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Rectal cancer

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

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Rectal cancer

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  1. Rectal cancer

  2. 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

  3. Survival

  4. 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 XRT T1 10% T2 15-35% T3 20-45% T4 >50% N+ 40-65%

  5. 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 depth Of tumor penetration & LN Status if available Depth of invasion & LN involvement help predict prognosis

  6. 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

  7. TRUS

  8. PREOPERATIVE STAGING OF RECTAL BOWEL WALL INVASION LYMPH NODES DISTANT METASTASIS CURRENT KEY CONCEPTS WELL DEFINED BY MRI DISTANCE TO MESORECTAL FASCIA SPHICNTER INVOLVEMENT VENOUS INVASION

  9. STEPS FORWARD in RECTAL CANCER: Surgery • 1875-1885 – 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

  10. Bill Heald 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

  11. TME

  12. 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 rate • CRM >2mm (5.6% LR) • CRM < 2mm (16% LR) • < 1 mm higher rate (37.6% LR ) and poorer survival • Preservation of sexual and urinary function

  13. Pathological section

  14. THE ROLE OF THE PATHOLOGIST CURRENT KEY PATHOLOGICAL CONCEPTS MACROSCOPICAL INTEGRITY OF MESORECTUM DISTANCE TO CIRCUMFERENTIAL RESECTION MARGIN STAGING AFTER PREOPERATIVE CHEMORADIATION

  15. 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

  16. 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%

  17. Stoma Astomais an opening (Greek for “mouth”) of a hollow viscus draining tothe 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

  18. Complications of colostomy

  19. TRANSRECTAL LOCAL EXCISION OR TRANSRECTAL ENDOSCOPIC MICROSURGERY (TEM)

  20. 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

  21. Local Excision • Transanal Approach • 1-3 cm margin • Full thickness • Oriented for pathology

  22. Transanal Endoscopic Microsurgery (TEM)

  23. TEM & Rectal Cancer • Indication for rectal carcinoma - T1. - Negative LN. - 3 cm. - 10 cm high. - mobile, non fixed - Exophytic. - Well to mod. diff. - Without signet ring cells.

  24. T1 Rectal Cancer Local / 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

  25. Kikuchi classification

  26. CONCLUSION (LE & TEM) • Local excision is NOT oncologically equivalent to Standard Excision -Can be used for benign lesionsabove the peritoneal reflection - Only T1 (preferablefor favorable T1 lesions (S1)) - T2: • Medical contraindications to radical surgery is present • The patient is unwilling to extensive surgery • For palliation

  27. 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

  28. Preoperative radiotherapy was introduced in 1997 (Swedish rectal cancer trial) (1168 pts) preop RT + surgery vs surgery alone LOCAL RECURRENCE11% vs 27% PROLONGED OS58% 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

  29. Are there benefits to Neoadjuvantchemoradiation 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?

  30. Summary of Randomized Trials • 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) • Does neoadjuvant CRT ↑ rate of sphincter-sparing surgeries? FFCD 9203 Trial:NO Polish Trial: NO EORTC 22921 Trial: NO German Trial: NO (Preop vs Postop CRT) All Studies Show ↑pCR with CRT No. But, in German Trial those Determined to need AR prior To randomization had ↑ rates of Sphincter-preservation with CRT Preoperatively.

  31. Summary of Randomized Trials • 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) • 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/DFS Seen in German Trial YES, ↓risk of local recurrence. NO ↓ risk of distant recurrence

  32. Summary of Randomized Trials • 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) • How is patient compliance with neoadjuvant CRT FFCD 9203 Trial: 93% Neoadj CT & 78.1% Adjuvant CT Polish Trial: Not reported EORTC 22921 Trial: 82%Neoadj & Adjuvant CT 42.9% German Trial: 92% Preop CT & 53% Postop CT

  33. 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?

  34. 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

  35. TNM Staging & Treatment Strategies T1-2/N0  Transanal Excision versus AR T3-4/N0 or any T/N1-2  Neoadjuvant chemotherapy • 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

  36. Thank you

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