Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71:209–49.

Article  PubMed  Google Scholar 

Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351:1731–40.

Article  CAS  PubMed  Google Scholar 

Bahadoer RR, Dijkstra EA, van Etten B, Marijnen CAM, Putter H, Kranenbarg EMK, et al. 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.

Article  CAS  PubMed  Google Scholar 

Conroy T, Bosset JF, Etienne PL, Rio E, François E, Mesgouez-Nebout N, 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;22:702–15.

Article  CAS  PubMed  Google Scholar 

Fokas E, Schlenska-Lange A, Polat B, Klautke G, Grabenbauer GG, Fietkau R, et al. Chemoradiotherapy plus induction or consolidation chemotherapy as total neoadjuvant therapy for patients with locally advanced rectal cancer: Long-term results of the CAO/ARO/AIO-12 randomized clinical trial. JAMA Oncol. 2022;8:e215445. https://doi.org/10.1001/jamaoncol.2021.5445.

Article  PubMed  Google Scholar 

Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373:23–34.

Article  PubMed  PubMed Central  Google Scholar 

Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020;382:1894–905.

Article  CAS  PubMed  Google Scholar 

Doki Y, Ajani JA, Kato K, Xu J, Wyrwicz L, Motoyama S, et al. Nivolumab combination therapy in advanced esophageal squamous-cell carcinoma. N Engl J Med. 2022;386:449–62.

Article  CAS  PubMed  Google Scholar 

Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372:2509–20.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cercek A, Lumish M, Sinopoli J, Weiss J, Shia J, Lamendola-Essel M, et al. PD-1 blockade in mismatch repair-deficient, locally advanced rectal cancer. N Engl J Med. 2022;386:2363–76.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chen G, Jin Y, Guan WL, Zhang RX, Xiao WW, Cai PQ, et al. Neoadjuvant PD-1 blockade with sintilimab in mismatch-repair deficient, locally advanced rectal cancer: An open-label, single-centre phase 2 study. Lancet Gastroenterol Hepatol. 2023;8:422–31.

Article  PubMed  Google Scholar 

Hu H, Kang L, Zhang J, Wu Z, Wang H, Huang M, et al. Neoadjuvant PD-1 blockade with toripalimab, with or without celecoxib, in mismatch repair-deficient or microsatellite instability-high, locally advanced, colorectal cancer (PICC): A single-centre, parallel-group, non-comparative, randomised, phase 2 trial. Lancet Gastroenterol Hepatol. 2022;7:38–48.

Article  PubMed  Google Scholar 

Rahma OE, Yothers G, Hong TS, Russell MM, You YN, Parker W, et al. Use of total neoadjuvant therapy for locally advanced rectal cancer: Initial results from the pembrolizumab arm of a phase 2 randomized clinical trial. JAMA Oncol. 2021;7:1225–30.

Article  PubMed  Google Scholar 

Bando H, Tsukada Y, Inamori K, Togashi Y, Koyama S, Kotani D, et al. Preoperative chemoradiotherapy plus nivolumab before surgery in patients with microsatellite stable and microsatellite instability-high locally advanced rectal cancer. Clin Cancer Res. 2022;28:1136–46.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Shamseddine A, Zeidan YH, El Husseini Z, Kreidieh M, Al Darazi M, Turfa R, et al. Efficacy and safety-in analysis of short-course radiation followed by mFOLFOX-6 plus avelumab for locally advanced rectal adenocarcinoma. Radiat Oncol. 2020;15:233.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bando H, Tsukada Y, Ito M, Yoshino T. Novel immunological approaches in the treatment of locally advanced rectal cancer. Clin Colorectal Cancer. 2022;21:3–9.

Article  PubMed  Google Scholar 

Seo I, Lee HW, Byun SJ, Park JY, Min H, Lee SH, et al. Neoadjuvant chemoradiation alters biomarkers of anticancer immunotherapy responses in locally advanced rectal cancer. J Immunother Cancer. 2021;9:e001610. https://doi.org/10.1136/jitc-2020-001610.

Article  PubMed  PubMed Central  Google Scholar 

Smith JJ, Chow OS, Gollub MJ, Nash GM, Temple LK, Weiser MR, et al. 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;15:767.

Article  PubMed  PubMed Central  Google Scholar 

Saito T, Nishikawa H, Wada H, Nagano Y, Sugiyama D, Atarashi K, et al. Two FOXP3(+)CD4(+) T cell subpopulations distinctly control the prognosis of colorectal cancers. Nat Med. 2016;22:679–84.

Article  CAS  PubMed  Google Scholar 

Habr-Gama A, Perez RO, Nadalin W, Sabbaga J, Ribeiro U Jr, e Sousa AHS Jr, et al. Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: Long-term results. Ann Surg. 2004;240:711–8.

Article  PubMed  PubMed Central  Google Scholar 

van der Valk MJM, Hilling DE, Bastiaannet E, Kranenbarg EMK, Beets GL, Figueiredo NL, et al. Long-term outcomes of clinical complete responders after neoadjuvant treatment for rectal cancer in the International Watch and Wait Database (IWWD): An international multicentre registry study. Lancet. 2018;391:2537–45.

Article  PubMed  Google Scholar 

Jin J, Tang Y, Hu C, Jiang LM, Jiang J, Li N, et al. Multicenter, randomized, phase III trial of short-term radiotherapy plus chemotherapy versus long-term chemoradiotherapy in locally advanced rectal cancer (STELLAR). J Clin Oncol. 2022;40:1681–92.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Maas M, Nelemans PJ, Valentini V, Das P, Rödel C, Kuo LJ, et al. Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: A pooled analysis of individual patient data. Lancet Oncol. 2010;11:835–44.

Article  PubMed  Google Scholar 

Shiraishi T, Sasaki T, Ikeda K, Tsukada Y, Nishizawa Y, Ito M. Predicting prognosis according to preoperative chemotherapy response in patients with locally advanced lower rectal cancer. BMC Cancer. 2019;19:1222.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Li S, Yu W, Xie F, Luo H, Liu Z, Lv W, et al. Neoadjuvant therapy with immune checkpoint blockade, antiangiogenesis, and chemotherapy for locally advanced gastric cancer. Nat Commun. 2023;14:8.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang Z, Shao C, Wang Y, Duan H, Pan M, Zhao J, et al. Efficacy and safety of neoadjuvant immunotherapy in surgically resectable esophageal cancer: A systematic review and meta-analysis. Int J Surg. 2022;104:106767.

Article  PubMed  Google Scholar 

Chalabi M, Fanchi LF, Dijkstra KK, den Berg JGV, Aalbers AG, Sikorska K, et al. Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers. Nat Med. 2020;26:566–76.

Article  CAS  PubMed  Google Scholar 

Rosner S, Reuss JE, Zahurak M, Zhang J, Zeng Z, Taube J, et al. Five-year clinical outcomes after neoadjuvant nivolumab in resectable non-small cell lung cancer. Clin Cancer Res. 2023;29:705–10.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang F, Guo W, Zhou B, Wang S, Li N, Qiu B, et al. Three-year follow-up of neoadjuvant programmed cell death protein-1 inhibitor (Sintilimab) in NSCLC. J Thorac Oncol. 2022;17:909–20.

Article  CAS  PubMed  Google Scholar 

Smith NJ, Barbachano Y, Norman AR, Swift RI, Abulafi AM, Brown G. Prognostic significance of magnetic resonance imaging-detected extramural vascular invasion in rectal cancer. Br J Surg. 2008;95:229–36.

Article  CAS  PubMed  Google Scholar