Higher rate of pathologic complete response in patients with early-onset locally advanced rectal cancer.

Background: Although incidence and mortality rates of colorectal cancer have progressively decreased during the past decades, early-onset rectal cancer (EORC; <50 years old) is rising alarmingly. EORC is often diagnosed at advanced stages and presents intrinsic molecular alterations. New strategies are necessary to increase early diagnosis and to improve therapeutic management. We present the analysis of our locally advanced EORC patients evaluating their specific response to chemoradiotherapy. Materials and methods: Patients diagnosed with locally advanced rectal cancer (LARC) and treated with curative surgery after neoadjuvant treatment (NAT) with chemoradiotherapy were retrospectively analysed, comparing differences between EORC and late-onset rectal cancer (LORC). Incidence rates between 2001 and 2020, as well as diagnostic and treatment response variables, were compared. Results: Up to 1140 patients were diagnosed with rectal cancer and underwent curative surgery. From them, there were 399 patients with LARC who received NAT before surgery, and 9% of them had EORC (36 patients). The incidence of locally advanced EORC increased from 6.6% to 12.7% (2001-2020). No differences were found considering diagnostic variables between the early- and late-onset cohorts, although slightly more deficient mismatch repair tumours were found within the EORC cohort. Mean disease-free survival and mean cancer-specific survival were similar. Notwithstanding, EORC patients achieve higher rates of pathological complete responses (pCRs), compared with LARC (36.3% versus12.4%; Conclusions: Our analyses confirm the increase in incidence of EORC from 2001 to 2020 in Navarra. EORC patients achieved a higher pCR rate, thus suggesting that the role of organ preservation strategies should be further investigated in this unique population.