Lokal fortgeschrittenes Rektumkarzinom

Die Behandlungsstrategien beim lokal fortgeschrittenen Rektumkarzinom sind stark im Wandel. Die in den Leitlinien für lokal fortgeschrittene Tumoren empfohlene Therapie einer neoadjuvanten Radio(chemo)therapie gefolgt von Chirurgie und ggf. adjuvanter Therapie wird zunehmend zugunsten neuer Optionen und Studienkonzepte verlassen. Im vorliegenden Beitrag sollen diese ausgehend vom leitlinienbasierten Status quo diskutiert werden.

Abstract

Treatment strategies for locally advanced rectal cancer are changing dramatically. The treatment recommended in the guidelines for locally advanced tumors of neoadjuvant radio(chemo)therapy (RChT), followed by surgery and, if necessary, adjuvant therapy, are increasingly be abandoned in favor of the following concepts: (i) prolonged neoadjuvant (RChT (i. e. “more chemotherapy before resection”, referred to as total neoadjuvant therapy, TNT); (ii) omission of radiotherapy in tumors with a low risk of local recurrence; (iii) organ preservation in patients with a complete clinical response after neoadjuvant radiochemotherapy. Herein, current strategies and study concepts are to be discussed based on the guideline-based status quo.

Schlüsselwörter

Rektumkarzinom - perioperative Therapie - totale neoadjuvante Therapie - Oxaliplatin

Key words

rectal cancer - perioperative treatment - total neoadjuvant therapy - oxaliplatin

Publication History

Article published online:
05 November 2021

• Literatur

• 1 Ngan SY, Burmeister B, Fisher RJ. et al. Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with T3 rectal cancer: Trans-Tasman Radiation Oncology Group trial 01.04. J Clin Oncol 2012; 30: 3827-3833
• 2 Hofheinz RD, Wenz F, Post S. et al. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol 2012; 13: 579-588
• 3 Schmiegel W, Buchberger B, Follmann M. et al. S3-Leitlinie – Kolorektales Karzinom. Z Gastroenterol 2017; 55: 1344-1498
• 4 Azria D, Doyen J, Jarlier M. et al. Late toxicities and clinical outcome at 5 years of the ACCORD 12/0405-PRODIGE 02 trial comparing two neoadjuvant chemoradiotherapy regimens for intermediate-risk rectal cancer. Ann Oncol 2017; 28: 2436-2442
• 5 Aschele C, Cionini L, Lonardi S. et al. Final results of STAR-01: A randomized phase III trial comparing preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer. J Clin Oncol 2016; 34: 3521
• 6 Allegra CJ, Yothers G, O'Connell MJ. et al. Neoadjuvant 5-FU or Capecitabine Plus Radiation With or Without Oxaliplatin in Rectal Cancer Patients: A Phase III Randomized Clinical Trial. J Natl Cancer Inst 2015; 107: djv248
• 7 Rödel C, Graeven U, Fietkau R. et al. Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 2015; 16: 979-989
• 8 Schmoll HJ, Stein A, Van Cutsem E. et al. Pre- and Postoperative Capecitabine Without or With Oxaliplatin in Locally Advanced Rectal Cancer: PETACC 6 Trial by EORTC GITCG and ROG, AIO, AGITG, BGDO, and FFCD. J Clin Oncol 2021; 39: 17-29
• 9 Des Guetz G, Landre T, Larrouy A. et al. Is there a benefit of oxaliplatin in neoadjuvant treatment of locally advanced rectal cancer? An updated meta-analysis. J Clin Oncol 2020; 38: 4098
• 10 Hofheinz RD, Arnold D, Fokas E. et al. Impact of age on the efficacy of oxaliplatin in the preoperative chemoradiotherapy and adjuvant chemotherapy of rectal cancer: a post hoc analysis of the CAO/ARO/AIO-04 phase III trial. Ann Oncol 2018; 29: 1793-1799
• 11 Fontana E, Zichi C, Smyth EC. et al. Neoadjuvant chemoradiation (CRT) for locally advanced rectal cancer (LARC) with or without oxaliplatin (OX): Individual patient data (IPD) meta-analysis of three randomized controlled trials (RCTs) with subgroup analyses of age cohorts. J Clin Oncol 2020; 38: 4074
• 12 Breugom AJ, Swets M, Bosset JF. et al. Adjuvant chemotherapy after preoperative (chemo)radiotherapy and surgery for patients with rectal cancer: a systematic review and meta-analysis of individual patient. Lancet Oncol 2015; 16: 200-207
• 13 Hong YS, Kim SY, Lee JS. et al. Oxaliplatin-Based Adjuvant Chemotherapy for Rectal Cancer After Preoperative Chemoradiotherapy (ADORE): Long-Term Results of a Randomized Controlled Trial. J Clin Oncol 2019; 37: 3111-3123
• 14 Arbeitsgemeinschaft Internistische Onkologie. Statement der AIO-KRK-Leitgruppe zur perioperativen Therapie des Rektumkarzinoms. Im Internet (Stand: 23.06.2021): http://www.aio-portal.de/tl_files/aio/stellungnahmen/Statement_AIO_KRK_Leitgruppe_072014_Rektum_Ca.pdf
• 15 Fokas E, Allgäuer M, Polat B. et al. 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; 37: 3212-3222
• 16 Bahadoer RR, Dijkstra EA, van Etten B. 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; 22: 29-42
• 17 Conroy T, Bosset JF, Etienne PL. et al. 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; 22: 702-715
• 18 Arbeitsgemeinschaft Internistischer Onkologen. AIO-ACO-ARO-Stellungnahme zur TNT. Im Internet (Stand 23.06.2021): https://www.aio-portal.de/tl_files/aio/stellungnahmen/Stellungnahme%20AIO_ACO_ARO%20Rektumkarzinom%20_%2007_2020.pdf
• 19 van der Valk MJM, Hilling DE, Bastiaannet E. et al. 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; 391: 2537-2545
• 20 Garcia-Aguilar J, Patil S, Kim JK. et al. Preliminary results of the organ preservation of rectal adenocarcinoma (OPRA) trial. J Clin Oncol 2020; 38: 4008
• 21 Ruppert R, Junginger T, Ptok H. et al. Oncological outcome after MRI-based selection for neoadjuvant chemoradiotherapy in the OCUM Rectal Cancer Trial. Br J Surg 2018; 105: 1519-1529
• 22 Kreis ME, Ruppert R, Ptok H. et al. MRI-Based Use of Neoadjuvant Chemoradiotherapy in Rectal Carcinoma: Surgical Quality and Histopathological Outcome of the OCUM Trial. Ann Surg Oncol 2020; 27: 417-427
• 23 Deng Y, Chi P, Lan P. et al. Neoadjuvant Modified FOLFOX6 With or Without Radiation Vs. Fluorouracil Plus Radiation for Locally Advanced Rectal Cancer: Final Results of the Chinese FOWARC Trial. J Clin Oncol 2019; 37: 3223-3233