Prostate Cancer Screening: Con - Dr. Petrylak

Report
Prostate Cancer
Screening: Con
Daniel P. Petrylak, MD
Yale University Cancer Center
Prostate Cancer “Screening” Trials

Norrköping
Deviations /
limitations
In statistical
methods

Quebec Study (RCT) – 1998

Swedish Study (RCT) – 2004

Tyrol Study – Population comparison (+ screen effect)

PLCO

ERSP

Göteborg
Thought to be well designed RCT
with appropriate controls and
respected steering committees,
reported from 2009-2012
• CAP and ProtecT (UK) are ongoing
Three Largest Randomized PSA
Screening Trials
 ERSPC
– PSA every 4 yrs in 182,000 men
 PLCO
– USA trial testing PSA every yr vs. no PSA
screening in 76,693 men analyzed in ITT analysis
 Göteborg
– Randomized 20,000 man screening trial showed
44% reduction in death with little press
– ERSPC subset
ERSPC = European Randomized Study of Screening for Prostate Cancer;
PLCO = prostate, lung, colorectal, ovarian; ITT = intent-to-treat.
Schroder et al, 2009; Andriole et al, 2009. Hugosson J, 2010
Two Conflicting Studies:
Originally Published Together
PLCO: No reduction in PCa mortality (76,000 USA)
– Large number pre-screened = contaminated control group
– Limited follow up w/ single cut point for PSA
– 85% of the screened group had a PSA but 52% of the nonscreened group had a PSA
ERSPC: 20% reduction in mortality (182,000 EU)
25% reduction in metastatic disease
– No DRE, multiple countries with variable criteria
– 41% reduced metastasis, more cancers, lower Gleason
– Screen 1410, treat 48 to benefit 1 death
PLCO: Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial
ERSPC: European Randomized Study of Screening for Prostate Cancer
Andriole G, et al. N Engl J Med. 2009;360:1310-1319. Schröder F, et al. N Engl J Med. 2009;360:13201328.
ERSPC: Cumulative Risk of Death
From Prostate Cancer
 ERSPC demonstrates 20% reduction in prostate cancer death after
8.8 yrs of follow-up. The adjusted rate ratio for death from prostate
cancer in the screening group was 0.8 (95% CI, 0.65–0.98; p = .04).
CI = confidence interval.
Schroder et al, 2009.
PLCO: Number of Prostate Cancers
and Prostate Cancer Deaths
PLCO trial
suggested that
PSA screening
increases risk
of cancer
diagnosis but
does not
decrease risk
of death
Andriole et al, 2009.
Pick level 1 evidence to make any point
No
PLCO: No reduction in prostate cancer mortality
Yes
ERSPC: 20% reduction in mortality
25% reduction in metastatic disease
Yes
Göteborg Trial: 44% reduction in mortality
Andriole G, et al. N Engl J Med. 2009;360:1310-1319.
Schröder F, et al. N Engl J Med. 2009;360:1320-1328.
PLCO
reanalysis:
improved PCSM
when
comorbidities
were considered.
(22 v 38 deaths)
Crawford, D
JCO 2010
PLCO: no benefit for entire group
–“contaminated” control arm
–~ 55% RRR for post-hoc defined
subgroup.
ERSPC: 20% RRR; 25% reduction in
metastatic disease
– reduces if Goteborg or Rotterdam
participants removed
–improvements continue with time in
NNS, NNT
Principles of Screening
•
Finding disease is not a measure of
success in screening
Increased survival is not a legitimate
measure of success outside of a
randomized clinical trial
Reduction of mortality in a randomized trial
is the only true proof of effective screening
Cancer Screening
•
Well designed clinical studies have demonstrated the
utility of:
•
•
•
Mammography and CBE for Breast Cancer
Stool Blood Testing, Sigmoidoscopy and
Colonoscopy for Colorectal Cancer
Pap and HPV testing for Cervical Cancer
Thoughts
•
•
•
•
Screening doesn’t work for all cancers: Lung,
neuroblastoma, and not all breast cancers
Need to separate diagnosis from treatment,
clearly over treating men
But, need to remember that 28,000 men
died in 2011 of CaP
We need to figure out who needs to be
diagnosed and effectively treated.
USPSTF Prostate Cancer History
•
•
•
2002: insufficient evidence to recommend for or against
routine screening
2008: against testing any man over age 75 years and
gives “I” rating for prostate-cancer screening, (current
evidence is insufficient to assess the balance of benefits
and harms, for men younger than 75.
2011: no healthy man undergo PSA screening unless
symptoms of prostate cancer
•
Open to public comment until 11/8/2011 (NEW since 2009
mammography controversy)
Urology USPSTF Replies
•
•
Marberger EAU: "Clearly mortality is reduced by PSA screening, but it has to
be done in younger and fit patients who have a life expectancy for whom this
slow growing cancer can really be a threat,”
Lacy AUA: "We are concerned that the task force's recommendations will
ultimately do more harm than good to the many men at risk for prostate
cancer, both here in the US and around the world.“
"Until there is a better widespread test for this potentially devastating disease,
the USPSTF -- by disparaging the test -- is doing a great disservice to the
men worldwide who may benefit from the PSA test."
Concern #1: Everybody Has Prostate
Cancer—You Die with It Not of It
Look at the prevalence of prostate cancer!
PIN=prostatic intraepithelial neoplasia
Sakr WA, et al. J Urol. 1993;150:379-385.
Concern #2: You Don’t Help Most Men
with Prostate Cancer When You Find It
Death from prostate cancer
Patient D
Patient C
Metastatic disease develops
Cancer spreads to lymph nodes
Zone of detection
when cure is possible
Cancer spreads beyond prostate
Patient B
Cancer detectable: PSA >4 ng/mL
Patient A
Prostate cancer develops
Annual PSA and DRE
Concern #2: You Don’t Help Most Men
with Prostate Cancer When You Find It
(cont’d)
Death from prostate cancer
Metastatic disease develops
Only this man
benefits
Cancer spreads to lymph nodes
Patient C
Zone of detection
when cure is possible
Cancer spreads beyond prostate
Cancer detectable: PSA >4 ng/mL
Prostate cancer develops
Annual PSA and DRE
Concern #2: You Don’t Help Most Men
with Prostate Cancer When You Find It
(cont’d)
Death from prostate cancer
Patient D
Metastatic disease develops
Cancer spreads to lymph nodes
These three guys
do not benefit
Zone of detection
when cure is possible
Cancer spreads beyond prostate
Patient B
Cancer detectable: PSA >4 ng/mL
Patient A
Prostate cancer develops
Annual PSA and DRE
Concern #3: It Costs Too
Much!
Cost
• Initial estimates of screening men age 50–70 for
prostate cancer
• $25 billion during first year alone
• Many countries don’t encourage it, fearing
screening will “break the bank” (eg, England,
Australia…)
Expenditures
• Prostate- 8 billion 11.2%
• Lung- 9.6 billion 13.3%
• Breast 8.1 billion 11.2&
Concern #4: High Risk
of Morbidity of Screening
• Risks of screening: anxiety
• Risks of biopsy: bleeding, infection, painful
• Risks of treatment: impotence,
incontinence, death, proctitis, cystitis,
stricture
• Risk of recurrence: as many as 1/3 of men
will require a secondary treatment
And the Final Concern: No Proof that It
Really Works in Reducing Deaths
•
•
•
•
Screening evaluated in
two trials
Prostate, lung, colorectal, ovarian (PLCO) screening
study in the US (148,000 men and women
randomized to screening or community standard of
follow-up)
Europe: Rotterdam screening trial
Results of both: PLCO –Negative. ERSPC-? positive
Conclusions
•
•
•
A more rational policy is to screen
appropriate men and treat only those with
significant PCa.
The USPHSTF findings should be viewed
as an opportunity to implement the above
Policy makers must consider risks and
benefits to the USPHSTF
recommendations on prostate cancer
screening.

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