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PowerPoint Presentation - UCSF at SFGH

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					   Cancer Screening:
What Interns Need To Know
  in 45 minutes or less!

             April, 2007

            Mike Potter, MD
    Family and Community Medicine
   Incidence and Burden of Cancer in the US
   Principles of Screening
   Current Recommendations
    •   Cervical Cancer
    •   Colorectal Cancer
    •   Breast Cancer
    •   Prostate Cancer
    •   Lung Cancer
   Cases and Controversies
   Emerging Technologies
Burden of Cancer in U.S., 2006
         (source: ACS Cancer Facts and Figures, 2006)

   1.4 million cancers diagnosed
   560,000 cancer deaths

   23% of deaths in the US

   $189 billion
    • $64 billion in medical costs
    • $16 billion in lost productivity
    • $109 billion in premature death
  2006 Estimated US Cancer
 Prostate                       33%          Men               Women      31%Breast
                                            720,280            679,510    12%Lung & bronchus
 Lung & bronchus                13%
 Colon & rectum                 10%                                       11%Colon & rectum

 Urinary bladder                 6%                                       6%     Uterus

 Melanoma of skin                5%                                       4%     Non-Hodgkin
 Non-Hodgkin                    lymphoma
                                  4%                                      4%     Melanoma
                                                                                   of skin
 Kidney                          3%
                                                                          3%     Thyroid
 Oral Cavity                     3%
                                                                          3%     Ovary
 Leukemia                        3%
                                                                          2%     Urinary Bladder
 Pancreas                        2%
                                                                          2%     Pancreas
 All Other Sites                18%
                                                                          22% All Other Sites

*Excludes basal and squamous cell skin cancers and in situ carcinomas except urinary bladder.
Source: American Cancer Society, 2006.
   2006 Estimated US Cancer
Lung & bronchus                31%                                        26%Lung & bronchus
                                              Men              Women
Colon & rectum                 10%           291,270           273,560    15%Breast
Prostate                        9%                                        10%Colon & rectum
Pancreas                        6%                                        6%      Ovary
Leukemia                        4%                                        6%      Pancreas
Esophagus                       4%                                        4%      Leukemia
Liver/intrahepatic              4%                                        3%      Non-Hodgkin
     bile duct                                                                         lymphoma
Non-Hodgkin            3%      Lymphoma                                   3% Uterus
Urinary bladder                 3%                                        2%      Multiple myeloma
Kidney                          3%                                        2%      Brain
All other sites                23%                                        23%All other sites

ONS=Other nervous system.
*Excludes basal and squamous cell skin cancers and in situ carcinomas except urinary bladder.
Source: American Cancer Society, 2006.
Cancer Death Rates*, for Men,
            Rate Per 100,000



                                                            Colon & rectum


                            Leukemia                                         Liver














*Age-adjusted to the 2000 US standard population.
Source: US Mortality Public Use Data Tapes 1960-2002, US Mortality Volumes 1930-1959,
National Center for Health Statistics, Centers for Disease Control and Prevention, 2005.
Cancer Death Rates*, for Women,
             Rate Per 100,000



 40          Uterus

                                                   Colon & rectum
 20                Stomach
















 *Age-adjusted to the 2000 US standard population.
 Source: US Mortality Public Use Data Tapes 1960-2002, US Mortality Volumes 1930-1959,
 National Center for Health Statistics, Centers for Disease Control and Prevention, 2005.
       When Is Screening Useful?
   When healthy lifestyle
    • Is not possible
    • Is not enough

   When early detection/treatment
    • Can save lives
    • Can prolong lives
    • Can improve lives
             What Makes a
          Good Screening Test?
   Easy
   Safe
   Accurate
    • Sensitive (few false negatives)
    • Specific (few false positives)
   Inexpensive
   Widely Available
Getting the Right Test, for the Right
     Person, at the Right Time

   Goal:
    • Minimize risks and maximize benefits

   Individual Risk varies according to:
    • Groups with high incidence and mortality
    • Age, Sex, Ethnicity
    • Environment, Lifestyle, Genetics
     Selecting Whom To Screen
   National guidelines are based on:
    • Population-based benefits of early detection
    • Values of Society

   Individual decisions you will make with
    patients are based on:
    • Individualized benefits
    • Values of the Patient
    • Shared, Informed Decision-Making
         Assessing the Evidence
   Guidelines (USPTF, ACS) help, but they
    not always in agreement with each other,
    and new data is always emerging.

   Study Design
    • Observational Studies
    • Case Control Studies
    • Randomized Controlled Trials

   Study Endpoints
    • 5 year Survival Rates vs. Mortality
          Cases #1, #2, #3, and #4:
          Who might need a Pap?
   A 17yo girl started having sex last year and she
    wants to know if she needs a Pap Test.

   A 30yo woman declines your offer for a Pap Test
    because she has sex only with women.

   A 48yo woman had a hysterectomy for fibroids
    last year asks for her annual Pap.

   A healthy 72yo woman has never had a Pap Test,
    and doesn’t want one now.
            Cervical Cancer
   Only 3,700 deaths predicted in 2006

   Caused by Human Papilloma Virus (HPV)
    • Persistent infections can cause dysplasia, and
      may develop into cancer over 10-15 years
    • HPV 16 and 18 account for 70% of cases.

   Modifiable Risks
    • Number of sex partners, Condoms, Smoking
      Cervical Cancer Screening
   Premise of Screening:
    • Treating dysplasia prevents cervical cancer
    • Cervical cancer curable when detected early

   Observational Data:
    • Incidence of cancer drops dramatically where
      screening and treatment is widespread.
    • 50%-70% of US deaths are in women with NO
      screening in the last 5 years
      Cervical Cancer Screening
   Pap Test
    • Developed over 50 years ago
    • Looks for abnormal cervical cytology
      associated with dysplasia and cervical cancer
    • Bethesda System (revised 2002), guides
      diagnosis, treatment, and follow-up
    • USPTF, ACS, ACOG agree about Pap Tests:
         Can prevent cancer
         Can detect cancer when curable
       Cervical Cancer Screening
   Start Screening:
    • 3 years after onset of sexual activity or
      by age 21, whichever comes first.

   Stop Screening:
    • At age 65 if 3 normal Pap Tests in the
      last 10 years and no other risks
    • After total hysterectomy for benign
         Cervical Cancer Screening
   Pap Test Every Year if
    •   Smoker
    •   Missed or Infrequent Pap Tests in past
    •   Prior abnormal Pap Tests
    •   New or multiple sex partners
    •   ACS and ACOG recommend for women <30

   Pap Test Every 3 Years if Lower Risk
    • Vast majority of invasive cases involve women
      with no Pap in the last 5 years
       Cervical Cancer Screening

   What about HPV testing?
    • Helps determine how to treat ASCUS
    • Controversial, but may also help to
      determine frequency of Pap Tests

   What about HPV Vaccines?
    • Vaccines are great, but they will not
      eliminate the need for Pap Tests any
      time soon!
     Case #5: What are the options for
      Colorectal Cancer Screening?

    A 51 year old woman comes to see you to
    establish care. Her brother’s doctor
    recently recommended that he have a
    colonoscopy, and she wants to know if she
    “has to have one done, too”.
           Colorectal Cancer
   #2 cause of cancer death in US
   Incidence increases after age 50
   Modifiable Risks
    • Smoking, obesity, diet and physical inactivity
   Other Risks
    • Family Hx, IBD, other genetic syndromes
   Chemoprevention
    • NSAIDS, calcium?, folate?, vitamin D?, others?
   Surgical Prevention
    • Total colectomy for adults at very highest risk
      Colorectal Cancer Screening
   Premise of Screening:
    • Prevent cancer by removal of adenomas
    • CRC often curable when detected early

   Observational Data:
    • Incidence and mortality decline since 1990’s

   RCT’s and Case Control Data:
    • Screening reduces CRC incidence
    • Screening reduces CRC mortality
         Colorectal Cancer Screening
   Begin Screening at age 50
    •   Yearly Home Fecal Occult Blood Testing, or
    •   Flexible Sigmoidoscopy Every 5 Years, or
    •   FOBT every year PLUS FS Every 5 years, or
    •   Barium Enema Every 5 Years, or
    •   Colonoscopy Every 10 Years

   ACS, AGA, and USPTF Agree:
    • Best test is one that gets done!
    Things to Remember about FOBT
   Negative In Office FOBT is NOT
    Reassuring – Don’t do it as a
    screening test!

   Must be done EVERY YEAR to achieve
    a 33% mortality reduction over 10
      Colorectal Cancer Screening

   CT Colonography (“Virtual Colonoscopy”)
    • Safer than colonoscopy
    • Requires similar prep to colonoscopy
    • Concern about false positives and costs

   DNA-Based Stool Tests
    • Looks for DNA from cancer in fecal material
    • Not very sensitive for polyps that you want to find early
    • Still many unanswered questions
     Colorectal Cancer Screening

   Early Screening
    • Family History of colorectal cancer or polyps
      in a parent or sibling before the age of 60.
    • Inflammatory Bowel Disease (IBD, Crohns)
    • Genetic Syndromes (FAP, HNPCC)
    • Women with history of ovarian or
      endometrial cancers

   What to Screen With
    • Usually colonoscopy
    Summary: Colorectal Cancer
     Prevention and Screening

   Identify high risk patients before age 50

   Offer options to average risk patients
    starting at age 50

   Stop screening when life expectancy is
    less than 10 years or in those who are
    unlikely to benefit from early detection

   Careful follow-up of abnormal results
               Case #6:
     Who should get a mammogram?

   A 43yo woman and her 77yo mother come
    to see you. They both want to know
    whether or not they need mammograms,
    and if so, how often.
             Breast Cancer
   #2 cause of cancer death in US women
   Incidence begins to increase after age 40
   Modifiable Risks:
    • Alcohol, obesity, HRT, possibly smoking
   Other Risks:
    • Genetics, dense breast tissue, delayed
   Surgical Prevention:
    • Prophylactic Mastectomy for women at highest
        Breast Cancer Screening
   Premise of Screening:
    • Early detection of reduces mortality.

   Observational data:
    • Since 1980:
        In situ cancer up > 150%

        Stage I cancer up > 60%

        Stage II-IV cancer down 10-15%

    • Since 1987:
        Mortality decreased by 15-20%
           Breast Cancer Screening
   Mammography
    • Introduced in 1960’s and 1970’s
    • Detects microcalcifications
    • False positives and false negatives common

   Mammography RCT’s
    • NCI: Mortality benefit
          17% reduction for women 40-49
          30% reduction for women 50-69
          Continued benefit for healthy women 70+
        Breast Cancer Screening
   The stakes for women 40-49
    • 20% of cases
    • 40% of years of life lost

   Limits of mammography for these women
    • More False Negatives (due to denser tissue)
    • More False Positives, requiring additional
      evaluation (PPV = 2-4% in 40’s)
          Breast Cancer Screening
   New Technologies
    • Digital Mammography – at SFGH
         15-28% more accurate for pre-menopausal
          women, or women with denser breasts
          (DMIST Study, 2005 -- 50,000 women)
    • MRI
         Many false positives
         Recommended for women who are very
          high risk – e.g. with a personal history of
          treated breast cancer to look for recurrences
        Breast Cancer Screening
   Clinician Breast Exam (CBE)
    • Mortality benefit is not well-established

   Self-Breast Exam (SBE)
    • 3 large studies -- no benefit (none in US)

   Why do Breast Exams?
    • Breast exams sometimes find cancers that will
      be missed by mammography
    • Lack of evidence doesn’t always prove lack of
      benefit for low cost interventions
        Breast Cancer Screening
   Whom to Screen Early
    • Parent or sibling diagnosed at young age
    • Multiple relatives with breast or ovarian cancer

   What to screen With
    • Mammography and Breast Exams
    • Genetic Counseling and Testing in some cases
         Summary: Breast Cancer
   Identify high risk patients early
   Start screening at age 40 for average risk
    • Informed decision-making for women 40-50 has a role
   Screen every 1-2 years
    • With Mammography
    • With CBE and/or SBE, though benefits uncertain
   Stop screening when life expectancy less
    than 5-10 years or in those unlikely to
    benefit from early detection
   Careful follow up of any abnormal results
    Case #7: What are the indications for
        prostate cancer screening?

   A 50 yo man just learned that his 72 year
    old father has prostate cancer. He asks
    you whether he needs screening for
    prostate cancer.
            Prostate Cancer
   #2 cause of cancer death in US men
   Incidence increases with:
    • Age
    • Family history
    • African American ancestry
   Modifiable risk factors:
    • Obesity?
   Chemoprevention:
    • Finasteride? Lycopenes? Statins? Vitamin D?
      Vitamin E?
      Prostate Cancer Screening
   Premise of Screening:
    • Early detection may improve long-term
      survival in healthy men
   Observational Data:
    • Detection increased dramatically with the
      introduction of screening
    • US mortality decreased 15-20% since 1991
    • Mortality drop in Britain without screening
   Case Control Data:
    • Conflicting results so far
   RCT’s
    • Results to come in 2009
      Prostate Cancer Screening
   Up to 90% of prostate cancers will never be life-
    threatening, and screening can lead to over-
    diagnosis, over-treatment and undesirable side

   Some men benefit from screening; some studies
    show a long-term survival advantage for healthy
    men who are treated vs. men who are not.

   Pro’s and Con’s should be discussed with the
    patient before ordering screening
       Prostate Cancer Screening
   When to Consider Screening?
    • Yearly testing at age 50
    • Consider in 40’s if African American or family
      history of aggressive prostate cancers at a
      young age
    • Potential benefits decline by age 75

   What to Screen With?
    • Annual Prostate Specific Antigen?
    • Annual Digital Rectal Examination?
       Prostate Cancer Screening
   Prostate Specific Antigen (PSA)
    • A substance made by prostate cells that is
      detected in the blood

    • Blood Levels Increase with
          Prostate Cancer
          Also Increases with Older Age, Prostate Infections,
           and Benign Prostatic Hypertrophy
       Prostate Cancer Screening
   PSA Uncertainties
    • Arbitrary cut point usually > 4.0 ng/ml
    • Many false positives and false negatives
    • Biopsy of men with PSA > 4.0 leads to the
      discovery of many non-aggressive cancers
    • Biopsy of men with PSA < 4.0 would also lead
      to discovery of many cancers, a few of which
      would probably turn out to be aggressive
       Prostate Cancer Screening
   PSA “refinements”
    • Age-specific cut points, such as
          3.0 for men in their 50’s
          4.0 for men in their 60’s
          5.0 for men in their 70’s
    • PSA velocity
          A change in PSA over time may be more useful than
           a single value
    • % Free PSA
          Low Free PSA (e.g. less than 20%) signifies higher
           risk of cancer on biopsy
          Higher Free PSA is reassuring
       Prostate Cancer Screening
   Digital Rectal Examination (DRE)
    • Can reach less than half of the prostate
    • DRE has limited reproducibility by different
    • Can detect some cancers that would not be
      found with PSA alone, but unknown how
      important those cancers are to find
    • Still frequently recommended and done in
      clinical practice
       Prostate Cancer Screening
   Treatments are improving, but still
    commonly cause

    • erectile dysfunction
    • urinary incontinence
    • proctitis or other bowel problems
    Summary: Prostate Cancer Screening

   Informed Decision Making
     • Describe potential risks and benefits of annual
       screening to average risk men after age 50
     • If increased risk, consider screening in 40’s
     • When to stop offering screening is
       controversial – depends on health of patient
     • Consider consequences abnormal tests
     • Listen to each patient’s concerns

   Careful follow-up of abnormal tests
                Case #8:
     Is Lung Cancer Screening Useful?

   A 52 yo smoker has heard that CT scans
    can help detect lung cancer early, and
    asks you how he can get one.
                 Lung Cancer
   173,000 cases/163,000 deaths in 2006

   More deaths than colorectal, breast, and
    prostate cancer combined

   Major Risk Factors:
    •   Smoking! Smoking! Smoking!
    •   Second Hand Smoke!
    •   Occupational exposures (asbestos, radon, etc.)
    •   Genetic factors under exploration
         Lung Cancer Screening
   Premise of Screening:
    • In smokers, ex-smokers, or other individuals
      at increased risk for lung cancer, detection and
      treatment of localized cancers could save lives

   Observational Data
    • Left untreated, stage 1 disease is believed to
      be fatal most of the time
    • Surgery on stage 1 lung cancer may cure 50%
            Lung Cancer Screening
   Low Dose CT Scans (LDCT)
    • Detects more lesions than Chest Xray
    • False positives are a concern
    • Recent observational study: 88% 10-year
      survival for stage 1 patients identified by LDCT
      and treated for lung cancer
          Potential Lead Time and Length Time Biases!
    • Large RCT of 50,000 smokers randomized to
      LDCT vs. CXR to be completed in 2009
    • Can’t be recommended yet.
                  Case #9:
                 What Next?
   A healthy 50 year old woman receives a
    birthday gift certificate for a Total Body CT
    Scan from her cousin who runs a company
    that promotes this service. Should she
    get the test?
          Total Body CT Scans
   Can they detect important disease early?
   Will early diagnosis improve outcomes?
   Do benefits of early diagnosis outweigh
    the risk of harms from false positive
   WE DON’T KNOW!!!
    Public Enthusiasm for Screening
          (Schwartz LM, et al. JAMA 2004;291:71-78)

   National survey of 500 adults in 2001-2.

    • 74% believed that finding cancer early saves
      lives most or all of the time.
    • 2/3 would be screened even if nothing could
      be done.
    • 73% “would rather have a Total Body CT Scan
      than receive $1000 in cash.”
   Cervical Cancer (ACS, ACOG, USPTF)
    • Pap within 3 years of first sexual activity or at
      age 21 and stop at 65 in low risk women
    • Stop after hysterectomy for benign disease
    • Frequency of 1-3 years according to risk
    • Evolving role of HPV testing

   Colorectal Cancer (ACS, AGA, USPTF):
    • Menu of options beginning at age 50
    • No single approach proven superior
    • Best test is the one that gets done
   Breast Cancer (ACS, ACOG, USPTF)
    • Mammogram 40+ every one to two years
    • CBE and SBE still controversial
    • IDM for women in their 40’s has a role

   Prostate Cancer (ACS, USPTF)
    • Annual PSA and DRE still controversial
    • Answers coming soon
    • IDM for men over 50
   Lung Cancer (ACS, ALA, USPTF)
    • Answers coming soon on LDCT for smokers
    • Smoking cessation!
    • Smoking prevention!

   Total Body CT…
    • Only proven beneficial on Star Trek!
           What I tell patients
   Live a healthy lifestyle
   Don’t smoke
   Learn your family history and share it with
    me regularly
   Ask me about screening
   Get the results
   Make sure you know what to do next
      Essentials for your practice
   Select tests that work.
   Select patients that can benefit.
   Discuss benefits and risks.
   Develop systems to help patients follow
    through with testing.
   Develop systems to track abnormal tests
    and assure proper treatment.