Identification of localized rectal cancer (RC) patients (pts) who may NOT require preoperative (preop) chemoradiation (CRT).

D. Roda1, M. Frasson2, E. García-Granero2, S. Roselló1, B. Flor2, E. Rodríguez1, P. Esclapez2, S. Campos3, S. García-Botello2, A. Cervantes1.

Department of Hematology Medical Oncology1, Colorectal Unit, Department of Surgery2, INCLIVA, University of Valencia, Valencia, Spain.

Abstract # 50936

AbstractBackground: Preop CRT is becoming the standard of care for patients with locally advanced RC. However, since the introduction of total mesorectal excision (TME), local recurrence rates are significantly reduced and some pts can be spared from a potentially toxic overtreatment. Preop staging with magnetic resonance imaging (MRI) and/or endorectal ultrasonography (ERUS) may help in selecting pts for preop CRT. This retrospective study was designed to assess factors predicting recurrence in an institutional series of RC pts with clinical stage T2N+, T3N0/+, treated by radical surgery without preop CRT.

Methods: Between Nov 1997 to Nov 2008, our multidisciplinary group staged preop 398 RC patients by ERUS and/or MRI. We selected for this analysis 154 consecutive pts, having uT2N+, uT3N0, and uT3N+ rc, who didn’t get preop CRT. Macroscopical assessment of mesorectal excision and microscopic study of all circumferential resection margins (CRM) was determined. Factors potentially related with local recurrence (LR), Disease free survival (DFS) and overall survival (OS) were studied. 

Results: Median follow-up was 34 months (range, 18 to 68,2 months). LR rate was 8.5%, and 5-year DFS and OS were respectively 64.5% and 75.4% for the whole group. Threatened mesorectal fascia at preop staging, defined as tumor located at < 2 mm, was seen in 19 patients and was the most powerful single factor to predict a higher risk for LR, shorter DFS and worse OS.  Other factors such as preop N+ or location of the tumor did not predict the risk of LR.

Conclusions: Threatening of mesorectal fascia as defined preoperative by US or MRI, was the only significant factor predicting LR as well as worse DFS and OS. RC pts clinically staged as T3N0/+ or T2N+ > 2 mm away from mesorectal fascia could be treated with TME alone with a risk of LR of less than 5%, and overtreatment with preop CRT could be avoided.

Abstract # 50936

Background

• Preop CRT is becoming the standard of care for patients with locally advanced RC. • However, since the introduction of total mesorectal excision (TME), local recurrence rates are significantly reduced and some pts can be spared from a potentially toxic overtreatment.

• Preop staging with magnetic resonance imaging (MRI) and/or endorectal ultrasonography (ERUS) may help in selecting pts for TME surgery alone.

• This retrospective study was designed to assess factors predicting local and overall recurrence in an institutional serie of RC pts with clinical stage T2N+, T3N0/+, treated by radical TME surgery without preoperative CRT.

Purpose

Methods:• Between Nov 1997 to Nov 2008, our multidisciplinary

group staged preop 398 RC patients by ERUS and/or MRI in a single institution.

• We selected for this analysis 154 consecutive pts, having cT2N+, cT3N0, and cT3N+ RC, who didn’t get preop CRT.

• TME was performed in all patients.

• Standard pathologic analysis was performed on all resection specimens: macroscopical assessment of mesorectal excision and microscopic study of all circumferential resection margins (CRM) was determined.

• Factors potentially related with local recurrence (LR), disease free survival (DFS) and overall survival (OS) were studied.

• Statistical analysis included 2 test for prognostic variables. Univariate analysis of survival were carried out by the Kaplan-Meier Method. A Cox multivariate survival analysis was performed with factors found to be statistically significant on the univariate analysis.

Methods:

Methods:

398 RC pts evaluated with ERUS and/or MRI

350 pts with cT2N+ or cT3 rectal cancer

cT1 :4 ptscT2N0 : 20 ptsc

T4 : 24 pts

160 patients treated with preoperative CRT

190 pts operated without preoperative CRT

36 pts M1

154 pts with R0 or R1 resection

Figure 1- Selection of patients

Median Age (range) 

70 (38-90)

Sex 

Male 94 (61%)

Female 60 (39%)

Tumor Location  

Upper rectum 17 (11%)

Medium rectum 55 (35,7%)

Lower rectum 82 (53,2%)

Preop staging  

Only ERUS 77 (50,0%)

Only MRI 15 (9,74%)

ERUS and MRI 62 (40,26%)

Preop CRM  

Free 111 (72,1%)

Threatened 19 (12,3%)

No Evaluable 24 (15,6%)

Surgical Procedure 

Miles' procedure 42 (27,3%)

Sphincter saving procedure 112 (72,7%)

Post-op Mortality 

6 (3,9%)

Quality mesorectum   

Complete 77 (50,0%)

Nearly Complete 26 (16,88%)

Incomplete 9 (5,85%)

Not evaluated 42 (27,27%)

Post-Op Therapy 

CT+RT 3 (2%)

CT 34 (22,1%)

Table 1. Patients characteristics

Results• Median follow-up was 39 months (range, 18 to

152 months).

• For the whole group, 5-year actuarial LR rate, 5-year actuarial LR rate, DFSDFS and OSOS were 9.5%9.5% 64.5%64.5% and 75.4% 75.4% respectively.

• Different preoperative factors were studied as predictors of recurrence :

• treatened vs free fascia• preoperative nodal status• surgery (Miles' procedure vs sphincter saving procedure)• tumor location.

Results

• Threatened mesorectal fascia at preop staging, defined as tumor located at < 2 mm, was seen in 19 patients and was the most powerful single factor to predict a higher risk for LR, shorter DFS and worse OS.  (fig 1 and 2).

Results

Crude Rate (%)Hazard Ratio

95% CI P value

Preoperative CRM

Threatened or not evaluable vs. free fascia

LR 21 vs. 4.5  7.2 1.9-27 0.004

DFS 63.1 vs.78.3  2.8 1.2-6.6 0.015

OS 73.6 vs. 86.4  3.2 1.1-8.9 0.025

Patological CRM

Affected vs. free fascia

LR 28.0 vs. 3.2 11.90 3.5-41.0 <0.0001

DFS 40.0 vs 80.6 4,81 2.5-9-3 <0.0001

OS 52.0 vs 89.7 5.42 2.5-11.7 <0.0001

Patological N

N+ vs N-

LR 19.5 vs 3.4 3.92 1.0-14.0 0.04

DFS 54.7 vs 87.5 4.80 2.4-9.6 <0.0001

OS 66.5 vs 93.2 6.15 2.4-15.1 <0.0001

Table 3. Univariate analysis for LR, DFS and OS.

• Pathological CRM and nodal status were studied as predictors of recurrence. In a univariate analysis both were significant predictors of LR, DFS and OS (Table 3).

Results

Hazard

Ratio95% CI P value

Patological CRM

Affected vs. free fascia

LR 9.62.39-38.49

0.001

DFS 2,6 1.32-5.34 0.006

OS 2.54 1.11-5.8 0.027

Patological N

N+ vs N-

LR 1.6 0.36-7.16 0.53

DFS 3.9 1.79-8.48 0.001

OS 5.571.94-15.94

0.001

• However, in a multivariate Cox regression analysis, only involved CRM resulted as an independent predictor of LR, while both were independent predictors of DFS and OS (Table 4).

Table 4. Multivariate analysis for LR, DFS and OS.

 

pN-(n)

pN+(n)

Total(n)

Overstaged(%)

Undesrtaged(%)

Accuracy(%)

cN- 43 12 55 - 21,8 78,2

cN+ 44 50 94 46,8 - 53,2

cNx 3 2 5 - - -

Total 90 64 154 28,6 7,8 60,4

Results

Table 2. Preoperative N staging vs Pathologic N examination

• Threatening of mesorectal fascia as defined preoperatively by ERUS or MRI, was the only preop significant factor predicting higher risk for LR as well as worse DFS and OS.

• RC pts clinically staged as T3N0/+ or T2N+ > 2 mm away from mesorectal fascia could be treated with TME alone with a risk of LR of less than 5%, and overtreatment with preop CRT could be avoided.

• To improve accuracy of preop staging may help in better selection of RC patients preoperative treatment.

Conclusions: