially low rectal cancer surgery. Specialized surgeons,
compared to a general surgeon performing CRC surgery,
significantly produce better results in terms of longer disease-
free survival, overall survival, reduced rates of permanent
colostomy, and lower rates of pelvic recurrence.4
Eversince the adventofstapling devices,surgery forvery low
rectal cancer has evolved remarkably. A good quality total
mesorectalresection(TME) combinedwithadouble-stapled low
rectal anastomosis is now the standard of care with excellent
results in skilled hands and in centers of excellence.5
A number
of cases, previously considered suitable for abdomino-perineal
resection, can now be offered sphincter conservation, thanks to
modern stapling devices. Cost remains a major constraint
though and consideration for re-usable stapling devices should
be the way forward to cut costs and make this technology more
widely available in a country that remains largely rural.
India in 2015 has very few dedicated units of colorectal
surgery, let alone CRC surgery. The Tata Memorial Hospital,
reporting an audit of 401 consecutive CRC resections with
morbidity 12.2% and 1.2% mortality, highlighted the need to
specialize and develop dedicated CRC units as an essential
step to improve standards of care across India.6
5. Impact of multidisciplinary care
CRC, especially low rectal cancer, has firmly evolved into a
multi-disciplinary treatment concept. MRI scans are crucial for
management of low rectal cancer7
and availability of MRI scans
remains a problem in this vast country. The German Rectal
Cancer Trial in 2004 established the defining role of neo-
adjuvant chemo-radiation prior to radical surgery in all rectal
tumors that were T3 or above and also in all tumors that were
likely to be node positive. It has been observed that patient
motivation and compliance is much better in the neo-adjuvant
setting prior to surgery rather than in the adjuvant setting. More
importantly, neo-adjuvant treatment reduces risk of local
recurrence and often helps in sphincter preservation.8
High
quality radiotherapy units are mushrooming all over India and
neo-adjuvant treatment should be widely encouraged for all
locally advanced and resectable low rectal cancers. It should
also be emphasized that these patients almost always need
adjuvant treatment after well-done surgery. Dedicated teams of
CRC nowadays comprise of the surgeon, gastroenterologist,
pathologist, radiologist, medical oncologist, radiation oncolo-
gist, and nutrition and stoma care specialists.
6. Minimal access CRC surgery
While minimal access surgery has made impressive strides
across oncology, the biggest impact has been in CRC resections.
There have been some landmark trials over the past decade and
they all have essentially concluded that laparoscopic colon
cancer surgery is as good as conventional surgery with some
benefits such as reduced blood loss and hospitalization. The
evidence has not been very compelling as far as rectal cancer
surgery is concerned.9
However, the evidence is mounting
favorably for abdomino-perineal resections and even for earlier
stages of low rectal cancer treated by laparoscopic low anterior
resection. It is estimated that a surgeon needs to perform
approximately 20 advanced laparoscopic colorectal procedures
to negotiate the learning curve. Thus, this progress in science
and technology needs to be matched by appropriate training
opportunities for the upcoming generation of CRC surgeons.10
Tata Memorial hospital recorded 3.2% laparoscopic CRC resec-
tions in 2010. This number has now increased to 36% in 2014.
The advent of Robotic technology has added another exciting
dimension to minimal invasive CRC surgery.
7. Recent concepts in CRC
7.1. Complete responders after neo-adjuvant
chemoradiation: operate or observe?
In low rectal cancer, a complete response after neo-adjuvant
chemoradiation poses a dilemma to the clinician. On the one
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4. hand, this is a sign of excellent response and favorable long-
term outcomes can be expected. On the other hand, the best
evidence has always been in favor of radical resection of the
tumor. While a wait and watch policy with serial scans and
colonoscopies with biopsy can occasionally be considered for
older and debilitated patients, patients who refuse surgery
where there is a high likelihood of stoma and in patients with
excellent compliance, radical resection in the form of TME is
still widely regarded as the best approach even in complete
responders.
7.2. Sphincter preservation: choice of procedure?
With a better understanding of anorectal anatomy and the
physiologyofthepelvicfloor,itisnowpossibletooffersphincter
preservation to a larger patient population even with very low
rectal tumors. The only absolute indications for an abdomino-
perineal resection today are non-availability of a negative distal
margin, frank infiltration of the external sphincter and an
incompetent sphincter complex. In addition to the double
stapling technique that11
has significantly increased the rate of
sphincter preservation in India, recent years have witnessed an
increased use of the intersphincteric approach.12
This is
classically performed transanally where varying extents of
the internal sphincter may be excised to obtain a negative distal
and circumferential resection margin. Functional results
following this procedure are acceptable in a large proportion
of these patients. However, post-rehabilitation and pelvic floor
exercises form an important part of the perioperative care.
7.3. Stoma care
Stoma care facilities in India still leave a lot to be desired.
Creation of a stoma requires expertise and care by a specialist
colorectal surgeon. The decision for creation of a stoma should
be carefully taken after weighing the risk–benefit ratio of this
procedure. Not all patients with a low anterior resection
should be subjected to a stoma. The Tata Memorial Hospital
policy is to consider a stoma in all anastomoses lower than a
conventional low anterior resection (i.e. ISR and Ultralow AR)
and those low anterior resections where the donuts are not
satisfactory, if patient age is over 60 years, significant co-
morbidities, and a suspicion of a positive leak test. While
meta-analysis seems to suggest creation of a stoma in all low
anterior resections, a judicious approach as mentioned above
is perhaps the best way forward in India considering the
comparative lack of dedicated stoma nurses and clinics across
the country.13
There is an urgent need to expand the scope of
stoma clinics across India.
7.4. Transanal resection: indications and outcomes
The introduction of Transanal Endoscopic MicroSurgery
(TEMS) and TransAnal Minimally Invasive Surgery (TAMIS)
offers a unique surgical approach for full thickness excision of
rectal lesions within 10 cm of the anal verge and involving up
to a third of the circumference of the rectal lumen.14
This is
particularly well suited for benign and premalignant lesions
which are too large to be excised endoscopically and may also
be used to resect T1, well-differentiated malignant lesions as
the incidence of nodal metastasis is very low in this patient
population. Although the indications for local resection have
been extended to T2 lesions in a few published case series, this
has not been universally accepted as a standard of care.
7.5. Metastatic CRC (mCRC)
mCRC has been increasingly recognized as a distinct entity.
The reasons are twofold. CRC is perhaps the only digestive
system cancer with a more favorable natural history. Second-
ly, advances in surgical techniques coupled with modern
chemotherapy (FOLFOX/FOLFIRI, etc.) and targeted therapy
(bevacizumab/cetuximab) have remarkably improved out-
comes in the past decade and a half.15
For all practical
purposes, mCRC comprises two groups of patients i.e. liver
limited disease (LLD) and metastatic disease with extra-
hepatic spread as well. The latter carries a more dismal
prognosis compared to the former. LLD is often considered as a
distinct entity separate from the primary and refinements in
aggressive liver surgery have improved cure rates in mCRC.16
The awareness about mCRC remains a major challenge not
only among lay people but also even in the medical fraternity.
7.6. Molecular biology in CRC
CRC has served as a model for the study of tumor biology and
three pathways for the development of CRC have been well
defined.17
These include the classical adenoma-carcinoma
sequence, the microsatellite instability pathway seen in
Hereditary Non-Polyposis CRC (HNPCC) and the CpG Island
Methylator Phenotype Pathway (CIMP). Elucidation of signal
transduction patterns has led to the development of mono-
clonal antibodies targeting key areas in these pathways. Both
Bevacizumab (against VEGF) and Cetuximab (against EGFR)
have an established role in the management of metastatic
CRC. All Ras testing is mandatory before the use of Cetuximab,
as it is only effective in patients with wild type (i.e. non-
mutated) Ras. Newer molecules like Panitumumab and
Regorafenib continue to emerge with reports of modest
activity in the metastatic setting. However, the high cost of
these molecules limits their use to a select few when
considering the global perspective of metastatic disease
burden in the Indian subcontinent.
8. Future perspectives
CRC will become an increasing health care challenge in the
Indian subcontinent in the coming years. Better awareness
and lifestyle modifications will result in improved outcomes
over time. Specialized CRC surgery will be crucial as also the
development of multimodal approaches in treatment of this
cancer. India-specific guidelines18
and compliance to the same
would enable us to answer important questions by conducting
multi-center studies across India.
Conflicts of interest
The authors have none to declare.
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