PREMANAGEMENT & MANAGEMENT OF Ca RECTUM.pptx

PREMANAGEMENT &
MANAGEMENT OF Ca RECTUM
DR ANJALIKRISHNA NP
PG RSIDENT
RADIOTHERAPY
AIIMS GORAKHPUR

Clinical Anatomy
• 12-15 cm from anal verge.
• Diameter
• 4 cm (upper part)
• Dilated (lower part)
LOCATION
• Posterior part of the lesser pelvis &
• In front of lower three pieces of sacrum &
the coccyx
• Begins at the rectosigmoid junction, at level
of third sacral vertebra S3
• Ends at the anorectal junction, 2-3 cm in
front of & a little below the coccyx

• Divided into 3 parts
• Upper third
• Middle third
• Lower third
• 3 distinct
intraluminal curves
( Valves of Houston)

• 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 boney 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.
Peritoneal Relations

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 nodes
• Below the dentate line
• Inguinal nodes and external iliac chain

EPIDEMIOLOGY
• 3rd most common malignancy
worldwide.
• Slight male predominance.
• Peak incidence: 6th to 7th
decade.
• Risk factors:
• Familial (Lynch Syndrome, FAP)
• IBD (UC > CD)
• Diet (low fiber, high fat, red
meat)
• Smoking, alcohol, obesity,
sedentary lifestyle.

CLINICAL PRESENTATION
Symptom / Sign
Approximate Frequency
(%) Comments
Rectal bleeding 60–80%
Most common symptom; may be mistaken for
hemorrhoids
Change in bowel habits 50–70% Constipation, diarrhea, alternating pattern
Tenesmus 30–40% Common in low rectal tumors
Mucus discharge 20–40% Due to mucinous tumors or irritation
Sense of incomplete
evacuation
20–30% Due to distal tumor bulk
Pelvic/rectal pain 20–30% More common in T4 or low-lying tumors
Obstructive symptoms 10–30%
More in bulky or low tumors; rarely complete
obstruction
Weight loss 20–30% Usually in advanced disease
Fatigue, anemia 15–25% Due to chronic blood loss
Palpable mass on DRE 60–70% Especially if tumor <8 cm from anal verge
Symptoms vary by location:
•Low rectal tumors: bleeding, tenesmus, pain, palpable on DRE
•Mid/upper rectal tumors: change in habits, occult bleeding, anemia

DIAGNOSIS AND WORKUP
• Digital Rectal Exam (DRE) – crucial.
• Colonoscopy with biopsy – gold standard.
• MRI pelvis with contrast – local staging.
• CT CAP – distant metastasis.
• Endorectal US – for early tumors (T1–T2).
• CEA levels – baseline and surveillance.
High CEA levels associated with poorer survival
• Optional: PET-CT for equivocal M1 lesions.

Figure: Mucinous adenocarcinoma of the
rectum. CT scan shows a large
heterogeneous mass (M) with areas of cystic
components. Note marked luminal
narrowing of the rectum (arrow).
Figure: Rectal cancer with uterine
invasion. CT scan shows a large
heterogeneous rectal mass (M) with
compression and direct invasion into the
posterior wall of the uterus (U).

Figure: Mucinous adenocarcinoma of the
rectum. T2-weighted MRI shows high signal
intensity (arrowheads) of the cancer lesion
in right anterolateral side of the rectal wall.
Figure: Normal rectal and perirectal anatomy on high-
resolution T2-weighted MRI.
Rectal mucosa (M), submucosa (SM), and muscularis
propria (PM) are well discriminated.
Mesorectal fascia appears as a thin, low-signal-intensity
structure (arrowheads) and fuses with the remnant of
urogenital septum making Denonvilliers fascia (arrows).

PREMANAGEMENT & MANAGEMENT OF Ca RECTUM.pptx

Pathological features
WHO Classification
• Adenocarcinoma in situ
• Adenocarcinoma
• Mucinous (colloid) adenocarcinoma (>50% mucinous)
• Signet ring cell carcinoma (>50% signet ring cells)
• Squamous cell (epidermoid) carcinoma
• Adenosquamous carcinoma
• Small-cell (oat cell) carcinoma
• Medullary carcinoma
• Undifferentiated Carcinoma
95% adenocarcinoma

Dukes classification-
Dukes A: Invasion into but not through the bowel wall.
Dukes B: Invasion through the bowel wall but not involving lymph nodes.
Dukes C: Involvement of lymph nodes
Dukes D: Widespread metastases
Modified astler coller classification-
Stage A : Limited to mucosa.
Stage B1 : Extending into muscularis propria but not penetrating through it; nodes
not involved.
Stage B2 : Penetrating through muscularis propria; nodes not involved
Stage C1 : Extending into muscularis propria but not penetrating through it. Nodes
involved
Stage C2 : Penetrating through muscularis propria. Nodes involved
Stage D: Distant metastatic spread

Tis T1 T2 T3 T4
Mucosa
Muscularis mucosae
Submucosa
Muscularis propria
Subserosa
Serosa
TNM Classification
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 submucosa
T2 Tumor invades muscularis propria
T3 Tumor invades through the muscularis propria into pericolorectal tissues
T4a Tumor penetrates to the surface of the visceral peritoneum
T4b Tumor directly invades or is adherent to other organs or structures

N Stage Description
N0 No regional lymph node metastasis
N1a Metastasis in 1 regional lymph node
N1b Metastasis in 2–3 regional lymph nodes
N1c Tumor deposits in subserosa/mesentery/pericolic fat
without nodal metastasis
N2a Metastasis in 4–6 regional lymph nodes
N2b Metastasis in ≥7 regional lymph nodes
M Stage Description
M0 No distant metastasis
M1a Metastasis confined to one distant organ/site (e.g., liver, lung, ovary)
M1b Metastases in more than one organ/site
M1c Peritoneal metastasis with or without other organ involvement

AJCC Stage Grouping – Rectal Carcinoma
Stage TNM Criteria
Stage 0 Tis N0 M0
Stage I T1–T2 N0 M0
Stage IIA T3 N0 M0
Stage IIB T4a N0 M0
Stage IIC T4b N0 M0
Stage IIIA T1–T2 N1/N1c M0 or T1 N2a M0
Stage IIIB
T3–T4a N1/N1c M0 or T2–T3 N2a M0 or T1–T2 N2b
M0
Stage IIIC T4a N2a–b M0 or T3–T4 N2b M0 or T4b any N1–2
M0
Stage IVA Any T, Any N, M1a
Stage IVB Any T, Any N, M1b
Stage IVC Any T, Any N, M1c
Notes:
•Circumferential resection
margin (CRM)
involvement is a key prognostic
indicator but not part of TNM.
•Tumor deposits (N1c) can
upstage node-negative disease
to N1.
•T4b tumors may require
multivisceral resection or
exenteration.

Importance of Depth of invasion
18
Kikuchi R, Dis Colon Rectum

Prognostic factors
 Good prognostic factors
 Old age
 Gender(F>M)
 Asymptomatic pts
 Polypoidal lesions
 Poor prognostic factors
 Obstruction
 Perforation
 Ulcerative lesion
 Adjacent structures
involvement
 Positive margins
 LVSI
 Signet cell carcinoma
 High CEA
 Tethered and fixed cancer

Treatment
Surgery Chemotherapy Radiotherapy

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: Perez

Types of Surgery
• Local excision- reserved for superficially invasive (T1) tumors with low
likelihood of LN metastases
• Should be considered a total biopsy, with further treatment based on
pathology
• With unfavorable pathology patient should undergo total mesorectal excision
with or without sphincter-preservation:
• positive margin (or <2 mm), lymphovascular invasion,
• poorly differentiated tumors, T2 lesion

• Low Anterior Resection
For tumors in upper/mid rectum;
Allows preservation of anal sphincter
• Abdominoperineal resection
• For tumors of distal rectum with distal edge up to 6 cm from anal verge
• Associated with permanent colostomy
• High incidence of sexual and genitourinary dysfunction

Parameter HAR (High Anterior Resection)
LAR (Low Anterior
Resection)
ISR (Intersphincteric
Resection)
APR (Abdominoperineal
Resection)
Tumor Location
Upper rectum (>10–12 cm from
anal verge)
Mid rectum (5–10 cm from
anal verge)
Low rectum (2–5 cm from
anal verge)
Very low rectum (<2 cm) or
involving anal sphincters
Level of
Anastomosis Sigmoid to upper rectum Colo-rectal or colo-anal Colo-anal
No anastomosis
(permanent colostomy)
Sphincter
Preservation
Preserved Preserved
Partially preserved
(removal of internal
sphincter)
Not preserved (both
sphincters removed)
Indications Early tumors of upper rectum
Mid rectal tumors without
sphincter involvement
Low rectal tumors without
external sphincter invasion
Tumors invading external
sphincter or levator ani
Perineal Wound Not needed Not needed Not needed
Required (perineal
dissection)
Colostomy No No No Yes (permanent stoma)
TME Performed? Usually partial Yes (Total Mesorectal
Excision) Yes Yes
Functional Outcome Best Good Risk of LARS (low anterior
resection syndrome)
Poor (permanent stoma)
Oncologic Outcome Excellent Excellent Oncologically safe in
selected cases
Gold standard for low
invasive tumors

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.
** referred from Perez

Pelvic Exenteration
15
cm
High Anterior Resection
Low Anterior Resection
Ultra-low Anterior Resection
Abdominoperineal Resection (APR)
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.

Stage Rectal cancer ~5-year LF/OS
I • TME with APR or LAR.
• If pT1-2N0, no adj. treatment.
• Local excision for favorable tumors (<3 cm size, <30%
circumference, within 8 cm of anal verge, well-moderately
differentiated; margin >3 mm, no LVSI/PNI).
 favorable T1 lesions- observation.
 T2 lesions - adjuvant 5-FU/RT
<5% LF
90% OS
II and III
(locally
resectable)
• Pre-op 5-FU/RT LAR/APR adjuvant 5-FU-based
therapy × 3 cycles (preferred)
• If surgery initially  then adjuvant 5-FU × 2 cycles 
concurrent chemoRT  5-FU ×2 cycles
T3N0 and T1-2N1:
5–10% LF
80% OS
T4N0 and T3N1:
10–15% LF
60% OS
T4N1 and T3/4N2:
15–20% LF
40% OS
Treatment Recommendations

Stage Rectal cancer ~5-year LF/OS
III
(T4/ Locally
unresectable)
If obstructed, diverting colostomy or stent placed  definitive
treatment. 5-FU/RT  resection if possible. Consider
IORT for microscopic disease (after 50 Gy EBRT, give IORT
12.5–15 Gy) or
brachytherapy for macroscopic disease  adjuvant 5-FU-
based therapy*
IV Individualized options, including combination 5-FU-based
chemo alone, or chemo ± resection ± RT
Recurrent Individualized options.
If no prior RT, then chemoRT  surgery ± IORT or
brachytherapy.
If prior RT, then chemo surgery ± IORT or brachytherapy as
appropriate.

30
How MR Imaging helps in contouring rectal cancers
• To assess bulky polyps >5mm thick
• Initial assessment of disease remote from the lumen
within entire mesorectum
• Identification of pelvic sidewall disease
• Identify site location of stalk or invasive border and
relationship to puborectalis sling, peritoneal
reflection, mesorectal or intersphincteric border
• Identification of high risk patients with extramural
venous invasion

Rectal Cancer Radiotherapy Contouring
Guideline for clinical target volumes (CTV) for neoadjuvant
chemoradiotherapy in locally advanced rectal cancer:
Gross tumor, peri-rectal, pre-sacral, internal iliac and external iliac.
NTUH practice (National Taiwan University Hospital)
• GTV: main tumor mass + involved lymph nodes
• CTV:
– GTV with 15 mm expansion
– Distal 20 mm margin to GTV for CTV
– Vessels with 7 mm expansion
– Contour CTV to include mesorectum and pre-sacrum
– Avoid bone and small bowel

33
RTOG CONSENSUS PANEL RECOMMENDATIONS
• Risk volumes defined as
CTVs: these were local and
nodal.
• Local CTV included
mesorectum, presacrum,
scar tissue and
anastomosis.
• Nodal CTV included
perirectal, iliac (external
and internal) and inguinal.
• Nodal CTVs:
– CTVA: Internal iliac,
presacral and peri-rectal
– CTVB: external iliac
– CTVC: inguinal
https://www.rtog.org/CoreLab/ContouringAtlases/Anorectal.aspx;

34
International consensus guidelines on Clinical Target
Volume delineation in rectal cancer
• Consensus was obtained for delineation of the CTV for
elective irradiation of all regional lymph node levels.
• Seven subsites at risk were identified:
Presacral space (PS), mesorectum (M), lateral lymph nodes
(LLN), external iliac nodes (EIN), inguinal nodes (IN),
ischiorectal fossa (IRF) and sphincter complex (SC).
Radiotherapy and Oncology 120 (2016) 195–201
http://dx.doi.org/10.1016/j.radonc.2016.07.017

IMMOBILIZATION DEVICES
• BELLY BOARD

Schematic presentation of belly board surface
• Belly board : in region of pelvis, the board has raised surface
…. To separate pelvic and abdominal structures
• Abdominal area has depression : to accommodate the bowel
loops……so that the intestines do not displace pelvic
structures.

37
Simulation Protocol
• Full bladder
• Prone on bowel displacement device
(if can do daily OBI On-Board Imaging)
• Anal marker & wire on distal edge of tumor if possible
• IV & oral contrast
• 2.5 to 5 mm CT slices

(a) The small-bowel
displacement system
consists of a Styrofoam
compression device and a
custom-made immobilisation
abdominal board to mount
the compression device for
easy set-up;
(b) (b) a patient positioned prone
over the small-bowel
displacement system for
typical computed tomography
simulation and treatment set-
up.

Contouring the GTV
40
• Scroll through slices
to view extent
of tumor.
• Start your
contour
where
the
obvious
• Check
your
tumor is
volume
against
colonoscopy findings
since imaging is less
sensitive

43
Differentiating a lymph node from a vessel
1. Use MRI overlay
2. Scroll up and down: nodes will be rounded
structures that disappear then reappear
3. Contour the vessels before contouring the GTV
4. Sub-centimeter perirectal nodes are contoured in the
GTV to show you they are in the standard CTV.
These DO NOT need to be contoured unless grossly
enlarged.

Enlarged
perirectal
lymph node
44

• Now turn off ALL contours
• Start at abdominal aorta
• Scroll inferiorly, following
branches
• Lymph nodes sit on vessels. This is
why we contour vessels in nodal
CTV
• Sequence of vessels:
– Aorta (artery) or IVC (vein)  Common
Iliacs (R and L)  Internal iliac (go
posterior/in front of sacrum) and
External Iliacs (go anterior  become
inguinal/femoral when exit pelvis)
Review anatomy of pelvic vessels
45

What is the CTV?
This is the RTOG 2009 Consensus Recommendation
48

Caudal (inferior) extent of CTV
(Muscles and connective tissue of pelvic floor are better
visualized with MRI)
1. CTV should extend at
least to the pelvic floor,
even if upper rectal
cancer
2. Extend to a minimum
of 2cm caudad to GTV
Mesorectum (peri-rectal)
Pelvic floor, Levator ani
49

Pelvic Divisions in Rectal Cancer Management
Pelvic Level Anatomical Boundaries Oncological Relevance Radiotherapy Notes
Upper Pelvis
From sacral promontory (S1) to
upper border of acetabulum /
sacroiliac joints
Contains common iliac and
proximal external iliac nodes
(involved in advanced or
recurrent cases)
Not routinely included unless
MRF+/EMVI+/T4b
(Mesorectal Fascia
involvement) (Extramural
Vascular Invasion)
Mid Pelvis
From upper acetabulum/SI joints to
upper edge of pubic symphysis
(approx. S2–S3)
Includes mesorectum,
internal iliac, presacral, and
obturator nodes – primary
field in rectal RT
Main target for standard
pelvic RT fields
Lower Pelvis
From upper pubic symphysis (S3–S4)
to ischial tuberosities/anal verge
Contains perirectal, levator
ani, ischiorectal fossa,
inguinal nodes (if tumor
extends below dentate line
or invades anal canal)
Inguinal nodes included if
tumor extends below
dentate line or into anal
canal

CTV in the
lower
pelvis
Posterior and
lateral margins:
Extend to lateral
pelvic muscles or
bone
Anterior margin: Extend
into prostate/seminal
vesicles in a male
(vagina for female)
52

CTV in Mid-
pelvis
CTVA covers: Rectum,
Mesorectum, Internal
iliac vessels, Presacral
space
Mesorectum Presacral space
Anterior margin:
Extends 1 cm into
Posterior bladder wall
54

CTV in Upper-
pelvis
4
2
DO NOT
include
muscle or bone
Include
internal
iliac arteries
and
veins;
posterior border
of CTV abuts
external iliac
vessels (which
we do NOT
include unless T4
tumor invading
prostate or vaginal
anteriorly)
Presacral space
Lymph Nodes

Superior
Extent of CTV
Continue contour up
to where the
common iliacs
bifurcate OR L5/S1
interspace
57

59
Designation of regions at risk of recurrence and their contouring
• The International working group identified following
subsites for risk of nodal recurrence:
– Presacral nodes (PN),
– Mesorectum (M),
– Lateral lymph nodes (LLN),
– External iliac nodes (EIN),
– Ischio-rectal fossa (IRF),
– Sphincter complex (SC),
– Inguinal Nodes (IN)

Elective subsites to be included in CTV according to
stage and tumour location
60
Mesorectum; PS = Pre-sacral space; LLN = Lateral lymph nodes

EIN=External iliac nodes; IRF = Ischio-rectal fossa; SC =
Sphincter complex
61
Elective subsites to be included in CTV according to
stage and tumour location

When a CTV Boost is required
Extend CTV to cover entire
mesorectum and presacral
region at level of GTV, with
a minimum 2cm margin on
GTV in the cephalad and
caudad directions
Add a margin of 7-10 mm
for PTV to the various CTVs
62

PTV from
the CTV
Add a margin of 7-10 mm
for PTV to the various CTVs
63

SAGITTAL VIEW
64
CORONAL VIEW
Always check final volumes in sagittal and coronal views to
make that the contoured volume makes sense in 3
dimensions

66
Pre-operative vs. Post-operative Therapy Rectal Ca
Parameter Preoperative RT (Neoadjuvant) Postoperative RT (Adjuvant)
Indication Locally advanced (T3/T4 or N+) Positive margins, T3/T4 or N+ after surgery
Goals Tumor downstaging, improve resectability, sphincter
preservation, better local control
Eradicate microscopic residual disease,
improve local control
Timing Before surgery (typically 5–8 weeks before)
After surgery (4–6 weeks post-op, after
wound healing)
Concurrent Chemotherapy Yes (Capecitabine or 5-FU based) Yes (Capecitabine or 5-FU)
Technique
IMRT/VMAT or 3DCRT; prone position with belly board; MRI-
based planning
IMRT/VMAT or 3DCRT
Surgical Timing
- Long-course: surgery after 6–10 weeks- Short-course: immediate
(within 1 week) or delayed Already done
Toxicity Profile Lower acute and late toxicity (esp. bowel, bladder, sexual) Higher risk of late toxicities (adhesions,
fibrosis)
Sphincter Preservation More likely with pre-op RT due to tumor shrinkage Less likely
Treatment Volume Entire mesorectum, presacral space, perirectal + internal iliac
nodes
Same, but field may need adjustment due to
postoperative anatomy
CRM Involvement Better sterilization of potential CRM positivity
Higher risk of involved CRM due to prior
surgery
Compliance Better tolerance pre-surgery
Reduced due to post-op complications or
fatigue
pCR (Pathological Complete
Response) ~10–25% with long-course CRT Not applicable
Evidence
German Rectal Cancer Trial: Better local control and sphincter
preservation in pre-op arm Not shown to be superior to pre-op

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
Phase 2 (optional)
5.4–9 Gy in 3–5 daily fractions of 1.8 Gy.

Polish Trial (Bujko et al., 2006)
Parameter Short-Course RT (SCRT) Conventional CRT
Radiation Dose 25 Gy / 5 fractions (5 Gy/fx) over 1 week
50.4 Gy / 28 fractions + 5-FU-
based chemotherapy
Chemotherapy None 5-FU continuous infusion
Surgery Timing Within 7 days 4–6 weeks after CRT
Number of Patients 312 311
Population cT3, resectable mid/low rectal cancers Same
Primary Endpoint Sphincter preservation
Sphincter Preservation No significant difference (61% in SCRT vs 58% in CRT)
Local Recurrence Similar: 10.6% (SCRT) vs 10.1% (CRT) at 4 years
OS (4-year) 66% (SCRT) 67% (CRT)
Toxicity (Acute) Lower Higher
Toxicity (Late) Comparable Comparable
pCR Rate 0.7% 16%
Tumor Downstaging Minimal Significant

•SCRT is non-inferior to CRT in terms of local control and overall
survival.
•CRT achieves higher pathological complete response and
tumor downstaging, but not higher sphincter preservation.
•SCRT is logistically easier, with fewer acute toxicities.
•Useful in resource-constrained settings or in patients unsuitable
for chemotherapy

• Palliative radiotherapy
Phase 1
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.
Symptom/Complication RT Goal
Bleeding Hemostasis
Pain (pelvic/perineal) Pain relief via tumor shrinkage
Tenesmus, obstruction Tumor size reduction
Ulcerating/fungating mass Local control, hygiene
Sacral/perineal invasion Pain relief, possible decompression

Chemotherapy in Rectal Carcinoma
Setting Purpose
Neoadjuvant Radiosensitization, downstaging, increased pCR, improve
resectability & sphincter preservation
Adjuvant Eradicate micrometastatic disease, reduce distant recurrence
Total Neoadjuvant Therapy (TNT)
Integrate systemic therapy early for better compliance & distant
control
Metastatic (M1)
Prolong survival, palliation of symptoms, convert unresectable to
resectable metastases

Neoadjuvant Chemoradiotherapy (CRT)
•Standard for locally advanced rectal carcinoma (cT3–T4 or N+)
•Concurrent chemotherapy enhances radiosensitization
Agent Regimen Dose
Capecitabine Oral 825 mg/m² BID (on RT days)
5-FU (infusional) IV infusion 225 mg/m²/day
(continuous, Mon–Fri during RT)
•RT dose: 45–50.4 Gy in 25–28 fractions over 5–5.5 weeks
📌 Capecitabine has largely replaced 5-FU due to convenience and comparable efficacy.

Adjuvant Chemotherapy
•Given post-surgery (usually after neoadjuvant CRT + TME)
•Based on ypStage II/III and pathological risk features
Preferred Regimens Schedule
FOLFOX 5-FU + Leucovorin + Oxaliplatin (q2w x 12 cycles)
CAPOX (XELOX) Capecitabine + Oxaliplatin (q3w x 6 cycles)
Capecitabine alone 1250 mg/m² BID x 14 days, every 21 days (in elderly/unfit)
📌 Evidence from MOSAIC trial supports oxaliplatin-based
regimens in node-positive disease

Total Neoadjuvant Therapy (TNT)
•Systemic chemo before or after CRT, before surgery
•Better compliance, higher pCR, early micrometastatic control
Strategies Example Trials
Induction chemo → CRT → surgery PRODIGE 23 (FOLFIRINOX → CRT)
CRT → consolidation chemo → surgery RAPIDO trial (CRT → CAPOX/FOLFOX)
Induction Chemo Regimens
FOLFIRINOX 5-FU + Irinotecan + Oxaliplatin
FOLFOX 5-FU + Leucovorin + Oxaliplatin
CAPOX Capecitabine + Oxaliplatin
✅ TNT improves pCR, DFS, and compliance compared to post-op chemotherapy

OPRA Trial
Organ Preservation in Rectal Cancer after TNT
Parameter Details
Study Type Phase II, randomized, multicenter
Objective
Compare outcomes of TNT delivered as induction vs
consolidation chemotherapy, and evaluate organ
preservation using a non-operative management (watch-and-
wait) approach
Enrollment 324 patients
Population Clinical stage II–III (cT3–T4 or N+) rectal adenocarcinoma,
<12 cm from anal verge
Arms 1. Induction Chemo → CRT2. CRT → Consolidation Chemo
Chemotherapy
Regimens
FOLFOX or CAPOX
Radiotherapy Long-course CRT (50.4 Gy + capecitabine/5-FU) in both arms
Surgery TME if no clinical complete response (cCR)
Follow-Up Close surveillance in W&W group
Primary Endpoint 3-year Disease-Free Survival (DFS)
Secondary Endpoints Organ preservation rate, OS, locoregional control, toxicity

Outcome Induction → CRT CRT → Consolidation
Organ Preservation
(W&W at 3 yrs)
41% 53%
3-year DFS 76% 76% (non-inferior)
3-year OS ~91% in both arms
Local Regrowth (in W&W) ~25%, most salvageable
Sphincter Preservation
Significantly better in consolidation
arm
Toxicity Similar in both arms
•Consolidation chemotherapy (CRT → chemo) led to higher organ preservation without compromising DFS or OS.
•Supports watch-and-wait strategy in patients with complete clinical response (cCR).
•Confirms feasibility and safety of non-operative management (NOM) in select patients.
•TNT improves compliance, response rates, and may reduce surgical morbidity

Chemotherapy in Metastatic Rectal Cancer
(Stage IV)
Goals: Prolong survival, downstage disease for
metastasectomy, symptom relief
Systemic Regimens When Used
FOLFOX/FOLFIRI First-line
FOLFIRINOX High response needed (young, good PS)
CAPOX Oral alternative
+ Bevacizumab If RAS mutant
+ Cetuximab/Panitumumab Only if RAS/BRAF wild-type, left-sided
Immunotherapy Use
PD-1 inhibitors (e.g., pembrolizumab) MSI-H/dMMR tumors only (10–15%)

PREMANAGEMENT & MANAGEMENT OF Ca RECTUM.pptx

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