A contemporary assessment of total neoadjuvant therapy (TNT) protocols for locally advanced rectal cancer: adoption and expert perspectives at German Cancer Society (DKG)-certified colorectal cancer centers

Abstract

Purpose: The treatment paradigm for locally advanced rectal cancer (LARC) is shifting toward the total neoadjuvant therapy (TNT) concept, which administered systemic chemotherapy in the neoadjuvant setting, either before or after chemoradiotherapy (CRT) or short-course radiotherapy (SCRT). First results have shown higher pathologic complete response (pCR) rates and a favorable impact on disease-free survival (DFS). Our study aimed to evaluate the current clinical practice and expert opinion regarding TNT for locally advanced rectal cancer across DKG (German Cancer Society)-certified colorectal cancer centers.

Methods: A comprehensive online questionnaire, constituted of 14 TNT-focused queries targeting patients with locally advanced rectal cancer, was conducted among DKG-certified colorectal cancer centers registered within the database of the Addz (Arbeitsgemeinschaft Deutscher Darmzentren) between December 2022 and January 2023.

Results: A significant majority (68%) indicated that they treated between 0 and 10 patients using a TNT protocol. Only a third (36%) of these centers participated in patient enrollment for a TNT study. Despite this, 84% of centers reported treating patients in a manner analogous to a TNT study, with the RAPIDO regimen being the most prevalent approach, employed by 60% of the respondents. The decision to adopt a TNT approach was primarily influenced by factors, such as the lower third of the rectum (93% of centers), cT4 stage (86% of centers), and a positive circumferential resection margin (80% of centers). Regarding concerns, 65% of the survey respondents expressed no reservations about the TNT concept, while 35% had concerns. In particular, there appears to be disagreement and uncertainty in regard to a clinical complete response and the "Watch and Wait" approach. While some centers adopt the watch-and-wait approach (42%), others only utilize it when extirpation is otherwise necessary (39%), and a portion still proceeds with surgery as initially planned (19%). The survey also addressed unmet needs, which were elaborated in the free-text responses. Overall, there was high interest in participating in planned observational studies.

Conclusions: This study presents an overview of current clinical practice and unmet needs within DKG-certified German colorectal cancer centers. It is noteworthy that total neoadjuvant therapy (TNT) is predominantly performed outside of clinical trials. Moreover, across the centers, there is significant heterogeneity in handling clinical complete response and adopting the "watch and wait" approach. Further research is needed to establish standardization in the care of locally advanced rectal cancer.

Keywords: DKG-certified colorectal cancer centers; Locally advanced rectal cancer; Rectal cancer; TNT; Total neoadjuvant therapy.

Fig. 1

TNT case load based on cancer center location

Fig. 2

Proportion of respondents enrolling patients with locally advanced rectal cancer in TNT studies

Fig. 3

Percentage of respondents implementing TNT protocols for patients with locally advanced rectal cancer

Fig. 4

Breakdown of TNT protocols chosen by respondents

Fig. 5

Importance of various characteristics in decision-making process: responses by percentage

Fig. 6

Respondent’s perspectives on TNT

Fig. 7

Strategies adopted by respondents for managing clinical complete response (cCR)