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Multicenter Study

Abandonment of Routine Radiotherapy for Nonlocally Advanced Rectal Cancer and Oncological Outcomes

Sanne-Marije J A Hazen et al. JAMA Oncol. .

Abstract

Importance: Neoadjuvant short-course radiotherapy was routinely applied for nonlocally advanced rectal cancer (cT1-3N0-1M0 with >1 mm distance to the mesorectal fascia) in the Netherlands following the Dutch total mesorectal excision trial. This policy has shifted toward selective application after guideline revision in 2014.

Objective: To determine the association of decreased use of neoadjuvant radiotherapy with cancer-related outcomes and overall survival at a national level.

Design, setting, and participants: This multicenter, population-based, nationwide cross-sectional cohort study analyzed Dutch patients with rectal cancer who were treated in 2011 with a 4-year follow-up. A similar study was performed in 2021, analyzing all patients that were surgically treated in 2016. From these cohorts, all patients with cT1-3N0-1M0 rectal cancer and radiologically unthreatened mesorectal fascia were included in the current study. The data of the 2011 cohort were collected between May and October 2015, and the data of the 2016 cohort were collected between October 2020 and November 2021. The data were analyzed between May and October 2022.

Main outcomes and measures: The main outcomes were 4-year local recurrence and overall survival rates.

Results: Among the 2011 and 2016 cohorts, 1199 (mean [SD] age, 68 [11] years; 430 women [36%]) of 2095 patients (57.2%) and 1576 (mean [SD] age, 68 [10] years; 547 women [35%]) of 3057 patients (51.6%) had cT1-3N0-1M0 rectal cancer and were included, with proportions of neoadjuvant radiotherapy of 87% (2011) and 37% (2016). Four-year local recurrence rates were 5.8% and 5.5%, respectively (P = .99). Compared with the 2011 cohort, 4-year overall survival was significantly higher in the 2016 cohort (79.6% vs 86.4%; P < .001), with lower non-cancer-related mortality (13.8% vs 6.3%; P < .001).

Conclusions and relevance: The results of this cross-sectional study suggest that an absolute 50% reduction in radiotherapy use for nonlocally advanced rectal cancer did not compromise cancer-related outcomes at a national level. Optimizing clinical staging and surgery following the Dutch total mesorectal excision trial has potentially enabled safe deintensification of treatment.

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Conflict of interest statement

Conflict of Interest Disclosures: Drs Hazen and Kusters reported grants from the Dutch Cancer Society during the conduct of the study. Dr de Wilt reported grants from Medtronic outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Inclusion Flowchart
DCRA indicates Dutch Colorectal Audit; W&S, wait and see.
Figure 2.
Figure 2.. Local and Distant Recurrence Rates and Disease-Free and Overall Survival
A, Hazard ratio (HR), 1.01 (95% CI, 0.94-1.08; P = .76). B, HR, 0.99 (95% CI, 0.95-1.02; P = .45). C, HR, 0.71 (95% CI, 0.61-0.82; P < .001). D, HR, 0.61 (95% CI, 0.51-0.74; P < .001). The presented HR is the adjusted HR after competing risk analyses, with death as competing risk. aData were missing for 17 patients in the 2011 cohort for the end point of local recurrence. bData were missing for 20 patients in the 2011 cohort for the end point of distant recurrence. cData were missing for 1 patient in the 2016 cohort for the end point of distant recurrence. dData were missing for 16 patients in the 2011 cohort for the end point of overall survival. eData were missing for 15 patients in the 2011 cohort for the end point of disease-free survival.
See this image and copyright information in PMC

References

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