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. 2023 Sep 1;158(9):910-919.
doi: 10.1001/jamasurg.2023.2521.

Time Interval Between the End of Neoadjuvant Therapy and Elective Resection of Locally Advanced Rectal Cancer in the CRONOS Study

Yoelimar Guzmán  1 , José Ríos  2   3 , Jesús Paredes  4 , Paula Domínguez  1 , Joan Maurel  5   6 , Carolina González-Abós  1 , Ana Otero-Piñeiro  1 , Raúl Almenara  1 , María Ladra  4 , Borja Prada  4 , Marta Pascual  7 , María Alejandra Guerrero  7 , Álvaro García-Granero  8 , Laura Fernández  9 , Aina Ochogavia-Seguí  9 , Margarita Gamundi-Cuesta  9 , Francesc Xavier González-Argente  9 , Lorenzo Viso Pons  10 , Ana Centeno  10 , Ángela Arrayás  10 , Andrea de Miguel  10 , Elena Gil-Gómez  11 , Beatriz Gómez  11 , José Gil Martínez  11 , Antonio M Lacy  1   12   13   14 , F Borja de Lacy  1
Affiliations

Time Interval Between the End of Neoadjuvant Therapy and Elective Resection of Locally Advanced Rectal Cancer in the CRONOS Study

Yoelimar Guzmán et al. JAMA Surg. .

Abstract

Importance: The treatment for extraperitoneal locally advanced rectal cancer (LARC) is neoadjuvant therapy (NAT) followed by total mesorectal excision (TME). Robust evidence on the optimal time interval between NAT completion and surgery is lacking.

Objective: To assess the association of time interval between NAT completion and TME with short- and long-term outcomes. It was hypothesized that longer intervals increase the pathologic complete response (pCR) rate without increasing perioperative morbidity.

Design, setting, and participants: This cohort study included patients with LARC from 6 referral centers who completed NAT and underwent TME between January 2005 and December 2020. The cohort was divided into 3 groups depending on the time interval between NAT completion and surgery: short (≤8 weeks), intermediate (>8 and ≤12 weeks), and long (>12 weeks). The median follow-up duration was 33 months. Data analyses were conducted from May 1, 2021, to May 31, 2022. The inverse probability of treatment weighting method was used to homogenize the analysis groups.

Exposure: Long-course chemoradiotherapy or short-course radiotherapy with delayed surgery.

Main outcome and measures: The primary outcome was pCR. Other histopathologic results, perioperative events, and survival outcomes constituted the secondary outcomes.

Results: Among the 1506 patients, 908 were male (60.3%), and the median (IQR) age was 68.8 (59.4-76.5) years. The short-, intermediate-, and long-interval groups included 511 patients (33.9%), 797 patients (52.9%), and 198 patients (13.1%), respectively. The overall pCR was 17.2% (259 of 1506 patients; 95% CI, 15.4%-19.2%). When compared with the intermediate-interval group, no association was observed between time intervals and pCR in short-interval (odds ratio [OR], 0.74; 95% CI, 0.55-1.01) and long-interval (OR, 1.07; 95% CI, 0.73-1.61) groups. The long-interval group was significantly associated with lower risk of bad response (tumor regression grade [TRG] 2-3; OR, 0.47; 95% CI, 0.24-0.91), systemic recurrence (hazard ratio, 0.59; 95% CI, 0.36-0.96), higher conversion risk (OR, 3.14; 95% CI, 1.62-6.07), minor postoperative complications (OR, 1.43; 95% CI, 1.04-1.97), and incomplete mesorectum (OR, 1.89; 95% CI, 1.02-3.50) when compared with the intermediate-interval group.

Conclusions and relevance: Time intervals longer than 12 weeks were associated with improved TRG and systemic recurrence but may increase surgical complexity and minor morbidity.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Ríos reported receiving lecture fees from Novartis, Lilly, LETI Pharma, Merck Sharp & Dohme de España, Vifor Fresenius Medical Care Renal Pharma, AstraZeneca, and Boehringer Ingelheim outside the submitted work. Dr Maurel reported receiving grants from Amgen, Merck, Guardant, Instituto de Salud Carlos III, and Incyte and personal fees from Advance Medical, Cancer Expert Now, Amgen, and Pierre-Fabre outside the submitted work. Dr Ochogavia-Seguí reported receiving grants from Takeda outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flow Diagram of Study Population
All patients underwent neoadjuvant therapy (NAT) and total mesorectal excision (TME).
Figure 2.
Figure 2.. Estimated Survival/Recurrence Functions for Patients With Locally Advanced Rectal Cancer Treated With Neoadjuvant Therapy (NAT)
Locoregional recurrence (A), systemic recurrence (B), and overall survival (C) proportional Cox models in patients with locally advanced rectal cancer treated with NAT and total mesorectal excision.
See this image and copyright information in PMC

Comment in

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