TOPLINE:

Analysis of 35,213 patients with stage II-III colon cancer revealed that recurrence risk drops below 0.5% at 6 years post-surgery, supporting a practical definition of cure. Women showed a significantly lower recurrence risk with a hazard ratio (HR) of 0.58.

METHODOLOGY:

• The definition of cure in stages II-III colon cancer remains unclear due to limitations in conventional endpoints, which include deaths and second primary tumors as events.
• Researchers conducted a pooled analysis of individual patient-level data from 15 phase 3 randomized clinical trials assessing time to colon cancer-related relapse using Kaplan-Meier and Aalen-Johansen methods.
• A total of 35,213 patients with stages II-III colon cancer who underwent adjuvant chemotherapy were included, with mean age of 60.2 years and 54.9% being men.
• Analysis included separating competing events from colon cancer recurrence, including death without recurrence and second primary tumors.
• Participants received adjuvant chemotherapy regimens including fluoropyrimidines alone or combined with oxaliplatin or biologic agents, with median follow-up of at least 6 years.

TAKEAWAY:

• The incidence rate of recurrence peaked at 6.4% between months 6 and 12 and then decreased continuously until year 10, never exceeding 0.5% after year 6.
• Women demonstrated a significantly lower cumulative incidence of relapse when death was a competing event (HR, 0.58; 95% CI, 0.45-0.76; P < .001).
• Patients aged 40 years or older showed a higher cumulative incidence of events than younger patients (HR, 2.93; 95% CI, 1.09-7.83; P = .02).
• Analysis revealed that death and second primary tumors inflated the apparent recurrence rate, particularly affecting older patients.

IN PRACTICE:

“From a scientific perspective, we still face challenges in the definition of cure in the adjuvant colon cancer setting. When answering patients’ questions about cure, we should use a restrictive definition of relapse-free survival, considering local and/or distant recurrence; this should be reported in adjuvant studies as a relevant secondary endpoint. In the setting of colon cancer, this leads us to advocate for 6 years after surgery free of relapse as constituting cure,” the authors of the study wrote.

SOURCE:

The study was led by Alessandro Pastorino, MD, IRCCS Ospedale Policlinico San Martino in Genova, Italy. It was published online on October 2 in JAMA Oncology.

LIMITATIONS:

According to the authors, the analysis pooled data from 15 randomized clinical trials conducted over two decades, with heterogeneous treatment regimens and follow-up schedules. Information on second primary malignant tumors and follow-up beyond 10 years was only available for a subset of studies, potentially limiting the interpretation of long-term results. Additionally, trial participants represent selected populations with controlled follow-up, which may reduce the generalizability of findings to more diverse, real-world settings.

DISCLOSURES:

The study received support from Italian Association for Research Against Cancer grant IG 2018 and NRG Oncology grants. Thomas J. George, MD, reported serving on data and safety monitoring boards for multiple companies and receiving institutional research support from various pharmaceutical companies including Bristol Myers Squibb, Merck, and AstraZeneca. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.