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onc.colorectal-cancer.core.v1

Colorectal cancer (core)

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Colorectal cancer (core) dossier — colon + rectum. Spans USPSTF 2021 screening (age 45-75), diagnostic colonoscopy + biopsy + tattoo, CT + rectal MRI staging (AJCC 8th), mandatory MSI/MMR + KRAS/NRAS/BRAF/HER2/NTRK biomarker workup, and 7-axis stage-and-biomarker-stratified regimen (IDEA-adjuvant, RAPIDO-TNT, CALGB 80405 metastatic left/right, TRIBE2 FOLFOXIRI, KEYNOTE-177/CheckMate-8HW MSI-H ICI, BEACON BRAF V600E, MOUNTAINEER HER2-amp + refractory regorafenib/TAS-102). 9 evidence PMIDs PubMed-MCP-verified 2026-05-26 (6 candidate PMIDs dropped: 29412061 = circadian T2DM, 33908452 = hybrid sponge, 38101412 = D-mannose senescence, 32702300 = COVID vaccine, 28526547 = gender ACS Switzerland, 33485780 = osteonecrosis shoulder). All 15 antineoplastic + biologic RxCUIs RxNav-verified 2026-05-26 (5-FU 4492, leucovorin 6313, oxaliplatin 32592, irinotecan 153329 HCl, capecitabine 194000, bevacizumab 253337, cetuximab 318341, panitumumab 263034, pembrolizumab 1547545, nivolumab 1597876, ipilimumab 1094833, encorafenib 2049106, binimetinib 2049122, regorafenib 1312397, trifluridine-tipiracil 1670310, tucatinib 2361285, trastuzumab 224905).

Entry points (6)

  • lab_abnormality
    Positive FIT or stool-DNA test on screening (USPSTF 2021)
    fit_or_cologuard_positive
  • imaging
    Polyp/mass identified at colonoscopy requiring biopsy or referral (USMSTF 2020)
    colonoscopy_polyp_or_mass
  • symptom
    Rectal bleeding, occult-blood-positive anemia, or change in bowel habit (NCCN Colon/Rectal 2026)
    rectal_bleeding_or_iron_deficiency_anemia
  • problem_list
    Biopsy-confirmed colorectal adenocarcinoma (NCCN Colon/Rectal 2026)
    confirmed_crc
  • demographic
    Age 45-75 for screening colonoscopy/FIT (USPSTF 2021)
    screening_age_45_75
  • history
    High-risk syndrome (Lynch, FAP, IBD with colitis) requiring earlier/more-frequent screening (NCCN germline 2024)
    lynch_or_fap_or_inflammatory_bowel_disease

Required inputs (15)

  • agerequired
    demographic • used at FRAME
    Screening eligibility (USPSTF 2021), surgical candidacy, IDEA adjuvant duration banding
  • family_history_lynch_faprequired
    history • used at CONTEXT
    Hereditary syndrome risk drives germline testing and earlier screening cadence (NCCN germline 2024)
  • ecog_psrequired
    history • used at CONTEXT
    Performance status drives FOLFOXIRI fitness, surgical candidacy, palliative-vs-curative intent
  • weightrequired
    vital • used at CONTEXT
    BSA for cytotoxic dosing (Mosteller)
  • heightrequired
    vital • used at CONTEXT
    BSA computation
  • colonoscopy_with_biopsyrequired
    imaging • used at INITIAL_WORKUP
    Diagnostic gold standard; lesion biopsy + tattoo + synchronous-polyp survey
  • ct_chest_abdomen_pelvisrequired
    imaging • used at INITIAL_WORKUP
    Staging — visceral/nodal metastases; AJCC stage assignment
  • rectal_mri
    imaging • used at INITIAL_WORKUP
    Rectal cancer only — CRM, mesorectal nodes, T-staging for TNT vs surgical-first decision
  • cea_baselinerequired
    lab • used at INITIAL_WORKUP
    Baseline CEA for post-treatment surveillance trending (NCCN Colon 2026)
  • cbcrequired
    lab • used at INITIAL_WORKUP
    Baseline cytopenias affect chemo dose intensity
  • lftrequired
    lab • used at INITIAL_WORKUP
    Hepatic function for chemo dosing + irinotecan UGT1A1 considerations
  • creatininerequired
    lab • used at INITIAL_WORKUP
    Renal function for oxaliplatin/capecitabine dosing + contrast staging
  • msi_mmr_statusrequired
    lab • used at BRANCHING_WORKUP
    MMR-IHC + MSI-PCR; MSI-H drives ICI first-line eligibility and Lynch screening
  • kras_nras_braf_her2_ntrk
    lab • used at BRANCHING_WORKUP
    Molecular panel drives first-line anti-EGFR vs anti-VEGF, BEACON triplet, MOUNTAINEER, and TRK inhibitor eligibility
  • tumor_sidedness_left_vs_right
    history • used at BRANCHING_WORKUP
    KRAS WT left-sided primary derives greater benefit from anti-EGFR vs anti-VEGF first-line (CALGB/SWOG 80405)

12-phase flow (12)

  1. 1FRAME
    Determine scope: screening vs polyp vs newly-confirmed CRC vs metastatic; colon vs rectum (rectal triggers MRI + TNT pathway) (NCCN Colon/Rectal 2026)
    inputs: age
    advance: Scope identified with anatomic site (colon vs rectum) (NCCN Colon/Rectal 2026)
  2. 2ENTRY
    Capture trigger: positive FIT, polyp at colonoscopy, symptomatic anemia/bleeding/obstruction, or known biopsy diagnosis (USPSTF 2021 + NCCN)
    inputs: age
    actions: workup.colorectal_screening, workup.colonoscopy_diagnostic
    advance: Entry trigger documented; diagnostic colonoscopy scheduled if not already done (NCCN Colon/Rectal 2026)
  3. 3CONTEXT
    ECOG-PS, comorbidities (IBD, prior abdominal RT), Lynch/FAP family history with cascade-testing flag, prior screening colonoscopy interval, baseline weight + BSA (NCCN Colon/Rectal 2026)
    inputs: ecog_ps, weight, height, family_history_lynch_fap
    actions: calc.bsa
    advance: Performance + family-risk + comorbidity profile established (NCCN Colon/Rectal 2026)
  4. 4RED_FLAGS
    Obstructing or perforating tumour (acute abdomen, faecal peritonitis), severe lower-GI haemorrhage, malignant spinal cord compression from bone mets, large-bowel obstruction with closed-loop pattern (NCCN Colon/Rectal 2026)
    advance: Emergencies screened; surgical/IR consult activated if positive (NCCN Colon/Rectal 2026)
  5. 5INITIAL_WORKUP
    Full colonoscopy with biopsy + tattoo + synchronous-lesion survey, CT chest/abdomen/pelvis with contrast, rectal MRI for rectal cancer (CRM/mesorectal nodes), baseline CEA, CBC, CMP with LFTs, AJCC 8th edition staging (NCCN Colon/Rectal 2026)
    inputs: colonoscopy_with_biopsy, ct_chest_abdomen_pelvis, cea_baseline, cbc, lft, creatinine
    actions: panel.cbc, panel.lft, panel.renal, panel.tumor
    advance: Stage assigned + baseline labs documented (NCCN Colon/Rectal 2026)
  6. 6BRANCHING_WORKUP
    MSI/MMR IHC + PCR mandatory at diagnosis (Lynch + ICI eligibility), KRAS/NRAS exon 2-4 + BRAF V600E + HER2 + NTRK/RET on biopsy or liquid biopsy; Lynch germline if MSI-H or family criteria; EUS for early rectal lesions (NCCN Colon/Rectal 2026)
    inputs: msi_mmr_status
    actions: workup.genetic_counseling
    advance: Biomarker panel + germline + tumour sidedness documented (NCCN Colon/Rectal 2026)
  7. 7DIFFERENTIAL
    Adenocarcinoma (vast majority) vs neuroendocrine vs lymphoma vs metastasis to bowel; hereditary (Lynch/FAP/MUTYH/PJS) vs sporadic; field cancerization in IBD-associated dysplasia (NCCN Colon/Rectal 2026)
    advance: Histologic + hereditary axis defined (NCCN Colon/Rectal 2026)
  8. 8RISK_STRATIFICATION
    AJCC 8th edition stage I-IV; IDEA risk bands (T1-3 N1 low-risk -> 3 mo CAPOX vs T4/N2 high-risk -> 6 mo FOLFOX); rectal MRI CRM-positive triggers TNT (NCCN Colon/Rectal 2026)
    advance: Stage + IDEA band + CRM status assigned (NCCN Colon/Rectal 2026)
  9. 9TREATMENT
    Stage + biomarker-stratified plan: stage I-III colon (surgery + adjuvant per IDEA), locally advanced rectal (TNT/RAPIDO or selective CRT/PROSPECT), metastatic (FOLFOX/FOLFIRI ± biologic per KRAS/sidedness, FOLFOXIRI + bev for fit, MSI-H ICI per KEYNOTE-177/CheckMate-8HW, BRAF V600E BEACON, HER2-amp MOUNTAINEER) (NCCN Colon/Rectal 2026)
    inputs: creatinine, lft, ecog_ps, msi_mmr_status
    advance: Stage + biomarker-matched regimen selected with toxicity profile reviewed (NCCN Colon/Rectal 2026)
  10. 10DISPOSITION
    Outpatient infusion suite for systemic therapy; inpatient for surgery (laparoscopic/robotic colectomy or TME for rectal), bowel obstruction relief, neutropenic fever, severe irAE, palliative escalation (NCCN Colon/Rectal 2026)
    advance: Care setting + treatment timeline established (NCCN Colon/Rectal 2026)
  11. 11MONITORING
    CEA q3-6 mo x 5 yr post-curative; CT chest/abdomen/pelvis q6-12 mo x 3 yr for high-risk resected; surveillance colonoscopy at 1 yr then per polyp/USMSTF 2020 intervals; oxaliplatin neuropathy monitoring; on-ICI irAE TSH/LFT/glucose q2-4 wk (NCCN Colon/Rectal 2026)
    inputs: cea_baseline
    actions: panel.cbc, panel.lft, panel.tumor
    advance: Surveillance schedule documented (NCCN Colon/Rectal 2026)
  12. 12FOLLOWUP
    NCCN survivorship intervals; Lynch cascade-testing for family if MMR-deficient; high-risk syndrome surveillance (annual EGD/colonoscopy for FAP, gynae screening for Lynch); long-term oxaliplatin neuropathy management; bowel-habit + ostomy care (NCCN Colon/Rectal 2026)
    advance: Survivorship + cascade-testing + syndrome-surveillance plan documented (NCCN Colon/Rectal 2026)