Clinical spectrum of rectal cancer identifies hallmarks of early‐onset patients and next‐generation treatment strategies

Abstract

Background The incidence of colorectal cancer is increasing among young adults and more rectal cancers are reported. This study aimed to identify the clinical features specific for early‐onset rectal cancer and provide insights on cancer management. Methods Early‐onset (<50 years) and late‐onset (≥50 years) rectal cancer patients from a referral tertiary care center (SYSU cohort) and Surveillance Epidemiology and End Results database (SEER cohort) were included to perform a comprehensive comparison on clinical information. Results A total of 552 and 80,341 patients with stages I–III rectal cancer were included in the SYSU and SEER cohorts, respectively. In the SYSU cohort, early‐onset diseases had significantly higher prevalence of family history of cancer and history of HBV infection and lower incidence of comorbidities ( p < 0.05). In addition, early‐onset patients presented more frequently with advanced node stage (N2 stage: 16.9 vs. 9.3%, p = 0.017) and high‐risk features, including mucinous or signet cell carcinomas (21.8 vs. 12.9%, p = 0.014), poorly differentiated tumors (28.8 vs. 15.4%, p = 0.002), and perineural invasion (14.5 vs. 7.9%, p = 0.027) compared with late‐onset patients. However, early‐onset patients received more neoadjuvant (18.5 vs. 11.2%, p = 0.032) and adjuvant treatments (71.0 vs. 45.8%, p < 0.001), and they had better overall survival in both SYSU (HR 0.57, 95% CI: 0.34–0.95; p = 0.029) and SEER (HR 0.38, 95% CI: 0.37–0.40; p < 0.001) cohorts. Conclusion Early‐onset rectal cancers are distinct from late‐onset cases in clinicopathological features, treatment modalities, and outcomes. The clinical trials and studies that are specific for young populations are needed to develop optimal strategies for cancer screening, treatment, and surveillance.

RNA demethylase ALKBH5 promotes colorectal cancer progression by posttranscriptional activation of RAB5A in an m6A‐YTHDF2‐dependent manner

“…To determine the correlation between ALKBH5 expression and clinic‐pathological characteristics of CRC, a total of 201 CRC patients combined with their fresh frozen tumour specimens originating from the institutional database program of colorectal disease (IDPCD) at our institute were also included in this study. The IDPCD cohort integrated patient data, including demographic and clinic‐pathological characteristics and follow‐up data, which was described in previous publications 20–22 …”

“…The IDPCD cohort integrated patient data, including demographic and clinic-pathological characteristics and follow-up data, which was described in previous publications. [20][21][22]…”

Early onset colorectal cancer in Canterbury, New Zealand

“…It is estimated that within 10 years, one in four rectal cancers will be in those under 50 years of age 9 . The clinical, pathological and epidemiologic landscapes of EOCRC are fundamentally distinct from CRC in those with late‐onset CRC (LOCRC) 10–12 . EOCRC is described most commonly in the distal colon and rectum 13,14 with more adverse histopathological features such as poor differentiation, mucosal and signet cell pathology relative to CRC in older adults 15–17 .…”

“…9 The clinical, pathological and epidemiologic landscapes of EOCRC are fundamentally distinct from CRC in those with late-onset CRC (LOCRC). [10][11][12] EOCRC is described most commonly in the distal colon and rectum 13,14 with more adverse histopathological features such as poor differentiation, mucosal and signet cell pathology relative to CRC in older adults. [15][16][17] Data reporting on the prognosis of EOCRC is sparse and controversial; several single-institution studies have indicated a poorer prognosis, [18][19][20] while others have found equivalent or higher survival rates compared to LOCRC.…”