Premature Exemplification: Two New Trials on Prostate Cancer Screening Anthony Fotenos St. John’s Department of Medicine, St. Louis, MO March 30, 2009

Dad regarding screening-based prostatectomy: “Was it all a fraud?” Chance of death from prostate cancer (median age 80): 3% Chance of prostate cancer diagnosis: 17% Chance of prostate cancer at autopsy, age > 60: 30-80% Chance of having had a PSA test, age 50-79: 70-75% Chance of positive PSA (>4) diagnosing cancer (PPV): 30% 249 Autopsies (%) Age Autopsy detected Clinically detected Prostate Cancer Epidemiology Screening for Prostate Cancer. UpToDate 17.1

Chance of death from prostate cancer (median age 80): 3%

Chance of prostate cancer diagnosis: 17%

Chance of prostate cancer at autopsy, age > 60: 30-80%

Chance of having had a PSA test, age 50-79: 70-75%

Chance of positive PSA (>4) diagnosing cancer (PPV): 30%

NEJM 3/26/2009: PLCO (Prostate, Lung, Colorectal, and Ovarian) and ERSPC (European Randomized Study of Screening for Prostate Cancer) trials Screening and prostate-cancer mortality in a randomized European study. NEJM 2009;260:;1320-8. PLCO 76,693 55-74 PLCO, >1 PSA/3yrs 7-10 (13 planned) 5-6 PSAx6, DREx4 4 85 ? (>52%) 94-174 (0.12-0.22%) ERSPC 162,243 55-69 Prostate CA 9 (mean) ? PSAx1.7 Variable (2.5-10) 82 ? (~20%) 540 (0.33%) N Age (yrs) Exclusion Criteria Follow-up (yrs) Cancer follow-up (yrs) Screening PSA cutoff Compliance (%) Controls with PSA testing Deaths from Prostate CA Mortality results from a randomized prostate-cancer screening trial. NEJM 2009;360:1310-9.

Increased detection of prostate cancer with screening PLCO: 7.3 vs 6% Gleason 8+: 289 vs 341 ERSPC: 8.2 vs 4.8% Gleason 7+: 27.8 vs 45.2% Years Cases of Prostate Cancer

ERSPC supports reduced prostate-cancer mortality with screening PLCO Rate Ratio: 0.75-1.70 (But < 1, baseline PSA vs. never) ERSPC Rate Ratio: 0.65-0.98 Per 1000: 34 more diagnosed, 0.71 saved from prostate CA (NNS 1410, NNT 48) Years Years Mortality

Conclusion: more questions than answers If PSA lead-time at least 5 yrs, why trial follow-ups so short? Why report now? How does risk of biopsy increase with screening? How prevent the earliest prostate cancer deaths in screening group? What is optimal risk-benefit? Of 100 men, 17 will be diagnosed with prostate CA 8, if not screened, would never know (= overdiagnosis) 6 will die of something else 3 will die of prostate CA 2 will still die of prostate CA with screening 0-1 will die of something else as a result of screening Philosophy 1: Why screen if no difference in all-cause mortality? Philosophy 2: Conversely, why expect diagnostic to cure? Would you want to know about a cancer even though large, 10-yr trials show that screening currently has no effect on your lifespan?

If PSA lead-time at least 5 yrs, why trial follow-ups so short? Why report now?

How does risk of biopsy increase with screening?

How prevent the earliest prostate cancer deaths in screening group?

What is optimal risk-benefit? Of 100 men,

17 will be diagnosed with prostate CA

8, if not screened, would never know (= overdiagnosis)

6 will die of something else

3 will die of prostate CA

2 will still die of prostate CA with screening

0-1 will die of something else as a result of screening

Philosophy 1: Why screen if no difference in all-cause mortality?

Philosophy 2: Conversely, why expect diagnostic to cure?

Would you want to know about a cancer even though large, 10-yr trials show that screening currently has no effect on your lifespan?

What is the gain in life expectancy from vaccinating infants against Hep B? Life expectancy quiz

What is the gain in life expectancy from vaccinating infants against Hep B?

What is the gain in life expectancy from vaccinating infants against Hep B? 8 days Life expectancy quiz

What is the gain in life expectancy from vaccinating infants against Hep B?

8 days

What is the gain in life expectancy from vaccinating infants against Hep B? 8 days From annual pap smears? Life expectancy quiz

What is the gain in life expectancy from vaccinating infants against Hep B?

8 days

From annual pap smears?

What is the gain in life expectancy from vaccinating infants against Hep B? 8 days From annual pap smears? 3 months Life expectancy quiz

What is the gain in life expectancy from vaccinating infants against Hep B?

8 days

From annual pap smears?

3 months

What is the gain in life expectancy from vaccinating infants against Hep B? 8 days From annual pap smears? 3 months From regular exercise? Life expectancy quiz

What is the gain in life expectancy from vaccinating infants against Hep B?

8 days

From annual pap smears?

3 months

From regular exercise?

What is the gain in life expectancy from vaccinating infants against Hep B? 8 days From annual pap smears? 3 months From regular exercise? 6 months Life expectancy quiz

What is the gain in life expectancy from vaccinating infants against Hep B?

8 days

From annual pap smears?

3 months

From regular exercise?

6 months

What is the gain in life expectancy from vaccinating infants against Hep B? 8 days From annual pap smears? 3 months From regular exercise? 6 months From quitting smoking at age 35? Life expectancy quiz

What is the gain in life expectancy from vaccinating infants against Hep B?

8 days

From annual pap smears?

3 months

From regular exercise?

6 months

From quitting smoking at age 35?

What is the gain in life expectancy from vaccinating infants against Hep B? 8 days From annual pap smears? 3 months From regular exercise? 6 months From quitting smoking at age 35? 9 months Life expectancy quiz

What is the gain in life expectancy from vaccinating infants against Hep B?

8 days

From annual pap smears?

3 months

From regular exercise?

6 months

From quitting smoking at age 35?

9 months

What is the gain in life expectancy from vaccinating infants against Hep B? 8 days From annual pap smears? 3 months From regular exercise? 6 months From quitting smoking at age 35? 9 months From quitting, if you have multiple cardiovascular risk factors? Life expectancy quiz

What is the gain in life expectancy from vaccinating infants against Hep B?

8 days

From annual pap smears?

3 months

From regular exercise?

6 months

From quitting smoking at age 35?

9 months

From quitting, if you have multiple cardiovascular risk factors?

What is the gain in life expectancy from vaccinating infants against Hep B? 8 days From annual pap smears? 3 months From regular exercise? 6 months From quitting smoking at age 35? 9 months From quitting, if you have multiple cardiovascular risk factors? 2.5 – 6 years Life expectancy quiz

What is the gain in life expectancy from vaccinating infants against Hep B?

8 days

From annual pap smears?

3 months

From regular exercise?

6 months

From quitting smoking at age 35?

9 months

From quitting, if you have multiple cardiovascular risk factors?

2.5 – 6 years

What is the gain in life expectancy from vaccinating infants against Hep B? 8 days From annual pap smears? 3 months From regular exercise? 6 months From quitting smoking at age 35? 9 months From quitting, if you have multiple cardiovascular risk factors? 2.5 – 6 years From routine post-MI beta blockers? Life expectancy quiz

What is the gain in life expectancy from vaccinating infants against Hep B?

8 days

From annual pap smears?

3 months

From regular exercise?

6 months

From quitting smoking at age 35?

9 months

From quitting, if you have multiple cardiovascular risk factors?

2.5 – 6 years

From routine post-MI beta blockers?

What is the gain in life expectancy from vaccinating infants against Hep B? 8 days From annual pap smears? 3 months From regular exercise? 6 months From quitting smoking at age 35? 9 months From quitting, if you have multiple cardiovascular risk factors? 2.5 – 6 years From routine post-MI beta blockers? 1-6 months Life expectancy quiz

What is the gain in life expectancy from vaccinating infants against Hep B?

8 days

From annual pap smears?

3 months

From regular exercise?

6 months

From quitting smoking at age 35?

9 months

From quitting, if you have multiple cardiovascular risk factors?

2.5 – 6 years

From routine post-MI beta blockers?

1-6 months

What is the gain in life expectancy from vaccinating infants against Hep B? 8 days From annual pap smears? 3 months From regular exercise? 6 months From quitting smoking at age 35? 9 months From quitting, if you have multiple cardiovascular risk factors? 2.5 – 6 years From routine post-MI beta blockers? 1-6 months From chemotherapy for men with testicular cancer? Life expectancy quiz

What is the gain in life expectancy from vaccinating infants against Hep B?

8 days

From annual pap smears?

3 months

From regular exercise?

6 months

From quitting smoking at age 35?

9 months

From quitting, if you have multiple cardiovascular risk factors?

2.5 – 6 years

From routine post-MI beta blockers?

1-6 months

From chemotherapy for men with testicular cancer?

What is the gain in life expectancy from vaccinating infants against Hep B? 8 days From annual pap smears? 3 months From regular exercise? 6 months From quitting smoking at age 35? 9 months From quitting, if you have multiple cardiovascular risk factors? 2.5 – 6 years From routine post-MI beta blockers? 1-6 months From chemotherapy for men with testicular cancer? 9 years Life expectancy quiz

What is the gain in life expectancy from vaccinating infants against Hep B?

8 days

From annual pap smears?

3 months

From regular exercise?

6 months

From quitting smoking at age 35?

9 months

From quitting, if you have multiple cardiovascular risk factors?

2.5 – 6 years

From routine post-MI beta blockers?

1-6 months

From chemotherapy for men with testicular cancer?

9 years

What is the gain in life expectancy from vaccinating infants against Hep B? 8 days From annual pap smears? 3 months From regular exercise? 6 months From quitting smoking at age 35? 9 months From quitting, if you have multiple cardiovascular risk factors? 2.5 – 6 years From routine post-MI beta blockers? 1-6 months From chemotherapy for men with testicular cancer? 9 years How much does a Snickers bar cost? A Camry? Life expectancy quiz

What is the gain in life expectancy from vaccinating infants against Hep B?

8 days

From annual pap smears?

3 months

From regular exercise?

6 months

From quitting smoking at age 35?

9 months

From quitting, if you have multiple cardiovascular risk factors?

2.5 – 6 years

From routine post-MI beta blockers?

1-6 months

From chemotherapy for men with testicular cancer?

9 years

How much does a Snickers bar cost? A Camry?

What is the gain in life expectancy from vaccinating infants against Hep B? 8 days From annual pap smears? 3 months From regular exercise? 6 months From quitting smoking at age 35? 9 months From quitting, if you have multiple cardiovascular risk factors? 2.5 – 6 years From routine post-MI beta blockers? 1-6 months From chemotherapy for men with testicular cancer? 9 years How much does a Snickers bar cost? A Camry? $1 and $20,000 Life expectancy quiz

What is the gain in life expectancy from vaccinating infants against Hep B?

8 days

From annual pap smears?

3 months

From regular exercise?

6 months

From quitting smoking at age 35?

9 months

From quitting, if you have multiple cardiovascular risk factors?

2.5 – 6 years

From routine post-MI beta blockers?

1-6 months

From chemotherapy for men with testicular cancer?

9 years

How much does a Snickers bar cost? A Camry?

$1 and $20,000

Medical interventions in perspective Gains in life expectancy from medical interventions – standardizing data on outcomes. NEJM 1998;339:380-6. Summary Interventions Gains in Life Expectancy (mos) Years from Randomization Trials with survival curves Probability of Survival

Life Expectancy Quiz Year Life Expectancy DHS National Vital Statistics Reports, vol 54., no. 19, June 28, 200 7 years gain 1960-2000 ~3.5 attributable to medicine United States life expectancy 1840-2006 The value of medical spending in the United States, 1960-2000. NEJM 2006;335:920-7.