Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data.
BACKGROUND
Locally advanced rectal cancer is usually treated with preoperative chemoradiation. After chemoradiation and surgery, 15-27% of the patients have no residual viable tumour at pathological examination, a pathological complete response (pCR). This study established whether patients with pCR have better long-term outcome than do those without pCR.


METHODS
In PubMed, Medline, and Embase we identified 27 articles, based on 17 different datasets, for long-term outcome of patients with and without pCR. 14 investigators agreed to provide individual patient data. All patients underwent chemoradiation and total mesorectal excision. Primary outcome was 5-year disease-free survival. Kaplan-Meier survival functions were computed and hazard ratios (HRs) calculated, with the Cox proportional hazards model. Subgroup analyses were done to test for effect modification by other predicting factors. Interstudy heterogeneity was assessed for disease-free survival and overall survival with forest plots and the Q test.


RESULTS
484 of 3105 included patients had a pCR. Median follow-up for all patients was 48 months (range 0-277). 5-year crude disease-free survival was 83.3% (95% CI 78.8-87.0) for patients with pCR (61/419 patients had disease recurrence) and 65.6% (63.6-68.0) for those without pCR (747/2263; HR 0.44, 95% CI 0.34-0.57; p<0.0001). The Q test and forest plots did not suggest significant interstudy variation. The adjusted HR for pCR for failure was 0.54 (95% CI 0.40-0.73), indicating that patients with pCR had a significantly increased probability of disease-free survival. The adjusted HR for disease-free survival for administration of adjuvant chemotherapy was 0.91 (95% CI 0.73-1.12). The effect of pCR on disease-free survival was not modified by other prognostic factors.


CONCLUSIONS
Patients with pCR after chemoradiation have better long-term outcome than do those without pCR. pCR might be indicative of a prognostically favourable biological tumour profile with less propensity for local or distant recurrence and improved survival.


BACKGROUND
None.
Maas
Monique
M
Department of Surgery, Maastricht University Medical Centre, Maastricht, Netherlands.
Nelemans
Patty J
PJ
Valentini
Vincenzo
V
Das
Prajnan
P
Rödel
Claus
C
Kuo
Li-Jen
LJ
Calvo
Felipe A
FA
García-Aguilar
Julio
J
Glynne-Jones
Rob
R
Haustermans
Karin
K
Mohiuddin
Mohammed
M
Pucciarelli
Salvatore
S
Small
William
W
Suárez
Javier
J
Theodoropoulos
George
G
Biondo
Sebastiano
S
Beets-Tan
Regina G H
RG
Beets
Geerard L
GL
D000970:Antineoplastic Agents / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D013505:Digestive System Surgical Procedures; D018572:Disease-Free Survival; D006801:Humans; D053208:Kaplan-Meier Estimate; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local; D011878:Radiotherapy; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D012189:Retrospective Studies; D016896:Treatment Outcome
D000970:Antineoplastic Agents