Benefit of adjuvant chemotherapy after preoperative chemoRT + surgery in rectal CAAnn Meredith U. Garcia, MD

Background• About 30% of all patients treated with curative intent will

eventually develop distant metastases.• Adjuvant chemotherapy might prevent distant metastases

by eliminating CTCs and micrometastases.• A clear benefit of adjuvant chemotherapy has been shown

for patients with stage III colon CA.• Levamisole and fluorouracil • Capecitabine• FOLFOX – (MOSAIC) trial

Background• For patients treated without preoperative (chemo)RT and

TME surgery, which results in high numbers of locoregional recurrences, adjuvant chemotherapy is effective.

• However, the use of adjuvant chemotherapy for patients with rectal CA treated with preoperative (chemo)RT and surgery is debated.

Search strategy & selection criteria• Published and unpublished European randomized,

controlled, phase 3 trials comparing observation with adjuvant chemotherapy after preoperative (chemo)RT and surgery for patients with non-metastatic rectal CA

• PubMed, Medline (OVID version), Embase (OVID version), Web of Science, the Cochrane Library, and CENTRAL

• Abstracts from the most important international meetings (ECCO, ESTRO, ESSO, and ESMO)

• Individual patient data for baseline characteristics, tumor characteristics, preoperative treatment, surgery, adjuvant treatment, and follow-up

Outcomes• Primary endpoint: Overall survival• Secondary endpoints:

• Disease-free survival• Distant recurrences

Study characteristicsFU+FA FU+FA; Cape FU+FA CapeOx

Patientcharacteristics

Overall survival

Disease-free survival

Distant recurrence

Distant recurrence

Conclusions• Fluorouracil-based adjuvant chemotherapy has no

benefit on overall survival, disease-free survival, and distant recurrences after a median follow-up of 7 years in patients with:• (y)pTNM stage II or III rectal CA• R0 resection• LAR or APR• Tumor located within 15 cm of the anal verge

• Adjuvant chemotherapy might improve disease-free survival and distant recurrences in patients with a tumor located 10–15 cm from the anal verge.

Limitations• Low adherence to treatment • Changes in practice over time• QUASAR trial excluded due to lack of individual patient

data

655 patients (cT3-4, Nx) treated with

chemoRT + SxFU+FA x 6 cycles

(N = 324)

Follow-up(N = 310)

RA

ND

OM

IZA

TIO

N

Median follow-up: 63.7 months

470 patients (stage II or III) treated with

(chemo)RT + TME FU+FA x 6-12 cycles

(N = 216)

Surveillance(N = 221)

RA

ND

OM

IZA

TIO

N

Median follow-up: 5 years

*840 patients

79.2% vs. 80.4%HR 0.93, 95% CI 0.62‐1.39; p=0.73

55.4% vs. 62.7%HR 0.80, 95% CI 0.60‐1.07; p=0.13

1,011 patients (cT3-4)

Preop RT surveillance(N = 252)

RA

ND

OM

IZA

TIO

N

Median follow-up: 10.4 years

Preop chemoRT surveillance(N = 253)

Preop RT adjuvant chemo(N = 253)

Preop chemoRT adjuvant chemo(N = 253)

51.8% vs. 48.4%HR 0·91, 95% CI 0·77–1·09; p=0·32

47.0% vs. 43.7%HR 0·91, 95% CI 0·77–1·08; p=0·29

113 patients (stage II or III) treated with chemoRT +

TME CapeOx x 6 cycles (N = 54)

Observation(N = 59)

RA

ND

OM

IZA

TIO

N

Median follow-up: 44.8 months

*800 patients

71.3% vs. 77.5%0.80 (95% CI: 0.38-1.69; p=0.56

87.8% vs. 88.8%1.18 (95% CI: 0.43-3.26; p=0.75