Cancers

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    Prostate Cancer

    • T1: Incidental finding, not palpable and not reliably found on imaging.
    • T2: Palpable, confined to prostate (a-c depending on lobes involved etc..)
    • T3: Tumor extends through prostate capsule
      • T3a - extracapsular extension
      • T3b - Invading seminal vesicles.
    • T4 - Invades adjacent structures.
       
    • N0 or N1 (spread to regional LN's or not
       
    • M (a-c non-regional LNs, bone etc..)

     

    • RiskProstateCa.png

    Treatment

    • "Definitive Treatment", is one of:
      • Radical Prostatectomy (RP)  - only if survival >10 years and disease localized to prostate
      • External Beam Radiation Therapy (EBRT)
      • Brachytherapy
         
    • For Extra-prostate disease:
      • Androgen Deprivation Therapy (ADT) + combinations of above
         
    • T1/T2 (localized, low or intermediate risk)  (Unchanged survival, 10% progression risk)
      • Active surveillance (can consider if low risk, or poor life extectancy)
        OR
      • Definitive Tx (RP, EBRT, Brachytherapy)  - all equal survival.
    • T3/T4 or HIGH RISK [us guidelines put high risk here, and not prev bullet point] (40-70% survival @10y)
      • EBRT+ADT (4-6mo)   [ or RP+adjuvant EBRT?]
    • N >0 or M >0
      • Hormone Therapy / Palliative XRT of mets, can consider combined androgen blockade.
      • Bilateral orchiectomy (90% testosterone removal)
      • GnRH agonists (Leuprolide [Lupron or Eligard], goserelin (Zoladex))
      • Estrogens (Diethylestrol - DES)
      • Antiandrogens [bicalutamide (Casodex)]
      • If hormone refractory:
        • Chemo: Docetaxel (or cabazitaxel or sipuleucel-T may improve survival)
           
    • NOTE: Rising PSA level post-definitive therapy --> start ADT!

    Lung Cancer

    Classification

    • Type Incidence Smoking? Location Histology Metastasis
      Adenocarcinoma M:35%, F40% Weak Peripheral Glandular, mucin producing Early, disant
      Squamous Cell Carcinoma 30% Strong Central Keratin, intercellular bridges Local invasion, distant spread, may cavitate
      SCLC 25% Strong Central Oat Cell, Neuroendocrine

      Disseminated @ presentation.

      Originates in endobronchial cells

      Large Cell Carcinoma 10-15% Strong Peripheral Anaplastic, undifferentiated Early, Distant

    Staging

    • SCLC Stages:
    • SCLC Stage Definition Treatment Survival
      Limited Stage

      Confirmed to single radiation port

      (i.e. one hemithorax and regional LNs)

      Radiation ± chemo

      (± prophylactic to brain)

      1-2 years 

      (12w w/o tx)

      Extensive Stage Extension beyond a single radiation port Chemo 6mo (5w w/o tx)

     

    • NSCLC Stages:
    •  
    • NSCLC Stage TNM Treatment 5 yr survival
      IA T1a-T1b N0M0

      Surgical resection

      +/- postop adjuvant chemo

      50-73%

      IB T2aN0M0 Chemo 43-58%
       
      IIA T1a-T2aN1M0 or T2bN0M0   36-46%
      IIB T2bN1M0 or T3N0M0   19-24%
      IIIA

      T1a-T2bN2M0 or T3N1-2M0

      or T4N0-1M0

        19-24%
      IIIB T4N2M0 or T1-4N3M0   7-9%
      IV T1-4N0-3M1a-1b   2-13%

     

    • T1a: ≤2cm
    • T1b: >2-3cm
    • T2a: >3-5cm
    • T2b: >5-7cm
    • T3: >7cm or carina, heart, great vessels, trachea, esophagus, spine.

     

    • N1: Ipsilateral (Hilar, and intrapulmonary nodes)
    • N2: Ipsilateral (Mediastinal, subcarinal)
    • N3: Contralateral

    Metastatic Workup

    • Stage I - Nothing
    • Stage II - III: PET, CT thorax/abdo/pelvis, MRI head (CT head if no MRI).
    • Stage IV: Same as II-III --> except no PET

     

    Treatment

    • Stage 1 & 2 --> Mainstay is surgery
      • Adjuvant Chemotherapy --> N1 & N2 (node positive), or big primary tumor with risk of recurrence (i.e. >= 4cm)
    • Stage III --> Combined concurrent Radiation (SABRT) + Chemotherapy (platinum-based w/ 
    • Stage IV --> Palliative chemotherapy

    Pancreatic Adenocarcinoma

    • 5year survival = 5%
    • One of the deadliest malignancies (no recent change in life expectancy).
    • Screening: NONE exists.
    • 80% of newly diagnosed have unresectable disease.
    • Risk Factors:
      • >50yo
      • Cigarette smoking
      • Chronic pancreatitis (20fold increase in risk)
      • Hereditary pancreatitis (mutation in cationic trypsinogen gene --> 40% pancreatic cancer) RARE.
    • Symptoms:
      • ***Painless jaundice*** if tumor is in pancreatic head
        • Typically painless jaundice >50yo = pancreatic or biliary malignancy.
      • B-sx: Anorexia, wt loss. 
      • 60% of pts have new or worsening glucose intolerance at time of dx.
      • Body and Tail of pancreas:
        • Back pain (effect on celiac ganglia)
      • Patients >50yo with idiopathic pancreatitis need CT! (R/O malignancy)
    • Signs:
      • Trousseau Sign of Malignancy (migratory thrombophlebitis)
      • Courvoisier Sign (palpable gallbladder from compression of the distal bile duct)
    • Staging:
    1. **Contrast-Enhanced Multiplanar CT** 90% Sn
    • Small lesions <2cm cannot be seen.
    • Assess vascular invasion, metastatic spread.
    • If no metastatic disease on CT, go onto EUS.
    1. Endoscopic US (EUS):
    • Only do if no mets on CT
    • More sensitive than CT (esp if <2cm tumors)
    • Can biopsy
    • DO NOT do EUS biopsy if resectable disease, can seed needle tract.  Indication for direct surgical resection.

     

    • Diagnosis:
      • Biopsy** --> Surgical if resectable, EUS if not resectable.
      • Ca19-9: Help support diagnosis, but not sensitive or specific enough to reliable diagnose.
    • Metastasis: (Hematogenous)
      • Portal and splenic veins.
      • Vascular involvement of Superior Mesenteric Artery or Celiac axis
      • Liver (Portal vein)
      • Lung
      • Peritoneal
    • Prognosis:
    • Stage

      Findings

      Treatment

      Prognosis

      Localized disease

      No vascular involvement of the celiac axis or SMA; no extrapancreatic metastases

      Surgical resection combined with neoadjuvant or adjuvant chemoradiotherapy

      20% survival at 5 years

      Locally advanced disease

      Vascular invasion of the celiac axis or SMA; occlusion of the portal/SMV; no extrapancreatic metastases

      Neoadjuvant chemoradiotherapy, with restaging thereafter

      10 months

      Metastatic disease

      Extrapancreatic metastases

      Palliative chemotherapy

      6 months

      NEW: 12mo FOLFIRINOX

      SMA = superior mesenteric artery; SMV = superior mesenteric vein.

     

    • Management
      • Surgery --> only curative intervention for resectable tumors and no metastasis.
        • Cure rate is low even if resectable disease.
        • Post-op care is controversial (Older trials used adjuvant chemo+rads, but had methodologic flaws)
          • Recent trial of post-op gemcitabine vs. observation = slight benefit of gemcitabine.
          • Controversial.
      • If involves critical vessels (SMA, Celiac trunk) --> Combined chemo + radiation
        • (sometimes can convert to resectable disease)
      • Metastatic Disease:
        • FOLFIRINOX is standard
        • Gemcitabine (6mo alone)  with Abraxane (9mo combination)
          • Combining with cisplatin or oxaliplatin increases response rate, but toxic and survival not yet shown.
        • Later trial: 12mo survival:
          • 5-FU, leucovorin, irinotecan, oxaliplatin (FOLFIRINOX) vs. gemcitabine (showed survival benefit 10.5mo vs. 6.9mo for FOLFIRINOX arm, but greater toxicity.  Population was extremely fit patients with excellent performance status.
        • Cetuximab and bevacizumab in phase III trial FAILED to improve survival.

    Bladder Cancer

    • Most "urothelial" or transitional cell in origin
    • Risk Factors:
      • Men > 60
      • Cigarette Smoking (proportional to pack years)
      • Metal, painters, leather
      • "Field cancerization effect" - Other transitional cells are at higher risk of cancer - such as renal pelvis
    • Symptoms:
      • Painless hematuria (gross bleeding = more likely malignancy)
    • Workup:
      • Look at ALL components of urinary tract
      • CT scan, MRI or IVP (intravenous pyelography)
      • Urine for cytology
      • Cystoscopy:
        • Urine for cytology (some urologists prefer only cystoscopy washings)
        • While cystoscopy --> can resect (TURBT - transurethral bladder resection of tumor)
        • Biopsy other normal-looking areas to rule out field cancerization effect
        • If malignant cells found on urine cytology - must biopsy prostatic urethra, bladder, ureters.
    • Staging:
      • Stage Notes
        Stage 1

        - T1 tumors

        - Invade submucosa (not muscle)

        Stage 2

        - T2

        - Muscle invasion, no regional LN involved

        Stage 3

        - T3-4

        - Locally advanced

        Stage 4 - LN involvement + distant metastasis
      • TNM staging basics:
        Stage Notes
        Ta

        - 60 % of presentations

        - Low grade papillary tumor

        Tis

        - Carcinoma in situ

        - Greatest risk of muscle invasion

        T1 - Invade submucosa
        T2 - Invade muscular wall
    • Treatment:
      • Stage 1 - TURBT (Trans-urethral resection of bladder tumor)
        • Risk of recurrence = number of tumors found, histologic grade, invasion.
        • HIGH risk of recurrence
          • Treat with "intravesicular agent" such as BCG Agent (Bacillus Calmette-Guerin)
            • (reduces recurrence, muscle invasion, need for cystectomy, improves survival)
            • 6-week induction + maintenance therapy x1 year
        • LOW risk of recurrence
          • Observation OR single dose intravesicular mitomycin or gemcitabine
        • Follow for recurrence: cystoscopy q3mo x2y, then q6mo x2y, then yearly
          • If recur --> intravesicular agent.
      • Stage 2  (T2-T4 - muscle invasion)
        • Radical cystectomy (bladder, adjacent pelvic organs, reginal LNs)
          • + non-continent cutaneous urinary diversion.
        • (Can consider patial cystectomy, "bladder-sparing" with chemo/rads sometimes)
        • 75-85% cure rate with cystectomy (20-55% with locally advanced) and 10-20% if LN's
        • Pre-op cisplatin-based chemotherapy (meta-analysis neoadjuvant chemo = 5% survival benefit)
      • Stage III and Stage IV
        • Adjuvant chemotherapy
      • Metastatic disease
        • Survival 8-12mo
        • Palliative platinum-based chemo; response 30-70%
    • Prognosis:
      • Anatomic (S) stage

     

    Anal Cancer

    • Typically squamous cell carcinoma.
    • Risk Factors:
      • HIV, HPV..etc
    • Usually removal of organ not advisable (permanent colostomy needed).
    • Typically do chemo + rads --> majority do not need surgery.
    • Chemo:
      • Mitomycin (not used in any other disease)
        +
      • 5-FU
    • Rads
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