Time to recurrence and its relation to survival after recurrence in patients resected for stage III colon cancer

Background: It is intuitively thought that early relapse is associated with poor survival after recurrence (SAR) in resected colon cancer (CC) patients, but this has never been formally studied.

Methods: We pooled data from stage III patients treated with oxaliplatin-based adjuvant therapy in two phase III trials, to analyse time to recurrence (TTR) and its relationship with SAR. TTR and SAR were also studied according to molecular status (mismatch repair (MMR), RAS, and BRAFV600E). Early relapsing patients were defined as patients having a TTR event within 12 months after starting adjuvant chemotherapy.

Results: 4548 stage III CC patients were included in the present analysis. Deficient MMR (dMMR) CC patients experienced fewer recurrences than proficient (p)MMR CC patients (18.8% versus 27.6%) but had a significantly shorter median TTR (mTTR; 0.74 versus 1.40 years, p < 0.0001). In pMMR patients, BRAF and RAS mutations were also associated with earlier mTTR as compared to double wild-type (WT) patients (0.99 versus 1.38 versus 1.54 years, respectively, p < 0.0001). Early recurrence occurred in 397 patients and was associated with a median SAR (2.2 versus 3.3 years, p = 0.0007). However, this association was mainly due to pMMR/RAS and BRAFV600E mutated tumours and was not confirmed in dMMR and pMMR/double WT subgroups.

Conclusion: In resected stage III CC treated with standard oxaliplatin-based adjuvant therapy, TTR varies between dMMR, pMMR/RAS, or BRAFV600E mutated and pMMR/double WT tumours. In addition, early relapse is associated with poor survival, mainly due to patients resected for a pMMR/RAS or BRAFV600E mutated tumour.