Long-course chemoradiation may improve organ preservation rates in rectal cancer
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A long course of chemoradiation therapy appeared associated with higher organ preservation rates vs. a short course among a cohort of patients with rectal cancer, according to a study presented at ASCO Gastrointestinal Cancers Symposium.
Planned ongoing research into the total neoadjuvant therapy strategies should definitively confirm the findings, researchers concluded.
Rationale
“Interest in organ preservation strategies for patients with rectal cancer persists,” Paul B. Romesser, MD, radiation oncologist in the department of radiation oncology at Memorial Sloan Kettering Cancer Center, and colleagues wrote in the abstract. “The efficacy of long-course chemoradiation vs. short-course radiation therapy relative to organ preservation is unknown. During the COVID-19 pandemic, we established an institutional short-course radiation therapy mandate with no exceptions. For comparison, we identified patients with rectal cancer treated with long-course radiation therapy immediately before and after the mandate period.”
Methods
Researchers compared organ preservation rates — defined as alive, total mesorectal excision-free, no evidence of disease in the pelvis — among 332 patients with rectal cancer (median age, 57 years; 62.1% men) who underwent short-course (n = 76) vs. long-course (n = 256) chemoradiation total neoadjuvant therapy.
Patient and tumor characteristics appeared similar between the groups, with no significant differences in high-risk features, and most patients (81.6%) had clinical stage III disease.
Researchers restaged patients after completion of total neoadjuvant therapy by clinical exam, endoscopy and MRI. They assigned patients with a clinical complete response to a watch-and-wait approach and recommended total mesorectal excision for those without complete response. They then performed survival analysis for local regrowth rate, organ preservation, DFS and OS.
Median follow up was 32 months for the long-course and 28 months for the short-course chemoradiation group.
Findings
Overall, induction chemotherapy followed by consolidative radiation appeared the most common treatment order for those who underwent a long course of chemoradiation in (77.7%) and for those who underwent a short course (69.7%).
Median time from end of total neoadjuvant therapy to clinical staging was 8 weeks with long-course chemoradiation and 9 weeks with short-course radiation therapy.
Results showed an overall clinical complete response rate of 46%. Patients who underwent radiation therapy first vs. chemotherapy first experienced numerically higher complete response rates with both long-course (53% vs. 44%) and short-course chemoradiation (52% vs. 43%).
Results showed 2-year OS rates of 95% with long-course vs. 92% with short-course chemoradiation, DFS rates of 78% vs. 70%, and distant recurrence rates of 20% vs. 21%.
Moreover, researchers observed a 2-year organ preservation rate of 40% (95% CI, 35-47) with long-course vs. 29% (95% CI, 20-42) with short-course chemoradiation and, among those managed with a watch-and-wait approach, 88% (95% CI, 81-94) with long-course and 67% (95% CI, 51-87) with short-course chemoradiation.
Among those with higher clinical complete response rates, researchers also observed a similar likelihood for watch-and-wait approach management for long- (98%) vs. short-course chemoradiation (94%). Patients managed by watch-and-wait experienced a 2-year local regrowth rate of 20% (95% CI, 12-27) with long-course chemoradiation compared with 36% (95% CI, 16-52) for short-course radiation therapy.
Implications
“In this nonrandomized comparison, while clinical complete response rates were similar, we observed a numerically higher organ preservation rate with [long-course chemoradiation-total neoadjuvant therapy] than with [short-course radiation therapy-total neoadjuvant therapy],” the poster stated. “The ongoing ACO/ARO/AIO-18.1 trial, hypothesizing that [the long-course strategy] will increase organ preservation rates relative to [the short-course strategy], should definitively answer this question.”
Perspective
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Manisha Palta, MD
These nonrandomized data resulting from practice change in response to COVID-19 are hypothesis generating and interesting. Much of the prospective and retrospective data surrounding a watchful waiting/nonoperative management approach has been with utilization of a long-course chemoradiation approach. To date, there are limited data — single-institution prospective studies — evaluating a potential watchful waiting/nonoperative management approach utilizing a total neoadjuvant therapy regimen with short-course radiation. Further clarity on the topic of long-course chemoradiation or short-course radiation as part of total neoadjuvant therapy will be answered with ongoing randomized trials, including the ongoing ACO/ARO/AIO-18 and NOM-ERA trials.
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Romesser PB, et al. Abstract 10. Presented at: ASCO Gastrointestinal Cancers Symposium; Jan. 19-21, 2023; San Francisco.
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