Skip to main content
Top
Published in:

Open Access 01-12-2024 | Rectal Cancer | Research

Neoadjuvant therapy in rectal cancer—one year follow-up results of standard versus total neoadjuvant strategies

Authors: Luís Correia Gomes, Bernardo Alves Pereira, Isália Miguel, Ana Luís, Ana Pina, Cátia Pedro, Daniela Cavadas, Daniela Pereira, Joana Lemos, João Maciel, João Oliveira, José Venâncio, Madalena Santos, Manuel Limbert, Miguel Braga, Miriam Abdulrehman, Pedro Freitas, Ricardo Fonseca, Teresa Ferreira, Isadora Rosa

Published in: World Journal of Surgical Oncology | Issue 1/2024

Login to get access

Abstract

Background

Locally advanced rectal cancer (LARC) poses a significantly challenge in clinical management, requiring a multimodal treatment approach. Among innovative strategies, Total Neoadjuvant Therapy (TNT) has emerged, delivering all planned chemotherapy before surgery.

Objective

Our aim was to evaluate the real-world application and efficacy of TNT and to compare it with the non-TNT standard strategy.

Methods

This retrospective study compared locally advanced rectal adenocarcinoma patients treated with Total Neoadjuvant Therapy (TNT) in 2022 with those who underwent traditional chemoradiotherapy (CRT) in 2020–2021. The primary endpoints were the pathologic complete response rate and the sustained clinical complete response rate in patients under W&W.

Results

Among 107 patients (54.2% male, mean age 62.48 years), non-TNT (67 patients) and TNT (40 patients) mean follow-ups were 26.7 and 8.2 months, respectively. No differences in gender(p = 0.163), staging (p = 0.707), or location (p = 0.727) were noted. TNT patients received more short-course radiotherapy (42.5% vs1.5%, p < 0.001). Clinical responses favored TNT (p = 0.030) with no significant differences in pathological responses, recurrence rates, or survival. TNT exhibited higher chemotherapy completion (p = 0.007) and lower adverse events (p < 0.001). Post-surgery events showed no significant differences (p = 0.470). Single center with retrospective design and carries limitations that may restrict the generalizability of the findings and the relatively short follow-up duration are our main limitations.

Conclusion

Our data add to the body of literature favoring the TNT treatment strategy for locally advanced rectal cancer, aiming to achieve comparable complete response rates with less adverse events.
Literature
1.
go back to reference Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021May;71(3):209–49. https://doi.org/10.3322/caac.21660. (Epub 2021 Feb 4 PMID: 33538338).CrossRefPubMed Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021May;71(3):209–49. https://​doi.​org/​10.​3322/​caac.​21660. (Epub 2021 Feb 4 PMID: 33538338).CrossRefPubMed
3.
go back to reference Maas M, Beets-Tan RG, Lambregts DM, Lammering G, Nelemans PJ, Engelen SM, van Dam RM, Jansen RL, Sosef M, Leijtens JW, Hulsewé KW, Buijsen J, Beets GL. Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer. J Clin Oncol. 2011D 10;29(35):4633–40. https://doi.org/10.1200/JCO.2011.37.7176. Epub 2011 Nov 7 PMID: 22067400.CrossRefPubMed Maas M, Beets-Tan RG, Lambregts DM, Lammering G, Nelemans PJ, Engelen SM, van Dam RM, Jansen RL, Sosef M, Leijtens JW, Hulsewé KW, Buijsen J, Beets GL. Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer. J Clin Oncol. 2011D 10;29(35):4633–40. https://​doi.​org/​10.​1200/​JCO.​2011.​37.​7176. Epub 2011 Nov 7 PMID: 22067400.CrossRefPubMed
4.
go back to reference van der Valk MJM, Hilling DE, Bastiaannet E, Meershoek-Klein Kranenbarg E, Beets GL, Figueiredo NL, Habr-Gama A, Perez RO, Renehan AG, van de Velde CJH; IWWD Consortium. Long-term outcomes of clinical complete responders after neoadjuvant treatment for rectal cancer in the International Watch & Wait Database (IWWD): an international multicentre registry study. Lancet. 2018 Jun 23;391(10139):2537–2545. https://doi.org/10.1016/S0140-6736(18)31078-X. PMID: 29976470. van der Valk MJM, Hilling DE, Bastiaannet E, Meershoek-Klein Kranenbarg E, Beets GL, Figueiredo NL, Habr-Gama A, Perez RO, Renehan AG, van de Velde CJH; IWWD Consortium. Long-term outcomes of clinical complete responders after neoadjuvant treatment for rectal cancer in the International Watch & Wait Database (IWWD): an international multicentre registry study. Lancet. 2018 Jun 23;391(10139):2537–2545. https://​doi.​org/​10.​1016/​S0140-6736(18)31078-X. PMID: 29976470.
5.
go back to reference Bahadoer RR, Dijkstra EA, van Etten B, Marijnen CAM, Putter H, Kranenbarg EM, Roodvoets AGH, Nagtegaal ID, Beets-Tan RGH, Blomqvist LK, Fokstuen T, Ten Tije AJ, Capdevila J, Hendriks MP, Edhemovic I, Cervantes A, Nilsson PJ, Glimelius B, van de Velde CJH, Hospers GAP; RAPIDO collaborative investigators. Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):29–42. https://doi.org/10.1016/S1470-2045(20)30555-6. Epub 2020 Dec 7. Erratum in: Lancet Oncol. 2021 Feb;22(2):e42. PMID: 33301740. Bahadoer RR, Dijkstra EA, van Etten B, Marijnen CAM, Putter H, Kranenbarg EM, Roodvoets AGH, Nagtegaal ID, Beets-Tan RGH, Blomqvist LK, Fokstuen T, Ten Tije AJ, Capdevila J, Hendriks MP, Edhemovic I, Cervantes A, Nilsson PJ, Glimelius B, van de Velde CJH, Hospers GAP; RAPIDO collaborative investigators. Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):29–42. https://​doi.​org/​10.​1016/​S1470-2045(20)30555-6. Epub 2020 Dec 7. Erratum in: Lancet Oncol. 2021 Feb;22(2):e42. PMID: 33301740.
6.
go back to reference van der Valk MJM, Marijnen CAM, van Etten B, Dijkstra EA, Hilling DE, Kranenbarg EM, Putter H, Roodvoets AGH, Bahadoer RR, Fokstuen T, Ten Tije AJ, Capdevila J, Hendriks MP, Edhemovic I, Cervantes AMR, de Groot DJA, Nilsson PJ, Glimelius B, van de Velde CJH, Hospers GAP; Collaborative investigators. Compliance and tolerability of short-course radiotherapy followed by preoperative chemotherapy and surgery for high-risk rectal cancer - Results of the international randomized RAPIDO-trial. Radiother Oncol. 2020 Jun;147:75–83. https://doi.org/10.1016/j.radonc.2020.03.011. Epub 2020 Mar 30. Erratum in: Radiother Oncol. 2020 Jun;147:e1. PMID: 32240909. van der Valk MJM, Marijnen CAM, van Etten B, Dijkstra EA, Hilling DE, Kranenbarg EM, Putter H, Roodvoets AGH, Bahadoer RR, Fokstuen T, Ten Tije AJ, Capdevila J, Hendriks MP, Edhemovic I, Cervantes AMR, de Groot DJA, Nilsson PJ, Glimelius B, van de Velde CJH, Hospers GAP; Collaborative investigators. Compliance and tolerability of short-course radiotherapy followed by preoperative chemotherapy and surgery for high-risk rectal cancer - Results of the international randomized RAPIDO-trial. Radiother Oncol. 2020 Jun;147:75–83. https://​doi.​org/​10.​1016/​j.​radonc.​2020.​03.​011. Epub 2020 Mar 30. Erratum in: Radiother Oncol. 2020 Jun;147:e1. PMID: 32240909.
7.
go back to reference Liberale G, Vankerckhove S, Caldon MG, et al. Patterns of response and progression to oLAR in patients undergoing TNT for rectal cancer: individual risk factors and critical considerations. Ann Surg. 2021;273(5):944–51. Liberale G, Vankerckhove S, Caldon MG, et al. Patterns of response and progression to oLAR in patients undergoing TNT for rectal cancer: individual risk factors and critical considerations. Ann Surg. 2021;273(5):944–51.
8.
go back to reference Moyer AM, Vogel JD, Lai SH, Kim H, Chin RI, Moskalenko M, Olsen JR, Birnbaum EH, Silviera ML, Mutch MG, Chapman BC. Total Neoadjuvant Therapy in Rectal Cancer: Multi-center Comparison of Induction Chemotherapy and Long-Course Chemoradiation Versus Short-Course Radiation and Consolidative Chemotherapy. J Gastrointest Surg. 2023May;27(5):980–9. https://doi.org/10.1007/s11605-023-05601-3. (Epub 2023 Feb 9 PMID: 36759387).CrossRefPubMed Moyer AM, Vogel JD, Lai SH, Kim H, Chin RI, Moskalenko M, Olsen JR, Birnbaum EH, Silviera ML, Mutch MG, Chapman BC. Total Neoadjuvant Therapy in Rectal Cancer: Multi-center Comparison of Induction Chemotherapy and Long-Course Chemoradiation Versus Short-Course Radiation and Consolidative Chemotherapy. J Gastrointest Surg. 2023May;27(5):980–9. https://​doi.​org/​10.​1007/​s11605-023-05601-3. (Epub 2023 Feb 9 PMID: 36759387).CrossRefPubMed
9.
go back to reference Fokas E, Allgäuer M, Polat B, Klautke G, Grabenbauer GG, Fietkau R, Kuhnt T, Staib L, Brunner T, Grosu AL, Schmiegel W, Jacobasch L, Weitz J, Folprecht G, Schlenska-Lange A, Flentje M, Germer CT, Grützmann R, Schwarzbach M, Paolucci V, Bechstein WO, Friede T, Ghadimi M, Hofheinz RD, Rödel C; German Rectal Cancer Study Group. Randomized Phase II Trial of Chemoradiotherapy Plus Induction or Consolidation Chemotherapy as Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: CAO/ARO/AIO-12. J Clin Oncol. 2019 Dec 1;37(34):3212–3222. https://doi.org/10.1200/JCO.19.00308. Epub 2019 May 31. PMID: 31150315. Fokas E, Allgäuer M, Polat B, Klautke G, Grabenbauer GG, Fietkau R, Kuhnt T, Staib L, Brunner T, Grosu AL, Schmiegel W, Jacobasch L, Weitz J, Folprecht G, Schlenska-Lange A, Flentje M, Germer CT, Grützmann R, Schwarzbach M, Paolucci V, Bechstein WO, Friede T, Ghadimi M, Hofheinz RD, Rödel C; German Rectal Cancer Study Group. Randomized Phase II Trial of Chemoradiotherapy Plus Induction or Consolidation Chemotherapy as Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: CAO/ARO/AIO-12. J Clin Oncol. 2019 Dec 1;37(34):3212–3222. https://​doi.​org/​10.​1200/​JCO.​19.​00308. Epub 2019 May 31. PMID: 31150315.
10.
go back to reference Dijkstra EA, Nilsson PJ, Hospers GAP, Bahadoer RR, Meershoek-Klein Kranenbarg E, Roodvoets AGH, Putter H, Berglund Å, Cervantes A, Crolla RMPH, Hendriks MP, Capdevila J, Edhemovic I, Marijnen CAM, van de Velde CJH, Glimelius B, van Etten B; Collaborative Investigators. Locoregional Failure During and After Short-course Radiotherapy Followed by Chemotherapy and Surgery Compared With Long-course Chemoradiotherapy and Surgery: A 5-Year Follow-up of the RAPIDO Trial. Ann Surg. 2023 Oct 1;278(4):e766-e772. https://doi.org/10.1097/SLA.0000000000005799. Epub 2023 Jan 20. PMID: 36661037; PMCID: PMC10481913. Dijkstra EA, Nilsson PJ, Hospers GAP, Bahadoer RR, Meershoek-Klein Kranenbarg E, Roodvoets AGH, Putter H, Berglund Å, Cervantes A, Crolla RMPH, Hendriks MP, Capdevila J, Edhemovic I, Marijnen CAM, van de Velde CJH, Glimelius B, van Etten B; Collaborative Investigators. Locoregional Failure During and After Short-course Radiotherapy Followed by Chemotherapy and Surgery Compared With Long-course Chemoradiotherapy and Surgery: A 5-Year Follow-up of the RAPIDO Trial. Ann Surg. 2023 Oct 1;278(4):e766-e772. https://​doi.​org/​10.​1097/​SLA.​0000000000005799​. Epub 2023 Jan 20. PMID: 36661037; PMCID: PMC10481913.
11.
go back to reference Schrag D, Shi Q, Weiser MR, Gollub MJ, Saltz LB, Musher BL, Goldberg J, Al Baghdadi T, Goodman KA, McWilliams RR, Farma JM, George TJ, Kennecke HF, Shergill A, Montemurro M, Nelson GD, Colgrove B, Gordon V, Venook AP, O’Reilly EM, Meyerhardt JA, Dueck AC, Basch E, Chang GJ, Mamon HJ. Preoperative Treatment of Locally Advanced Rectal Cancer. N Engl J Med. 2023Jul 27;389(4):322–34. https://doi.org/10.1056/NEJMoa2303269. (Epub 2023 Jun 4 PMID: 37272534).CrossRefPubMedPubMedCentral Schrag D, Shi Q, Weiser MR, Gollub MJ, Saltz LB, Musher BL, Goldberg J, Al Baghdadi T, Goodman KA, McWilliams RR, Farma JM, George TJ, Kennecke HF, Shergill A, Montemurro M, Nelson GD, Colgrove B, Gordon V, Venook AP, O’Reilly EM, Meyerhardt JA, Dueck AC, Basch E, Chang GJ, Mamon HJ. Preoperative Treatment of Locally Advanced Rectal Cancer. N Engl J Med. 2023Jul 27;389(4):322–34. https://​doi.​org/​10.​1056/​NEJMoa2303269. (Epub 2023 Jun 4 PMID: 37272534).CrossRefPubMedPubMedCentral
12.
go back to reference Conroy T, Bosset JF, Etienne PL, Rio E, François É, Mesgouez-Nebout N, Vendrely V, Artignan X, Bouché O, Gargot D, Boige V, Bonichon-Lamichhane N, Louvet C, Morand C, de la Fouchardière C, Lamfichekh N, Juzyna B, Jouffroy-Zeller C, Rullier E, Marchal F, Gourgou S, Castan F, Borg C; Unicancer Gastrointestinal Group and Partenariat de Recherche en Oncologie Digestive (PRODIGE) Group. Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2021 May;22(5):702–715. https://doi.org/10.1016/S1470-2045(21)00079-6. Epub 2021 Apr 13. PMID: 33862000. Conroy T, Bosset JF, Etienne PL, Rio E, François É, Mesgouez-Nebout N, Vendrely V, Artignan X, Bouché O, Gargot D, Boige V, Bonichon-Lamichhane N, Louvet C, Morand C, de la Fouchardière C, Lamfichekh N, Juzyna B, Jouffroy-Zeller C, Rullier E, Marchal F, Gourgou S, Castan F, Borg C; Unicancer Gastrointestinal Group and Partenariat de Recherche en Oncologie Digestive (PRODIGE) Group. Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2021 May;22(5):702–715. https://​doi.​org/​10.​1016/​S1470-2045(21)00079-6. Epub 2021 Apr 13. PMID: 33862000.
13.
go back to reference Liu S, Jiang T, Xiao L, Yang S, Liu Q, Gao Y, Chen G, Xiao W. Total Neoadjuvant Therapy (TNT) versus Standard Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer: A Systematic Review and Meta-Analysis. Oncologist. 2021 Sep;26(9):e1555-e1566. https://doi.org/10.1002/onco.13824. Epub 2021 Jun 7. PMID: 33987952; PMCID: PMC8417863. Liu S, Jiang T, Xiao L, Yang S, Liu Q, Gao Y, Chen G, Xiao W. Total Neoadjuvant Therapy (TNT) versus Standard Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer: A Systematic Review and Meta-Analysis. Oncologist. 2021 Sep;26(9):e1555-e1566. https://​doi.​org/​10.​1002/​onco.​13824. Epub 2021 Jun 7. PMID: 33987952; PMCID: PMC8417863.
14.
go back to reference Smith JJ, Chow OS, Gollub MJ, Nash GM, Temple LK, Weiser MR, Guillem JG, Paty PB, Avila K, Garcia-Aguilar J; Rectal Cancer Consortium. Organ Preservation in Rectal Adenocarcinoma: a phase II randomized controlled trial evaluating 3-year disease-free survival in patients with locally advanced rectal cancer treated with chemoradiation plus induction or consolidation chemotherapy, and total mesorectal excision or nonoperative management. BMC Cancer. 2015 Oct 23;15:767. https://doi.org/10.1186/s12885-015-1632-z. PMID: 26497495; PMCID: PMC4619249. Smith JJ, Chow OS, Gollub MJ, Nash GM, Temple LK, Weiser MR, Guillem JG, Paty PB, Avila K, Garcia-Aguilar J; Rectal Cancer Consortium. Organ Preservation in Rectal Adenocarcinoma: a phase II randomized controlled trial evaluating 3-year disease-free survival in patients with locally advanced rectal cancer treated with chemoradiation plus induction or consolidation chemotherapy, and total mesorectal excision or nonoperative management. BMC Cancer. 2015 Oct 23;15:767. https://​doi.​org/​10.​1186/​s12885-015-1632-z. PMID: 26497495; PMCID: PMC4619249.
15.
16.
go back to reference Habr-Gama A, Perez RO, Nadalin W, Sabbaga J, Ribeiro U Jr, Silva e Sousa AH Jr, Campos FG, Kiss DR, Gama-Rodrigues J. Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Ann Surg. 2004 Oct;240(4):711–7; discussion 717–8. https://doi.org/10.1097/01.sla.0000141194.27992.32. PMID: 15383798; PMCID: PMC1356472. Habr-Gama A, Perez RO, Nadalin W, Sabbaga J, Ribeiro U Jr, Silva e Sousa AH Jr, Campos FG, Kiss DR, Gama-Rodrigues J. Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Ann Surg. 2004 Oct;240(4):711–7; discussion 717–8. https://​doi.​org/​10.​1097/​01.​sla.​0000141194.​27992.​32. PMID: 15383798; PMCID: PMC1356472.
Metadata
Title
Neoadjuvant therapy in rectal cancer—one year follow-up results of standard versus total neoadjuvant strategies
Authors
Luís Correia Gomes
Bernardo Alves Pereira
Isália Miguel
Ana Luís
Ana Pina
Cátia Pedro
Daniela Cavadas
Daniela Pereira
Joana Lemos
João Maciel
João Oliveira
José Venâncio
Madalena Santos
Manuel Limbert
Miguel Braga
Miriam Abdulrehman
Pedro Freitas
Ricardo Fonseca
Teresa Ferreira
Isadora Rosa
Publication date
01-12-2024
Publisher
BioMed Central
Published in
World Journal of Surgical Oncology / Issue 1/2024
Electronic ISSN: 1477-7819
DOI
https://doi.org/10.1186/s12957-024-03590-4
SPONSORED

Mastering chronic pancreatitis pain: A multidisciplinary approach and practical solutions

  • Webinar | 06-02-2024 | 20:00 (CET)

Severe pain is the most common symptom of chronic pancreatitis. In this webinar, experts share the latest insights in pain management for chronic pancreatitis patients. Experts from a range of disciplines discuss pertinent cases and provide practical suggestions for use within clinical practice.

Sponsored by:
  • Viatris
Developed by: Springer Healthcare
Watch now