Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer.
OBJECTIVE
We assessed the impact of tumor regression grading (TRG) and its value in correlation to established prognostic factors in a cohort of rectal carcinoma patients treated by preoperative chemoradiotherapy (CRT).


METHODS
TRG was evaluated on surgical specimens of 385 patients treated within the preoperative CRT arm of the CAO/ARO/AIO-94 trial: 50.4 Gy was delivered, fluorouracil was given in the first and fifth week, and surgery was performed 6 weeks thereafter. TRG was determined by the amount of viable tumor versus fibrosis, ranging from TRG 4 when no viable tumor cells were detected, to TRG 0 when fibrosis was completely absent. TRG 3 was defined as regression more than 50% with fibrosis outgrowing the tumor mass, TRG 2 was defined as regression less than 50%, and TRG 1 was defined basically as a morphologically unaltered tumor mass. We performed an initially unplanned, hypothesis-generating analysis with respect to the prognostic value of this TRG system.


RESULTS
TRG 4, 3, 2, 1, 0 was found in 10.4%, 52.2%, 13.8%, 15.3%, and 8.3% of the resected specimens, respectively. Five-year disease-free survival (DFS) after CRT and curative resection was 86% for TRG 4, 75% for grouped TRG 2 + 3, and 63% for grouped TRG 0 + 1 (P = .006). On multivariate analysis, the pathologic T category and the nodal status after CRT were the most important independent prognostic factors for DFS.


CONCLUSIONS
In this exploratory analysis, complete (TRG 4) and intermediate pathologic response (TRG 2 + 3) suggested improved DFS after preoperative CRT. TRG assessment should be implemented in pathologic evaluation and prospectively validated in further studies.
Rödel
Claus
C
Department of Radiation Therapy, University of Erlangen, Universitätsstr 27, D-91054 Erlangen, Germany. claus.roedel@strahlen.med.uni-erlangen.de
Martus
Peter
P
Papadoupolos
Thomas
T
Füzesi
Laszlo
L
Klimpfinger
Martin
M
Fietkau
Rainer
R
Liersch
Torsten
T
Hohenberger
Werner
W
Raab
Rudolf
R
Sauer
Rolf
R
Wittekind
Christian
C
D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy; D002288:Adenocarcinoma, Mucinous / Q000473:pathology / Q000628:therapy; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D002277:Carcinoma / Q000473:pathology / Q000628:therapy; D018279:Carcinoma, Signet Ring Cell / Q000473:pathology / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D013505:Digestive System Surgical Procedures; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011300:Preoperative Care; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil