Time From Colorectal Cancer Surgery to Adjuvant Chemotherapy: Post Hoc Analysis of the SCOT Randomized Clinical Trial

Mikail Gögenur; Andreas Weinberger Rosen; Timothy Iveson; Rachel S. Kerr; Mark P. Saunders; Jim Cassidy; Josep Tabernero; Andrew Haydon; Bengt Glimelius; Andrea Harkin; Karen Allan; Sarah Pearson; Kathleen A. Boyd; Andrew H. Briggs; Ashita Waterston; Louise Medley; Richard Ellis; Amandeep S. Dhadda; Mark Harrison; Stephen Falk; Charlotte Rees; Rene K. Olesen; David Propper; John Bridgewater; Ashraf Azzabi; David Cunningham; Tamas Hickish; Simon Gollins; Harpreet S. Wasan; Caroline Kelly; Ismail Gögenur; Niels Henrik Holländer

doi:10.1001/jamasurg.2024.1555

Time From Colorectal Cancer Surgery to Adjuvant Chemotherapy: Post Hoc Analysis of the SCOT Randomized Clinical Trial

Mikail Gögenur, Andreas Weinberger Rosen, Timothy Iveson, Rachel S. Kerr, Mark P. Saunders, Jim Cassidy, Josep Tabernero, Andrew Haydon, Bengt Glimelius, Andrea Harkin, Karen Allan, Sarah Pearson, Kathleen A. Boyd, Andrew H. Briggs, Ashita Waterston, Louise Medley, Richard Ellis, Amandeep S. Dhadda, Mark Harrison, Stephen FalkCharlotte Rees, Rene K. Olesen, David Propper, John Bridgewater, Ashraf Azzabi, David Cunningham, Tamas Hickish, Simon Gollins, Harpreet S. Wasan, Caroline Kelly, Ismail Gögenur, Niels Henrik Holländer

Research output: Contribution to journal › Journal article › Research › peer-review

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Abstract

IMPORTANCE: The timing of adjuvant chemotherapy after surgery for colorectal cancer and its association with long-term outcomes have been investigated in national cohort studies, with no consensus on the optimal time from surgery to adjuvant chemotherapy.

OBJECTIVE: To analyze the association between the timing of adjuvant chemotherapy after surgery for colorectal cancer and disease-free survival.

DESIGN, SETTING, AND PARTICIPANTS: This is a post hoc analysis of the phase 3 SCOT randomized clinical trial, from 244 centers in 6 countries, investigating the noninferiority of 3 vs 6 months of adjuvant chemotherapy. Patients with high-risk stage II or stage III nonmetastatic colorectal cancer who underwent curative-intended surgery were randomized to either 3 or 6 months of adjuvant chemotherapy consisting of fluoropyrimidine and oxaliplatin regimens. Those with complete information on the date of surgery, treatment type, and long-term follow-up were investigated for the primary and secondary end points. Data were analyzed from May 2022 to February 2024.

INTERVENTION: In the post hoc analysis, patients were grouped according to the start of adjuvant chemotherapy being less than 6 weeks vs greater than 6 weeks after surgery.

MAIN OUTCOMES AND MEASURES: The primary end point was disease-free survival. The secondary end points were adverse events in the total treatment period or the first cycle of adjuvant chemotherapy.

RESULTS: A total of 5719 patients (2251 [39.4%] female; mean [SD] age, 63.4 [9.3] years) were included in the primary analysis after data curation; among them, 914 were in the early-start group and 4805 were in the late-start group. Median (IQR) follow-up was 72.0 (47.3-88.1) months, with a median (IQR) of 56 (41-66) days from surgery to chemotherapy. Five-year disease-free survival was 78.0% (95% CI, 75.3%-80.8%) in the early-start group and 73.2% (95% CI, 72.0%-74.5%) in the late-start group. In an adjusted Cox regression analysis, the start of adjuvant chemotherapy greater than 6 weeks after surgery was associated with worse disease-free survival (hazard ratio, 1.24; 95% CI, 1.06-1.46; P = .01). In adjusted logistic regression models, there was no association with adverse events in the total treatment period (odds ratio, 0.82; 95% CI, 0.65-1.04; P = .09) or adverse events in the first cycle of treatment (odds ratio, 0.77; 95% CI, 0.56-1.09; P = .13).

CONCLUSIONS AND RELEVANCE: In this international population of patients with high-risk stage II and stage III colorectal cancer, starting adjuvant chemotherapy more than 6 weeks after surgery was associated with worse disease-free survival, with no difference in adverse events between the groups.

TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN59757862.

Original language	English
Journal	JAMA Surgery
Volume	159
Issue number	8
Pages (from-to)	865-871
Number of pages	7
ISSN	2168-6254
DOIs	https://doi.org/10.1001/jamasurg.2024.1555
Publication status	Published - Aug 2024

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Gögenur, M., Rosen, A. W., Iveson, T., Kerr, R. S., Saunders, M. P., Cassidy, J., Tabernero, J., Haydon, A., Glimelius, B., Harkin, A., Allan, K., Pearson, S., Boyd, K. A., Briggs, A. H., Waterston, A., Medley, L., Ellis, R., Dhadda, A. S., Harrison, M., ... Holländer, N. H. (2024). Time From Colorectal Cancer Surgery to Adjuvant Chemotherapy: Post Hoc Analysis of the SCOT Randomized Clinical Trial. JAMA Surgery, 159(8), 865-871. https://doi.org/10.1001/jamasurg.2024.1555

@article{40f5ac0ab2794b0aa6b2f09bc4bd6b82,

title = "Time From Colorectal Cancer Surgery to Adjuvant Chemotherapy: Post Hoc Analysis of the SCOT Randomized Clinical Trial",

abstract = "IMPORTANCE: The timing of adjuvant chemotherapy after surgery for colorectal cancer and its association with long-term outcomes have been investigated in national cohort studies, with no consensus on the optimal time from surgery to adjuvant chemotherapy.OBJECTIVE: To analyze the association between the timing of adjuvant chemotherapy after surgery for colorectal cancer and disease-free survival.DESIGN, SETTING, AND PARTICIPANTS: This is a post hoc analysis of the phase 3 SCOT randomized clinical trial, from 244 centers in 6 countries, investigating the noninferiority of 3 vs 6 months of adjuvant chemotherapy. Patients with high-risk stage II or stage III nonmetastatic colorectal cancer who underwent curative-intended surgery were randomized to either 3 or 6 months of adjuvant chemotherapy consisting of fluoropyrimidine and oxaliplatin regimens. Those with complete information on the date of surgery, treatment type, and long-term follow-up were investigated for the primary and secondary end points. Data were analyzed from May 2022 to February 2024.INTERVENTION: In the post hoc analysis, patients were grouped according to the start of adjuvant chemotherapy being less than 6 weeks vs greater than 6 weeks after surgery.MAIN OUTCOMES AND MEASURES: The primary end point was disease-free survival. The secondary end points were adverse events in the total treatment period or the first cycle of adjuvant chemotherapy.RESULTS: A total of 5719 patients (2251 [39.4%] female; mean [SD] age, 63.4 [9.3] years) were included in the primary analysis after data curation; among them, 914 were in the early-start group and 4805 were in the late-start group. Median (IQR) follow-up was 72.0 (47.3-88.1) months, with a median (IQR) of 56 (41-66) days from surgery to chemotherapy. Five-year disease-free survival was 78.0% (95% CI, 75.3%-80.8%) in the early-start group and 73.2% (95% CI, 72.0%-74.5%) in the late-start group. In an adjusted Cox regression analysis, the start of adjuvant chemotherapy greater than 6 weeks after surgery was associated with worse disease-free survival (hazard ratio, 1.24; 95% CI, 1.06-1.46; P = .01). In adjusted logistic regression models, there was no association with adverse events in the total treatment period (odds ratio, 0.82; 95% CI, 0.65-1.04; P = .09) or adverse events in the first cycle of treatment (odds ratio, 0.77; 95% CI, 0.56-1.09; P = .13).CONCLUSIONS AND RELEVANCE: In this international population of patients with high-risk stage II and stage III colorectal cancer, starting adjuvant chemotherapy more than 6 weeks after surgery was associated with worse disease-free survival, with no difference in adverse events between the groups.TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN59757862.",

author = "Mikail G{\"o}genur and Rosen, {Andreas Weinberger} and Timothy Iveson and Kerr, {Rachel S.} and Saunders, {Mark P.} and Jim Cassidy and Josep Tabernero and Andrew Haydon and Bengt Glimelius and Andrea Harkin and Karen Allan and Sarah Pearson and Boyd, {Kathleen A.} and Briggs, {Andrew H.} and Ashita Waterston and Louise Medley and Richard Ellis and Dhadda, {Amandeep S.} and Mark Harrison and Stephen Falk and Charlotte Rees and Olesen, {Rene K.} and David Propper and John Bridgewater and Ashraf Azzabi and David Cunningham and Tamas Hickish and Simon Gollins and Wasan, {Harpreet S.} and Caroline Kelly and Ismail G{\"o}genur and Holl{\"a}nder, {Niels Henrik}",

year = "2024",

month = aug,

doi = "10.1001/jamasurg.2024.1555",

language = "English",

volume = "159",

pages = "865--871",

journal = "JAMA Surgery",

issn = "2168-6254",

publisher = "American Medical Association",

number = "8",

}

Gögenur, M, Rosen, AW, Iveson, T, Kerr, RS, Saunders, MP, Cassidy, J, Tabernero, J, Haydon, A, Glimelius, B, Harkin, A, Allan, K, Pearson, S, Boyd, KA, Briggs, AH, Waterston, A, Medley, L, Ellis, R, Dhadda, AS, Harrison, M, Falk, S, Rees, C, Olesen, RK, Propper, D, Bridgewater, J, Azzabi, A, Cunningham, D, Hickish, T, Gollins, S, Wasan, HS, Kelly, C, Gögenur, I & Holländer, NH 2024, 'Time From Colorectal Cancer Surgery to Adjuvant Chemotherapy: Post Hoc Analysis of the SCOT Randomized Clinical Trial', JAMA Surgery, vol. 159, no. 8, pp. 865-871. https://doi.org/10.1001/jamasurg.2024.1555

TY - JOUR

T1 - Time From Colorectal Cancer Surgery to Adjuvant Chemotherapy: Post Hoc Analysis of the SCOT Randomized Clinical Trial

AU - Gögenur, Mikail

AU - Rosen, Andreas Weinberger

AU - Iveson, Timothy

AU - Kerr, Rachel S.

AU - Saunders, Mark P.

AU - Cassidy, Jim

AU - Tabernero, Josep

AU - Haydon, Andrew

AU - Glimelius, Bengt

AU - Harkin, Andrea

AU - Allan, Karen

AU - Pearson, Sarah

AU - Boyd, Kathleen A.

AU - Briggs, Andrew H.

AU - Waterston, Ashita

AU - Medley, Louise

AU - Ellis, Richard

AU - Dhadda, Amandeep S.

AU - Harrison, Mark

AU - Falk, Stephen

AU - Rees, Charlotte

AU - Olesen, Rene K.

AU - Propper, David

AU - Bridgewater, John

AU - Azzabi, Ashraf

AU - Cunningham, David

AU - Hickish, Tamas

AU - Gollins, Simon

AU - Wasan, Harpreet S.

AU - Kelly, Caroline

AU - Gögenur, Ismail

AU - Holländer, Niels Henrik

PY - 2024/8

Y1 - 2024/8

N2 - IMPORTANCE: The timing of adjuvant chemotherapy after surgery for colorectal cancer and its association with long-term outcomes have been investigated in national cohort studies, with no consensus on the optimal time from surgery to adjuvant chemotherapy.OBJECTIVE: To analyze the association between the timing of adjuvant chemotherapy after surgery for colorectal cancer and disease-free survival.DESIGN, SETTING, AND PARTICIPANTS: This is a post hoc analysis of the phase 3 SCOT randomized clinical trial, from 244 centers in 6 countries, investigating the noninferiority of 3 vs 6 months of adjuvant chemotherapy. Patients with high-risk stage II or stage III nonmetastatic colorectal cancer who underwent curative-intended surgery were randomized to either 3 or 6 months of adjuvant chemotherapy consisting of fluoropyrimidine and oxaliplatin regimens. Those with complete information on the date of surgery, treatment type, and long-term follow-up were investigated for the primary and secondary end points. Data were analyzed from May 2022 to February 2024.INTERVENTION: In the post hoc analysis, patients were grouped according to the start of adjuvant chemotherapy being less than 6 weeks vs greater than 6 weeks after surgery.MAIN OUTCOMES AND MEASURES: The primary end point was disease-free survival. The secondary end points were adverse events in the total treatment period or the first cycle of adjuvant chemotherapy.RESULTS: A total of 5719 patients (2251 [39.4%] female; mean [SD] age, 63.4 [9.3] years) were included in the primary analysis after data curation; among them, 914 were in the early-start group and 4805 were in the late-start group. Median (IQR) follow-up was 72.0 (47.3-88.1) months, with a median (IQR) of 56 (41-66) days from surgery to chemotherapy. Five-year disease-free survival was 78.0% (95% CI, 75.3%-80.8%) in the early-start group and 73.2% (95% CI, 72.0%-74.5%) in the late-start group. In an adjusted Cox regression analysis, the start of adjuvant chemotherapy greater than 6 weeks after surgery was associated with worse disease-free survival (hazard ratio, 1.24; 95% CI, 1.06-1.46; P = .01). In adjusted logistic regression models, there was no association with adverse events in the total treatment period (odds ratio, 0.82; 95% CI, 0.65-1.04; P = .09) or adverse events in the first cycle of treatment (odds ratio, 0.77; 95% CI, 0.56-1.09; P = .13).CONCLUSIONS AND RELEVANCE: In this international population of patients with high-risk stage II and stage III colorectal cancer, starting adjuvant chemotherapy more than 6 weeks after surgery was associated with worse disease-free survival, with no difference in adverse events between the groups.TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN59757862.

AB - IMPORTANCE: The timing of adjuvant chemotherapy after surgery for colorectal cancer and its association with long-term outcomes have been investigated in national cohort studies, with no consensus on the optimal time from surgery to adjuvant chemotherapy.OBJECTIVE: To analyze the association between the timing of adjuvant chemotherapy after surgery for colorectal cancer and disease-free survival.DESIGN, SETTING, AND PARTICIPANTS: This is a post hoc analysis of the phase 3 SCOT randomized clinical trial, from 244 centers in 6 countries, investigating the noninferiority of 3 vs 6 months of adjuvant chemotherapy. Patients with high-risk stage II or stage III nonmetastatic colorectal cancer who underwent curative-intended surgery were randomized to either 3 or 6 months of adjuvant chemotherapy consisting of fluoropyrimidine and oxaliplatin regimens. Those with complete information on the date of surgery, treatment type, and long-term follow-up were investigated for the primary and secondary end points. Data were analyzed from May 2022 to February 2024.INTERVENTION: In the post hoc analysis, patients were grouped according to the start of adjuvant chemotherapy being less than 6 weeks vs greater than 6 weeks after surgery.MAIN OUTCOMES AND MEASURES: The primary end point was disease-free survival. The secondary end points were adverse events in the total treatment period or the first cycle of adjuvant chemotherapy.RESULTS: A total of 5719 patients (2251 [39.4%] female; mean [SD] age, 63.4 [9.3] years) were included in the primary analysis after data curation; among them, 914 were in the early-start group and 4805 were in the late-start group. Median (IQR) follow-up was 72.0 (47.3-88.1) months, with a median (IQR) of 56 (41-66) days from surgery to chemotherapy. Five-year disease-free survival was 78.0% (95% CI, 75.3%-80.8%) in the early-start group and 73.2% (95% CI, 72.0%-74.5%) in the late-start group. In an adjusted Cox regression analysis, the start of adjuvant chemotherapy greater than 6 weeks after surgery was associated with worse disease-free survival (hazard ratio, 1.24; 95% CI, 1.06-1.46; P = .01). In adjusted logistic regression models, there was no association with adverse events in the total treatment period (odds ratio, 0.82; 95% CI, 0.65-1.04; P = .09) or adverse events in the first cycle of treatment (odds ratio, 0.77; 95% CI, 0.56-1.09; P = .13).CONCLUSIONS AND RELEVANCE: In this international population of patients with high-risk stage II and stage III colorectal cancer, starting adjuvant chemotherapy more than 6 weeks after surgery was associated with worse disease-free survival, with no difference in adverse events between the groups.TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN59757862.

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U2 - 10.1001/jamasurg.2024.1555

DO - 10.1001/jamasurg.2024.1555

M3 - Journal article

C2 - 38865139

SN - 2168-6254

VL - 159

SP - 865

EP - 871

JO - JAMA Surgery

JF - JAMA Surgery

IS - 8

ER -

Time From Colorectal Cancer Surgery to Adjuvant Chemotherapy: Post Hoc Analysis of the SCOT Randomized Clinical Trial

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