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Rectal cancer
OLD APPROACH TO RECTAL CANCER
CURRENT APPROACH TO RECTAL CANCER
Surgical resection
Pathology assessment and estimation of risk
Treatment based upon classical TNM factors
Postoperative concurrent chemo-radiation
Staging workup (MRI,TRUS,PET CT)
MDT discussion
Preoperative chemo-radiation if indicated
TME Surgical resection
Pathology assessment and estimation of risk
Postoperative chemotherapy if indicated
Survival
Local recurrence Usually seen within 2 years
Factors influencing local recurrence include:
• TNM Stage• Surgical experience/technique and completeness of resection (spillage)• Use of adjuvant therapy• Tumor differentiation and macroscopic appearance• LVI, NVI Stage 5 year, no adjuvant XRTT1 10%T2 15-35%T3 20-45%T4 >50%N+ 40-65%
Staging workup
Physical Exam Colonoscopy Rigid proctoscopy (measurement of distance from
anal verge) CEA CT chest/abdomen/pelvis
PET CT TRUS MRI
Recommended to assess depthOf tumor penetration & LN
Status if available
Depth of invasion & LN involvement help predict prognosis
TRUS TRUS is ideal for staging T1/T2 tumors (sensitivity and specificity of 94% and 86%, respectively)
Nodal staging using TRUS is more challenging (sensitivity and specificity are approximately 55% and 78%, respectively)
Limitations of TRUS:
• stenotic circumferential rectal tumors
• lesions treated with preoperative radiotherapy
TRUS
PREOPERATIVE STAGING OF RECTAL
BOWEL WALL INVASION LYMPH NODES
DISTANT METASTASIS
CURRENT KEY CONCEPTS
WELL DEFINED BY MRI
DISTANCE TOMESORECTAL
FASCIA
SPHICNTERINVOLVEMEN
T
VENOUSINVASION
STEPS FORWARD in RECTAL CANCER: Surgery1875-1885 – Paul Kraske – sacral approach
1908 - Ernest Miles established the abdominoperineal resection (APR) as conventional treatment for the rectum tumors
1960 – Dixon – anterior resection 1970 – circular stapler
1982 – Bill Heald - introduced TME has increased cure rates while reducing local recurrence.
1993 - TEM developed by G. Buess
TME
• A professor of surgery at North Hampshire Hospital
• Surgical director of the pelican cancer foundation,Basingstoke, Hampshire, UK.
• For more than 30 years, his focus has been research and development of the total mesorectal excision (TME) technique for rectal cancer, which is now the gold standard treatment for bowel cancer.
• TME has increased cure rates while reducing local recurrence
Bill Heald
TME
TME Total mesorectal excision
- Sharp and accurate dissection in the extrafascial plane (the plane between the fascia propria
of the rectum and the presacral fascia)
- The “holy” plane
- 2.8% local recurrence rate( probably 6%) Circumferential rectal margin - independent
predictor of local recurrence rateCRM >2mm (5.6% LR) CRM < 2mm (16% LR) < 1 mm higher rate (37.6% LR ) and poorer survival
Preservation of sexual and urinary function
Pathological section
THE ROLE OF THE PATHOLOGIST
CURRENT KEY PATHOLOGICAL CONCEPTS
MACROSCOPICALINTEGRITY OFMESORECTUM
DISTANCE TOCIRCUMFERENTIA
LRESECTION
MARGIN
STAGING AFTER PREOPERATIVE CHEMORADIATION
Anastomotic leak and stoma
LAR for rectal cancer has 3-30% risk anastomotic leak
6-22% mortality rate with symptomatic anastomotic leak
Role of protective enterostomy?
One objection stoma is that it requires second operation to close, including added risk of complication and death
Few studies investigating role of stoma
No significant difference in overall leak rate b/w 2 groups
Patients with stoma incidence of leak, that required surgical
intervention significantly post-op morbidity
significantly post-op mortality general post- closure complication rate of 4.7%
overall morbidity rate for closure 19.8%
Stoma A stoma is an opening (Greek for “mouth”) of a hollow viscus
draining to the skin
“end” stoma “loop” stoma
Purpose of stomas
Permanent stoma Temporary “defunctioning” stoma Complications of stomas
Parastomal hernia (prolapse) Stricture Retraction Abscess or fistula around stoma
Diarrhoea Intestinal obstruction Skin excoriation
Complications of colostomy
TRANSRECTAL LOCAL EXCISION OR TRANSRECTAL ENDOSCOPIC MICROSURGERY
(TEM)
Goals of Therapy
Traditional Endpoints
Perioperative M&M
Recurrence Locoregional Distant
Survival Disease Free Overall
The New Endpoints
Psychological – living with a bag
Urinary and sexual function
Minimizing scars on abdomen
‘Organ’ preservation– continence vs stoma
Local ExcisionTransanal Approach
1-3 cm margin
Full thickness Oriented for pathology
Transanal Endoscopic Microsurgery (TEM)
TEM & Rectal CancerIndication for rectal carcinoma
- T1.
- Negative LN.
- 3 cm.
- 10 cm high.
- mobile, non fixed
- Exophytic.
- Well to mod. diff.
- Without signet ring cells.
T1 Rectal CancerLocal / regional
tumor recurrence
5 year follow up:
• LE 12.7%• SR 6.1% p <
0.03
8 year follow up:
• LE 14.4%• SR 9.5% p
<0.01
Limitation: lymph node resection
T1 rectal cancer - 5% LN
T2 rectal cancer - 12-22% LN
Source: N You, N Baxter, S Nelson H Nelson, J Clin Onc 2005 Vol 23 No 16
Kikuchi classification
CONCLUSION (LE & TEM)Local excision is NOT oncologically equivalent to
Standard Excision
- Can be used for benign lesions above the peritoneal reflection
- Only T1 (preferable for favorable T1 lesions (S1))
- T2:
Medical contraindications to radical surgery is
present
The patient is unwilling to extensive surgery
For palliation
STEPS FORWARD in RECTAL CANCER: Radiation
1970s-80s: -- Trials of Radiation vs. Surgery alone
(GITSG;NSABP;NCCTG) -- Meta-analysis of 22 RCTs
• Post-op RT reduces LRR by 46%• No impact on OS, 62 vs 63% (p=0.06)
-- NSABP R-02 showed that postoperative chemo-radiation
reduced the incidence of LR from 13% to 8% at 5-year follow-up
1990: Post-operative chemo-radiation becomes standard
1990s: Total Mesorectal Excision established as superior surgical modality
Preoperative radiotherapy was introduced in 1997 (Swedish rectal cancer trial) (1168 pts)
preop RT + surgery vs surgery alone LOCAL RECURRENCE 11% vs 27% PROLONGED OS 58% vs 48%
Dutch TME trial (2003) (1861 pts)
preop RT + TME vs TME alone LOCAL RECURRENCE 2.4% vs 8.2% PROLONGED OS no difference
Are there benefits to Neoadjuvant chemoradiation in rectal cancer?
Are rectal tumors downstaged with neoadjuvant CRT?
Does neoadjuvant CRT ↑ rate of sphincter-sparing surgeries?
Does neoadjuvant CRT ↑ OS or DFS?
Does neoadjuvant CRT ↓ risk of local recurrence or distant recurrence?
Is there a significant ↑ in toxicity with neoadjuvant CRT?
How is patient compliance with neoadjuvant CRT?
Summary of Randomized Trials
1. Are rectal tumors downstaged (pCR) with neoadjuvant CRT?
FFCD 9203 Trial: YES (11.4% CRT v. 3.6% RT; p<0.0001)Polish Trial: YES (16.1% CRT v. 0.7% RT; p<0.001)EORTC 22921 Trial: YES (13.7% CRT v. 5.3%; p<0.001)German Trial: YES (8% CRT v. 0% CRT)
2. Does neoadjuvant CRT ↑ rate of sphincter-sparing surgeries?
FFCD 9203 Trial: NOPolish Trial: NOEORTC 22921 Trial: NOGerman Trial: NO (Preop vs Postop CRT)
All Studies Show↑pCR with CRT
No. But, in German Trial those Determined to need AR priorTo randomization had ↑ rates ofSphincter-preservation with CRTPreoperatively.
Summary of Randomized Trials
1. Does neoadjuvant CRT ↑ OS or DFS?
FFCD 9203 Trial: NO - 67.4% / 59.4% (5-year)Polish Trial: NO - 66.2% / 55.6% (4-year)EORTC 22921 Trial: NO - 64.8% / 56.1% (5-year)German Trial: NO - 76% / 68% (5-year)
3. Does neoadjuvant CRT ↓risk of local recurrence // distant recurrence?
FFCD 9203 Trial: YES (8.1% CRT v. 16.5% RT) // NO (36%)Polish Trial: NO (15.6% CRT v. 10.6% RT) // NO (34.6%)EORTC 22921 Trial: YES (13.7% CRT v. 5.3%) // NO (34.4% all grps)German Trial: YES (6% Preop CRT v. 13% Postop CRT) // NO (36% Pre)
NO. But better OS/DFSSeen in German Trial
YES, ↓risk of local recurrence.NO ↓ risk of distant recurrence
Summary of Randomized Trials
5. Is there an in grade 3-4 toxicity with neoadjuvant CRT?
FFCD 9203 Trial: YES (14.9% CRT v. 2.9%; p<0.0001)Polish Trial: YES (18.2% CRT v. 3.2% RT; p<0.001)EORTC 22921 Trial: YES (Slight ↑ in toxicity CRT>RT)German Trial: NO (27% Preop v. 40% Postop; p=0.001)
6. How is patient compliance with neoadjuvant CRT
FFCD 9203 Trial: 93% Neoadj CT & 78.1% Adjuvant CTPolish Trial: Not reportedEORTC 22921 Trial: 82% Neoadj & Adjuvant CT 42.9%German Trial: 92% Preop CT & 53% Postop CT
Status Quo for Resectable Stage II/III Rectal Cancer
Pre-operative tumor staging:• Endorectal US or Pelvic MRI
Pre-operative Radiation/Chemoradiation:• For tumors ≤ 12 cm
Capecitabine or Inf 5-FU if Long Course Radiation
Post-operative chemotherapy:• Clinical or Pathologic stage?• Stage II: Capecitabine or 5-FU/Leucovorin• Stage III: FOLFOX – evidence?
OTHER STUDY
Camma etal. (meta-analysis) JAMA 2000 14 studies , 6426 patients Early rectal cancer(T1/T2) show no benefit from pre-
op RCT
Lopes – Kostner etal. (Cleveland) Surgery 1998
Upper third rectal cancer behave like colon cancer in terms of LR and disease profile
T1-2/N0 Transanal Excision versus AR
T3-4/N0 or any T/N1-2 Neoadjuvant chemotherapy
TNM Staging & Treatment Strategies
Definitive Indications:•T3-T4 tumors
Relative Indications:•T1-T2 / N+ tumors (by TRUS / MRI)•Distal rectal tumors likely to require APR•Invasion of mesorectal fascia
Thank you