<abstract xmlns="http://www.w3.org/1999/xhtml">

<p>The optimal management of locally advanced rectal cancer (LARC) often presents a therapeutic challenge. Balancing the benefits of treatment against toxicities and reducing the risk for local and distal recurrences are the mainstay of therapeutic approaches. Recently, several studies have compared a more aggressive approach of delivering several cycles of systemic chemotherapy to the established standard of combined chemoradiation. This approach is termed total neoadjuvant therapy and appears to be beneficial, at least for a subset of patients. The results of the main Phase III studies along with their variations in study design are hereby discussed with the goal of extracting useful clinical suggestions for treatment.</p>
</abstract>

The optimal management of locally advanced rectal cancer (LARC) often presents a therapeutic challenge. Balancing the benefits of treatment against toxicities and reducing the risk for local and distal recurrences are the mainstay of therapeutic approaches. Recently, several studies have compared a more aggressive approach of delivering several cycles of systemic chemotherapy to the established standard of combined chemoradiation. This approach is termed total neoadjuvant therapy and appears to be beneficial, at least for a subset of patients. The results of the main Phase III studies along with their variations in study design are hereby discussed with the goal of extracting useful clinical suggestions for treatment.

Total neoadjuvant therapy in rectal cancer: a review across studies

Forum of Clinical Oncology

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

{"article-title":"Total neoadjuvant therapy in rectal cancer: a review across studies"}

The optimal management of locally advanced rectal cancer (LARC) often presents a therapeutic challenge. Balancing the benefits of treatment against toxicities...

Study	Stage	N	Arms	pCR (%)	DFS (%)	OS (%)
RAPIDO	cT4, or EMVI+, CN2, MRF+, or LPLN+	450	Standard: 5FU-CRT→Surgery→ ±FOLFOX(12)/CAPOX(8)	14.3	*DRTF: 30	89
RAPIDO	cT4, or EMVI+, CN2, MRF+, or LPLN+	462	Consolidation: SCRT→FOLFOX(9)/CAPOX(6)→Surgery	28.42	DRTF: 24DRTF:	89
PRODIGE-23	cT3 or cT4	230	Standard: 5FU-CRT→Surgery→mFOLFOX/capecitabine(3)	12.1	62.5	76.1
PRODIGE-23	cT3 or cT4	231	Induction: FOLFIRINOX(6)→ 5FU-CRT→Surgery→mFOLFOX/capecitabine(6)	27.8	67.6	81.9
POLISH II	Primary or locally recurrent cT4, or a palpable fixed cT3	254	Standard: 5FU/OX-CRT→Surgery→± ChT	12	43	49
POLISH II	Primary or locally recurrent cT4, or a palpable fixed cT3	261	Consolidation: SCRT→FOLFOX(3)→Surgery→± ChT	16	41	49
STELLAR	Primary cT3–4 or N+ in mid to distal rectum	293	Standard: CAPE-CRT→Surgery→CAPOX(6)	12.3	62	75
STELLAR	Primary cT3–4 or N+ in mid to distal rectum	298	Consolidation: SCRT→CAPOX(4)→Surgery→CAPOX(2)	21.8	65	87
CAO/ARO/AIO-12	cT3 if < 6 cm from AV; > cT3b if 6–12 cm from AV; cT4, or LPLN+	156	Consolidation: 5FU/OX-RT→FOLFOX(3)→Surgery	25	73	92
CAO/ARO/AIO-12		150	Induction: FOLFOX(3)→ 5FU/OX-CRT→Surgery	17	73	92
OPRA	AJCC stage III–IV	155	Consolidation: 5FU-CRT→ FOLFOX/CAPOX(4 mo)→Surgery	NR	76	NR
OPRA	AJCC stage III–IV	152	Induction: FOLFOX/CAPOX(4 mo)→5FU-CRT→Surgery	NR	76	NR

Trial	T2	T3	T4	N0	MRF+	EMVI	LLN
RAPIDO	3	66	31	9	61	30	15
POLISH II	3	34	64	NS	NS	NS	NS
STELLAR	3	84	14	15	56	48	NS
Prodige-23	0	83	17	10	22	NS	10
CAO/AIO/ARO-12	4	71	15	10	27	NS	NS
OPRA	10	77	13	29	NS	NS	NS

Total neoadjuvant therapy in rectal cancer: a review across studies

Article Category: Research Article

Published Online: Apr 25, 2024

Page range: -

Received: Oct 26, 2023

Accepted: Dec 15, 2023

DOI: https://doi.org/10.2478/fco-2023-0014

Keywords
rectal cancer, total neoadjuvant therapy, Phase III studies, induction, consolidation, organ preservation

© 2024 Ioannis Gavalas et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Major total neoadjuvant randomized controlled trials.

Disease characteristics of patients enrolled in major TNT RCTs.

Total neoadjuvant therapy in rectal cancer: a review across studies

Article Category: Research Article

Published Online: Apr 25, 2024

Page range: -

Received: Oct 26, 2023

Accepted: Dec 15, 2023

DOI: https://doi.org/10.2478/fco-2023-0014

Keywordsrectal cancer, total neoadjuvant therapy, Phase III studies, induction, consolidation, organ preservation

© 2024 Ioannis Gavalas et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Major total neoadjuvant randomized controlled trials.

Disease characteristics of patients enrolled in major TNT RCTs.

Keywords
rectal cancer, total neoadjuvant therapy, Phase III studies, induction, consolidation, organ preservation