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Does a Longer Interval Before Surgery Among Patients With Locally Advanced Rectal Cancer Lead to Worse Survival?


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In an Italian retrospective cohort study reported in JAMA Surgery, Deidda et al found that a longer vs shorter delay to surgery among patients with locally advanced rectal cancer with minor or no pathologic response to neoadjuvant chemoradiotherapy was associated with significantly poorer overall and disease-free survival.

As stated by the investigators, “Extending the interval between the end of neoadjuvant chemoradiotherapy and surgery may enhance tumor response in patients with locally advanced rectal cancer. However, data on the association of delaying surgery with long-term outcome in patients who had a minor or poor response are lacking.”

Study Details

The study involved data from 1,701 consecutive patients with rectal cancer treated at 12 Italian referral centers between January 2000 and December 2014. Among these, 1,064 had a minor or null tumor response (ypT stage of 2 to 4 or ypN stage greater than 0) to neoadjuvant chemoradiotherapy and were included in the analysis. The primary outcome measures were overall and disease-free survival among patients with shorter wait time to surgery (defined as ≤ 8 weeks) vs those with longer wait time (defined as > 8 weeks). 

In this cohort study, a longer interval before surgery after completing neoadjuvant chemoradiotherapy was associated with worse overall and disease-free survival in tumors with a poor pathological response to preoperative chemoradiotherapy. Based on these findings, patients who do not respond well to chemoradiotherapy should be identified early after the end of chemoradiotherapy and undergo surgery without delay.
— Deidda et al

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Key Findings

Of the 1,064 patients, 579 (54.4%) had a shorter wait time and 485 (45.6%) had a longer wait time. The median wait time was 7 weeks (interquartile range [IQR] = 6–8 weeks) in the shorter interval group and 10.6 weeks (IQR = 9–12.3 weeks) in the longer interval group.

Patients with longer vs shorter wait times had higher rates of abdominal perineal resection (33.2% vs 21.9%, odds ratio [OR] = 1.71, 95% confidence interval [CI] = 1.3–2.2, P < .001), positive circumferential resection margin (1.7% vs 0.5%, OR = 3.6, 95% CI = 1.1–12.4, P = .04), 30-day morbidity (19.6% vs 14.8%, OR = 1.4, 95% CI = 1.0–1.9, P = .04), and surgical complications (15.1% vs 10.0%, OR = 1.6, 95% CI = 1.1–2.3, P = .01).

For patients with longer vs shorter wait times, overall survival was 67.6% (95% CI = 63.1%–71.7%) vs 80.3% (95% CI = 76.5%–83.6%) at 5 years and 40.1% (95% CI = 33.5%–46.5%) vs 57.8% (95% CI = 52.1%–63.0%) at 10 years (P < .001).

For patients with longer vs shorter wait times, disease-free survival was 59.6% (95% CI = 54.9%–63.9%) vs 72.0% (95% CI = 67.9%–75.7%) at 5 years and 36.2% (95% CI = 29.9%–42.4%) vs 53.9% (95% CI = 48.5%–59.1%) at 10 years (P < .001).

On multivariate analysis, longer wait time was associated with significantly increased risk of death (hazard ratio [HR] = 1.84, 95% CI = 1.50–2.26, P < .001) and significantly increased risk of disease recurrence or death (HR = 1.69, 95% CI = 1.39–2.04, P < .001).

The investigators concluded, “In this cohort study, a longer interval before surgery after completing neoadjuvant chemoradiotherapy was associated with worse overall and disease-free survival in tumors with a poor pathological response to preoperative chemoradiotherapy. Based on these findings, patients who do not respond well to chemoradiotherapy should be identified early after the end of chemoradiotherapy and undergo surgery without delay.”

Angelo Restivo, MD, of the Department of Surgical Science, University of Cagliari, is the corresponding author for the JAMA Surgery article.

Disclosure: For full disclosures of the study authors, visit jamanetwork.com.


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