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Multimodality Therapy of Rectal Cancer. Robert D. Madoff, MD University of Minnesota. rectal cancer clinical issues. colostomy or anastomosis? local or radical surgery? functional outcomes? neoadjuvant therapy?. rectal cancer therapy. morbidity mortality function. optimal cure rate.
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Multimodality Therapy of Rectal Cancer Robert D. Madoff, MD University of Minnesota
rectal cancerclinical issues • colostomy or anastomosis? • local or radical surgery? • functional outcomes? • neoadjuvant therapy?
rectal cancer therapy morbidity mortality function optimal cure rate
total mesorectal excision • the rectum and its mesentery are a single fascia-enveloped unit, anatomically separate from surrounding pelvic structures • surgical violation of this anatomic package leads to a positive circumferential margin, a known predictor of local recurrence
circumferential resection margin % Adam 1995
rectal cancer stage dictates therapy
rectal cancer know your enemy!
Preop Staging • Review of 83 studies including 4897 patients Kwok 2000
Prediction of Involved CRM Beets-Tan 2004
local recurrencesurgeon as risk factor 50 % surgeon minimum 25 rectal cancer operations per surgeon Holm 1997
rectal cancer know your surgeon!
circumferential resection margin % Adam 1995
rectal cancer surgeryimpact of technique p < 0.0001* p < 0.002* % * Stockholm I and II vs TME project Lehander Martling 2000
Combined postoperative chemotherapy and radiation therapy improves local control and survival in Stage II and III patients and is recommended. NIH Consensus Statement, 1990
rectal cancerradiation + chemo local recurrence (%) Krook 1991
rectal cancerradiation + chemo, vs. TME alone local recurrence (%) Krook 1991 Heald 1998
radiation therapy friend or friendly fire?
radiation therapydisadvantages • cost • convenience • complications • covering stomas • quality of life
postop chemoradiationfunctional results CT/RT surgery only (%) (%) BM / 24 hr 7 2 nighttime BMs 46 14 occasional incontinence 39 17 frequent incontinence 7 0 pad 41 10 unable to defer BM 15' 78 19 Kollmorgen 1994
short course rtlong-term morbidity Holm 1996
radiation therapycontroversies • patient selection • who needs adjuvant therapy? • timing • pre- or postoperative? • technique • short or conventional course?
surgery +/- rt 2-year survival p=0.84 % Dutch TME Trial
rectal cancerradiation timing • biology • downstaging • resectability • sphincter salvage • margins • sb complications • functional results pre post • staging accuracy • avoids overtreatment • anastomotic leak risk • covering stomas
German rectal cancer study 823 patients - Stage II-III 50.4 Gy RT + Chemo OR (TME) 50.4 Gy RT + Chemo OR (TME) Sauer 2003
German rectal cancer study Pre-Op Post-Op Leak 10% 12%Bleed 2% 3%Delayed healing 4% 6%Stricture 4% 12%*Acute toxicity 27% 40%* Sauer, NEJM 2005
German rectal cancer study Pre-Op Post-Op Downstaging 8%Sphincter Preservation 39% 19%*LocalRecurrence 6% 13%*Survival 76% 74% Sauer, NEJM 2005 * p<0.05
short vs. long course United States: 45-54 Gy OR 6 weeks Europe: 25 Gy OR 1 week
short course radiation • convenience • cost • effectiveness pro con • unsafe if given improperly • ? higher rate of late toxic effects • cannot give simultaneously with chemotherapy
radiation therapycurrent status (USA) • optimally stage patient (ERUS) • conventional (long course) RT plus chemotherapy for stage II (T3), stage III (N1) or stage IV cancers • postoperative chemoradiation for positive circumferential margin • consider postoperative chemoradiation for understaged T3 or N1 lesions
RECTAL CANCERLOCAL EXCISION pro low morbidity/mortality avoids sexual/urinary/bowel dysfunction avoids colostomy con nodal status not pathologically assessed involved nodes not excised ? equivalent oncologic results to radical excision
…ma prima assicurati che sia proprio ad una pulce che stai sparando!
local therapyresults 25 local recurrence (%) T1: local excision T2: local excision plus chemoradiation CALGB 8984
local excision vs.radical surgery local recurrence (%) T1: local excision T2: local excision; no chemoradiation Garcia-Aguilar 2000
“Dr. Mellgren and colleagues deserve to be congratulated for their honesty…” Steele 2000