RAMB - AGOSTO 2017

PSA

screening

for

prostate

cancer

ssoc

ras

2017; 63(8):722-725

723

By not fulfilling all these criteria, the screening of pros-

tate cancer with PSA is a controversial topic. One part of

the controversy is due to the confusion between population

screening and early diagnosis, another derives from prob-

lems related to the quality of existing studies, the results

of radical curative treatment and the complications arising

from these treatments that affect patient quality of life,

such as urinary incontinence and erectile dysfunction.

There are five studies on population screening of

prostate cancer. Two of them, which are now old, were

performed in Quebec in Canada and Norrköping in Swe-

den and presented discordant results.

6,7

A review by the

Cochrane Library concluded that these two studies had

enormous methodological limitations, preventing any

appropriate conclusions.

Three other more recent stud-

ies presented a better level of evidence.

9-11

The European Prostate Cancer Screening Trial (ERSPC)

randomized a population of 162,243 men between 55

and 69 years for PSA screening (n = 81,816) or control

without PSA (n = 99,184). Several centers participated in

the study, but the protocol was not the same across all

centers. Most of them used a PSA value ≥ 3.0 ng/mL to

indicate prostate biopsy. The PSA level was performed,

on average, only every four years. After monitoring for

11 years, screening reduced the risk of metastases by 41%

and the chance of death from prostate cancer by 21%

(p=0.04). Given the total number of patients submitted

to biopsy, 76% had benign tissue, demonstrating a high

index of false-positive results. Of the 781 patients that

needed to be screened, 27 were diagnosed and treated to

prevent tumor-related death.

9,10

The American Prostate Cancer Screening Trial

(PLCO) study randomized 76,693 men aged 55 to 74 years

for annual screening with PSA and rectal exam (n =

38,343) or control group with the “usual urological care,”

that is, at the discretion of the urologist (n = 38,350). The

PSA value used to indicate biopsy was ≥ 4.0 ng/mL. After

seven years of monitoring, mortality was similar between

the two groups (p, non-significant).

The problem in this

study was the control group. Since “usual care” in the

USA includes PSA, in this case almost half of the patients

in the control group did the test compared to the ran-

domized group. Therefore, it was to be expected that

there would be no difference between groups. At the time

of publication, this study was interpreted as being a

comparative analysis between two types of PSA screening,

one more intense than the other. However, a recent re-

analysis of the data showed that in fact more than 85%

of the men in the control group had also undergone PSA

testing (and not about 40%, as originally described), which

explains more clearly the reason why the result of the

study was negative.

In a study conducted in Gothemburg, in Sweden,

20,000 men were randomized 1:1 for PSA screening every

two years or control without PSA. Their age ranged from

50 to 64 years (median = 56 years). The PSA value used to

indicate the biopsy was between 3.0 and 4.0 ng/mL. After

a 14-year follow-up, there was a relative decrease in pros-

tate cancer mortality of 44%. Prostate cancer was diag-

nosed in 12.7% of the patients in the screening group and

in 8.2% of those in the control group. In this study, 293

cases needed to be screened and 12 treated for prostate

cancer to prevent one tumor-related death.

These figures

are similar to those for breast cancer screening.

However, at the end of 2011 the United States Preven-

tive Services Task Force (USPSTF) issued a report oppos-

ing the use of PSA in screening for prostate cancer giving

equal weight for all studies. This recommendation has

received a “D” grade recommendation, meaning that, in

the committee’s view, existing scientific data demonstrate

that there is more harm than good with the use of this

test.

The reasons for this recommendation were diverse.

A major problem for prostate cancer screening with

PSA is tumor hyper-detection or over-diagnosis, character-

ized by excessive diagnosis of clinically insignificant tumors.

In fact, in the ERSPC study the finding of low risk tumors

(PSA < 10 ng/mL and Gleason score ≤ 6) was almost three

times higher in the screened group than the control group.

9,10

In the randomized PIVOT trial comparing radical

prostatectomy versus observation in the PSA era, it was

shown that there was no benefit from radical surgery for

patients with low-risk tumors, which are precisely the

majority of cases found in screening programs. In this

study, there was no difference in mortality after 20 years

of monitoring for patients with prostate adenocarcinoma

with a Gleason score of 6 between those who did and did

not undergo surgery. There was only increased survival

in the cases of more aggressive tumors.

Prostate biopsy indications have also changed over the

years. After the Prostate Cancer Prevention Trial (PCPT)

study showed cancer in at least 15% of patients with PSA

< 4 ng/mL, prostate biopsy began to be recommended with

lower PSA values of around 2.5 ng/mL, and this has con-

tributed to the progressive finding of clinically insignificant

tumors of lower biological aggressiveness.

The interpretation of the role of PSA becomes even

more complex when, in addition to this tumor over-di-

agnosis, we include the lead time bias and the migration

of the screening programs in survival analyses, due to

their potential to artificially modify the statistics.