OBJECTIVE: Conditional survival accounts for the time already survived after surgery and provides additional survival information. The aim was to assess conditional survival in stages I-III early onset colorectal cancer patients and to create nomograms predicting the conditional overall survival and cancer-specific survival after surgery.
METHODS: A total of 7058 patients who underwent surgical resection of early onset colorectal cancer were identified from surveillance, epidemiology and end results database. The formula used for conditional survival calculation was conditional survival(x|y) = S(x + y)/S(x), where S(x) represents the survival at x years. Conditional survival nomograms were then developed to predict the 5-year conditional overall survival and cancer-specific survival.
RESULTS: The 5-year overall survival and cancer-specific survival after surgery increases gradually with additional survival time. Race, tumour site, grade, histology, T stage, N stage, lymph node ratio, preoperative carcinoma embryonic antigen level and perineural invasion status were independent predictors of cancer-specific survival, while age and sex were another two independent risk factors for overall survival. The nomograms based on these factors were successfully developed to predict 5-year overall survival and cancer-specific survival given 1-4 years already survived.
CONCLUSIONS: The probability of achieving postoperative 5-year overall survival and cancer-specific survival for early onset colorectal cancer increases gradually with additional time survived. The developed nomograms are fairly valuable and informative in facilitating clinical treatment and follow-up schemes.

UNASSIGNED: Early onset colorectal cancer (EO CRC) is a heterogeneous colorectal cancer subtype with obvious hereditary tendencies and increasing incidence. We sought to determine the susceptibility genes and molecular characteristics of EO CRC.
UNASSIGNED: 330 EO metastatic CRC (mCRC) (≤55 years) and 110 average-onset (AO) mCRC patients (>55 years) were enrolled. Capture-based targeted sequencing was performed on tumor tissue and paired white blood cells using a sequencing panel of 520 genes. The association between molecular alterations and overall survival (OS) was analyzed.
UNASSIGNED: Of the 330 EO mCRC patients, 31 carried pathogenic or likely pathogenic germline mutations, with 16 of them diagnosed with lynch syndrome. Fifteen patients had germline mutations in non-mismatch repair genes, including four in MUTHY, three in RAD50, one in TP53, and eight in other genes. Twenty-nine genes were recurrently mutated in EO mCRC, including TP53, APC, KRAS, SMAD4, and BRCA2. The majority of genomic alterations were comparable between EO and AO mCRC. EO mCRC patients were more likely to have a high tumor mutation burden (p < 0.05). RNF43, RBM10, TSC, and BRAF V600E mutations were more commonly observed in EO mCRC, while APC, ASXL1, DNMT3B, and MET genes were more commonly altered in AO patients. At the pathway level, the WNT pathway was the only differentially mutated pathway between EO and AO mCRC (p < 0.0001). The wild-type WNT pathway (p = 0.0017) and mutated TGF-β pathway (p = 0.023) were associated with unfavorable OS in EO mCRC.
UNASSIGNED: Approximately one in 10 EO mCRC was associated with hereditary tumors. The spectrum of somatic alterations was largely comparable between EO and AO mCRC with several notable differences.