Different Oncologic Outcomes in Early-Onset and Late-Onset Sporadic Colorectal Cancer: A Regression Analysis on 2073 Patients

Abstract

The incidence of colorectal cancer (CRC) is increasing in the population aged ≤ 49 (early-onset CRC-EOCRC). Recent studies highlighted the biological and clinical differences between EOCRC and late-onset CRC (LOCRC-age ≥ 50), while comparative results about long-term survival are still debated. This study aimed to investigate whether age of onset may impact on oncologic outcomes in a surgical population of sporadic CRC patients. Patients operated on for sporadic CRC from January 2010 to January 2022 were allocated to the EOCRC and LOCRC groups. The primary endpoint was the recurrence/progression-free survival (R/PFS). A total of 423 EOCRC and 1650 LOCRC was included. EOCRC had a worse R/PFS (p < 0.0001) and cancer specific survival (p < 0.0001) compared with LOCRC. At Cox regression analysis, age of onset, tumoral stage, signet ring cells, extramural/lymphovascular/perineural veins invasion, and neoadjuvant therapy were independent risk factors for R/P. The analysis by tumoral stage showed an increased incidence of recurrence in stage I EOCRC (p = 0.014), and early age of onset was an independent predictor for recurrence (p = 0.035). Early age of onset was an independent predictor for worse prognosis, this effect was stronger in stage I patients suggesting a potentially—and still unknown—more aggressive tumoral phenotype in EOCRC.

Early Age of Onset Is an Independent Predictor for a Worse Response to Neoadjuvant Therapies in Sporadic Rectal Cancer Patients

“…Previous studies hypothesized that aggressive pathological features and advanced stage at diagnosis in EORC patients may be the cause for a worse response to neoadjuvant therapies [21,22,[25][26][27][28][29]. However, in the present study, and in previous studies by our group [9,10,15], we did not report any difference in pathological features between EOand LORC patients. Although it is well known that young patients are diagnosed at a more advanced stage [9,10,15], the present study-focused on preoperatively treated locally advanced RC patients-presented a very homogeneous population in terms of pretreatment MRI stage.…”

“…However, in the present study, and in previous studies by our group [9,10,15], we did not report any difference in pathological features between EOand LORC patients. Although it is well known that young patients are diagnosed at a more advanced stage [9,10,15], the present study-focused on preoperatively treated locally advanced RC patients-presented a very homogeneous population in terms of pretreatment MRI stage. Hence, neither pathological features nor stage disease at diagnosis resulted in the peculiar characteristic of EORC patients and could not be hypothesized as causes for a worse response.…”

“…In fact, a study [14] reported that patients achieving a >95% response to preoperative multimodal treatments have an improved long-term oncologic outcome. Our group reported a worse pathologic response to neoadjuvant therapies in EOCRC patients [15]. To better explore this finding, we decided to compare the pathologic tumor response to neoadjuvant therapies in sporadic EORC and LORC patients, and to explore the factors associated with a worse response.…”

Early-Onset Colorectal Cancer: Current Insights

“…A multicenter study reported a better prognosis for EOCRC compared to LOCRC [ 117 ]. Conversely, a single-center retrospective study showed worse recurrence, PFS and cancer-specific survival for EOCRC compared to LOCRC [ 118 ]. A multicenter randomized trial [ 119 ] and a retrospective study from the Memorial Sloan Kettering Cancer Center [ 94 ] showed no significant difference in survival between patients with metastatic EOCRC and those with metastatic LOCRC.…”

Early versus Late Onset Colorectal Cancer: Pathological Distinctions and Optimal Screening Age Determination in a Decade-Long Study

“…EOCRC patients have a low prevalence of family history (25%) and pathogenic cancer susceptibility genes (16%) [12]. The causes of EOCRC are unclear, and the cancer-related mortality of EOCRC patients may increase in the next decade [13,14]. Liu et al found that early-onset patients may have higher overall survival (OS) [15,16], but Gao et al found no difference in prognosis between EOCRC and LOCRC patients [17].…”