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

Abstract

ImportanceThe 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.ObjectiveTo 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 ParticipantsThis 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.ExposureLong-course chemoradiotherapy or short-course radiotherapy with delayed surgery.Main outcome and MeasuresThe primary outcome was pCR. Other histopathologic results, perioperative events, and survival outcomes constituted the secondary outcomes.ResultsAmong 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 RelevanceTime intervals longer than 12 weeks were associated with improved TRG and systemic recurrence but may increase surgical complexity and minor morbidity.

Retrospective analysis of preoperative application of triple-modal pre-rehabilitation on postoperative recovery of colorectal cancer patients

“…Furthermore, we focused on whether pre-rehabilitation therapy was bene cial for patients who required neoadjuvant therapy. Neoadjuvant therapy is a standard clinical treatment for patients suffering from advanced CRC [19,20]. Interestingly, we found that the triple-modal pre-rehabilitation strategies produced noticeable bene ts in reducing the nutritional risk for patients in the common groups, with lower pre-rehabilitation time compared to the neoadjuvant chemotherapy group.…”

Management of Locally Advanced Rectal Cancer—Building the Plane as We Fly

“…The Interval Between Neoadjuvant Therapy and Surgery in the Treatment of Locally Advanced Rectal Cancer (CRONOS) study is a large multi-institutional retrospective analysis across several large hospitals in Spain. The authors should be commended on their effort and collaboration to bring together investigators across several large institutions and an impressive database of over 1500 patients.…”

“…Though important, the application of the conclusions of this article in the modern era of total neoadjuvant therapy (TNT) is unclear. Over the last decade, TNT is becoming more popular as the treatment of choice for locally advanced rectal cancer with the goal of higher rates of pathologic complete response .…”

“…Although this trial attempted to account for selection bias via propensity matching, the model is subject to shortcomings of all retrospective matching models in lieu of randomized clinical trial. The inverse probability of treatment weighting model used by the authors can be noted to have drastic differences in treatment intervals based on treatment location.…”

“…Despite the drawbacks in relevancy to current practice patterns, the study highlights the challenges faced with modern management of locally advanced rectal cancer. It also underscores the importance of the need to perform a large randomized clinical trial on the timing of surgery after radiation, especially if induction chemotherapy becomes more popularized …”