CARCINOMA RECTUM

Presenter:
Dr. Janak Raman Parajuli
Phase B resident
Dept. of Oncology, BSMMU
 CLINICAL ANATOMY
 12-15 cm from anal verge.
 Diameter
 4 cm (upper part)
 Dilated (lower part)
 Posterior part of the
lesser pelvis and in front
of lower three pieces of
sacrum and the coccyx
 Begins at the
rectosigmoid junction, at
level of third sacral
vertebra
 Ends at the anorectal
junction, 2-3 cm in front
of and a little below the
coccyx
 Divided into 3
parts
3 distinct
intraluminal
curves ( Valves
of Houston)
• Lower rectum : 3
– 6 cm from the
anal verge
• Mid rectum: 6
cm to 8 -10cm
from anal verge
• Upper rectum: 8
cm to 12 -15cm
from anal verge
 PERITONEAL RELATIONS
 Superior 1/3rd of the rectum
• Covered by peritoneum on the
anterior and lateral surfaces

 Middle 1/3rd of the rectum

• Covered by peritoneum on the
anterior surface

 Inferior 1/3rd of the rectum

• Devoid of peritoneum
• Close proximity to adjacent
structure including bony pelvis.

Note: - distal rectal tumors have no

serosal barrier to invasion of adjacent
structures and are more difficult to resect
given the close confines of the deep
pelvis.
 NEURO-VASCULAR SUPPLY
 Arterial supply
• Superior rectal A – from IMA;
supplies upper and middle
rectum
• Middle rectal A- from Internal
iliac A. (supplies lower
rectum)
• Inferior rectal A- from. Internal
pudendal A.

 Venous drainage
• Superior rectal V- upper & middle third
rectum
• Middle rectal V- lower rectum and
upper anal canal
• Inferior rectal vein- lower anal canal

 Innervations
• Sympathetic: L1-L3,
Hypogastric nerve
• ParaSympathetic: S2-S4
 LYMPHATIC DRAINAGE
 Upper and middle rectum
• Pararectal lymph nodes, located
directly on the muscle layer of the
rectum
• Inferior mesenteric lymph nodes,
via the nodes along the superior
rectal vessels

 Lower rectum
• Sacral group of lymph nodes or
internal iliac lymph node

 Nodal Groups
 Perirectal
 Internal iliac
 Common iliac
 Paraortic
 EPIDEMIOLOGY

According to GLOBOCAN 2018:

 Globally, nearly 1,849,518 new CRC cases (10.2% of
all incident of cancers)
 Mortality around 880,792(9.2% of all cancers)
worldwide
 Incidence rate in Bangladesh is quite low about
3.8 per 100,000
 Incidence increases above 45-50 years for all age
group
 Men>Women
** Globocan IARC 2008
 Cecum 14 %
 Ascending colon 10 %
 Transverse colon 12 %
 Descending colon 7 %
 Sigmoid colon 25 %
 Rectosigmoid junct 0.9 %
 Rectum 23 %
 ETIOLOGY
 Genetic
 Environmental and Dietary
Increased incidence Decreased incidence
High calorie diet High-fiber diet
High red meat consumption Antioxidant vitamins
Overcooked red meat Fresh fruit/vegetables
High saturated fats Nonsteroidal anti-inflammatory
Excess alcohol consumption Coffee
Cigarette smoking High calcium
Sedentary lifestyle High Magnesium
Obesity, Diabetes Bisphosphonates

 Others
 Biomarkers such as CRP, amyloid A, leptin, insulin like
growth factors I & II.
 HPV, E. Coli
 FAMILIAL COLORECTAL CANCER
 Syndromes with Adenomatous Polyps
• APC gene mutations
• Familial adenomatous polyposis(FAP)
• Attenuated APC
• Turcot syndrome
• MMR gene mutation
• Hereditary nonpolyposis colorectal cancer(HNPCC) type I & II
• Muir-Torre Syndrome
• Turcot syndrome

 Syndromes with Hamartomatous Polyp

• Peutz- Jeghers(LKB1)
• Juvenile polyposis(SMAD4, PTEN)
• Cowden(PTEN)
 Others
• Family History of adenomatous polyps
• Family history of colon cancer
 PATHOLOGICAL FEATURES
WHO Classification
 Adenocarcinoma in situ
 Adenocarcinoma
 Serrated adenocarcinoma
 Mucinous adenocarcinoma
 Signet ring cell carcinoma
 Squamous cell carcinoma
 Medullary carcinoma
 Adenosquamous carcinoma
 Small-cell neuroendocrine carcinoma
 Large cell neuroendocrine carcinoma
 Medullary carcinoma
 Micropapillary carcinoma
 Undifferentiated Carcinoma
 TNM CLASSIFICATION
T category T criteria
Tx Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ: intraepithelial or invasion of lamina propria
T1 Tumor invades sub mucosa
T2 Tumor invades muscularis propria
T3 Tumor invades through the muscularis propria into pericolo-rectal tissues
T4a Tumor invades through the visceral peritoneum

T4b Tumor directly invades or adheres to adjacent organs or structures

Tis T1 T2 T3 T4

Mucosa
Muscularis mucosae

Submucosa

Muscularis propria

Subserosa
Serosa
Extension to an adjacent organ
 TNM CLASSIFICATION (CONTD.)
N category N criteria

Nx Regional lymph nodes(LN) cannot be assessed

N0 No regional LN metastasis

N1 1-3 LN are positive(tumor in LN >=0.2mm), or any number of

tumor deposits present and all identifiable LN negative
N1a 1 regional LN is positive

N1b 2 or 3 regional LN are positive

N1c No regional LN are positive, but there are tumor deposits in

• Subserosa,
• Mesentery, or
• Non-peritonealized pericolic, or perirectal, or meso-rectal
tissues
N2 4 or more LN are positive

N2a 4 to 6 regional LN are positive

N2b 7 or more regional LN are positive

TNM CLASSIFICATION (CONTD.)
M category M criteria

M0 No distant metastasis by imaging

M1 Metastasis to 1 or more distant sites or organs or

peritoneal metastasis
M1a Metastasis to 1 site or organ without peritoneal metastasis

M1b Metastasis to 2 or more sites or organs without peritoneal

metastasis
M1c Metastasis to peritoneal surface with/without other site or
organ metastasis
STAGE GROUPING
 PROGNOSTIC FACTORS

 Good prognostic  Poor prognostic

factors factors
• Old age
• Obstruction, perforation,
• Gender(F>M)
ulcerative lesion
• Asymptomatic pts
• Adjacent structures involvement
• Polypoidal lesions • Positive margins, LVSI
• Signet cell carcinoma
• High CEA
• Tethered and fixed cancer
 DIAGNOSIS

 History
 Physical examination
 Laboratory values
 Colonoscopy/proctoscopy
 Imaging:
• Computed tomography (CT) scan
• MRI or endoscopic ultrasound

 Newer molecular biology techniques

 HISTORY
Symptoms
 Asymptomatic
 Change in bowel habit (diarrhoea, constipation, narrow
stool, incomplete evacuation, tenesmus).
 Lower GI bleeding.
 Abdominal discomfort (pain, fullness, cramps,
bloating, vomiting).
 Loss of appetite
 Weight loss, tiredness.

Acute presentations
 Intestinal obstruction.
 Perforation.
 Massive bleeding.
 PHYSICAL EXAMINATION
Signs
 Pallor
 Abdominal mass
 DRE and (complete pelvic examination in women):
size, location, ulceration, mobile vs. Tethered vs. Fixed,
distance from anal verge and sphincter functions.

 Metastatic disease
• Lymphadenopathy
• Jaundice
• Hepatomegaly
• Ascites
• Pulmonary signs

Rectal metastasis travel along portal drainage to liver via

superior rectal vein as well as systemic drainage to lung via
middle and inferior rectal veins.
 LABORATORY VALUES

 Complete blood count

 Serum electrolytes
 Liver function tests
 Kidney function tests
 Carcinoembryonic antigen (CEA)
• May be elevated
• Helpful in monitoring
 Proctoscopy/Colonoscopy

 Including assessment of mobility, minimum diameter

of the lumen, and distance from the anal verge
 Biopsy from the primary tumor
 To evaluate remainder of large bowel to rule out
synchronous tumor or presence of polyp syndrome.
 CT SCAN(pan-body)
 Part of routine workup of patients
 Useful in identifying enlarged pelvic lymph-nodes and
metastasis outside the pelvis
 Limited utility in small primary cancer
 Sensitivity 50-80%
 Specificity 30-80%
 Ability to detect pelvic and para-aortic lymph nodes is
higher than peri-rectal lymph nodes.
Figure: Rectal cancer with uterine Figure: Mucinous adenocarcinoma of the
invasion. CT scan shows a large rectum. CT scan shows a large
heterogeneous rectal mass (M) with heterogeneous mass (M) with areas of cystic
compression and direct invasion into the components. Note marked luminal
posterior wall of the uterus (U). narrowing of the rectum (arrow).
 TRANSRECTAL ULTRASOUND –
EUS

 Used for clinical staging.

 80-95% accurate in tumor staging
 70-75% accurate in meso-rectal lymph
node staging
 Very good at demonstrating layers of
rectal wall
 Use is limited to lesion<14cm from
anus, not applicable for upper rectum
and for stenosing tumor
Figure. Endorectal
 Very useful in determining extension ultrasound of a T3 tumor of
of disease into anal canal (clinically the rectum with extension
important for sphincter preserving through the muscularis
surgery) propria and into perirectal
fat.
MAGNETIC RESONANCE IMAGING
(MRI)
 Greater accuracy in defining extent of rectal cancer
extension and also location & stage of tumor
 Also helpful in lateral extension of disease, critical in
predicting circumferential margin for surgical
excision.
 Different approaches (body coils, endorectal MRI &
phased array technique)
 Mercury study:
• 711 patients from 11 European centers.
• Extramural tumor depth by MR & histo-pathological
evaluation equivalent.
Figure: Normal rectal and perirectal Figure: Mucinous adenocarcinoma of
anatomy on high-resolution T2-weighted the rectum. T2-weighted MRI shows high
MRI. Rectal mucosa (M), submucosa signal intensity (arrowheads) of the
(SM), and muscularis propria (PM) are cancer lesion in right anterolateral side
well discriminated. Mesorectal fascia of the rectal wall.
appears as a thin, low-signal-intensity
structure (arrowheads) and fuses with the
remnant of urogenital septum making
Denonvilliers fascia (arrows).
 PET WITH FDG
 Shows promise as the most
sensitive study for the detection of
metastatic disease in the liver and
elsewhere.
 Sensitivity of 97% and specificity of
76% in evaluating for recurrent
colorectal cancer.

Small bowel
cancer
bladder
rectum
prostate pubic bone
 NEWER MOLECULAR BIOLOGIC
TECHNIQUES

 Extraction of genomic DNA or protein from stool and

assay for evidence of genetic alterations
 Automated multitarget sDNA assay (fecal
immunochemical testing)
• 90% specificity & 98% sensitivity
• 83% sensitivity for advanced adenoma with high grade
dysplasia
 Treatment

Surgery Chemotherapy Radiotherapy

 AIMS OF TREATMENT

 Local control
 Long-term survival
 Restoration of bowel continuity and preservation of
anal sphincter.
 Bladder and sexual function preservation and
maintenance or improvement in QOL.
 SURGERY
 Surgery is the mainstay of treatment of RC
 After surgical resection, local failure is
common
 Local recurrence after conventional surgery:
20%-50% (average of 35%)**
 Radiotherapy significantly reduces the
number of local recurrences

** Reference: facts taken from Perez

 RESECTION MARGIN
 Traditional margin of 5cm
 NSABP demonstrated no difference in survival or local
recurrence in distal margin of 2, 2-2.9, >3cm
 Therefore, 2cm distal margin is now acceptable considering
the limitation of distal intramural spread of 2cm below the
peritoneal reflection
 Circumferential radial margin is more crucial
 Length of mesorectum removed beyond the primary tumor
is between 3 to 5 cm as tumor implants have not been
shown further than 4cm
 TYPES OF SURGERY
 Local excision
 Lower anterior resection
 Abdominoperineal resection
 With unfavourable pathology patient should undergo
total meso-rectal excision(TME) with or without
sphincter- preservation:
• Positive margin (or <2 mm),
• Lympho-vascular invasion,
• Poorly differentiated tumors,
• T2 lesion
 LOCAL EXCISION
 For superficially invasive (T1) tumors with low
likelihood of LN metastases
 Total biopsy, with further T/t based on pathology
 Tumors within 8 to 10 cm of anal verge,
 Encompass less than 40% of circumference of bowel
wall,
 Well or moderately well differentiated histology,
 No pathological evidence of venous or lymphatic
vessel invasion on biopsy
 LOW ANTERIOR RESECTION

 For tumors in upper/mid rectum allows preservation of

anal sphincter
 Join colon to low rectum
 Permanent colostomy if tumor is too low
 Local recurrence with conventional surgery averages
approx. 25-30% vs. TME 4-7% by several groups

ABDOMINOPERINEAL RESECTION

 With distal edge up to 6 cm from anal verge

 Associated with permanent colostomy and high
incidence of sexual and genitourinary dysfunction.
 TOTAL MESORECTAL EXCISION
 Local failures are most often due to inadequate surgical
clearance of radial margins.

 Conventional resection violates the mesorectal

circumference during blunt dissection, leaving residual
mesorectum.

 TME involves precise dissection and removal of the

entire rectal mesentery as an intact unit.

 Local recurrence with conventional surgery averages

approx. 25-30% vs. TME 4-7% by several groups
(although several series have higher recurrence)

** referred from Perez

 PELVIC EXENTERATION

• The surgeon removes the rectum as well as nearby

organs such as the bladder, prostate, or uterus if the
cancer has spread to these organs. A colostomy is
needed after this operation. If the bladder is removed,
a urostomy (opening to collect urine) is needed.
 PURPOSE OF
(RADIO/CHEMO)THERAPY IN RECTAL
CANCER
 To lower local failure rates and improve survival in
resectable cancers
 To allow surgery in primarly inoperable cancers
 To facilitate a sphincter-preserving procedure
 To cure patients without surgery: very small cancer
or very high surgical risk
Surgery alone With adjuvant CRT
Local failure 25% 40-50%
Overall survival 10-15% 50-60%
CHEMOTHERAPY AGENTS
Combinations
 5Fu  FOLFOX
 Leucovorin  CAPEOX
 Capecitabine
 FOLFIRI
 Oxaliplatin
 Leucovorin/5FU
 Irinotecan
 Bevacizumab  FOLFIRINOX
 cetuximab  Bevacizumab in
combination with
the above regimens.
 RADIOTHERAPY
Prone position:
Radio-opaque markers include
anal,
vaginal,
rectal,
perineal skin; wire perineal scar if present;
small bowel contrast, ensure bladder full.
Target volume:
Primary tumor or tumor bed, with margin presacral, and internal iliac
nodes
(if T4›› external iliac nodes also).
Energy
• 6 MV LINAC or Cobalt-60
Portals
• 4 fields (AP, PA, two lateral fields)
• 3 fields (PA, Rt. Lateral , lt. lateral fields)
 DOSE
 Preoperative radiotherapy
• Short course
25 Gy in 5 daily fractions of 5 Gy given in 1 week.
• Long course
 Phase 1
45 Gy in 25 daily fractions of 1.8 Gy given in 5 weeks.
 Phase 2 (optional)
5.4–9 Gy in 3–5 daily fractions of 1.8 Gy

 Postoperative radiotherapy
 Phase 1
45 Gy in 25 daily fractions of 1.8 Gy given in 5 weeks.
 Phase 2 (optional)
5.4–9 Gy in 3–5 daily fractions of 1.8 Gy.
 Palliative radiotherapy
Phase 1
 45 Gy in 25 daily fractions of 1.8 Gy given in 5
weeks.
Phase 2 (optional)
 5.4–14.4 Gy in 3–8 daily fractions of
1.8 Gy or a hypofractionated regimen
can be used
 30–36 Gy in 5–6 fractions of 6 Gy once weekly
given in 5–6 weeks.
 Dose limitations (at standard fractionation)
• Small bowel 45–50 Gy
• Femoral head and neck 42 Gy
• Bladder 65 Gy
• Rectum 60 Gy
 FIELD ARRANGEMENT
Whole pelvic field:
 A : Posterior-anterior
Lateral borders: 1.5 cm lateral to the widest bony margin of the true
pelvic side walls.
Distal border: 3 cm below the primary tumor or at the inferior
aspect of the obturator foramina, whichever is the most inferior.
Superior border: L5-S1 junction.
 B : Laterals
Posterior border: 1 to 1.5 cm behind the anterior bony sacral
margin.
Anterior border:
T3 disease: Posterior margin of the symphysis pubis (to treat only
the internal iliac nodes).
T4 disease: Anterior margin of the symphysis pubis (to include the
external iliac nodes).
 Boost field:
• A : Treat the primary tumor bed plus a 3-cm
margin (not the nodes).

 After an abdominoperineal resection:

• A :Wire the perineal scar and create a 1.5-cm
margin beyond the wire in all fields.
• B : Never use an electron or photon boost for the
perineum—there will be overlap between the
fields.

 Blocks are used to spare the posterior muscle and

soft tissues behind the sacrum and small bowel.
Fig A: Treatment fields after a low anterior
resection for a T3N1M0 rectal cancer 8 cm
from the anal verge. The distal border is at
the bottom of the obturator foramen and the
perineum is blocked. Since the tumor was a
T3, the anterior field is at the posterior
margin of the symphysis pubis (to treat only
the internal iliac nodes).
Fig B: For a T4N1M0 rectal
cancer 8 cm from the anal
verge. Since the tumor was a
T4, the anterior field is at the
anterior margin of the
symphysis pubis (to include
the external iliac nodes).
Fig C: Treatment fields following an
abdominoperineal resection for a T4N1M0
rectal cancer 2 cm from the anal verge,
because the tumor was a T4, the anterior
field is at the anterior margin of the
symphysis pubis (to include the external
iliac nodes). Since the distal border is
being extended only to include the scar
and external iliac nodes, the remaining
normal tissues can be blocked
CLINICAL TRIALS
 PRE-OP RT VS. SURGERY
ALONE
Swedish Rectal Cancer Trial(NEJM 1997;336:980 ): 1168 patients
randomised to 25 Gy (5x5) PRT or no RT.
Surgery alone Preop. RT
Rate of local recurrence 27% 11% p<0.001
5-year overall survival 48% 58% p=0.004

Dutch Colorectal Cancer Group (Kapiteijn E. NEJM 2001;345:638):

1861 patients randomised TME vs PRT+TME
TME PRT+TME
Recurrence rate 2.4% 8.2%
OS ns ns
PRE-OP VS. POST-OP CHEMO
RT
Randomized trial of the German Rectal Cancer study
Group (Sauer R et al. N Engl J Med 2004;351:1731-40):
▫ cT3 or cT4 or node-positive rectal cancer
▫ 50,4 Gy (1.8 Gy per day)
▫ 5-FU: 1000 mg/m2 per day (d1-5) during 1. and 5. week

Preop CRT Postop CRT

Patients N=415 N=384

5 y. OS 76% 74% p=0.8
5 y. local relapse 6% 13% p=0.006
G3,4 toxic effects 27% 40% p=0.001

• Increase in sphincter-preserving surgery with preop Th.

• MRC CR07/NCIC-CTG C016 (Sebag-Montefiore et al. 2009):
1350 pt. with resectable rectal cancer randomized.
▫ 25 Gy/5# + Surgery (TME)
▫ Surgery (TME) + (45 Gy & 5 FU)

Preop RT Postop
CRT

5 y. OS 80.8% 78.7%
5 y. local relapse 4.4% 10.6%
DFS 79.5% 74.5%
 POLISH TRIAL
• Polish Study (Br J Surg. 2006): 316 pts with resectable T3-4 rectal
cancer, no sphincter involvement, tumor palpable on DRE
(1999-2002).

– RT  short-course RT with 5 Gy/d x 5 days + Surgery (TME)

– CRT  50.4 Gy (1.8 Gy /# over 5.5 weeks) + bolus 5-FU 325
mg/m²/d + LV x 5 days 1st and 5th wks of RT + Surgery (TME)

Preop SCRT Preop LCRT

5 y. OS 67.2% 66.2%
5 y. local relapse 9.0% 14.2%
DFS 58.4% 55.6%
POST-OP CHEMO, RT, AND/OR CHEMO-
RT
• GITSG 7175 (Thomas and Lindblad, 1988): 227 patients with stage B2-C
rectal CA randomized postoperatively to:
▫ no adjuvant therapy vs.
▫ chemo alone vs.
▫ RT alone vs.
▫ concurrent chemoRT.
Result: Chemo-RT arm improved 5-year OS (54%) and LR(10%) over
observational arm OS (27%) & LR (25%).

• Mayo NCCTG 79-47-51 (NEJM 1991): 204 patients with T3/4 or LN+(B2-C)
randomized to
▫ post-op RT (45–50.4 Gy) vs.
▫ chemoRT (bolus 5-FU concurrent).
Result: Chemo-RT improved LF (25 14%), DFS, and OS (48 58%) vs.
RT alone.
 TREATMENT RECOMMENDATIONS

Clinical stages
1. pT1, N0 without high risk features
2. pT1-T2, N0 with high risk features or pt2,nx
3. T3, any N with clear CRM; T1-2, N1-2
4. T3, any N with involved CRM, or
T4 any N, or
locally unresectable or medically inoperable
 pT1, Nx
(Without high risk features)
Transanal
local
exicision
1)cT1, N0 pT1, Nx (with high risk features)

pT2, Nx
 A)Transabdominal
resection (preferred for
T2 lesions)
pT1, Nx with high risk
features, or
pT2, Nx
B)Concurrent
chemoradiation(CCRT)
 CCRT
Or
pT3,N0,M0
observation

Observe
pT1-2,N0,M0
A)Transabdominal
resection
Chemotherapy(CT)
Then
CCRT
pT4,N0,M0 or Then
pT1-4,N1-2 Chemotherapy

(OR),
CCRT followed by
Chemotherapy
 Observation(if no surveillance
evidence of disease)

B)CCRT Transabdominal
resection (if evidence CT
of disease)

chemotherapy
Surveillance
 Concurrent
chemotherapy with
long course RT
*Consider
2) cT3,N any with clear CRM, or

Short course restaging

RT
cT1-2, N1-2

Neoadjuv CCRT, or
ant
therapy CT Short course Transabdominal
RT
resection

Restaging
Short course
RT f/b 12-16
weeks of CT
Resection
contraindicated
Systemic
therapy(CT)
 CT
Node FOLFOX or
Transabdo negative CAPEOX(both
minal before preferred) or
CCRT 5FU/Leucovorin
resection
or Capecitabine

Node
*Consider positive
restaging before
CCRT FOLFOX or
CAPEOX

Resection Systemic
contraindicated therapy
 CCRT #Restaging at 6
4)cT3, weeks post RT
Nany
with
involved CT Observe
CRM, Transabdo
minal
or Neoadj CCRT resection
uvant Short
cT4,
therapy course
Nany, Restaging
RT
or followed Resection
by 12-16 contraind
Surgery icated
not weeks of
possible CT
Systemic
therapy
 Transabdo
minal
resection
f/b CT
Involved
CRM, or
Bulky CT 12-16
# Restaging
residual weeks
Restaging disease
at 6 weeks If resection
post RT contraindic
ated then
Systemic
Therapy
Clear
CRM
 Resectable
Liver only &/or
lung only mets
Unresectable or
medically
inoperable
With synchronous **Abdominal/peri
metastasis toneal mets

Unresectable
Systemic therapy
mets of other sites
 CT f/b
Clear CRM short course
RT or CCRT

Resectable
CT f/b CCRT Restaging

Involved
CRM Short course
RT or CCRT
f/b
CT
• After restaging
• Staged or synchronous resection and/or local
therapy for metastases and resection of rectal
lesion
 CT with
1. FOLFOX Resectable
2. CAPEOX
Unresectable 3. FOLFOXIRI+/-
Bevacizumab, or
FOLFOX/FOLFIRI/FOLF Unresectable
OXIRI +/-
Panitumumab/Cetuximab
 Short course RT or
Progression of
CCRT f/b
primary tumor
Systemic therapy
Unresectable

No progression Systemic therapy

 Non-
Systemic therapy
obstructing

Synchronous Resection
abdominal/ or
peritoneal Diverting ostomy
metastasis
or
Obstructed
or imminent Bypass of impending
obstruction obstruction
or
Stenting(upper rectal
lesions)
SURVEILLANCE
SOME SYSTEMIC THERAPY
REGIMENS
THANK YOU
!!