Do all patients with T2-3 mid-high rectal

adenocarcinomas require RT as part of their

neoadjuvant therapy?

- Yes -

Bruce Minsky

Colon vs. Rectal Cancer

Colon: Time to Recurrence

Sargent et al JCO 2007

CAO/ARO/AIO 94

Roedel et al JCO 2012

Preoperative Staging

TRUS or MRI: T stage: 90%N stage: 60-70%

MRI + contrast*:T stage: 90%N stage: 70-80% (↑ appx 10%)

*Gadofosveset (Lambregts, Ann Surg 2011)*Iron oxide (Will et al, Lancet Oncol 2006)

Risk of LN+ by Distance

· 188 Pts with cT3N0 s/p preop CMT · 6 international centers

Cm from AV # % ypN+0-5 103 23 5-12 85 20

High tumors have equivalent risk of LN+Guillem et al JCO 2008

Guillem pooled analysis

cT3N0 @ 10 cm: CMT vs. LAR

PREOP CMT- improved local control- less toxicity- but over treat 20% (pT1-2N0)

SURGERY- avoid RT- but if N+ (22% s/p preop CMT*)

then need postop CMT- decreased local control- higher toxicity- poor function

Guillem et al JCO 2008

Distance from the AV

Caveats:

· All are subset analysis · Include cT1-3 tumors· Variable methods to measure distance· 5 Gy x 5

· Dutch: flexible scope, < 15 cm, TME · German: rigid scope, < 16 cm, TME· SRCT: no details, variable surgery

Distance from the AV

Surgery Preop RTCm % 5-Yr LF % 5-Yr LF p

DutchHigh 10.1-15 6 4 -Mid 5.1-10 14 4 <0.001Low < 5 12 11 -

SRCTHigh > 11 12 8 -Mid 6-10 26 9 <0.001Low < 5 27 10 0.003

Distance from the AV

Pre-op Location # %10-Yr LF< 6 cm 166 116- <12 cm 166 512-16 cm 37 10

German

Preop CMT – Selective RT

Schrag et al JCO 2014

∙ 32 Pts, LAR eligible, uT2N1, uT3N0-1

FOXFOX/BEV x 4 FOLFOX x 2 Surgery

∙ If preop POD salvage preop RT∙ If pT4, N2, or margin+ post RT

∙ R0: 30/30∙ pCR: 25%∙ No preop RT, 2 postop RT∙ 4 years: 0 LF, 84% DFS

* Alliance N1048 – 1000 pt trial

Preop CMT – Selective RT

• 28 pts, Multicenter phase II• MRI: T3 or > 2mm from mesorectal fascia (? LN)• Mid rectal (> 5 cm from AV)• 4 cycles Induction CAPOX-B

• None required preop CMT• 15 % pCR, all R0 • 2 pts with pN2 needed postop CMT• 50% Gr 3+ toxicity

Fernandez-Martos et al, ProcASCO 2012

….Yes

· Local recurrences in rectal cancer occur late

· LN+ is primary cause of LF

· 22% ypN+ even after preop CMT for cT3N0

· LN + is independent of distance from AV

·CT alone data are investigational and may have higher toxicity