Delayed surgery after neoadjuvant chemoradiation linked to worse outcomes in rectal cancer
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Delaying surgery appeared associated with worse OS and DFS among patients with locally advanced rectal cancer and poor tumor pathologic response to neoadjuvant chemoradiotherapy, according to study results published in JAMA Surgery.
These findings highlight the need for early identification of patients who do not respond well to chemoradiotherapy so they can undergo surgery without delay, researchers noted.
“In recent years, there has been a consistent trend toward increasing the waiting period after neoadjuvant therapy for rectal cancer before proceeding to surgical resection, which has been driven by the increasing rates of complete pathologic responses that are known to be time-dependent — the more we wait, the more complete responses we see,” Angelo Restivo, MD, researcher in the department of surgical science at University of Cagliari in Italy, told Healio. “Although this may seem to be a good thing, we never assessed the overall oncologic results of expanding this strategy to almost every patient, especially those who do not achieve an optimal tumor response.”
Investigators assessed short and long wait times between chemoradiotherapy and surgery among 1,064 patients (median age, 64 years; 61.5% men) with rectal cancer who had minimal or no tumor response to chemoradiotherapy. All patients received treatment across 12 referral centers in Italy between 2000 and 2014.
Most patients (54.4%) experienced wait times to surgery of 8 weeks or less, whereas 45.6% of patients had wait times of more than 8 weeks.
OS and DFS among patients with shorter vs. longer wait times to surgery served as primary outcomes.
Results showed patients with longer wait times had lower rates of 5-year OS (67.6% vs. 80.3%) and 10-year OS (40.1% vs. 57.8%) than those with shorter wait times (P < .001 for both). Researchers also observed lower rates of 5-year DFS (59.6% vs. 72%) and 10-year DFS (36.2% vs. 53.9%) among those with longer delays (P < .001 for both).
Results of multivariate analysis showed that a longer wait time was associated with an augmented risk for death (HR = 1.84; 95% CI, 1.5-2.26) and death or recurrence (HR = 1.69; 95% CI, 1.39-2.04).
“Postponing surgical resection for a certain period may be dangerous for some patients,” Restivo said. “As a result, waiting for a better response is not a good strategy. If we have a poor responder, we should recognize him/her early on and proceed as soon as possible to surgical resection whenever feasible.”
The study cannot be conclusive as it has clear limits related to the retrospective design, Restivo added.
“We have built a collaborative national platform that will help us clarify many open questions through randomized studies,” he said. “We aim to tune the therapeutic strategy in rectal cancer to the needs of every single patient. Giving the best optimal therapy and in the right time is one of the major challenges that we have.”
Few studies have determined the optimal time interval between neoadjuvant chemoradiation therapy and surgery, which is traditionally 6 to 12 weeks, with the fundamental intent that extending the time interval to total mesorectal excision achieves further tumor regression or a pathologic complete response, according to an accompanying editorial by Ranim Alsaad, MD, researcher in the department of surgery, and Sandy Hwang Fang, MD, researcher in the departments of surgery and oncology, both at The Johns Hopkins Hospital.
“As we move toward individualized multimodal rectal cancer treatment, it will be essential to identify better diagnostic cancer biomarkers and functional imaging ... in order to further elucidate tumor biology,” Alsaad and Fang wrote.
References:
Alsaad R and Fang SH. JAMA Surg. 2021;doi:10.1001/jamasurg.2021.4567.
Deidda S, et al. JAMA Surg. 2021;doi:10.1001/jamasurg.2021.4566.
For more information:
Angelo Restivo, MD, can be reached at University of Cagliari, Monserrato, S.S. 554 Bivio Sestu, Cagliari 09042, Italy; email: arestivo@unica.it.
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