Friday, December 19, 2008

Rectal Cancer - Chemoradiotherapy

Rectal Cancer:

5y OS:
I 90-95%
II 75-95%
III 40-70%
IV 5%

Local Excision

RTOG 8902: Postoperative study. Low risk <3cm, T1, Gr 1-2, no LVSI, nl CEA. Treated with Observation after Local Excision 4% failure in T1. T2 and T3 were given CTRT and failure rates were 20-30%.

CALGB Local Excision update: Updated 2008
T1s were observed, T2 treated with postoperative CTRT after local excision. 10year LR for T1 were 8%; in T2 the rates were 18%, with a number of late local recurrences. This calls into question the ability to treat T2 tumors with local excision even with postoperative treatment.

MSKCC series (Paty, Ann Surg, 2002). Failure rates after LE were ~10% in T1, ~25% in T2 wether or not RT+/- chemotherapy was given.

Local Recurrence without further treatment beyond surgery was 25-40% in the pre-TME era. This is improved to 10-15% with TME technique.

Postop Data:
Oconnell NEJM 1994: Postoperative T3-T4 or N+ rectal cancer (n=666), randomized to RT with concurrent PVI vs bolus FU. Improved RFS and OS in the PVI group.

Smalley JCO 2006: Intergroup 0144 compared three different concurrent chemotherapy regimens. CI still looked better for LC and for heme toxicity (other arms were two different bolus regimens).

Preop Data:
Swedish Preop Trial (NEJM 1997):
n=1,168 T3+ or N+ treated in the preTME era. Randomized to preoperative RT 5Gy x 5 vs. observation. This is the only trial to show not only a LC benefit, but also an overall survival benefit to preoperative RT.

Dutch TME trial (Ann Surg, 2007)
n=1,861 all treated with TME, randomized to preoperative RT (5Gyx5) vs no neoadjuvant treatment. 5y LR 11% vs 6% (SS). No difference in overall survival. This is important in that it proved that RT was still needed for optimal local control, even after optimized surgery.

German Preop vs Postop Trial (NEJM 2004)
n=823, T3+ or N+. Randomized to preoperative CTRT (50.4Gy) with CI 5FU, or postoperative CTRT (55.8Gy) with CI 5FU. OS and DFS not different. 5 year Local Control 6 vs 13% (SS). Both acute and late toxicities were better with preoperative treatment. More sphincter preserving therapy in the preop group, in the subgroup that were determined not to be candidates prior to treatment (19 vs 39%, SS).

EORTC 22921 (NEJM 2006)
n=1,011. T3+, randomized to four arms, all recieved preop RT. The analysis is confused due to the multiple arms, but the take home is that chemotherapy is necessary, wether concurrent or postoperatively. LC was worse in the single arm that had no chemotherapy.

FFCD 9203 (JCO 2006)
T3-4 recieving preoperative RT then randomized to concurrent vs sequential chemotherapy. LC 17% vs 8% p=0.04. This proves the need for concurrent chemotherapy with Preoperative treatment.

Polish trial (B J Surg, 2006)
T3-4 n=2 randomized to 5Gyx5 or 50.4Gy with 5FU preoperatively. Higher toxicity in the CTRT arm. No difference in OS, DFS or LC. No difference in sphincter preservation. This trial is interesting in that it shows equivalence in a short course treatment and the more conventional prolonged CTRT approach. An additional article looking at late toxicities showed no difference between the arms (Rad Onc 2007).

Our approach-
EUS should be obtained in the majority of patients.

T1: Surgery alone. local excision can be considered an option, with careful consenting.

T2: Would reccomend more definitive TME surgery over local excision with postop CTRT.

T3-T4 or N+: Preoperative CTRT- WPRT to 45Gy in 1.8 Gy/fx, with concurrent CI 5FU or capecitabine, usually treated prone with a three field technique (PA, two laterals). An additional 5.4 Gy is delivered with lateral reduced fields, excluding small bowel, to the tumor and associated mesorectum/presacral region. Surgery with TME technique is then reccomended 6-8 weeks thereafter.

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