Total Neoadjuvant Therapy vs Standard Therapy in Locally Advanced Rectal Cancer

Abstract

Key Points Question Is total neoadjuvant therapy (TNT) associated with improved outcomes when compared with standard concurrent chemoradiotherapy followed by surgery and adjuvant chemotherapy (CRT plus A) for locally advanced rectal cancer? Findings In this systematic review and meta-analysis of 7 unique studies including 2416 unique patients, TNT was found to be associated with a significantly higher rate of achieving a pathologic complete response and disease-free survival compared with the standard CRT plus A approach. No significant difference was found in rates of sphincter-preserving surgery or ileostomy requirements between the 2 approaches. Meaning Total neoadjuvant therapy was associated with improved pathologic complete response rates and has a potential disease-free survival advantage compared with the standard CRT plus A strategy in locally advanced rectal cancer.

Multidisciplinary management of elderly patients with rectal cancer: recommendations from the SICG (Italian Society of Geriatric Surgery), SIFIPAC (Italian Society of Surgical Pathophysiology), SICE (Italian Society of Endoscopic Surgery and new technologies), and the WSES (World Society of Emergency Surgery) International Consensus Project

“…Either preoperative short-course radiotherapy (PSCRT) of 25 Gy in 5 consecutive days or preoperative long-course chemo-radiotherapy with 45–50 Gy, 1.8-2 Gy/fr with concomitant 5-FU-based chemotherapy (PLCCRT) followed by radical TME is effective for local control and are regarded as the two main standards of care for patients with high-risk rectal cancer [ 83 , 84 ]. Recently, an alternative strategy known as total neoadjuvant therapy (TNT), that involves administration of CRT plus neoadjuvant chemotherapy before surgery with the goal of delivering uninterrupted systemic therapy to eradicate micrometastases, has shown promising results in locally advanced rectal cancer, with superior rates of pathologic complete response (pCR) compared with standard therapy [ 85 ].…”

Molecular and Dynamic Evaluation of Proteins Related to Resistance to Neoadjuvant Treatment with Chemoradiotherapy in Circulating Tumor Cells of Patients with Locally Advanced Rectal Cancer

“…On the other hand, for non-responders, the standard NCRT must be reevaluated in order to avoid unnecessary toxicities or, eventually, establish new treatment strategies capable of optimizing the response of these patients, such as the adoption of more intense treatments according to the reasoning proposed by the TNT’s strategy [ 7 , 49 ]. In view of this, numerous efforts with studies evaluating the intensification of NCRT are underway and the recently published RAPIDO study and the PRODIGE 23 phase III study reinforced the importance of the TNT strategy with the addition of chemotherapy (FOLFOX/CAPOX or FOLFIRINOX) in increasing the rate of pCR and reducing about 7% of distant metastases [ 8 , 9 ].…”

Radical Resection for Locally Advanced Pancreatic Cancers in the Era of New Neoadjuvant Therapy—Arterial Resection, Arterial Divestment and Total Pancreatectomy

“…Another recent topic relevant to extremely radical pancreatectomy for PCs is the rationale of TNT. TNT has been advocated for LA gastrointestinal cancers, i.e., esophageal cancers [ 97 ] or rectal cancers [ 98 , 99 ], wherein the surgical burden of resection likely hampers prompt postoperative recovery and adequate adjuvant systemic chemotherapy. For LAPCs, due to a lack of effective regimens, TNT has long been out of the question, and the efficacy of TNT was suggested only recently.…”