Preoperative chemoradiotherapy is commonly used to treat rectal cancer. It can reduce the tumor size and increase the likelihood of sphincter-sparing surgery. Studies have shown that preoperative chemoradiotherapy results in lower local recurrence rates compared to postoperative chemoradiotherapy or radiotherapy alone, without increasing distant metastases or mortality. Short-course radiotherapy followed by surgery within a week is also effective at reducing local recurrence compared to surgery alone, especially when combined with total mesorectal excision.

1. Preoperative Treatment in
Carcinoma Rectum
Dr.Bhavin Vadodariya
Senior Resident Doctor
Dept.of Surgical Oncology
Apollo CBCC Cancer Care
Ahmedabad

2. OUTLINE
 INTRODUCTION-Concept of CRM
 LCRT PREOP
 SCRT
 ADJUVANT CHEMO AFTER PREOP CTRT
 TOTAL NEOADJUVANT TREATMENT
 NONOPERATIVE MANAGEMENT

3. Rectal Anatomy
15 cm
Rectosigm
oid
junction
https://quizlet.com/127778324/hsf-anatomy-of-rectum-and-anus-flash-cards/
http://www.radiologyassistant.nl/en/p56195b237699d/rectal-cancer-mr-
staging-
20.ht
ml
 Upper - >10 cm from anal verge. Ant and
lateral walls are peritonealized, higher risk
of peritoneal perforation
 Middle - 5-10 cm from anal verge. Ant
wall covered by peritoneum,
posteriorly by mesorectal fascia (MRF)
 Lower - < 5 cm from anal verge.
Relationship to anal sphincter determines
surgery
MR
F

4. Concept of Mesorectum
 Enclosed by MRF, forms natural boundary to the
tumor
 Contains rectum, fat, lymph nodes and draining vessels
 Total Mesorectal Resection (TME)
¤ Circumferential extent of tumor into surrounding
mesorectum is strongly associated with local
recurrence than longitudinal tumor
¤ En bloc excision of mesorectum has less likelihood of
cell spillage, residual tumor and recurrences
¤ Preserved genitourinary functions (Inferior
hypogastric nerves)
 Mesorectal fascia corresponds to CRM
http://www.radiologyassistant.nl/en/p56195b237699d/rectal-cancer-mr-staging-
20.html
Rectum
CRM is closest distance
from tumor/node to MRF

5. Concept of Mesorectum
Coronal
T2WI
Mesorectal
Fascia Levator
Coronal
T2WI
Axial
T2WI

8. CRM
 CRM measured at the closest distance of the tumor to the
mesorectal fascia.
 Involved CRM:
 Middle third tumor - within 1mm of mesorectal fascia; or,
 Lower third rectal tumors- within 1 mm from levator muscle;
 Anal canal lesions- invasion into or beyond the intersphincteric
plane

9. CRM(Circumferential Resection margin)
 • A tumor–MRF distance >2 mm is CRM negative
 • A distance of <1 mm between the advancing tumor
edge and MRF is indicative of a CRM-positive status
 Also, CRM positivity could be due to tumor/perirectal
nodes/deposits/tumor stranding reaching <1 mm of the
MRF
 • When the tumor/node/deposit–MRF distance is
between 1 and 2 mm, the CRM is regarded thretened

11. Mercury study
 n=111 pts
 Treated with pre-op long-course RT alone or long-course
chemoRT who underwent preoperative MRI 4 to 6 weeks
following pre-op treatment.
 All pts had to have at least 5 mm of initial tumor extension
beyond muscularis propria. Results:
 Tumor regression on MRI was significantly predictive of OS (HR
4.4) and DFS (HR 3.3).

12. Importance of CRM- Mercury
 CRM is the best predictor of local recurrence and poor survival.
 Conclusion:
 Tumor regression as documented by MRI predicts DFS and OS
 MRI predicted CRM involvement is associated with increased risk of LR.
Parameter CRM negative(%) CRM positive(%)
LR 6.5 26(stat. significant)
OS 63 30(stat. significant)
DFS 63 34(stat. significant)

13. Mercury Data
MRI Sensitivity% Specificity%
T stage 87 75
Lymph node 77 71
CRM 77 94

16. Indication of Neoadjuvant therapy
 Upper rectum- Involvement of peritoneal reflection
 Middle and lower Rectum
 T3,T4
 CRM +, Threatened CRM
 EMVI
 N+

17. ESMO Risk stratification

20. Why neoadjuvant treatment-Advantages
 Reducing tumor volume may facilitate resection and increase the
likelihood of a sphincter-sparing procedure.
 Irradiating tissue that is surgery-naïve and thus better
oxygenated may result in increased sensitivity to RT.
 Decrease radiation-induced injury to small bowel trapped in the
pelvis by post-surgical adhesions.
 The anastomosis remains unaffected by the effects of RT because
irradiated tissue is resected).

21. Disadvantages
 Over-treating early-stage tumors that do not require adjuvant
radiation.

22. LONG COURSE RT
 XRT + continuous infusion 5-FU (category 1)- German Trial
5-FU 225 mg/m2 IV over 24 hours 5 or 7 days/week1,5 during XRT
 • XRT + Capecitabine(category 1)- NSABP R04
Capecitabine 825 mg/m2 PO twice daily 5 days/week + XRT x 5 weeks
 XRT + 5-FU/leucovorin NSABP R-03(Category 2A)
 5-FU 400 mg/m2 IV bolus + leucovorin 20 mg/m2 IV bolus for 4 days
during week 1 and 5 of XRT (category 2A)

23. RT dosage and fields
 50.4 Gy (1.8gy/Fraction), 5 fractions/Week for 5 week
The initial fields (45 Gy),
 The superior border should be 1.5 cm above the level of the
sacral promontory,
 The lower border of the field should be 4 to 5 cm below the
defined tumor bed.
 Laterally, the AP-PA fields extend 1 to 1.5 cm beyond the true
bony pelvis.

24. RT Fields
 To treat the entire presacral space with adequate margins and
the full dose, the lateral fields are designed so that the posterior
border encompasses the entire sacrum with a 1 cm margin
posterior to the sacrum.
 Anteriorly, the fields are designed to encompass the previous
tumor bed, including the posterior wall of the vagina for females
and a large portion of the prostate for male

25. Which is beneficial of preoperative versus
postoperative adjuvant chemoradiotherapy?


26. German Trial

27. T3,T4 N+ -2 arms
1. Preoperative Chemoradiation
 50.4Gy in 1.8 Gy/day, 5 days/week
 Concomitant 5FU 1000mg/m2 as 120 hr infusion in 1st and 5th
week of RT
 Sx - 6 weeks after CT+RT
 1 month after Sx - 4cycles of 5 days 5FU infusion (500mg/m2/day)
2. Postoperative Chemoradiation
Exactly same protocol after surgery + 540cGy radiation boost

28. Results

29. Results
Parameter at 10 yr PREOP CRT Postop CRT
OS overall Survival 59.9% 59.6%(NS)
DFS Disease free
survival
68% 68%(NS)
LR Local recurrence 7.1 % 10.1 % (S)
DM Distant mets 30 % 30 % (NS)
Sphincter
preservation rate
39% 19%

30.  N=823, 17% did not receive postop CRT(HR- 3.86) for recurrence
 Median time of recurrence (15 vs 30 month )
 PCR- 13% in preop arm
 Significantly more number of patients in the preop CTRT arm had
tumours 5cm or less from the anal verge

31. Parameter at 10 yr PREOP CRT(%) Postop CRT(%)
Anastomotic
leakage
11 12(NS)
Postoperative cx 36 34(NS)
Mortality 0.7 1.3(NS)

32.  NSABP R3- 5FU LV ,prematurely terminated
 Korean- Capecitabine 1650 mg/m2 ,prematurely terminated

33. How capecitabine came in Preop
CRT-
850 mg/m2 BD for 5 days/week for 5
week during RT

34. NSABP R 04

35. NSABP-R04 1200 pts
***Capecitabine is 825 mg /m2 bid for 5/7(Rad days)
OxaliplatinNo Oxaliplatin
Roh et al ASCO 2011

36. Roh et al ASCO 2011

37. Roh et al ASCO 2011

38. NSABP-R04
Roh et al ASCO 2011

39. NSABP-R04
Pathologic Complete Response by Treatment
Oxaliplatin vs None
Sphincter Saving Surgery by Treatment
Oxaliplatin vs None
Roh et al ASCO 2011

40. CAVEAT- NSABP R04
 The local recurrence rate was similar (6 versus 7 percent with
infusional FU),
 The distant metastasis rate was lower with capecitabine (19
versus 28 percent).
 Capecitabine was not inferior to FU for five-year overall survival
(the primary endpoint).
 Patients in the capecitabine group had more hand-foot skin
reactions, fatigue, and proctitis than did those in the FU group,
whereas leucopenia was more frequent with FU

41. Tumor regression?-
Prognsotic?

45. Prognosis-
TRG
 Poor outcomes seen in patients with ypN2 disease in this
 Prognosis has also correlated with tumor regression grade (TRG),
which incorporates the degree of fibrosis as well as the
percentage of viable tumor cells
 The better prognosis with higher TRG was maintained with long-
term follow-up

46. Chemoradiotherapy versus radiotherapy ?-
CRT is better

47.  Pre-op chemoRT and post-
op CHT.
 RT was 45 Gy/25 fx to
posterior pelvis
 5-FU was given 350
mg/m2/day.
 TME not routine.
 Primary endpoint OS

48. No OS benefit
But lowest LR
in PREOP CRT
with adjuvant
chemo group

49. Does adding oxaliplatin in
PREOP CRT give benefit?
NSABP R04

51. Caveat- Unclear
 Increase pCR at the time of surgery(33% more)
 Reduced the likelihood of a distant recurrence
 These benefits did not translate into improvements in overall
survival or local recurrence
 The addition of a platinum agent increased rates of grade 3 or 4
toxicities, including diarrhea, nausea, neurosensory toxicity, and
fatigue

52. Timing of surgery?

53. Guidelines-ESMO
 No specific recommendation other than to state that in practice,
there is wide variation in the timing of surgery (4 to 12 weeks).
 That longer intervals may enhance pCR rates, but this risks
repopulation, delays the use of postoperative chemotherapy, and
risks subsequent metastases

54. National Comprehensive Cancer Network
(NCCN)
 They suggest that surgery be performed 5 to 12 weeks following
full-dose neoadjuvant chemoradiotherapy.

55. Traditionally
 the interval between completion of neoadjuvant conventional
fractionation RT and surgery in rectal adenocarcinoma has been
six weeks (approximately 11 to 12 weeks after the start of RT) as
this was the duration used in the seminal German Rectal Cancer
Study Group trial.

56. Why we want to delay surgery?
 Increase pCR?

57. GRECCAR 6

58. PCR
 The rate of pCR was statistically equivalent between the 7-week
and the 11-week groups (15% versus 17.4%, P = NS).

59. Problem with timing- Longer interval
 Increased medical complications with the longer interval (44.5%
versus 32%)
 More difficult rectal resection, including increased pelvic fibrosis
leading to higher Lap to open conversion rates
 Longer operative time.
 Most importantly, the quality of the mesorectal dissection was
significantly worse( complete mesorectum, 78.7% versus 90%; P
= .0156)

60. SCRT- When & Why?


61. 25Gy/5#
1week
Surgery after one week
Concurrent CT no
Acute toxicity obscured
Late toxicity <10%
Down staging no unless delayed sx
11 - 12weeks
50Gy/25#
5weeks
4-6 weeks
Yes
10-23% G3
<10%
Approx 50%
SCRT LCRT
Potential difference

62. SCRT evidence
1. SCRT vs Surgery alone
 Pre- TME era- Swedish trial
 Post TME era- Dutch TME trial , MRC CR07
2. SCRT VS LCRT
 Polish trial
 TROG 0104
3. SCRT f/b immediate or delayed surgery
 Stockhom III trial
4. SCRT with Concurrent CT
 STELLAR Trial

63. Evidences SCRT
Pre TME era
Swedish rectal trial
1168 patients ( stage I-III)
Sx vs Sx +RT (5x5)
OS- 38 vs 30 % (p=0.008)
LF 9% vs 26 %
IMPROVING OS WAS A BIG
LEAP FORWARD

64. Evidences SCRT
Post TME era
Dutch rectal trial
1805 patients (resectable)
SCRT -TME vs only TME
OS same
10yr LRR (5% vs 11%)
WITH TME RESULTS
IMPROVED
LC ^
NO ADJUVANT
CT

65. MRC CR07 / NCIC-CTG (C016)
• 1350 ,RCT, Stage I - III
• SCRT / no preop RT ➔ Sx.
• Median follow-up 4 years,
• LR preop RT(4.4 % vs 10.6 %,p<0.001)
• with TME, LR was 1 % SCRT vs 6 % no RT group
• 3-yr DFS improved with SCRT (78 % vs 72 %, p = 0.013)
• OS same
By this time it was clear
that SCRT + Sx was well
tolerated, compliance was
good with LC Standard CT
was given.

66. SCRT VS LCRT-Polish study
• 312 patients cT3/T4
,Two-arm
• SCRT ➔ TME < 7 days
• RT (50.4 Gy/28 fx)
• bolus 5-FU wk 1 and 5
• ➔ TME after 4–6 weeks
• 4 yrs ,no significant difference
Sphincter preservation, DFS,OS
• CRM +13 % vs 4 %,p = 0.017
• pCR:1% vs 16 %,no p value
• AT: 3 % vs 18 %, p<0.001
• LT:10 % vs 7 %, p=0.36
• 4-yrLR:11 %vs16 %, p=0.21

67. SCRT VS LCRT-TROG 0104
• 326 patients cT3N0-2M0, two-
arm
• SCRT ➔ TME surgery ➔
• 5-FU x 6 cycles
• RT (50.4 Gy/28 #) + continuous
• infusion 5-FU ➔ TME surgery
➔ 5-FU x 4 cycles
• Median follow-up 5.9 years)
• 5-year LR: 7.5 % vs 5.7 %, NS
• 5-year OS: 74 % vs 70 %, NS
• pCR: 1 % vs 15 %, no p value
• No significant differences in
• acute or late toxicity
• No significant difference in
sphincter preservation ,distant
reccurence, os

68. SCRT ( Metanalysis)
Stockholm 1 (1980)
Stockholm 2
Swedish
Uppsala
Dutch TME trial
MRC CR07
Polish
TROG 01 04 (2006)

69. SCRT ( Metanalysis)
 SCRT - signicant benefit LARC in LC, the effect is equivalent with LCRT.
 SCRT no benefit in OS when compared selective post op RT ±
chemother-apy or LCRT.
 SCRT toxicity acceptable and SCRT decreased short-term toxicity
compared to LCRT in LARC.
 conclusion - SCRT reasonable alternative for resectable rectal cancer .

70. SCRT
Now we know that SCRT & LCRT are equivalent in
terms of LC/DFS/OS.
 We have two unanswered questions.
What about pCR.?
Wht about concurrent CT. ?

71. SCRT vs LCRT-Stockholm III trial interim analysis
• RCT , 3 arms ,SCRT immediate Sx,
• SCRT / Sx after 4–8 wks
• LCRT / Sx 4–8 wks.
•
• Preplanned interim analysis
• 462 of 545 SCRT patients for
• assessment.
• pCR SCRT (11.8 % vs 1.7 %, p<0.001).
•
ENHANCED
pCR
RATES WITH
DELAYED SX

72. SCRT + concurrent CT
 STELLAR trial
 SCRT + CT vs LCRT + CT
 Phase 3 ,
 middle / lower, cT3-4,N1-2 ,n -100.
 Interim analysis
 Published in IJORP / ESMO
PCR 26.9% VS 5.3% (P=.011)
RO - 92.9% VS 89.5% (P=0.593)
Completed whole planned treatment
76.5% vs 49%
Grade 3 / 4 toxicity 17.6 vs 4.1
(p=0.076)
Conclusion - acute toxicity &
Sx complications acceptable &
comparable in both grps ,
SCRT showed better treatment
completion

73. ARLINGTON, Va., July 20, 2016
Intermediate-(IR) and moderately-high-risk(MHR) cases
with clear CRM and may be appropriate for other
scenarios.
T1- 2 N1, T3N0, >2mm MRF, <10cm from Anal verge (IR).
T 1- 2 N2, T3N1 ,>2mm MRF , < 5cm > (MHR)

74. SCRT indicated in.
 T3 N any with clear CRM by MRI.
 T1-2 , N 1-2.
 Avoid in low rectum or CRM+

75. Intermediate Risk
cT3a/b very low,
levators clear, MRF clear
or cT3a/b mid/high ,
cN1-2 (not extranodal),
no EMVI
(TME) - only if (good- quality)
Or
SCRT >TME
High risk
cT3c/d or very low localisation
levators +, MRF clear
cT3c/d mid,
cN1–N2(extranodal),
EMVI+,
cT4aN0
SCRT >TME

76. SCRT in oligomets
SCRT AFTER CT
UPFRONT SCRT

77. Summary SCRT
 Excellent compliance ( No treatment breaks)
 local control comparable / some trials better.
 Early initiation of systemic therapy
 Can be used in low volume metastatic disease.( oligometastatic
disease).
 It is cost effective ( less fractions) , lesser hospitalisation.

78. Adjuvant chemotherapy after NACTRT

79. Evidence
 EORTC trial 22921
 The Dutch colorectal PROCTOR/SCRIPT trials
 The United Kingdom phase III Chronicle trial

80. EORTC 22921 – unplanned subgroup analysis
of 785 patients with R0 resection N0
 The addition of postoperative chemotherapy significantly
improved overall survival in those whose tumors were
downstaged to postresection pathologic (yp) stage T0-2 disease
but not stage ypT3-4 disease
 However, the interaction between the tumor downstaging effect
of preoperative therapy and the benefit of adjuvant
chemotherapy disappeared at later follow-up of this stud

81. Little benefit
 Adjuvant chemotherapy may be of little benefit to patients who
have undergone preoperative treatment followed by definitive
surgery.
 The I-CNR-RT study, which randomized patients to six cycles of 5-
FU/folinic acid versus observation postoperatively, demonstrated
no significant difference in 5-year OS or DFS.
 Rates of pCR and overall downstaging were similar between the
two groups

82. Breugom et al. IPD Meta analysis (I-CNRRT,
CHRONICLE, PROCTO-SCRIPT, and EORTC 22921)
 There was no improvement in OS, DFS, or distant recurrences
with the addition of adjuvant chemotherapy.

83. Limitations of all this study included
 Suboptimal compliance with chemotherapy regimens (ranging
from 43% to 73%) as well as variable adherence to
 TME, which became standard of care midway through the trial
accrual periods.
 Clearly, further investigation and risk stratification of patients is
necessary to determine who would ultimately benefit from
additional postoperative therapy

84. Adjuvant CT in non
responders-yPT3N1 shows
benefit

85. Evidence
 EORTC 22921
 German Rectal Cancer Study Group
 French Fédération Francophone de Cancérologie Digestive (FFCD)
9203
 ADORE Trial

86. Randomized phase II ADORE trial
 Support for a greater intensity of chemotherapy (ie, an
oxaliplatin-containing versus non-oxaliplatin-containing regimen)
demonstrated preferential benefit for the oxaliplatin-containing
regimen in patients with ypN2 stage III disease and those with
minimally regressed tumors.

87. NCCN
 All such patients receive chemotherapy, even if they have a
pathologic complete response to neoadjuvant therapy.

88. ESMO
 yp stage III and "high-risk" yp stage II patients
 Although only DFS benefit 4% German trial

89. Choice of Regimen

90. German
trial
CAPEOX
Regimen
FolFOX
Regimen
Adjuvant
Regimen

91. NCCN
 Clinical T3N0 tumors and a clear CRM
 Involved or threatened CRM
 T4 primary tumor
 locally unresectable or medically
inoperable disease,
 T1-T3, N1,2
CAPOX, or FOLFOX; in all
case, the oxaliplatin-
containing regimens are
preferred.

92. 2 Weekly 12 cycles for 6
month
3 Weekly 8 cycles for 6
month

93. ESMO
Reasonable to consider adjuvant chemotherapy in rectal cancer
patients with yp stage III and "high-risk" yp stage II tumors,
Although they do not elaborate on the specific characteristics that
define "high-risk" yp stage II tumors.
The decision on whether to choose a fluoropyrimidine alone or
combined with oxaliplatin should be risk balanced, taking into
account both the predicted toxicity for a particular patient and the
risk of relapse; the decision should be made jointly by the clinician
and patient

94. Total Neoadjuvant
treatment – What,When?

95. Regimen
 Preoperative oxaliplatin-based chemotherapy(12-16 week)
 followed by long-course chemoradiotherapy) .
 Re asses after 2 month of chemotherapy ,if no response start
CTRT

96. TNT

97. Indications
 Locally advanced rectal cancer who are at high risk for a margin-
positive resection (ie,
 T4 disease or an involved mesorectal fascia,
 Clearly node-positive disease and a low-lying rectal tumor

98. Rationale
 The increased compliance with chemotherapy .
 The greater tolerability in the preoperative as compared with the
postoperative setting)
 The improved local control,
 The ability to consider nonoperative treatment if the patient declines
surgery.
 Higher pCR rates are attributed to the chemotherapy or to increasing
the interval from RT to surgery
 Addressing potential systemic disease early
 In patients with colostomy don’t have to tolerate chemotherapay with
colostomy

99. Don’t advise- TNT
 Patients with lower risk locally advanced cancers
 Early cT3N0 disease without a threatened mesorectal fascia,
especially involving the upper rectum,
 Distal cT1-2N0 tumors) because these patients may not need
chemotherapy at all

100. Evidence
 Mostly phase II and Retrospective studies
 Given that the comparative analysis was derived from few
randomized publications, large confirmatory trials should be
carried out before a strong recommendation is made in favor of
TNT.
Petrelli et al.
Annals of surgery
March 2020

101. Petrelli et al.
 Total of 28 studies (3 retrospective and 25 prospective for a total
of 3579 patients)
 n = 2688 treated with TNT and n = 891 with neoadjuvant
chemoradiotherapy therapy).
 The pooled pCR rate was 22.4% (95% CI 19.4%-25.7%) in all
patients treated with TNT (n = 27 studies with data available).
 Addition of induction or consolidation chemotherapy to standard
neoadjuvant chemoradiotherapy results in a higher pCR rate.

102. MSKCC study-phase r non randomized
Group PCR(%) Toxicities(%) Grade 3,4
1= LCRT f/b 6-8 weeks later surgery 18 -
2= LCRT – 2 cycle FOLFOX6 25 3
3=LCRT – 4 cycle FOLFOX6 30 18
4=LCRT – 6 cycle FOLFOX6 38 28

103.  the "complete response rate" (which included both the pCRs in
those who underwent surgery and the sustained cCR rate [for at
least 12 months posttreatment] in those who did not undergo
surgery)
 Higher with total neoadjuvant therapy 6 week FOLFOX arm (36
versus 21 percent)

104. Nonoperative management?

105. The OnCore project,
Renehan et al.
Lancent
Oncology DEC
2016

106. 228
31
259

107.  Median follow-up 33 months
 34% had local regrowths (3-year actuarial rate 38%)
 (88%) patients with non-metastatic local regrowths were
salvaged
 No differences in 3-year non-regrowth DFS (88 vs 78%) stastically
significant
 No difference in 3-year OS (96% vs 87%) stastically significant
 Better 3-year colostomy-free survival than did those who had
surgical resection (74 (WW)vs 47%)

108. JAMA Jan19
MSKCC Update
 Jan 2006-15,1070 pts
 Median follow up-43 months
 957 TME
 Wait & Watch(WW)-cCR(Complete Clinical Response) after
NAT(NeoAdjuvantTherapy) & salvage surgery(n=113,10.6%) or
TME & have pCR(Pathological Complete Response n=136,13%)

109. JAMA Jan19
MSKCC Update
Results
 WW-22(19.5%) local recurrence-all had salvage surgery
 No pelvic recurrence in pCR group
 5 years OS of 73% in WW group & 92% in pCR & DFS of 75% vs.
92%
 Distant mets. rate of 36% vs. 1% in local recurrence vs. none

110. Rationale for Organ Preservation in Rectal Cancer
 Different organ-preserving strategies for the treatment of rectal cancer
have gained popularity in the last few years. The main reasons for
avoiding a proctectomy include the significant postoperative morbidity,
including
 Long-term urinary, and sexual and fecal continence dysfunction,
 The requirement for temporary or definitive stomas
 Also, depending on the associated comorbidities and patient’s age,
postoperative mortality may also be quite significant.

111. Ann Surg 2004; 240: 711–7; discussion 717–8.
• N=173 pts
• from 1991 to 2009
• Neoadjuvant chemoRT 50.4
to 54 Gy with concurrent 5-
FU;
• 63% cT3/T4,
• 21% cTxN1-2.
• MFU of 65 mos.
2014
• 39% developed cCR.
• 13% underwent rectal biopsy
• 87% were managed without
surgical procedures.
• 5-yr OS was 96% and
• 5-yr DFS was 72%.
• Recurrences rate(21%)
• 12% pts developed local only recurrence
• 9% developed DM.
• Median time to recurrence was 38 mos.
• 88% who recurred locally were successfully
salvaged.

112. Conclusion
 Patients managed by watch and wait did no worse than patients
managed by radical surgery with pCR.
 Even patients initially suspected for cCR with local recurrence
requiring salvage fared no worse than those undergoing
immediate surgery after CRT completion.

113. Habr-Gama trial
 It was only after the study comparing patients with cCR managed non-
operatively compared to pCR after radical surgery in 2004 showing no
benefit of radical surgery in these patients that watch and wait and
organ preservation after neoadjuvant CRT was brought to the centre
stage in the tailored management of rectal cancer.

114. Habr-Gama trial
 Recurrences after watch and wait were frequently amenable to successful
salvage, excellent local disease control following salvage and often
underwent sphincter preservation or even organ preservation (through
transanal local excisions of the recurrent primary restricted to the bowel
wall).

115. Habr-Gama trial
 The increase in the dose of radiation to 54 Gy (therefore nearly
doubling the boost to the primary tumour),
 The addition of four cycles of chemotherapy (total of six cycles of
fluorouracil throughout the radiation therapy and the waiting periods
compared to the original two cycles) and
 The slight stretch in the waiting period to a minimum of 10 weeks (in
order to accommodate six cycles every 21 days) led to a significant
increase in cCR rates, allowing nearly 50% of consecutive patients with
T2/T3 rectal cancer to ultimately avoid radical surgery.

116. Many studies support this approach

117. CCR -Definition
Although not universally agreed, a cCR is defined as the
 Absence of any palpable tumour or irregularity at DRE,
 No visible lesion at scopy except a flat scar, telangiectasia or whitening
of the mucosa.
 Absence of any residual tumour in the primary site and draining lymph
nodes on imaging with MRI or ERUS, and
 Negative biopsies from the scar.
 An initially raised CEA level which returns to normal (< 5 ng/ml) after
CRT is associated with an increased likelihood of cCR and pCR,

118. Clinical and endoscopic features consistent with a cCR
 mere whitening of the mucosa,
 the presence of telangiectasias and
 modest loss of pliability of the rectal wall in the area of the
original cancer to be present.

120. Problem with evaluation
PET CT Scan, Perez et al.
 93% sensitivity
 53% specificity,
 73% negative predictive value,
 87% positive predictive value for the detection of residual cancer.
 Accuracy of PET/CT was 85%, which was inferior to that of clinical
assessment alone at 91%.

121. MRI
 Role of MRI in evaluating tumor burden at all stages of rectal
cancer management.
 DWI has been particularly useful for predicting tumor response
in multiple sites and has the advantage of providing a
quantitative measurement (apparent diffusion coefficient),
which can be tracked longitudinally and compared to
pretreatment values.

122. Endoscopic Biopsy-Most unreliable
NPV-11% ,Why?
 Most residual tumor burden at deepest layer so full thickness
biopsy is required
 56% of tumor cells located outside ulcer(1 to 3 cm outside)
 Lymphnode can not be detected

124. NCCN on nonoperative management
 For patients who achieve a cCR with no evidence of residual
tumor on DRE, rectal MRI, and direct endoscopic evaluation, an
initial nonoperative approach may be considered with an
experienced multidisciplinary team.
 However, given the degree to which the risk of local and distant
relapse has not been adequately characterized, any decision for
nonoperative management should involve a careful discussion
with the patient as to his/her risk tolerance.
 LR -20% Distant mets-36%

126. Caveat
 Taken together, most of the data suggest that a careful
endoscopic, clinical, and radiographic evaluation might be able to
identify patients who have a good likelihood of local tumor
control and may not need surgery.
 However, none of these data are from prospective randomized
trials, and they all suffer from significant limitations.
 In my view, longer term follow-up (including outcomes of salvage
surgery larger numbers of patients, and well-designed
prospective randomized trials are needed to validate this
approach

129. Take home message
 LCRT- CRM+, T4 ,Node+ mid and low rectal tumors (CAT 1 NCCN)
 SCRT- Preferable in (CAT 2A NCCN)
 Mid rectum clear CRM and T3 lesions
 Avoid in low bulky tumour and CRM

130. TNT- Total neoadjuvant treatment
 considered in (CAT 2A NCCN)
 Bulky T4 tumor or CRM+
 Low rectal tumour with bulky node ,
 Unresectable disease ,
 Medically inoperable

131. Upper rectum
 Preop SCRT/LCRT if peritoneal reflection is involved

132. Adjuvant after Preop CTRT
 12 week of adjuvant therapy preferred in all patient of stage
II,III who underwent preop CTRT
 Choice of Regimen
 FolFOX or CapeOX ,(ADORE Trail)
 Adding oxaliplatin give 4 % DFS benefit(German Trial)
 Duration of chemotherapy
 Total 6 month of chemotherapy should be given including
preoperative and adjuvant setting.
 Although 4 month is suffice in TNT setting

133. Timing of Surgery
 7 week after completion of radiotherapy(GRECCAR 6 Trial)
 6 week after completing SCRT- Stockholm III trial

134. Non-operative Management
 At present should be offered in experienced centres where
patient can be subjected to rigorous and meticulous followup,
&MRI surveillance is available with more frequent than routine
surveillance to ensure that surgical salvage is feasible and timely
 More prospective studies are needed to validate .
 Patients should be informed that the strategy remains unproven
and that a small increased oncological risk of uncontrolled
pelvic and metastatic disease (14-30%)exists, although the
prognosis of patients with cCR is excellent even without surgery.

135. No Strong evidence uptill now- not
recommended
 Only Preop Chemo vs Preop CTRT( FOWAC Trial)
 Only Preop RT vs Preop CTRT( EORTC 22921)
 Preop CTRT in T1,T2 No lesions to preserve sphincter

136. Thank You