Incidence of Recurrence and Time to Recurrence in Stage I to III Colorectal Cancer: A Nationwide Danish Cohort Study

Abstract

Importance: Management of colorectal cancer (CRC) has been updated continuously over the past 2 decades. While the combination of these initiatives has had implications for improved survival, the implications for rates of recurrence remain unexplored.

Objective: To ascertain the rates of recurrence and describe time to recurrence within 5 years of surgery with curative intent for stages I to III CRC.

Design, setting, and participants: This cohort study used the Danish Colorectal Cancer Group Database to identify patients with Union for International Cancer Control (UICC) stages I to III CRC who underwent primary surgery between January 1, 2004, and December 31, 2019. They were followed up until recurrence (event), death (competing event), diagnosis of a second cancer (competing event), emigration (censoring event), 5 years postoperatively (censoring event), or January 1, 2023 (censoring event), whichever came first. Recurrence status was ascertained through individual-level linked data from the Danish Cancer Registry, Danish National Patient Registry, and Danish Pathology Registry using a validated algorithm. Data were analyzed from January 1 to August 8, 2023.

Exposure: Primary surgery performed during 3 calendar periods (2004-2008, 2009-2013, and 2014-2019) stratified by tumor site (colon or rectum) and UICC stage (I, II, and III).

Main outcomes and measures: Stage-specific 5-year recurrence reported as the cumulative incidence function (CIF) of recurrence, the association between calendar period of primary surgery and recurrence risk reported as subdistribution hazard ratios (sHRs), and the time from surgery to recurrence.

Results: Of the 34 166 patients with UICC stages I to III CRC (median [IQR] age, 70 [62-77] years); 18 552 males [54.3%]) included in the study, 7027 developed recurrence within 5 years after the primary surgery. For colon cancer, the 5-year CIF of recurrence decreased over the 3 calendar periods from 16.3% to 6.8% for UICC stage I, from 21.9% to 11.6% for UICC stage II, and from 35.3% to 24.6% for UICC stage III colon cancer. For rectal cancer, the 5-year CIF decreased over the 3 periods from 19.9% to 9.5% for stage I, from 25.8% to 18.4% for stage II, and from 38.7% to 28.8% for stage III disease. Patients with stage III disease had a shorter time from surgery to recurrence compared with those with stage I disease (time ratio stage III vs stage I = 0.30; 95% CI, 0.28-0.32). Cancers detected through screening were associated with lower stage-adjusted risks of recurrence (sHR, 0.81; 95% CI, 0.73-0.91) compared with cancers not detected through screening.

Conclusions and relevance: In this cohort of patients with CRC, the risk of recurrence decreased in patients with stages I to III disease during the study period. Cancer detection by screening was associated with an even lower risk of recurrence. Time to recurrence differed according to UICC stage. Because the risk of recurrence was so low in selected patient groups, future research is warranted to explore risk-stratified surveillance protocols in patients with CRC.

Figure 1.. Cumulative Incidence Function Curves for Colorectal Cancer Recurrence Stratified by Tumor Site and Compared by Calendar Period of Curative Surgery

Curves were constructed using the Aalen-Johansen estimator. Patients were right-censored at emigration, 5 years of follow-up, or on January 1, 2023, whichever came first. sHR indicates subdistribution hazard ratio calculated using Fine-Gray regression adjusted for sex, age, comorbidities, and Union for International Cancer Control stage.

Figure 2.. Time From Surgery to Colorectal Cancer Recurrence by Union for International Cancer Control (UICC) Stage

Vertical dashed lines represent median time from curative surgery to recurrence. Shaded areas represent time points of surveillance imaging at 12 and 36 months after surgery (as per Danish guidelines since 2009).

Figure 3.. Cumulative Incidence Function Curves for Colorectal Cancer Recurrence According to Cancer Detection Method (Screening or Not Screening) Stratified by Union for International Cancer Control (UICC) Stage

Curves were constructed using the Aalen-Johansen estimator. Patients were right-censored at emigration, 5 years of follow-up, or on January 1, 2023, whichever came first. sHR indicates subdistribution hazard ratio calculated using Fine-Gray regression adjusted for sex, age, comorbidities, and UICC stage.