Long-course chemoradiation vs short-course radiation in total neoadjuvant therapy for rectal cancer: Propensity score case-matched analysis.
Authors: Ochiai Kentaro , Bhutiani Neal , Uppal Abhineet , You Y. Nancy , Bednarski Brian K. , White Michael , Holliday Emma , Das Prajnan , Chang George J. , Konishi Tsuyoshi 
Published: January 2025

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Background:
Short-course radiotherapy (Short-TNT) is not widely used in the United States as part of total neoadjuvant therapy (TNT) for rectal cancer, due to concerns for lower tumor regression, increased local recurrence, and poorer quality of surgical specimens compared to long-course chemoradiotherapy (Long-TNT). However, there have been few studies that directly compared outcomes of Long-TNT versus Short-TNT. This study aimed to evaluate outcomes of Short-TNT versus Long-TNT.
Methods:
Consecutive patients with stage II-III rectal cancer who underwent TNT at an NCI-designated comprehensive cancer center from 2019 to 2022 were identified. Outcomes after Short-TNT and Long-TNT were compared using 1:1 propensity score matching.
Results:
Among 318 patients, 170 (85 Short-TNT, 85 Long-TNT) were eligible for the matched analysis (Table). The median follow-up was 31 months. The two groups were similar in tumor distance from anal verge (5cm vs. 6cm), clinical stage (stage III: 90.6% vs. 89.4%), radiologic high-risk features, and treatment sequence (induction chemotherapy: 30.5% vs. 28.2%). The Long-TNT was associate with a higher proportion of nonoperative management (38.8% vs. 24.7%, p=0.03). A local regrowth rate with long-TNT was not lower than short-TNT (39.4% vs. 28.6%, p=0.42). There were no differences in rates of clinical complete plus near-complete response (52.9% vs. 52.9%, p=1.00), overall complete response (pathologic plus sustained clinical complete response; 32.2% vs. 29.9%, p=0.74), and surgical outcomes including retrieved lymph nodes number (19 vs. 22, p=0.27), sphincter preservation (46.2% vs. 62.5%, p=0.10), distal margin (3cm vs. 3.5cm, p=0.77), CRM+ (83.8% vs. 3.1%, p=0.42) and postoperative complications (overall: 34.6% vs. 25.0%, p=0.14; ≥Grade3: 5.8% vs. 9.4%, p=0.60).
Conclusions:
Short-TNT had a comparable overall complete response rate with equivalent surgical outcomes to Long-TNT. Short-TNT should be revisited in the US as a viable alternative TNT strategy both for nonoperative management and for treatment of locally advanced rectal cancer.

Propensity score case-matched analysis.

Outcomes
Total (n=170)
Long-TNT (n=85)
Short-TNT (n=85)
p value

Clinical complete/near complete response, number (%)
90 (52.9)
45 (52.9)
45 (52.9)
1.00

Non-operative management, number (%)
54 (31.8)
33 (38.8)
21 (24.7)
0.03

Overall complete response, number (%)*
54 (31.0)
26 (30.6)
28 (32.9)
0.74

Surgical outcomes

Surgery (n=116)

Surgery after Long-TNT (n=52)

Surgery after Short-TNT (n=64)

Sphincter-preserving surgery, number (%)
64 (55.2)
24 (46.2)
40 (62.5)
0.10

Circumferential resection margin +, number (%)
4 (3.4)
2 (3.8)
2 (3.1)
0.42

Distal margin, cm (range)
3.4 (0.1-12)
3 (0.2-6.5)
3.5 (0.1-12)
0.77

Major complications (≥Grade3), number (%)
9 (7.8)
3 (5.8)
6 (9.4)
0.60

*Pathologic + sustained clinical complete response.