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