Recurrence-free survival dynamics following adjuvant chemotherapy for resected colorectal cancer: A systematic review of randomized controlled trials.
adenocarcinoma
adjuvant therapy
chemotherapy
colon cancer
rectal cancer
recurrence
Journal
Cancer medicine
ISSN: 2045-7634
Titre abrégé: Cancer Med
Pays: United States
ID NLM: 101595310
Informations de publication
Date de publication:
08 Jan 2024
08 Jan 2024
Historique:
revised:
15
11
2023
received:
13
07
2023
accepted:
17
12
2023
medline:
8
1
2024
pubmed:
8
1
2024
entrez:
8
1
2024
Statut:
aheadofprint
Résumé
Several cytotoxic chemotherapies have demonstrated efficacy in improving recurrence-free survival (RFS) following resection of Stage II-IV colorectal cancer (CRC). However, the temporal dynamics of response to such adjuvant therapy have not been systematically quantified. The Cochrane Central Register of Trials, Medline (PubMed) and Web of Science were queried from database inception to February 23, 2023 for Phase III randomized controlled trials (RCTs) where there was a significant difference in RFS between adjuvant chemotherapy and surgery only arms. Summary data were extracted from published Kaplan-Meier curves using DigitizeIT. Absolute differences in RFS event rates were compared at matched intervals using multiple paired t-tests. The initial search yielded 1469 manuscripts. After screening, 18 RCTs were eligible (14 Stage II/III; 4 Stage IV), inclusive of 16,682 patients. In the absence of adjuvant chemotherapy, the greatest rate of recurrence was observed in the first year (mean RFS event rate; 0-0.5 years: 0.22 ± 0.21; 0.5-1 years: 0.20 ± 0.09). Adjuvant chemotherapy was associated with significant decreases in the RFS event rates for the intervals 0-0.5 years (0.09 ± 0.09 vs. 0.22 ± 0.21, p < 0.001) and 0.5-1 years (0.14 ± 0.11 vs. 0.20 ± 0.09, p = 0.001) after randomization, but not at later intervals (1-5 years). In Stage IV trials, RFS event rates significantly differed for the interval 0-0.5 years (p = 0.012), corresponding with adjuvant treatment durations of 6 months. In Stage II/III trials, which included therapies of 6-24 months duration, there were marked differences in the RFS event rates between surgery and chemotherapy arms for the intervals 0-0.5 years (p < 0.001) and 0.5-1 years (p < 0.001) with smaller differences in the RFS event rates for the intervals 1-2 years (p = 0.012) and 2-3 years (p = 0.010). In a systematic review of positive RCTs comparing adjuvant chemotherapy to surgery alone for Stage II-IV CRC, observed RFS improvements were driven by early divergences that occurred primarily during active cytotoxic chemotherapy. Late recurrence dynamics were not influenced by adjuvant therapy use. Such observations may have implications for the use of chemotherapy for micrometastatic clones detectable by cell-free DNA-based methodologies.
Sections du résumé
BACKGROUND
BACKGROUND
Several cytotoxic chemotherapies have demonstrated efficacy in improving recurrence-free survival (RFS) following resection of Stage II-IV colorectal cancer (CRC). However, the temporal dynamics of response to such adjuvant therapy have not been systematically quantified.
METHODS
METHODS
The Cochrane Central Register of Trials, Medline (PubMed) and Web of Science were queried from database inception to February 23, 2023 for Phase III randomized controlled trials (RCTs) where there was a significant difference in RFS between adjuvant chemotherapy and surgery only arms. Summary data were extracted from published Kaplan-Meier curves using DigitizeIT. Absolute differences in RFS event rates were compared at matched intervals using multiple paired t-tests.
RESULTS
RESULTS
The initial search yielded 1469 manuscripts. After screening, 18 RCTs were eligible (14 Stage II/III; 4 Stage IV), inclusive of 16,682 patients. In the absence of adjuvant chemotherapy, the greatest rate of recurrence was observed in the first year (mean RFS event rate; 0-0.5 years: 0.22 ± 0.21; 0.5-1 years: 0.20 ± 0.09). Adjuvant chemotherapy was associated with significant decreases in the RFS event rates for the intervals 0-0.5 years (0.09 ± 0.09 vs. 0.22 ± 0.21, p < 0.001) and 0.5-1 years (0.14 ± 0.11 vs. 0.20 ± 0.09, p = 0.001) after randomization, but not at later intervals (1-5 years). In Stage IV trials, RFS event rates significantly differed for the interval 0-0.5 years (p = 0.012), corresponding with adjuvant treatment durations of 6 months. In Stage II/III trials, which included therapies of 6-24 months duration, there were marked differences in the RFS event rates between surgery and chemotherapy arms for the intervals 0-0.5 years (p < 0.001) and 0.5-1 years (p < 0.001) with smaller differences in the RFS event rates for the intervals 1-2 years (p = 0.012) and 2-3 years (p = 0.010).
CONCLUSIONS
CONCLUSIONS
In a systematic review of positive RCTs comparing adjuvant chemotherapy to surgery alone for Stage II-IV CRC, observed RFS improvements were driven by early divergences that occurred primarily during active cytotoxic chemotherapy. Late recurrence dynamics were not influenced by adjuvant therapy use. Such observations may have implications for the use of chemotherapy for micrometastatic clones detectable by cell-free DNA-based methodologies.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCI NIH HHS
ID : P30CA072720
Pays : United States
Organisme : NCI NIH HHS
ID : PO1CA250957
Pays : United States
Organisme : NCI NIH HHS
ID : RO1 CA243547
Pays : United States
Organisme : NCI NIH HHS
ID : RO1CA233662
Pays : United States
Informations de copyright
© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
Références
van der Stok EP, Spaander MCW, Grünhagen DJ, Verhoef C, Kuipers EJ. Surveillance after curative treatment for colorectal cancer. Nat Rev Clin Oncol. 2017;14(5):297-315. doi:10.1038/nrclinonc.2016.199
Elferink MAG, de Jong KP, Klaase JM, Siemerink EJ, de Wilt JHW. Metachronous metastases from colorectal cancer: a population-based study in North-East Netherlands. Int J Colorectal Dis. 2015;30(2):205-212. doi:10.1007/s00384-014-2085-6
Aguirre-Ghiso JA. Models, mechanisms and clinical evidence for cancer dormancy. Nat Rev Cancer. 2007;7(11):834-846. doi:10.1038/nrc2256
Francescangeli F, De Angelis ML, Rossi R, et al. Dormancy, stemness, and therapy resistance: interconnected players in cancer evolution. Cancer Metastasis Rev. 2023;42(1):197-215. doi:10.1007/s10555-023-10092-4
Cuccu A, Francescangeli F, De Angelis ML, Bruselles A, Giuliani A, Zeuner A. Analysis of dormancy-associated transcriptional networks reveals a shared quiescence signature in lung and colorectal cancer. Int J Mol Sci. 2022;23(17):9869. doi:10.3390/ijms23179869
Rehman SK, Haynes J, Collignon E, et al. Colorectal cancer cells enter a diapause-like DTP state to survive chemotherapy. Cell. 2021;184(1):226-242.e21. doi:10.1016/j.cell.2020.11.018
Demicheli R. Tumour dormancy: findings and hypotheses from clinical research on breast cancer. Semin Cancer Biol. 2001;11(4):297-306. doi:10.1006/scbi.2001.0385
Chan GHJ, Chee CE. Making sense of adjuvant chemotherapy in colorectal cancer. J Gastrointest Oncol. 2019;10(6):1183-1192. doi:10.21037/jgo.2019.06.03
Ramirez M, Rajaram S, Steininger RJ, et al. Diverse drug-resistance mechanisms can emerge from drug-tolerant cancer persister cells. Nat Commun. 2016;7:10690. doi:10.1038/ncomms10690
Shamseer L, Moher D, Clarke M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ. 2015;350:g7647. doi:10.1136/bmj.g7647
Hamaguchi T, Shirao K, Moriya Y, et al. Final results of randomized trials by the National Surgical Adjuvant Study of colorectal cancer (NSAS-CC). Cancer Chemother Pharmacol. 2011;67:587-596. doi:10.1007/s00280-010-1358-1
Quasar Collaborative Group, Gray R, Barnwell J, et al. Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study. Lancet. 2007;370(9604):2020-2029. doi:10.1016/S0140-6736(07)61866-2
Watanabe M, Kodaira S, Takahashi T, et al. Randomized trial of the efficacy of adjuvant chemotherapy for colon cancer with combination therapy incorporating the oral pyrimidine 1-hexylcarbamoyl-5-fluorouracil. Langenbecks Arch Surg. 2006;391(4):330-337. doi:10.1007/s00423-006-0044-6
Akasu T, Moriya Y, Ohashi Y, et al. Adjuvant chemotherapy with uracil-tegafur for pathological stage III rectal cancer after mesorectal excision with selective lateral pelvic lymphadenectomy: a multicenter randomized controlled trial. Jpn J Clin Oncol. 2006;36(4):237-244. doi:10.1093/jjco/hyl014
Kato T, Ohashi Y, Nakazato H, et al. Efficacy of oral UFT as adjuvant chemotherapy to curative resection of colorectal cancer: multicenter prospective randomized trial. Langenbecks Arch Surg. 2002;386(8):575-581. doi:10.1007/s00423-002-0278-x
Zaniboni A, Labianca R, Marsoni S, et al. GIVIO-SITAC 01: a randomized trial of adjuvant 5-fluorouracil and folinic acid administered to patients with colon carcinoma-long term results and evaluation of the indicators of health-related quality of life. Gruppo Italiano Valutazione Interventi in Oncologia. Studio Italiano Terapia Adiuvante Colon. Cancer. 1998;82(11):2135-2144. doi:10.1002/(sici)1097-0142(19980601)82:11<2135::aid-cncr7>3.0.co;2-u
O'Connell MJ, Mailliard JA, Kahn MJ, et al. Controlled trial of fluorouracil and low-dose leucovorin given for 6 months as postoperative adjuvant therapy for colon cancer. J Clin Oncol. 1997;15(1):246-250. doi:10.1200/JCO.1997.15.1.246
Ito K, Yamaguchi A, Miura K, et al. Oral adjuvant chemotherapy with carmofur (HCFU) for colorectal cancer: five-year follow-up. Tokai HCFU study group-third study on colorectal cancer. J Surg Oncol. 1996;63(2):107-111. doi:10.1002/(SICI)1096-9098(199610)63:2<107::AID-JSO7>3.0.CO;2-I
Efficacy of adjuvant fluorouracil and folinic acid in colon cancer. International Multicentre Pooled Analysis of Colon Cancer Trials (IMPACT) investigators. Lancet. 1995;345(8955):939-944.
Moertel CG, Fleming TR, Macdonald JS, et al. Fluorouracil plus levamisole as effective adjuvant therapy after resection of stage III colon carcinoma: a final report. Ann Intern Med. 1995;122(5):321-326. doi:10.7326/0003-4819-122-5-199503010-00001
Five-year results of a randomized controlled trial of adjuvant chemotherapy for curatively resected colorectal carcinoma. The colorectal cancer chemotherapy study Group of Japan. Jpn J Clin Oncol. 1995;25(3):91-103.
Francini G, Petrioli R, Lorenzini L, et al. Folinic acid and 5-fluorouracil as adjuvant chemotherapy in colon cancer. Gastroenterology. 1994;106(4):899-906. doi:10.1016/0016-5085(94)90748-x
Hasegawa K, Saiura A, Takayama T, et al. Adjuvant Oral uracil-tegafur with leucovorin for colorectal cancer liver metastases: a randomized controlled trial. PloS One. 2016;11(9):e0162400. doi:10.1371/journal.pone.0162400
Portier G, Elias D, Bouche O, et al. Multicenter randomized trial of adjuvant fluorouracil and folinic acid compared with surgery alone after resection of colorectal liver metastases: FFCD ACHBTH AURC 9002 trial. J Clin Oncol. 2006;24(31):4976-4982. doi:10.1200/JCO.2006.06.8353
Kotani D, Oki E, Nakamura Y, et al. Molecular residual disease and efficacy of adjuvant chemotherapy in patients with colorectal cancer. Nat Med. 2023;29:127-134. doi:10.1038/s41591-022-02115-4
Sahin IH, Lin Y, Yothers G, et al. Minimal residual disease-directed adjuvant therapy for patients with early-stage colon cancer: CIRCULATE-US. Oncology (Williston Park). 2022;36(10):604-608. doi:10.46883/2022.25920976
Lei GX, Zhang M, Ling TY, Hua LX. Cancer cell dormancy: mechanisms and implications of cancer recurrence and metastasis. Onco Targets Ther. 2017;10:5219-5228. doi:10.2147/OTT.S140854
Park SY, Nam JS. The force awakens: metastatic dormant cancer cells. Exp Mol Med. 2020;52(4):569-581. doi:10.1038/s12276-020-0423-z
Zhang XW, Yang HY, Fan P, Yang L, Chen GY. Detection of micrometastasis in peripheral blood by multi-sampling in patients with colorectal cancer. World J Gastroenterol. 2005;11(3):436-438. doi:10.3748/wjg.v11.i3.436
Kreso A, O'Brien CA, van Galen P, et al. Variable clonal repopulation dynamics influence chemotherapy response in colorectal cancer. Science. 2013;339(6119):543-548. doi:10.1126/science.1227670
Echeverria GV, Ge Z, Seth S, et al. Resistance to neoadjuvant chemotherapy in triple-negative breast cancer mediated by a reversible drug-tolerant state. Sci Transl Med. 2019;11(488):eaav0936. doi:10.1126/scitranslmed.aav0936
Naumov GN, Townson JL, MacDonald IC, et al. Ineffectiveness of doxorubicin treatment on solitary dormant mammary carcinoma cells or late-developing metastases. Breast Cancer Res Treat. 2003;82(3):199-206. doi:10.1023/B:BREA.0000004377.12288.3c
Álvarez-Varela A, Novellasdemunt L, Barriga FM, et al. Mex3a marks drug-tolerant persister colorectal cancer cells that mediate relapse after chemotherapy. Nat Cancer. 2022;3:1052-1070. doi:10.1038/s43018-022-00402-0
Watanabe H, Nakagomi H, Hirotsu Y, et al. TP53-positive clones are responsible for drug-tolerant persister and recurrence of HER2-positive breast cancer. Breast Cancer Res Treat. 2022;196(2):255-266. doi:10.1007/s10549-022-06731-z
Grothey A, Sobrero AF, Shields AF, et al. Duration of adjuvant chemotherapy for stage III colon cancer. N Engl J Med. 2018;378(13):1177-1188. doi:10.1056/NEJMoa1713709
Des Guetz G, Uzzan B, Morere JF, Perret G, Nicolas P. Duration of adjuvant chemotherapy for patients with non-metastatic colorectal cancer. Cochrane Database Syst Rev. 2010;(1):CD007046. doi:10.1002/14651858.CD007046.pub2
Taieb J, Taly V, Henriques J, et al. Prognostic value and relation with adjuvant treatment duration of ctDNA in stage III colon cancer: a post hoc analysis of the PRODIGE-GERCOR IDEA-France trial. Clin Cancer Res. 2021;27(20):5638-5646. doi:10.1158/1078-0432.CCR-21-0271
Kanemitsu Y, Shimizu Y, Mizusawa J, et al. Hepatectomy followed by mFOLFOX6 versus hepatectomy alone for liver-only metastatic colorectal cancer (JCOG0603): a phase II or III randomized controlled trial. J Clin Oncol off J Am Soc Clin Oncol. 2021;39(34):3789-3799. doi:10.1200/JCO.21.01032
Kemeny MM, Adak S, Gray B, et al. Combined-modality treatment for resectable metastatic colorectal carcinoma to the liver: surgical resection of hepatic metastases in combination with continuous infusion of chemotherapy-an intergroup study. J Clin Oncol. 2002;20(6):1499-1505. doi:10.1200/JCO.2002.20.6.1499
Sakamoto J, Ohashi Y, Hamada C, et al. Efficacy of oral adjuvant therapy after resection of colorectal cancer: 5-year results from three randomized trials. J Clin Oncol. 2004;22(3):484-492. doi:10.1200/JCO.2004.04.065
Wolmark N, Fisher B, Rockette H, et al. Postoperative adjuvant chemotherapy or BCG for colon cancer: results from NSABP protocol C-0112. J Natl Cancer Inst. 1988;80(1):30-36. doi:10.1093/jnci/80.1.30
Luo D, Yang Y, Shan Z, et al. Clinicopathological features of stage I-III colorectal cancer recurrence over 5 years after radical surgery without receiving neoadjuvant therapy: evidence from a large sample study. Front Surg. 2021;8:666400. doi:10.3389/fsurg.2021.666400
Nordlinger B, Sorbye H, Glimelius B, et al. Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC 40983): long-term results of a randomised, controlled, phase 3 trial. Lancet Oncol. 2013;14(12):1208-1215.