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Search strategy & selection criteria• Published and unpublished European randomized,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