Long-Term Follow-Up of neoadjuvant chemotherapy for colorectal cancer
DOI:
https://doi.org/10.5281/zenodo.22813254Keywords:
colorectal cancer, neoadjuvant chemotherapy, long-term follow-up, disease-free survival, pathologic complete responseAbstract
Background: Neoadjuvant chemotherapy has become standard for locally advanced colorectal cancer, but most reported outcomes extend only to five years.
Methods: We retrospectively analyzed 196 patients with locally advanced colorectal adenocarcinoma completing neoadjuvant chemotherapy and curative-intent resection (2011-2015), minimum eight-year follow-up. Overall survival (OS), disease-free survival (DFS), recurrence pattern, and predictors of outcome, including regression grade and circumferential resection margin (CRM), were assessed by Kaplan-Meier and Cox regression.
Results: Median follow-up was 9.7 years. Ten-year OS and DFS were 61.4% and 54.8%. Complete responders had markedly better ten-year DFS than those with residual tumor (84.4% vs 48.2%, p<0.001). Local recurrence was rare with negative CRM (2.1%) versus positive CRM (26.8%). Complete response, negative CRM, and lower stage independently predicted DFS.
Conclusion: Neoadjuvant chemotherapy for locally advanced colorectal cancer produces durable ten-year survival paralleling landmark trials, driven by depth of pathologic response and margin adequacy, supporting intensified neoadjuvant therapy and response-based patient selection.
References
Sung, H., Ferlay, J., Siegel, R.L., Laversanne, M., Soerjomataram, I., Jemal, A., et al. (2021) Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 71(3): 209-249. DOI: 10.3322/caac.21660
Siegel, R.L., Giaquinto, A.N., Jemal, A. (2024) Cancer statistics, 2024. CA: A Cancer Journal for Clinicians, 74(1): 12-49. DOI: 10.3322/caac.21820
Sauer, R., Becker, H., Hohenberger, W., Rodel, C., Wittekind, C., Fietkau, R., et al. (2004) Preoperative versus postoperative chemoradiotherapy for rectal cancer. New England Journal of Medicine, 351(17): 1731-1740. DOI: 10.1056/NEJMoa040694
Kapiteijn, E., Marijnen, C.A., Nagtegaal, I.D., Putter, H., Steup, W.H., Wiggers, T., et al. (2001) Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. New England Journal of Medicine, 345(9): 638-646. DOI: 10.1056/NEJMoa010580
Sauer, R., Liersch, T., Merkel, S., Fietkau, R., Hohenberger, W., Hess, C., et al. (2012) Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. Journal of Clinical Oncology, 30(16): 1926-1933. DOI: 10.1200/JCO.2011.40.1836
Bosset, J.F., Collette, L., Calais, G., Mineur, L., Maingon, P., Radosevic-Jelic, L., et al. (2006) Chemotherapy with preoperative radiotherapy in rectal cancer. New England Journal of Medicine, 355(11): 1114-1123. DOI: 10.1056/NEJMoa060829
FOxTROT Collaborative Group. (2012) Feasibility of preoperative chemotherapy for locally advanced, operable colon cancer: the pilot phase of a randomised controlled trial. Lancet Oncology, 13(11): 1152-1160. DOI: 10.1016/S1470-2045(12)70348-0
Morton, D., Seymour, M., Magill, L., Handley, K., Glasbey, J., Glimelius, B., et al. (2023) Preoperative chemotherapy for operable colon cancer: mature results of an international randomised controlled trial (FOxTROT). Journal of Clinical Oncology, 41(8): 1541-1552. DOI: 10.1200/JCO.22.00046
Conroy, T., Bosset, J.F., Etienne, P.L., Rio, E., Francois, E., Mesgouez-Nebout, N., et al. (2021) Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23). Lancet Oncology, 22(5): 702-715. DOI: 10.1016/S1470-2045(21)00079-6
Bahadoer, R.R., Dijkstra, E.A., van Etten, B., Marijnen, C.A.M., Putter, H., Kranenbarg, E.M., et al. (2021) Short-course radiotherapy followed by chemotherapy before total mesorectal excision versus preoperative chemoradiotherapy for locally advanced rectal cancer (RAPIDO). Lancet Oncology, 22(1): 29-42. DOI: 10.1016/S1470-2045(20)30555-6
Fokas, E., Allgauer, M., Polat, B., Klautke, G., Grabenbauer, G.G., Fietkau, R., et al. (2019) Randomized phase II trial of chemoradiotherapy plus induction or consolidation chemotherapy as total neoadjuvant therapy for locally advanced rectal cancer: CAO/ARO/AIO-12. Journal of Clinical Oncology, 37(34): 3212-3222. DOI: 10.1200/JCO.19.00308
Habr-Gama, A., Perez, R.O., Nadalin, W., Sabbaga, J., Ribeiro, U. Jr, Silva e Sousa, A.H. Jr, et al. (2004) Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Annals of Surgery, 240(4): 711-717. DOI: 10.1097/01.sla.0000141194.27992.32
Maas, M., Beets-Tan, R.G., Lambregts, D.M., Lammering, G., Nelemans, P.J., Engelen, S.M., et al. (2011) Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer. Journal of Clinical Oncology, 29(35): 4633-4640. DOI: 10.1200/JCO.2011.37.7176
van der Valk, M.J.M., Hilling, D.E., Bastiaannet, E., Meershoek-Klein Kranenbarg, E., Beets, G.L., Figueiredo, N.L., et al. (2018) Long-term outcomes of clinical complete responders after neoadjuvant treatment for rectal cancer in the International Watch & Wait Database. Lancet, 391(10139): 2537-2545. DOI: 10.1016/S0140-6736(18)31078-X
Garcia-Aguilar, J., Patil, S., Gollub, M.J., Kim, J.K., Yuval, J.B., Thompson, H.M., et al. (2022) Organ preservation in patients with rectal adenocarcinoma treated with total neoadjuvant therapy. Journal of Clinical Oncology, 40(23): 2546-2556. DOI: 10.1200/JCO.22.00032
Benson, A.B., Venook, A.P., Al-Hawary, M.M., Cederquist, L., Chen, Y.J., Ciombor, K.K., et al. (2018) NCCN Guidelines Insights: Colon Cancer, Version 2.2018. Journal of the National Comprehensive Cancer Network, 16(4): 359-369. DOI: 10.6004/jnccn.2018.0021
Glynne-Jones, R., Wyrwicz, L., Tiret, E., Brown, G., Rodel, C., Cervantes, A., et al. (2017) Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology, 28(suppl 4): iv22-iv40. DOI: 10.1093/annonc/mdx224
Roh, M.S., Colangelo, L.H., O'Connell, M.J., Yothers, G., Deutsch, M., Allegra, C.J., et al. (2009) Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03. Journal of Clinical Oncology, 27(31): 5124-5130. DOI: 10.1200/JCO.2009.22.0467
Gerard, J.P., Conroy, T., Bonnetain, F., Bouche, O., Chapet, O., Closon-Dejardin, M.T., et al. (2006) Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. Journal of Clinical Oncology, 24(28): 4620-4625. DOI: 10.1200/JCO.2006.06.7629
Rodel, C., Liersch, T., Becker, H., Fietkau, R., Hohenberger, W., Hothorn, T., et al. (2012) Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (German CAO/ARO/AIO-04). Lancet Oncology, 13(7): 679-687. DOI: 10.1016/S1470-2045(12)70187-0
Rodel, C., Graeven, U., Fietkau, R., Hohenberger, W., Hothorn, T., Arnold, D., et al. (2015) Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: final results of the CAO/ARO/AIO-04 randomised phase 3 trial. Lancet Oncology, 16(8): 979-989. DOI: 10.1016/S1470-2045(15)00159-X
Hofheinz, R.D., Wenz, F., Post, S., Matzdorff, A., Laechelt, S., Hartmann, J.T., et al. (2012) Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncology, 13(6): 579-588. DOI: 10.1016/S1470-2045(12)70116-X
Mandard, A.M., Dalibard, F., Mandard, J.C., Marnay, J., Henry-Amar, M., Petiot, J.F., et al. (1994) Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Cancer, 73(11): 2680-2686. DOI: 10.1002/1097-0142(19940601)73:11<2 680::AID-CNCR2820731105>3.0.CO;2-C
Dworak, O., Keilholz, L., Hoffmann, A. (1997) Pathological features of rectal cancer after preoperative radiochemotherapy. International Journal of Colorectal Disease, 12(1): 19-23. DOI: 10.1007/s003840050072
Taylor, F.G., Quirke, P., Heald, R.J., Moran, B.J., Blomqvist, L., Swift, I.R., et al. (2014) Preoperative magnetic resonance imaging assessment of circumferential resection margin predicts disease-free survival and local recurrence: 5-year follow-up results of the MERCURY study. Journal of Clinical Oncology, 32(1): 34-43. DOI: 10.1200/JCO.2012.45.3258
Park, I.J., You, Y.N., Agarwal, A., Skibber, J.M., Rodriguez-Bigas, M.A., Eng, C., et al. (2012) Neoadjuvant treatment response as an early response indicator for patients with rectal cancer. Journal of Clinical Oncology, 30(15): 1770-1776. DOI: 10.1200/JCO.2011.39.7901
Sclafani, F., Brown, G., Cunningham, D., Wotherspoon, A., Tait, D., Peckitt, C., et al. (2017) Comparison between MRI and pathology in the assessment of tumour regression grade in rectal cancer. British Journal of Cancer, 117(10): 1478-1485. DOI: 10.1038/bjc.2017.320
Guillem, J.G., Chessin, D.B., Cohen, A.M., Shia, J., Mazumdar, M., Enker, W., et al. (2005) Long-term oncologic outcome following preoperative combined modality therapy and total mesorectal excision of locally advanced rectal cancer. Annals of Surgery, 241(5): 829-838. DOI: 10.1097/01.sla.0000161980.46727.a4
Deng, Y., Chi, P., Lan, P., Wang, L., Chen, W., Cui, L., et al. (2019) Neoadjuvant modified FOLFOX6 with or without radiation versus fluorouracil plus radiation for locally advanced rectal cancer: final results of the Chinese FOWARC trial. Journal of Clinical Oncology, 37(34): 3223-3233. DOI: 10.1200/JCO.18.02309
Heald, R.J., Ryall, R.D. (1982) Recurrence and survival after total mesorectal excision for rectal cancer. Lancet, 1(8496): 1479-1482. DOI: 10.1016/S0140-6736(86)91510-2
Andre, T., Boni, C., Mounedji-Boudiaf, L., Navarro, M., Tabernero, J., Hickish, T., et al. (2004) Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. New England Journal of Medicine, 350(23): 2343-2351. DOI: 10.1056/NEJMoa032709
Andre, T., Boni, C., Navarro, M., Tabernero, J., Hickish, T., Topham, C., et al. (2009) Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. Journal of Clinical Oncology, 27(19): 3109-3116. DOI: 10.1200/JCO.2008.20.6771
Petersen, S.H., Harling, H., Kirkeby, L.T., Wille-Jorgensen, P., Mocellin, S. (2012) Postoperative adjuvant chemotherapy in rectal cancer operated for cure. Cochrane Database of Systematic Reviews, 3: CD004078. DOI: 10.1002/14651858.CD004078.pub2
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