Management of patients with locally advanced rectal cancer in the total neoadjuvant therapy (TNT) era: Experience from Argentina.
Authors: Faura Maria Victoria , Sifon Maria del Rosario , Tamburelli Mercedes , Castillo Javier Omar , Zoppi Manuel Ignacio , Fariña Danisa , Grasselli Julieta , Bella Quero Luciana 
Published: January 2025

85

Background:
In the last years a paradigm shift has changed the way we manage non metastatic rectal cancer. The varied options within TNT have gradually been adapted in our country. This study aims to depict the strategies implemented.
Methods:
A prospective and retrospective observational study was performed from 2020 to 2024 including stage II-III rectal cancer patients treated at three centers in Buenos Aires, Argentina. Data was extracted from medical records.
Results:
68 patients were included in the analysis. Median age was 59 years (IQR 48–71). 72% were male. 88% (60) had stage III disease, and 12% (8) stage II. Geriatric assessment was performed in 7 of 19 patients aged over 70 (5 frail). All patients were staged with high resolution MRI and discussed in multidisciplinary tumor board. Mismatch repair was assessed in 72%(49) of patients, only one had MLH1 deficiency. 79%(54) patients received TNT: 22%(12) short course vs 78%(42) long course radiotherapy; 24%(13) induction vs 76%(41) consolidation chemotherapy. Preferred chemotherapy regimen was CAPOX both in induction and consolidation chemotherapy (69.7% and 63.4%, respectively) Despite small numbers non significant differences in risk factors were found between TNT vs non TNT groups (Table). We registered 13 Grade 3-4 toxicity events: 3 in induction chemotherapy, 7 in consolidation and 3 in radiotherapy. Clinical complete response was achieved in 25.9% of TNT (11 consolidation, 3 induction) and 7.1%(1) of non-TNT (p=0.25). Watch and Wait was employed in 9 patients in TNT and 1 in non TNT group. 40 patients underwent surgery in the TNT and 11 in the non-TNT group; complete pathological response was reached in 17.5% (7) and 9% (1), respectively. Overall relapse rate was 19.14% (13): 2.94% (2) local and 16.2% (11) systemic. (TNT: 1.85%(1) local vs 18.5%(10) metastatic; nonTNT: 7.14%(1) both local and metastatic) p=0.4. At a median follow-up of 20 months (IQR 15–32 months), 2-year progression-free survival (PFS) rate was 87% (95% CI: 38–98%) in the non-TNT group and 78% (95% CI: 61–88%) in the TNT group.
Conclusions:
This study highlights the feasibility of worldwide adoption of TNT. We describe the preferred regimens and results of TNT in three high volume centers in Argentina. Long course radiotherapy and consolidation treatment with CAPOX are the predominant strategies. Non operative management is routinely offered to complete responders. Our efficacy results are comparable with published literature. Comprehensive geriatric assessment is recommended but still partially applied. In line with recent findings MMR testing has been widely adopted as an initial workup parameter.

TNT %(n=54)
non-TNT %(n=14)
p

T4 disease
26 (14)
21 (3)
0.99

N2
37 (20)
29 (4)
0.75

EMVI positivity
49 (26)
18 (3)
0.16

Circumferential resection margin <1 mm
29.6 (16)
28.57 (4)
0.23

Low-lying tumors
33 (18)
43 (6)
0.54