3. Palliative
Curative
◦ Surgery
◦ Surgery + neoadjuvant Tx
◦ Surgery + neoadjuvant + adjuvant Tx
◦ Surgery + adjuvant Tx
◦ (Radiotherapy)
4.
5. Dukes A = T1/T2, N0
Dukes B = T3/T4, N0
Dukes C = Any T, Node positive
(Dukes D = Any T, Any N, M1)
Applies to rectal and colon cancers
6. Surgery alone provides high cure rate for early
stage disease
5yr survival rates Stage I = 80-90%
5yr survival rates Stages II or III = <70%
7. Pts who have undergone a potentially curative
resection, disease recurrence is thought to be due
to micrometastases present at the time of surgery.
The aim of adjuvant therapy is to eradicate these.
8. Rectal cancer adjuvant therapy = chemotherapy
+/- radiotherapy
Colon cancer adjuvant therapy = chemotherapy
Don’t forget neoadjuvant CRT or DXT or chemo
alone
9. After recovery from surgery
In general, six to eight weeks
No trials specifically looking at effects of delay
Delay beyond 2 months may compromise the
effectiveness of chemo.
10.
11. Operations:
1. Anterior resection
2. Low anterior resection
3. Abdomino-perienal excision of rectum (APER)
4. TART / TEMS
12. After surgery alone:
◦ <10% T1-2
◦ 15-35% T3N0
◦ 45-65% T3-T4, node positive
Figures above before the use of TME excision
(Now <10%)
13.
14. Meta-analysis of RCTs in 1980s showed:
◦ Improved local control
◦ Increased time to local recurrence
With adjuvant RT in stage II or III disease
5yr risk of LR 17% vs 28% (surgery alone)
However, no survival benefit (58 vs 59%)
15. RCTs in 1980s & 1990s showed survival advantage if 5-
Fluorouracil (5FU)-based chemo added to RT Trials used
chemo high risk of leukaemia = methyl-CCNU
2012 Meta-analysis of 9,221 pts (21 trials) sig reduction
in risk of
◦ disease relapse (HR for relapse 0.75, 95% CI 0.68-0.83), and
◦ death (HR for death 0.83, 95% CI 0.76-0.91)
◦ (chemo alone vs no chemo)
16. 5FU sensitises tissues to RT
◦ Miller et al 2002, showed improved survival and
decreased metastases, but no difference in LR
◦ Smalley et al 2006, showed no difference
?higher risk of acute reaction with infusion, plus
cost, inconvenience and risks of CVP line
17. Orally active fluoropyrimidine which is converted
to 5FU
Can be used as neoadjuvant or adjuvant therapy
in combination with RT
However, no long term studies available
comparing infusional 5FU and capecitabine
18. No specific trails for rectal cancer, but has been
shown to improve outcomes in colon cancer
19. ‘Sandwich’ technique
◦ 1 or 2 cycles of chemo (2 months)
◦ Combined modality (6 weeks)
◦ Additional chemo (2 months)
No trial have shown disadvantage or benefit for
giving RT early or in the middle of sequence
22. Stage I – surgery alone
Stage II or III – sig local control & survival benefit
for adjuvant CRT
Fluoropyrimidine as radiation sensitiser (5FU)
Leucovorin,oxaliplatin
23. 3 or 4 field approach (PA, left & right lateral +/-
AP)
Lower level of L5 to 5cm below anastomosis or
perineum (APER)
1.5cm beyond bony pelvis laterally
Prone position
Full bladder
24. 1.8Gy, five fractions per week to a total dose of
45Gy
Field size then reduced and a ‘boost’ dose is
delivered to the tumour bed
Avoid excess radiation to small bowel
25.
26. Operations
◦ Right hemicolectomy (extended)
◦ Left hemicolectomy (extended)
◦ Subtotal colectomy
◦ Sigmoid colectomy
◦ Total colectomy
27.
28. Stage III Disease (node +ve)
◦ ~30% rel reduction in risk of disease recurrence
◦ 22-32% rel reduction in mortality
Stage II Disease (node –ve)
◦ Benefits less certain, and chemo use is varaible.
29.
30. Fluoropyrimidine-based chemo
◦ Multiple trials have included stage II & III pts
◦ QUASAR & IMPACT B2 trial looked at stage II disease
only
Non-significant trend towards improved survival comapred to
observation alone
Neither trial enrolled enough pts though
31. Intergroup 2004
◦ 3302 pts with stage II or III colon cancer
◦ Stat sig improvement in 5-yr DFS (76 vs 72%)
◦ No sig difference in overall survival (81 vs 76%)
Ontario Group 2004
◦ Systematic review, 4187 pts
◦ 5-10% sig improvement in DFS
◦ No sig diff in overall survival
◦ ∴ASCO does not support the routine use of
adjuvant chemotherapy for stage II colon cancer
32. 6 months of adjuvant 5-FU/LV versus FOLFOX
(Oxaliplatin, leucovorin, 5-FU/capecitabine) in pts
with resected stage II or stage III colon cancer
Min 6 yrs FU
◦ Stat sig increase in overall survival (76 vs 79%, HR for
death 0.84, p=0.046), but this was limited to stage III
disease.
◦ Stage II = 87% both Tx arms
◦ DFS 80 vs 84%, p=0.26
33. Worse prognosis:
◦ T4 primary
◦ Poorly differentiated
◦ Lymphovascular or perineural invasion
◦ Bowel obstruction or perforation
◦ Close or positive margins
◦ <13 LN sampled
◦ High pre-op CEA level
34. Worse prognosis:
◦ T4 primary
◦ Poorly differentiated
◦ Lymphovascular or perineural invasion
◦ Bowel obstruction or perforation
◦ Close or positive margins
◦ <13 LN sampled
◦ High pre-op CEA level
5yr DFS with 0, 1 or ≥2 = 95%, 85%, 57%
35. No evidence that these high-risk factors are more
likely to benefit from chemo
Factors with a poorer prognosis are not
necessarily predictive of chemo response
However, ASCO 2002 suggested that adjuvant
therapy be discussed in medically fit pts with high-
risk clinicpathological features
36. Various research studies ongoing to identify
factors which may influence prognosis & response
to chemotherapy
Only one identified is microsatellite instability (MSI
= biologic footprint of DNA mismatch repair
deficiency) which is assd
with resistance to 5-FU,
but these tend to be less aggressive cancers
37. Adjuvant! Online
Estimates risk of recurrence & death based on
clinicopathologic features
www.adjuvantonline.com
US SEER tumor registry
38. Role is poorly defined
Subgroups to offer:
◦ Est local recurrence risk ≥ 30%
◦ Ascending or descending colon primary with T4 disease
or positive resection margin
39. 5-FU-based chemo does NOT exceed an absolute
improvement in 5yr survival of 5%
Should NOT be standard care
However, risks & benefits should be discussed
(SE, risk of recurrence or death)
‘High-risk factors’
RT for limited no. of pts.
40.
41. International Multicentre Pooled Analysis of Colon
Cancer Trails
◦ 1526 pts with Dukes’ B or C
◦ Observation vs 6 cycles of 5-FU/LV
Significant 22% reduction in death
◦ 3yr overall survival 83% vs 78%
◦ Benefit almost entirely limited to stage III disease
42. FOLFOX vs 5-FU/LV alone
Stat sig improvement in overall survival
5yr DFS 73% vs 69%, HR 0.80, p= 0.023)
Febrile neutropaenia (1.8% vs 0.2%)
Grade 3 or 4 diarrhoea (10.8% vs 6.6%)
92% developed peripheral neuropathy (severe in
13%)
43. 2407 pts with stage II or III
FOLFOX vs 5-FU/LV
5yr DFS 69% vs 64%, HR 0.82
Overall survival not significant
◦ 80% vs 78%, HR 0.88
Toxicity for both groups
45. Adjuvant systemic therapy initiated within 6-8
weeks of surgery
6/12 of oxaliplatin-based regimen (if pt likely to
tolerate it)
◦ Contraindications inc pre-existing neuropathy
Or, 5-FU/LV (but ?less favourable outcomes)
RT for high risk local recurrence (T4 &
penetration to a fixed structure, or postive
resection margins)
46. Rectal cancer = chemotherapy +/- radiotherapy
Stage II colon cancer = chemotherapy if high risk
& fit
Stage III colon cancer = oxaliplatin-based
chemotherapy
Stage IV disease = chemotherapy
Don’t forget lifestyle changes?!?
Don’t forget neoadjuvant treatment
