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Original Investigation
September 29, 2021

Association of Delayed Surgery With Oncologic Long-term Outcomes in Patients With Locally Advanced Rectal Cancer Not Responding to Preoperative Chemoradiation

Author Affiliations
  • 1Department of Surgical Science, University of Cagliari, Cagliari, Italy
  • 2Division of Gastrointestinal Surgery, San Raffaele Hospital, Milan, Italy
  • 3Department of Surgical, Oncological, and Gastroenterological Sciences, University of Padova, Padua, Italy
  • 4Division of General Surgery, E. Agnelli Hospital, Pinerolo, Italy
  • 5Department of General Surgery, Polytechnic University of Marche, Ancona, Italy
  • 6Oncologic Surgical Unit, Policlinico San Martino Genova, Genoa, Italy
  • 7Department of Health Sciences, Operative Unit of General Surgery, University of Catanzaro, Catanzaro, Italy
  • 8Department of Medical and Surgical Sciences, Operative Unit of General Surgery, University of Catanzaro, Catanzaro, Italy
  • 9Division of General Surgery 2, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
  • 10Department of Surgical Oncology, CRO Aviano National Cancer Institute IRCCS, Aviano, Italy
  • 11Division of Radiotherapy, CRO Aviano National Cancer Institute IRCCS, Aviano, Italy
  • 12University of Torino, School of Medicine, Department of Oncology, Digestive Surgery and Surgical Oncology, San Luigi University Hospital, Orbassano, Torino, Italy
  • 13Colorectal Surgical Oncology, National Cancer Institute, IRCCS, G. Pascale Foundation, Napoli, Italy
  • 14Division of General Surgery, Civil Hospital of Lentini, Siracusa, Italy
  • 15Medical Oncology Unit, Department of Oncology, Ospedale Sant’Andrea, La Spezia, Italy
JAMA Surg. Published online September 29, 2021. doi:10.1001/jamasurg.2021.4566
Key Points

Question  Is delayed surgery associated with long-term survival outcomes in patients with locally advanced rectal cancer who do not respond to neoadjuvant treatment?

Findings  In this cohort study of 1064 patients, a longer interval before surgery after completing neoadjuvant chemoradiotherapy was associated with worse survival in patients with tumors with a poor pathological response to preoperative chemoradiation.

Meaning  Based on these findings, patients who do not respond well to chemoradiotherapy should be identified early after the end of chemoradiation and undergo surgery without delay.

Abstract

Importance  Extending the interval between the end of neoadjuvant chemoradiotherapy (CRT) 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.

Objective  To assess a large series of patients who had minor or no tumor response to CRT and the association of shorter or longer waiting times between CRT and surgery with short- and long-term outcomes.

Design, Setting, and Participants  This is a multicenter retrospective cohort study. Data from 1701 consecutive patients with rectal cancer treated in 12 Italian referral centers were analyzed for colorectal surgery between January 2000 and December 2014. Patients with a minor or null tumor response (ypT stage of 2 to 3 or ypN positive) stage greater than 0 to neoadjuvant CRT were selected for the study. The data were analyzed between March and July 2020.

Exposures  Patients who had a minor or null tumor response were divided into 2 groups according to the wait time between neoadjuvant therapy end and surgery. Differences in surgical and oncological outcomes between these 2 groups were explored.

Main Outcomes and Measures  The primary outcomes were overall and disease-free survival between the 2 groups.

Results  Of a total of 1064 patients, 654 (61.5%) were male, and the median (IQR) age was 64 (55-71) years. A total of 579 patients (54.4%) had a shorter wait time (8 weeks or less) 485 patients (45.6%) had a longer wait time (greater than 8 weeks). A longer waiting time before surgery was associated with worse 5- and 10-year overall survival rates (67.6% [95% CI, 63.1%-71.7%] vs 80.3% [95% CI, 76.5%-83.6%] at 5 years; 40.1% [95% CI, 33.5%-46.5%] vs 57.8% [95% CI, 52.1%-63.0%] at 10 years; P < .001). Also, delayed surgery was associated with worse 5- and 10-year disease-free survival (59.6% [95% CI, 54.9%-63.9%] vs 72.0% [95% CI, 67.9%-75.7%] at 5 years; 36.2% [95% CI, 29.9%-42.4%] vs 53.9% [95% CI, 48.5%-59.1%] at 10 years; P < .001). At multivariate analysis, a longer waiting time was associated with an augmented risk of death (hazard ratio, 1.84; 95% CI, 1.50-2.26; P < .001) and death/recurrence (hazard ratio, 1.69; 95% CI, 1.39-2.04; P < .001).

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

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