Colon/Rectal Cancer

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    Colon Cancer

    • 4rth most common cancer in US (2nd leading cause of death)
    • If metastasis to liver (few isolated lesions), hepatic resection may be curative.
    • Staging is most accurate predictor of outcome (TNM staging)
    • Presentation/Symptoms:
      • Most asymptomatic until stage is very high
      • Rectal Bleeding, Melena
      • Cramping, bloating, change in frequency/caliber of BMs
      • Iron deficiency anemia!!! (very common presentation)
    • Sites of Metastasis:
      • Liver 
      • Lung

     

    Important Notes on Colon Ca:

    • The only cancers where we resect mets -->if confined to liver or lung --> can still be curable.
    • One of few cancers (unlike lung/breast) where palliative chemo has huge survival advantage.
      • I.e. stage IV --> survival 5mo if no treatment.  and up to 24mo if treated.
    • Mets in spine --> no concern unless there are symptoms.  (early initiation of palliative chemotherapy no difference compared to late).  Can initiate palliative chemo if heavy disease burden or symptoms.
    • No radiation for Colon Ca --> risk of local recurrence very small.
    • YES radiation for Rectal Ca --> local recurrence real risk

    Screening Recommendations

    • Screening colonoscopy ≥ 50yrs q10h
    • Younger if:
      • History of Colorectal Ca, Adenomatous Pollyps, or Symptoms

     

    Staging

    • Workup:
      • Complete colonoscopy (if possible)
      • Contrast Enhanced CT of Chest/Abdo/Pelvis
        • May require transrectal U/S or pelvic MRI to define level of invasion (i.e. involving anal muscles)
      • (PET scan not yet validated) - 2014
      • Serum CEA Levels
    • Stage Description 5-year survival 
      I

      - Not involve full thickness of bowel wall (T1/T2)

      - LN's not involved (N0)

      90--95%
      II

      - Invades full thickness of bowel wall + pericolonic/perirectal fat (T3/T4); 

      - LN's not involved

      70-85%
      III - One or more LN's involved (N1, N2)  25-70%
      IV - Metastatic (M1)  (Any T, Any N) 0-10%

     

    • TNM Highlights
      • T1 - T2 (Beginning to invade muscular wall, but not through it)
      • T3 - Invading through muscular wall
      • T4 - Invading adjacent organs

     

    Treatment

    • Biggest Patient Fears: almost never results in permanent colostomy (unless involves rectal sphincter)
    • Standard of Care: Resection of Tumor (allows staging) (usually only necessary therapy) Except:
    • Stage II
      • Need for adjuvant chemo is complex.
        • Only if "high risk" (T4 stage, poor LN sampling [<12LNs], lymphovascular invation, poorly differentiated histology, clinical perforation/obstruction)
        • Most studies: no benefit of adjuvant chemo (unless high risk features present)
    • Stage III
      • Adjuvant Chemotherapy
      • 5-FU single most active agent since 1957 - (Studies: adjuvant 5-FU reduces risk of death)
        • Best agent --> newer agents only used in combination.
      • FOLFOX (folinic acid [leucovorin], 5-FU, and oxaliplatin) x6mo = standard of care for Stage III
        • Leucovorin amplifies 5FU effect (also more toxic)
        • Oral Version of 5-FU called "Capecitabine"
        • Now called "CapOx" (oral formulation)
      • Survival: ~40%, with adjuvant chemo: ~60%.
    • Stage IV (metastatic)
      • Unlike other cancers: Can still be curable if metastasis confined to single organ and resectable! (liver or lung lobe) --> resect!
        • I.e. breast Ca --> we do not screen for metastatic disease because not curable, won't change mgmt (unless symptomatic).
        • Sometimes remove one lobe --> allow the other to hypertrophy --> remove more cancer.
      • Test for K-ras mutation (if negative, then can use multiple monoclonal antibodies (below), if positive, they won't be effective).  (Cetuximab, panitumumab)
      • In metastatic - Usually hold chemo until symptomatic.  Chemo only effective for several months.
      • Chemo options:
        • 5-FU
        • Leucovorin (added to 5-FU to make it bind tighter to enzyme, amplies 5FU effect)
        • Capecitabine (alterative to 5-FU)
        • Irinotecan, oxaliplatin
        • Bevacizumab (mAb against VEGF)
        • Cetuximab, panitumumab mAbs that block ligand-binding of EGFR [if no k-ras gene]
          • S/E: acneiform rash (can be socially debilitating, but indicates it has anti-tumor effects, if no rash = little effect)
    • Post-Resection Surveillance
      • Depends on Cancer Stage
      • Typically involves conoloscopy (i.e. in 6mo, then 3y, then q5y thereafter)
      • CT Scans of chest/abdo q1y x5yrs (For Stage II-III, no need for stage 0-I)
      • CEA levels each visit for Stage II-III

    Rectal Ca

    • Rectum is hard to remove! (need mesorectum excision)
      • Remember: Rectum is beneath peritoneal reflection (location changes)
      • Very difficult surgery --> prostate, bladder, bony structures.... (uterus, ovaries).
        • Very hard to create good margins
        • Experienced surgeon is important!
    • NOTE: Very high incidence of local recurrence (does not exist with colon cancer), which means that surgery with good margins is very important and adjuvant radiation is very important too!
      • Stage II disease gets chemo/rads (unlike colon ca)
    • Workup:
      • Same workup as Colon Ca
      • Except Also:
        • Endorectal USS or pelvic MRI required (for depth of penetration T-stage)
    • Management:
      • T1-2, N0  (not full thickness, no LNs)
        • Surgical resection
      • T3/T4 (full thickness invading into muscle, or LN's) (Stage II and higher)
        • Local recurrence risk is high --> offer radiation
        • Pre-Op Rads/Chemo is better than Post-Op (standard of care)
          • RCT: Pre-op vs. Post-op Rads --> equally effective, but Pre-Op rads cause less toxicity (once remove rectum, small bowel falls into pelvis, and get small bowel toxicity) 
        • Chemo-rads post-op only if stage changed post-op - i.e. Stage T1 --> T3)
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