Rectal Cancer

== Rectal Cancer Trials ==

Surgery

Local Failure After Surgery Alone[1] [4]

T Stage Local Failure Rate
with APR/LAR only
Local Failure
with TME
T1 4-12% ~5%
T2 12-28% ~20% (8%-48%)
T3 36-79%

Surgical Techniques

Low Anterior Resection (LAR)

  • removes rectal cancer, adjacent normal tissue, and surrounding lymph nodes
  • incision is made in the lower abdomen
  • temporary colostomy

Abdominoperineal Resection (APR)

  • remove rectal cancer, adjacent normal rectum, rectal sphincter or anus, and surrounding lymph nodes
  • incision is in the lower abdomen and the perineum
  • permanent colostomy
  • Tumors < 5 cm from anal verge have traditionally required APR

Total Mesorectal Excision (TME)

  • sharp dissection along the mesorectal fascia to remove the rectum and its surrounding adventitia en bloc
  • mesorectum contains the blood supply and the lymphatic drainage for lower, middle and upper rectum
  • consequence of TME can be bladder and erectile dysfunction
  • TME resulted in marked decrease in local recurrence rates to 1.6-17.8%[3]
  • The type of primary operation, LAR or APR, does not seem to affect the LR rate.

Transabdominal Resection

  • Abdominoperineal resection (APR) or low anterior resection (LAR) using total mesorectal excision (TME)

Transanal Excision

  • no incisions
  • instruments though the anal opening
  • a type of wide local excision

Lymph Node Assessment

  • 7-14 lymph nodes need to be assessed per Rectal Intergroup Trial 0114.

Radiation Issues

Comparison of Pre-operative vs. Post-operative Radiation:

Advantages to Pre-op

  • convert APR to a sphincter sparing procedure
  • oxygenated tumor bed
  • no tumor spill
  • lower dose
  • smaller fields
  • less bowel in the field.

Advantages to Post-op

  • pathologic staging
  • spare the 10-15% patients with T1-2 tumors adjuvant treatment
  • tumor bed located by clips.

Pre-operative Radiation

Summary

  • Improves local control (~ 10%) and DFS (~ 5%) for doses of RT > 30 Gy BED
  • Surival beneift is uncertain
    • Some randomized trials show improved OS
    • In one meta-analysis DFS benefit was cancelled by equivalent early non-cancer deaths
    • A 2nd meta-analysis by Camma did show a overall survival benefit (p = 0.03)
      • but absolute % benefit was not given.

Post-op Radiation

Summary[6] [5]

  • Local control benefit with post-op radiation
  • 2 of 5 randomized trial showed local control benefit with radiation
  • NSABP B-01 (46-47 Gy) and MRCRWP
    • NSABP is the trial to give continuous course of radiation using modern techinques.

Pre- vs. Post-operative ChemoRT Trials (Randomized)

Summary of German Rectal Cancer Study Group (NEJM 2004) and Swedish Trial

  • No difference in DFS or OS
  • Improved sphincter sparing and local control with pre-operative chemoradiation

Combined modality treatment

GITSIG:
202 patients T3 and or N+ randomized to
1) surgery alone 2) post-op RT alone 3) chemotherapy alone 4) post-op RT + 5Fu/CCNU.
Patients receiving CMT did better than surgery alone with survival at 54% vs. 27%.
No difference between RT, chemotherapy, or surgery alone groups.
Mayo-NCCTG 79-47-51:

Post-op RT vs. RT + chemotherapy and
combined group showed improved LC (14% vs. 25%), DFS (63% vs. 42%), and control of DM rate (30% vs.46%).
Do not use post-op RT alone.

Chemotherapy Issues

Continuous Venous Infusion

  • When combined with radiation, continuous 5-FU has 10% DFS and 10% OS benefit over bolus 5FU (INT 86-47-51)

INT 86-47-51 (NCCTG)[7]

  • Continuous (PVI) 5-FU 225 mg/m2 over 24 h 7 d/wk during RT vs. Bolus 5-FU concurrent with RT
  • DFS 63 vs 53 (0.01) in favor of PVI + RT
  • OS 70 vs 60 (.005) in favor of PVI + RT
  • No difference in local control

Post Operative Therapy

  • Post operative chemotherapy is required in all patients receiving pre-operative therapy regardless of pathology.
  • (Need for post-operative therapy may be based on colorectal trials, just 2 trials listed below)
    • NSABP C-01 MOF OS advantage over surgery alone (p = .05).
    • NSABP C-03 OS-3 years was superior for the post-op 5-FU/leucovorin arm vs MOF (84% vs. 77%; P = .003).
  • NCCN recommendation is for 5FU (380 mg/m2/day) + leucovorin(20mg/m2) days 1-5 q 28 days for 4 cycles.

Treatment and Outcome by Stage

Very Favorable Rectal Cancer

Risk Factors

  • T1 N0
  • < 30% of circumference
  • < 3 cm, mobile
  • < 8 cm of anal verge
  • No LVI, PNI, or poor differentiation

Treatment

  • transanal resection

Results

  • Local failure is <10%.

Early Rectal Cancer

Risk Factors

  • T1/T2 N0 Tumors that are not very favorable early rectal cancer

Treatment

  • Transabdominal Resection
  • No radiation
  • No chemotherapy

Results

  • Local failure rate and nodal incidence vary depending on report (see table above).

Locally Advanced Tumors

  • cT3 patients should receive pre-operative chemoradiation (not post-operative) based on the German trial.

Unresectable

  • pre-operative chemoradiation to convert it into a resectable lesion
  • 40-60% can become resectable.
  • Despite high-rate of conversion the local failure is about 25-55%.

== Rectal Cancer Trials ==

Specific Issues

Sphincter Preservation

  • Tumors < 5 cm from anal verge have traditionally required APR
  • Pre-operative treatment with RT and CT can "convert" APR to LAR ~70% of the time.

8 prospective nonrandomized trials of patients who were declared to need an APR. All used conventional RT doses and techniques. 3 used RT alone (5 used combined modality). NSABP R-03 had 23% sphincter preservation rate. Lyon had 44% sphincter preservation rate. Others had ~ 70% sphincter preservation rate. [2]

Bibliography
1. Cox J, Ang K. Radiation Oncology: rationale Technique Results. 8th ed. New York: Mosby, 2003.
2. Gunderson L, Tepper J: Clinical Radiation Oncology. 2nd ed. China: Elsevier 2007.
3. Kapiteijn E, van de Velde CJ. The role of total mesorectal excision in the management of rectal cancer. Surg Clin North Am. 2002 Oct;82(5):995-1007.
4. Lee W, Lee D, Choi S, Chun H. Transanal endoscopic microsurgery and radical surgery for T1 and T2 rectal cancer. Surg Endosc. 2003 Aug;17(8):1283-7.
5. Fisher B, Wolmark N, Rockette H, Redmond C, Deutsch M, Wickerham DL, Fisher ER, Caplan R, Jones J, Lerner H, et al. Postoperative adjuvant chemotherapy or radiation therapy for rectal cancer: results from NSABP protocol R-01. J Natl Cancer Inst. 1988 Mar 2;80(1):21-9. PMID: 3276900
6. [No authors listed] Randomised trial of surgery alone versus surgery followed by radiotherapy for mobile cancer of the rectum. Medical Research Council Rectal Cancer Working Party. Lancet. 1996 Dec 14;348(9042):1610-4. PMID: 8961990
7. O'Connell MJ, Martenson JA, Wieand HS, Krook JE, Macdonald JS, Haller DG, Mayer RJ, Gunderson LL, Rich TA. Improving adjuvant therapy for rectal cancer by combining protracted-infusion fluorouracil with radiation therapy after curative surgery. N Engl J Med. 1994 Aug 25;331(8):502-7. PMID: 8041415
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